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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Adenosine is a nucleoside that is composed of adenine and d-ribose and plays many important biological roles in addition to being components of DNA and RNA.
Synonyms: Adenine riboside; D-Adenosine; NSC 627048
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Lan, Zhenwei ; Yang, Rui ; Wang, Hu ; Xue, Xingyang ; Sun, Yue ; Wang, Shumei , et al.
Abstract: Turmeric (Curcuma longa), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa. 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC50 values were measured (IC50 of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 μM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 μM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish (Danio rerio), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 μg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods.
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Keywords: Turmeric ; UPLC-Q Exactive-Orbitrap-MS ; Anti-inflammation ; Zebrafish ; COX-2
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Zou, Caomin ; Chen, Qianru ; Li, Jiasheng ; Lin, Xiguang ; Xue, Xingyang ; Cai, Xinhang , et al.
Abstract: Moutan Cortex (MC) has been used in treating inflammation-associated diseases and conditions in China and other Southeast Asian countries. However, the active components of its anti-inflammatory effect are still unclear. The study aimed to screen and identify potential cyclooxygenase-2 (COX-2) inhibitors in MC extract. The effect of MC on COX-2 was determined in vitro by COX-2 inhibitory assays, followed by bio-affinity ultrafiltration in combination with ultra-performance liquid chromatography-mass spectrometry (BAUF-UPLC-MS). To verify the reliability of the constructed approach, celecoxib was applied as the positive control, in contrast to adenosine which served as the negative control in this study. The bioactivity of the MC components was validated in vitro by COX-2 inhibitor assay and RAW264.7 cells. Their in vivo anti-inflammatory activity was also evaluated using LPS-induced zebrafish inflammation models. Finally, molecular docking was hired to further explore the internal interactions between the components and COX-2 residues. The MC extract showed an evident COX-2-inhibitory effect in a concentration-dependent manner. A total of 11 potential COX-2 inhibitors were eventually identified in MC extract. The COX-2 inhibitory activity of five components, namely, gallic acid (GA), methyl gallate (MG), galloylpaeoniflorin (GP), 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG), and 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG), were validated through both in vitro assays and experiments using zebrafish models. Besides, the molecular docking analysis revealed that the potential inhibitors in MC could effectively inhibit COX-2 by interacting with specific residues, similar to the mechanism of action exhibited by celecoxib. In conclusion, BAUF-UPLC-MS combining the molecular docking is an efficient approach to discover enzyme inhibitors from traditional herbs and understand the mechanism of action.
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Keywords: Moutan cortex ; cox-2 inhibitors ; bio-affinity ultrafiltration ; UPLC-MS ; anti-inflammatory
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Fluorescent ratiometric supramolecular tandem assays for phosphatase and phytase enzymes
Kirk M. Atkinson ; Bradley D. Smith ;
Abstract: Ratiometric fluorescent assays have a built-in correction factor which enhances assay accuracy and reliability. We have developed fluorescent ratiometric supramolecular tandem assays for phosphatase and phytase enzymes using a mixture of three molecular components. One of the molecules is a tetra-cationic fluorescence quencher called CalixPyr which can bind and quench the polyanionic pyrene fluorophore, CMP, that emits at 430 nm. Polyphosphates can disrupt the CMP/CalixPyr complex and alter the fluorescence intensity (responsive signal). CalixPyr has no effect on the fluorescence emission of cationic pentamethine cyanine fluorophore, cCy5, which emits at 665 nm and acts as a non-responsive reference signal. The continuous ratiometric fluorescent assay for alkaline phosphatase monitored hydrolytic consumption of adenosine triphosphate (ATP). The continuous ratiometric fluorescent assay for phytase activity monitored hydrolytic consumption of phytate. With further development this latter assay may be useful for high throughput assessment of phytase activity in individual batches of fortified animal feed. It is likely that the three-molecule mixture (CMP, CalixPyr, cCy5) can become a general assay platform for other enzymes that catalyse addition/removal of phosphate groups from appropriate molecular substrates.
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Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.
Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.
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Purchased from AmBeed: 2086772-26-9 ; 29908-03-0 ; 73-24-5 ; 83948-53-2 ; 39684-80-5 ; 58-61-7 ; 2004-06-0 ; 2038-57-5 ; 199915-38-3 ; 2040291-27-6 ; 3218-02-8 ; 1561178-17-3 ; 58944-73-3
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| CAS No. : | 58-61-7 |
| Formula : | C10H13N5O4 |
| M.W : | 267.24 |
| SMILES Code : | O[C@H]1[C@H](N2C=NC3=C(N)N=CN=C23)O[C@H](CO)[C@H]1O |
| Synonyms : |
Adenine riboside; D-Adenosine; NSC 627048
|
| English Name : | (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol |
| MDL No. : | MFCD00005752 |
| InChI Key : | OIRDTQYFTABQOQ-KQYNXXCUSA-N |
| Pubchem ID : | 60961 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 52% | With N-chloro-succinimide; acetic acid In N,N-dimethyl-formamide at 20℃; for 48 h; | Procedure 2: Adenosine (1.09g, 4.08 mmol) was suspended in DMF (50 mL) and glacial acetic acid (10 mL) was added. A solution of N-chlorosuccinimide (2 g, 15 mmol) in DMF (15 mL) was added dropwise. The reaction mixture was stirred at rt for 48 hours and the volatiles were evaporated in vacuo to give yellow gum. The crude was absorbed on silica and purified by silica gel CC (packed in 5percent MeOHICHC13, eluted with 7percent MeOHICHC13) to yield a white powder (0.65 g, 52 percent).‘H NIVIR (500 MHz, DMSO-d6) 8.16 (s, 1H, H-2), 7.55 (br s, 2H, NH2), 5.86 (d, J = 6.8 Hz, 1H, Hi’), 5.48 (d, J 6.2 Hz, iH, 2’OH), 5.45 (d, J 4.0 Hz, iH, 5’-OH), 5.23 (d, J4.6 Hz, iH, 3’OH), 5.08-5.06 (m, iH, H-2’), 4.23-4.i8 (m, iH, H3’), 4.01-3.96 (m, iH, H4’),3.72-3.65 (m, iH, H5’), 3.57-3.50 (m, iH, H5’). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 65% | With acetic acid In methanol; N,N-dimethyl-formamide | Method B to a solution of adenosine (1.09 g, 4.1 mmol) in DMF (50 mL) and AcOH (10 mL) was added N-Chlorosuccinamide (NCS, 2.0 g, 15 mmol). The reaction mixture was stirred at room temperature for 6 days. The solvents were evaporated to dryness and the residue was purified by HPLC on a C-18 reverse phase column using MeOH:AcOH:H2 O (18:1:18, v/v) to give 0.8 g (65percent) of 2, which was identical to the title compound prepared by Method A. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | With toluene-4-sulfonic acid; orthoformic acid triethyl ester at 20℃; | |
| 100% | With p-toluenesulfonic acid monohydrate for 3h; Inert atmosphere; | |
| 99% | With toluene-4-sulfonic acid at 20℃; for 1h; Inert atmosphere; |
| 99% | With toluene-4-sulfonic acid at 0 - 20℃; Inert atmosphere; | 2’,3’-O-Isopropylideneadenosine (S1) p-Toluenesulfonic acid (19 g, 110.2 mmol) was added to a solution of adenosine (3 g, 11.2 mmol) in acetone (300 mL) at 0 °C. The reaction mixture was stirred at room temperature overnight. While cooling in an ice bath, a saturated sodium bicarbonate solution (300 mL) was added to the reaction mixture until the pH of the solution was slightly basic. Then the acetone was evaporated using rotary evaporator and the remaining aqueous layer was extracted with ethyl acetate. The combined organicl ayers were washed with brine and dried over sodium sulfate. The product was dried under high-powered vaccum to afford compound S1 as a white solid (3.56 g, 99%). |
| 99% | With perchloric acid for 2h; Cooling; | |
| 99% | With perchloric acid for 2h; Cooling with ice; | 6.A A. 2′, 3′-O-isopropylidene Adenosine (11) A. 2', 3'-O-isopropylidene Adenosine (11) To adenosine (2.02 g, 7.56 mmol) suspended in acetone (150 ml) was added catalytic amount of perchloric acid (0.91 ml) drop-wise while under ice-bath. The milky white reaction mixture turned clear after 2 hours of stirring. The solution was then neutralized using two equivalent of ammonium hydroxide under ice-bath. The reaction mixture was then evaporated to under rotary evaporator to complete dryness and purified using flash silica gel chromatography (gradient: 0% for 4 min, 0-15% for 4-10 min and eluted at 15% MeOH:dichloromethane). The fractions containing the product were evaporated to obtain the product (2.3 g, 3.58 mmol) in 99% yield. The 1H NMR spectrum was (DMSO-d6): 1.33 (s, 3H), 1.55 (s, 3H), 3.54-3.56 (m, 2H), 4.22 (m, 1H), 4.97 (dd, 1H), 5.23 (t, 1H), 5.35 (d, 1H), 6.12 (d, 1H), 7.34 (s, 2H), 8.17 (s, 1H) and 8.35 (s, 1H). 13C-DMSO-d6: 156.60, 153.09, 149.28, 140.16, 119.57, 113.51, 90.07, 86.82, 83.68, 81.82, 62.05, 27.55 and 25.66 ppm. HRMS (ESI+) calcd for C13H18N5O4 [(M+H)+] 308.1359 found 308.1351. |
| 99% | With toluene-4-sulfonic acid at 20℃; for 1h; | 1.1a 1a) 2',3'-O-isopropylidene-5'-O-p-toluenesulfonyladenosine Adenosine (5.0 g, 18.7 mmol, 1.0 eq),TsOH·H2O (32.2 g, 187 mmol, 10.0 eq) was dissolved in 1 L of acetone.Stir at room temperature for 1 h. Saturated NaHCO3 solution was added to the reaction solution under ice bath.Adjust the pH ≥ 7, and remove the acetone by rotary evaporation to obtain a white solid.Namely, 8.6 g of 2',3'-O-isopropylidene adenosine, yield 99%.The above obtained 2',3'-O-isopropylidene adenosine (4.16 g, 10 mmol, 1.0 eq), TsCl (2.48 g, 13 mmol, 1.3 eq) andDMAP (1.83 g, 15 mmol, 1.5 eq) was dissolved in DCM.Stir at room temperature for 3 h.The solvent was evaporated under reduced pressure and the residue was diluted with EA.Wash with saturated NaHCO3 solution and saturated NaCl solution in turn.The organic phase was collected and dried over anhydrous Na 2 SO 4 .Silica gel column chromatography (DCM: MeOH = 50:1)The product was obtained as a white solid, 3.50 g, yield 76%. |
| 95% | With perchloric acid In water at 0 - 20℃; for 7h; | |
| 95% | With toluene-4-sulfonic acid at 20℃; | |
| 95% | With toluene-4-sulfonic acid In methanol at 20℃; for 6h; | ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (2) To a solution of adenosine (100.0 g, 374.5 mmol) in methanol and acetone (1:1, 300 ml) was dropwise added the solution of p-toluenesulfonic acid (284.6 g, 1498.1 mmol) in methanol, mixtures were stirred at room temperature for 6 h. The mixture was quenched with saturated NaHCO3 at 0 , the acetone was evaporated, the water layer was extracted with chloroform, the organic layer was washed with deionized water and saturated brine, dried with Na2SO4, filtered and evaporated. To give the compound 2 in 95% yield, white solid (109.2 g). 1H NMR (400 MHz, DMSO-d6) δ 1.38 (s, 3H), 1.65 (s, 3H), 3.80 (d, J = 12.4 Hz, 1H), 3.89 (d, J = 12.8 Hz, 1H), 4.55 (s,1H), 5.11 (d, J = 5.6 Hz, 1H), 5.19 (t, J = 5.2 Hz, 1H), 5.88 (d, J = 4.8 Hz, 1H), 7.89 (s, 1H), 8.33 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 25.4, 27.8, 63.5, 81.8, 83.1, 86.2, 94.5, 114.2, 121.2, 140.4, 148.5, 152.6, 156.0. |
| 95% | With perchloric acid In water at 0 - 20℃; for 2h; Inert atmosphere; | |
| 95% | With perchloric acid In water at 0 - 20℃; for 2h; | To a solution of adenosine (6.68 g, 25.0 mmol) in 500 mL of acetone was treated with perchloroic add (3.0 mL, 70% in water) at 0 °C then stirred at room temperature for 2 h. The resulting solution was neutralized with Na2CO3 at 0 °C and the resulting white solid removed by filtration. The filtrate was concentrated under reduced pressure to yield acetonide (4.67 g, 95 ). (0129) 1H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 8.07 (s, 1H), 6.03 (d, J = 3.0 Hz, 1H), 5.25 (dd, J = 6.1, 3.1 Hz, 2H), 5.16 (s, 1H), 4.87 (dd, J = 6.1, 2.4 Hz, 2H), 4.12 (q, J = 4.6 Hz, 2H), 3.45 (qd, J = 11.7, 4.8 Hz, 3H), 1.45 (s, 3H), 1.23 (s, 3H). |
| 95% | With perchloric acid In water at 0 - 20℃; for 2h; | To a solution of adenosine (6.68 g, 25.0 mmol) in 500 mL of acetone was treated with perchloroic add (3.0 mL, 70% in water) at 0 °C then stirred at room temperature for 2 h. The resulting solution was neutralized with Na2CO3 at 0 °C and the resulting white solid removed by filtration. The filtrate was concentrated under reduced pressure to yield acetonide (4.67 g, 95 ). (0129) 1H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 8.07 (s, 1H), 6.03 (d, J = 3.0 Hz, 1H), 5.25 (dd, J = 6.1, 3.1 Hz, 2H), 5.16 (s, 1H), 4.87 (dd, J = 6.1, 2.4 Hz, 2H), 4.12 (q, J = 4.6 Hz, 2H), 3.45 (qd, J = 11.7, 4.8 Hz, 3H), 1.45 (s, 3H), 1.23 (s, 3H). |
| 93% | Stage #1: acetone; adenosine With toluene-4-sulfonic acid at 20℃; for 0.5h; Stage #2: With orthoformic acid triethyl ester for 48h; | A11 Pre aration of intermediate 42 A solution of adenosine (20 g, 74.8 mmol) and p-toluenesulfonic acid monohydrate (14.8 g, 77.9 mmol) in acetone (786 mL) was stirred for 30 min at r.t. and then triethyl orthoformate anhydrous (57 mL, 342.8 mmol) was added. After 2 days volatiles were evaporated and the residue was partitioned in NaHC03 aq. and CH2CI2. The solid was filtered and was washed with water and ether to give 20.2 g of intermediate 42. The filtrate was evaporated and the residue was partitioned in NaHC03 ac and CH2CI2. The separated organic layer was washed with brine, dried over MgSC^ and evaporated. The yellow solid was washed with ether to give another 1.89 g of intermediate 42 In total 22.1 g of intermediate 42 (22.1 g, 69.7 mmol, 93% yield)) is formed and isolated. |
| 93% | With toluene-4-sulfonic acid at 20℃; for 3h; | |
| 92% | With perchloric acid for 2h; Inert atmosphere; | 2',3'-Isopropylidene -adenosine (1). Adenosine (0,5 g; 1,9 mmoli) was suspended in 15 mL of acetone under Ar obtaining a white suspension. After the addition of 0.4 mL of HClO4 the solution became clear. After 2 h the solution was treated with NH3 until pH 7 and evaporated. The residue was purified by flash chromatography (eluent: CH2Cl2/MeOH 96/4 v/v) to afford desiderated compound 1 (yield 92%). 1H-NMR (400 MHz, DMSO-d6) d: 1.3 (3H, s, (CH3)2C), 1.5 (3H, s, (CH3)2C), 3.5 (2H, m, H-5, H-5’), 4.2 (1H, m, H-4), 5.0 (1H, dd, H-3), 5.6 (1H, dd, H-2), 6.0 (1H, d, H-1), 8.1 (1H, s, H-8). ESI MS: m/z 310.2 Da [M+H]+, C13H19N5O4 Mol. Wt. 309.32. |
| 92% | With toluene-4-sulfonic acid; orthoformic acid triethyl ester at 20℃; for 16h; | 1 Synthesis of compound 9a ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4- yl)methanol (1).19 To a solution of adenosine (10.0 g, 37.4 mmol, 1 equiv.) in acetone (1 L), was added CH(OEt)3 (31.1 mL, 187 mmol, 5 equiv.) and pTsOH (35.6 g, 187 mmol, 5 equiv.) . The mixture was stirred at rt for 16 h, then quenched with aqueous saturated NaHCO3, concentrated until a precipitate was obtained. The precipitate was dissolved in MeOH/CH2Cl2, filtered and evaporated to give the final product (10.5 g, 34.4 mmol, 92%) as a white solid. 1H NMR (500 MHz, DMSO-d6) d 8.33 (s, 1H), 8.15 (s, 1H), 7.33 (s, 2H), 6.11 (d, J = 3.1 Hz, 1H), 5.33 (dd, J = 6.2, 3.1 Hz, 1H), 5.29 (d, J = 21.9 Hz, 1H), 4.96 (dd, J = 6.2, 2.5 Hz, 1H), 4.20 (td, J = 4.8, 2.5 Hz, 1H), 3.59 - 3.48 (m, 2H), 1.53 (d, J = 0.7 Hz, 3H), 1.31 (d, J = 0.8 Hz, 3H). 13C NMR (101 MHz, DMSO) d 156.1, 152.5, 148.8, 139.6, 119.0, 113.0, 89.5, 86.3, 83.2, 81.3, 61.5, 27.0, 25.1. Rf : 0.31 (4 % MeOH in CH2Cl2; + 2 % NH37 M in MeOH). HRMS (ESI): calcd. for C13H17N5O4 [M+H ]+: 308.13 found: 308.13 |
| 92% | With toluene-4-sulfonic acid; orthoformic acid triethyl ester In water at 20℃; | |
| 91% | With thionyl chloride; orthoformic acid triethyl ester at 20℃; | |
| 89% | With toluene-4-sulfonic acid; orthoformic acid triethyl ester at 20℃; | 1.0 Synthesis of 2',3'-O-isopropylideneadenosine To a stirring solution of adenosine (13.36 g, 50 mmol) in 1 .5 L of dry acetone was added p-toluenesulfonic acid monohydrate (10.46 g, 55 mmol) and triethyl orthoformate (42 mL, 250 mmol). The mixture was stirred at room temperature overnight and then neutralized with a saturated aqueous solution of ammonium-hydroxide. The volatiles were removed under reduced pressure and the residues were cooled to crystallize. After filtration, 2',3'-O- isopropylideneadenosine was obtained as a white solid (13.66 g, 89% yield). LRMS (ESI) m/z calcd for C13H17N5O4 [M+H]+ : 308.13; Found : 308.12. |
| 87% | With toluene-4-sulfonic acid | |
| 86% | With toluene-4-sulfonic acid at 20℃; for 3h; Inert atmosphere; | S.1.1 ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-d][1 ,3]dioxol-4-yl)methanol (3) Adenosine (2.0 g, 7.5 mmol) was stirred in acetone (400 mL) with para- toluene sulfonic acid monohydrate (14.3 g, 75 mmol) for three hours at room temperature under nitrogen. Upon completion, the reaction was basified with saturated sodium bicarbonate (400 mL) until the pH was slightly basic via litmus paper detection. The acetone was concentrated and the product was extracted from the aqueous layer using ethyl acetate (5 x 200 mL washes). The organic layer was washed with brine, dried over sodium sulfate and solvent removed in vacuo to yield a white solid (1.91 g, 86%).1H NMR (400 MHz, CD30D) δ 8.31 (s, 1H), 8.18 (s, 1H), 6.16-6.12 (d, J = 2.5 Hz, 1H), 5.29-5.24 (m, 1H), 5.05-5.01 (m, 1H), 4.39-4.34 (br, 1H), 3.81-3.75 (dd, J = 12.2 Hz, 2.5 Hz, 1H), 3.74-3.67 (dd, J = 12.2 Hz, 2.8 Hz, 1H), 1.61 (s, 3H), 1.37 (s, 3H); 13C NMR (100 MHz, CD30D) δ 155.9, 152.2, 148.5, 140.2, 119.1, 113.7, 91.3, 86.5, 83.7, 81.4, 62.0, 26.0, 24.0; LRMS (ESI): m/z [M+Na]+ calc'd for C13H17N5Na04+ 330.12, found 330.13. |
| 86% | With toluene-4-sulfonic acid at 20℃; for 3h; Inert atmosphere; | ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (4) Adenosine (2.0 g, 7.5 mmol) was stirred in acetone (400 mL) with para-toluene sulfonic acid monohydrate (14.3 g, 75 mmol) for three hours at room temperature under nitrogen. Upon completion, the reaction was basified with saturated sodium bicarbonate (400 mL) until the pH was slightly basic via litmus paper detection. The acetone was concentrated and the product was extracted from the aqueous layer using ethyl acetate (5 x 200 mL washes). The organic layer was washed with brine, dried over sodium sulfate and solvent removedin vacuoto yield a white solid (1.91 g, 86%).1H NMR (400 MHz, CD3OD) δ 1.38 (s, 3H, COC(CH3)2), 1.62 (s, 3H, COC(CH3)2), 3.71 (dd,J= 12.0 and 2.8 Hz, 1H, 5’CH2), 3.79 (dd,J= 12.3 and 2.0 Hz, 1H, 5’CH2), 4.38 (s, 1H, 4’H), 5.04 (d,J= 4.4 Hz, 1H, 3’H), 5.24-5.31 (m, 1H, 2’H), 6.15 (d,J= 2.4 Hz, 1H, 1’H), 8.19 (s, 1H, C2-H), 8.32 (s, 1H, C8-H);13C NMR (100 MHz, CD3OD) δ 25.53, 27.60, 63.57, 82.97, 85.30, 88.10, 92.85, 115.26, 120.69, 141.73, 150.03, 153.77, 157.51; LRMS (ESI): m/z [M+Na]+calc’d for C13H17N5NaO4+330.12, found 330.13. |
| 85% | With toluene-4-sulfonic acid at 20℃; for 6h; Cooling with ice; | 3.1 Synthesis of 2′,3′-O-isopropylideneadenosine Adenosine (1 mmol of) was dissolved in 10 ~ 30ml (preferably 20 ml) of acetone, p-toluenesulfonic acid 8 ~ 12mmol (preferably 10 mmol) was dissolved in 10 ~ 30ml (preferably 20 ml) of acetone. Under ice cooling, p-toluenesulfonic acid in acetone was slowly added dropwise to a solution of 2-amino-adenosine in acetone, stirred at room temperature 24 ~ 72 h (preferably 6H), poured into ice 4% sodium hydrogencarbonate aqueous solution, a white precipitate, suction filtration, and dried. Soxhlet extraction with chloroform and purified to give a white powder after drying. Yield 85%. |
| 81% | With perchloric acid at 20℃; for 5h; Inert atmosphere; | |
| 79% | With toluene-4-sulfonic acid at 20℃; for 50h; | Synthesis of 2',3'-O-isopropylideneadenosine (2) A mixture of adenosine (4.96 g, 18.56 mmol), p-toluenesulfonicacid monohydrate (3.53 g, 18.56 mmol) and acetone (150 mL) wasstirred at room temperature in an open vessel. After 46 h fromstarting reaction, 5.10 g of p-toluenesulfonic acid monohydratewas added. After 2 h, 5.21 g of p-toluenesulfonic acid monohydratewas added (total 13.94 g, 73.3 mmol). After 2 h from adding theacid, the spot of compound 1 disappeared. The mixture turned intoa yellow solution. The reaction mixture was quenched by adding12.3 mL of triethylamine (88.4 mmol, 4.73 eq.). The mixture wasevaporated and purified by column chromatography (chloroform/methanol 20:1) to give compound 2 (4.50 g, 14.6 mmol, 79%). 1HNMR (300 MHz, DMSO-d6) d 1.33 and 1.55 (2s, 6H, CMe2), 3.52-3.56 (m, 2H, H50), 4.19-4.23 (m, 1H, H40), 4.95-4.98 (m, 1H, H30), 5.25 (vbs, 1H, OH), 5.33-5.36 (m, 1H, H 20), 6.11-6.12 (m,1H,H 10), 7.34 (bs, 2H, NH2), 8.15 (s, 1H, H2), 8.34 (s, 1H, H8);ESI-TOF-MS for C13H17N5O4: (MNa+) calcd: 330.12, found: 330.03. |
| 78% | Stage #1: acetone; adenosine With perchloric acid at 20℃; for 1.5h; Stage #2: With ammonia In water at 20℃; for 3h; | |
| 78% | With perchloric acid at 0 - 20℃; for 21h; | |
| 77% | Stage #1: acetone; adenosine at 20 - 30℃; for 0.0833333h; Stage #2: With perchloric acid at 20 - 30℃; for 1h; | 1 Example 1 : Acetonide protection Adenosine 1 (100 g) and acetone (4 L, 40 v/w) were stirred for 5 minutes at 20-30 °C for 5 minutes. Perchloric acid (40 mL, 0.4 v/w) was added to the reaction mixture and stirred at 20-30 °C for 1 h, monitoring by UPLC. The reaction mass was quenched with 7 % sodium bicarbonate solution (1 L, 10 v/w) at 20-30 °C and cooled to -5 °C to 5 °C. The reaction mass was stirred for 1 hour. The obtained product was filtered, the filter cake was washed with acetone (200 mL, 2.0 v/w) and dried under vacuum for 8 h to yield compound 2.Yield: 89 g, 77 %HPLC purity: 97.96 % |
| 75% | With toluene-4-sulfonic acid at 20℃; for 3h; | |
| 73% | With toluene-4-sulfonic acid Inert atmosphere; | |
| 72% | With toluene-4-sulfonic acid; orthoformic acid triethyl ester | I.2 Preparation of adenosine 2',3'-Isopropylidene(Nucleic Acid Chemistry, part 2, Editors Townsend, Tipson, Wiley Interscience, John Wiley & Sons p. 768, (1978))Ethyl orthoformate (12.44 ml, 74.8 mmol) is added dropwise, under argon, to a suspension of adenosine (5 g, 18.7 mmol) in acetone (10 ml) containing APTS (para-toluene-sulfonic acid) (3.9 g, 20.6 mmol). After reaction overnight, 110 ml of water containing 1.86 ml of aqueous ammonia at 27% are added. After stirring for 30 minutes, the reaction mixture is evaporated until white crystals appear. After 12 h at +40° C., a white precipitate is obtained which is recrystallized in water. 4.17 g (13.5 mmol, 72%) of product is obtained in the form of a white powder. This intermediate was characterized by proton NMR. |
| 70.1% | With Trimethyl orthoacetate; thionyl chloride at 20℃; for 6h; | Synthesis of 2',3'-O-isopropylideneadenosine (14) In a 250 mL, three-neck round-bottom flask were placedadenosine 2 (4.01 g, 15 mmol) and acetone (40 mL). Trimethylorthoacetate (6 mL) was added to the reactionmixture upon stirring and thionyl chloride (SOCl2, 3.3 mL)was added dropwise to the solution for acidification. Afteraddition of thionyl chloride, the mixture was stirred atroom temperature for another 6 h. After reaction completion,the mixture was filtered and the residue was addedinto saturated sodium bicarbonate solution to adjust the pHvalue to 7 or 8. After 30 min of standing, the crude productwas obtained by filtration and was dried at 50 C in avacuum drying oven. Recrystallization from water affordedpure 14 as a light yellow solid (3.23 g, 70.1%) with thepurity of 98.7% (HPLC). 1H NMR (500 MHz, DMSO-d6)d 8.35 (s, 1H, 2-H), 8.16 (s, 1H, 8-H), 7.40 (s, 2H, -NH2),6.13 (d, J = 3.1 Hz, 1H, 10-H), 5.35 (dd, J = 6.2, 3.1 Hz,1H, 20-H), 5.25 (s, 1H, 50-OH), 4.97 (dd, J = 6.2, 2.5 Hz,1H, 30-H), 4.23-4.21 (m, 1H, 40-H), 3.58-3.51 (m, 2H, 50-H), 1.55 (s, 3H, -CH3), 1.33 (s, 3H, -CH3).13C NMR(101 MHz, DMSO) d 156.60 (6-C), 153.10 (2-C), 149.25(4-C), 140.17 (8-C), 119.56 (5-C), 113.49 (quaternarycarbon), 90.09 (10-C), 86.80 (40-C), 83.67 (20-C), 81.82 (30-C), 62.05 (50-C), 27.54 (-CH3), 25.64 (-CH3). |
| 69% | With perchloric acid; 4 A molecular sieve for 2h; Ambient temperature; | |
| unter Zusatz von ZnCl2; | ||
| With camphor-10-sulfonic acid | ||
| Stage #1: acetone; adenosine With methanesulfonyl chloride for 0.5h; Stage #2: With sodium carbonate In water for 0.5h; | 1 2',3' isoproylidene adenosine 2',3' isoproylidene adenosine A 250 ml round bottom flask was charged with 10 gm adenosine and to it was added 100 ml acetone. Methanesulfonyl chloride (10 ml) was then added drop-wise to the above solution. The solution was stirred for 30 minutes, after which time 100 ml of 1M Na2CO3 was carefully added. This sample was stirred for another 30 minutes and the solution filtered. The filtrate was taken up in dichloromethane, washed with water, and dried. The organic solvent was removed to afford the 4.45 grams pure 2',3' isopropylidene adenosine as the product. | |
| With thionyl chloride; trimethyl orthoformate | ||
| With thionyl chloride; trimethyl orthoformate | It was prepared according to Scheme 1. To a suspension of adenosine (8.03 g, 30 mmol) in 100 mL dry acetone was added trimethyl orthoformate (2.4 mL), followed by SOCl2 (6.75 mL, 90 mmol) dropwise. After stirring overnight, the solid was filtered, dissolved in saturated NaHCO3, and neutralized to pH 7. The solid was collected by filtration, washed with ether (20 mL), and dried in vacuo to give 2′,3′-isopropylidene-N6-methyl-adenosine, to which (3.07 g, 10 mmol) in dry THF (20 mL) were added phthalimide (1.62 g, 11 mmol) and PPh3 (2.88 g, 11 mmol), followed by diisopropyl azodicarboxylate (DIAD, 1.08 g, 11 mmol). After 2.5 h, the white solid was filtered, washed with 20 mL of cold Et2O. The crude Mitsunobu product and hydrazine hydrate (2.4 mL, 50 mmol) were refluxed overnight in ethanol (20 mL). After cooling, the reaction mixture was filtered and the filtrate evaporated to dryness. To the product (612 mg, 2.0 mmol) in THF (5 mL) were added Et3N (0.9 mL, 6.4 mmol) and ethyl bromoacetate (0.28 mL, 2.5 mmol). After stirring overnight, the resulting mixture was filtered and evaporated to dryness. The residue oil thus obtained was dissolved in THF (10 mL) and cooled to -20° C., followed by addition of LiAlH4 (166 mg, 4.4 mmol). The reaction was allowed to warm to room temperature over 2.5 h, quenched with saturated NaHCO3, and the product was extracted with 50 mL of EtOAc, washed successively with saturated NaHCO3, water, and saturated NaCl. | |
| With phthalic acid dimethyl ester; toluene-4-sulfonic acid at 20℃; for 24h; Inert atmosphere; | ||
| With sulfuric acid at 20℃; for 0.5h; | ||
| With toluene-4-sulfonic acid at 20℃; | ||
| With toluene-4-sulfonic acid In water at 20℃; for 1h; | ||
| unter Zusatz von ZnCl2; | ||
| With perchloric acid at 0℃; for 2h; | 26 To a suspension of adenosine in acetone at 0°C was added HC104 and stirring continued for 2h. Aq. NH3 was then added and the solution concentrated in vacuo. The solution was cooled to-20°C and the resulting white precipitate of 2'3'-O- isopropylidene-adenosine collected and washed with acetone | |
| With Dess-Martin periodane; toluene-4-sulfonic acid at 20℃; | ||
| With perchloric acid | Adenosine 5′-H-Phosphonate Synthesis The synthesis approach for 135 can be seen in Scheme 4 (FIG. 4). First, adenosine was protected using a catalytic amount of perchloric acid in acetone to give 129. This was benzoylated at the 5′ position, as well as on the exocyclic amine, using benzoyl chloride (BzCl) in pyridine to afford 130. Here, it is also possible to form a compound with two Bz protecting groups on the exocyclic amine It was observed that this had started to form before the starting material was fully consumed, so the reaction was stopped. Varying conditions may be altered to optimize this procedure, including by moving forward with an adenosine compound obtaining three Bz protecting groups. Fully protected 130 then underwent acidic hydrolysis using dilute hydrochloric acid in dioxane to give 131. Again, this saw low crude yields. Compound 131 was selectively silylated at the 2′ position using tert-butyldimethylsilyl chloride and silver nitrate (AgNO3) in a mixture of pyridine and tetrahydrofuran. Compound 132 was then protected using dimethoxytrityl chloride in pyridine to give 133 with a crude yield of 88%, which was pushed forward to attempt the selective deprotection using 2N sodium hydroxide (NaOH) in pyridine and methanol which failed. Compound 133 should be purified before going forward to ensure a single, pure product to test the reaction with. As stated before, the scheme could be modified as in the case of guanosine to remove the need to use an isopropylidene protecting group on the 2′ and 3′ hydroxyls, which should reduce the number of steps used and increase the overall yields. | |
| With perchloric acid for 2h; Inert atmosphere; | ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol13 (S1) Adenosine (1.0 g, 3.7 mmol) was suspended in 50 mL acetone under argon. Dropwise addition of 800 μL of HClO4 gavea clear solution. After 2 h the solution was treated with concentrated NH4OH until the pH was 7. The solvent was evaporated, and the product purified by flash chromatography using CH2Cl2/MeOH (95%). | |
| With toluene-4-sulfonic acid; trimethyl orthoformate |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With RNase T2 at 37℃; for 24h; Yield given. Yields of byproduct given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 20 % Spectr. | With boric acid In water at 50℃; for 24h; Further byproducts given. Yields of byproduct given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In water at 50℃; for 24h; Yields of byproduct given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92% | In tetrahydrofuran at 60℃; for 17h; Candida antarctica lipase (SP435); |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | With pyridine | |
| 95% | With pyridine at 20℃; for 5h; | |
| 94% | With pyridine In dichloromethane; water; toluene | R.1.1 (1) (1) 3',5'-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl)-adenosine Adenosine (4.61 g, 17.3 mmol.) was subjected to azeotropic distillation with anhydrous pyridine. To the residue were added anhydrous pyridine (43 mL) and 1,1,3,3-tetraisopropyl-1,3-dichlorodisiloxane (5.70 mL, 1.72 mmol.). The resulting mixture was stirred at room temperature for 5 hours. Then, to the mixture were added dichloromethane (30 mL) and a mixture of pyridine and water (1:1, vol/vol, 20 mL). The organic layer was extracted three times with dichloromethane (30 mL x 3). The extracts were combined and placed under reduced pressure to remove the solvent. To the residue was added toluene, and the resulting solution was subjected to azeotropic distillation, to remove pyridine. The residual solution was placed on a silica gel column and eluted with 0.5% pyridine-methanol/ dichloromethane (1/50) to give the subject compound (8.30 g, 94%). |
| 94% | With pyridine In dichloromethane; water; toluene | R.1.1 (1) (1) 3',5'-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl) adenosine Adenosine (4.61 g, 17.3 mmol.) was subjected to azeotropic distillation with anhydrous pyridine. To the residue were added anhydrous pyridine (43 mL) and 1,1,3,3-tetraisopropyl-1,3-dichlorodisiloxane (5.70 mL, 1.72 mmol.). The mixture was stirred at room temperature for 5 hours. Then, to the mixture were added dichloromethane (30 mL) and a mixture of pyridine and water (1:1, vol/vol, 20 mL). The organic layer was extracted three times with dichloromethane (30 mL x 3). The extracts were combined and placed under reduced pressure to remove the solvent. To the residue was added toluene, and the resulting solution was subjected to azeotropic distillation, to remove pyridine. The residual solution was placed on a silica gel column and eluted with 0.5% pyridine-methanol/ dichloromethane (1/50) to give the subject compound (8.30 g, 94%). |
| 94% | With pyridine; dmap at 20℃; for 24h; | 3',5'-0-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl)adenosine (1) To a suspension of adenosine (3 g, 11 mmol) in anhydrous pyridine (40 mL)were added dimethylaminopyridine (0.7 g, 5.6 mmol) and dichloro-1,1,3,3-tetraisopropyldisiloxane (4 mL, 13 mmol). After stirring for 24h, the reaction mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (CH2Cl2/ MeOH: 95/05) to afford 1 as a white solid (5.3 g, 94%). 1H NMR (300 MHz, DMSO-d6) δ 8.21 (s, 1H, H8), 8.07 (s, 1H, H2),7.32 (br, 2H, NH2), 5.87 (s, 1H, H1’), 5.62 (d, J = 4.6 Hz, 1H, OH), 4.79 (m, 1H, H3’), 4.51 (t, J = 4.7 Hz, 1H, H2’), 4.08-3.90 (m, 3H,2H5’ and H4’), 1.09-0.98 (m, 28H); UV (EtOH) λmax= 260 nm (εmax=16700); MS (ESI+): m/z = 510.2 (M+H)+; HRMS calculated for C22H40N5O5Si2(M+H+): 510. 2575, found 510.2568. |
| 93% | With pyridine | |
| 92% | With pyridine | |
| 91% | With pyridine for 3h; Ambient temperature; | |
| 90% | With pyridine for 2h; Ambient temperature; | |
| 89% | With pyridine at 0 - 23℃; for 48h; Inert atmosphere; | |
| 88% | With pyridine In N,N-dimethyl-formamide for 1h; Ambient temperature; | |
| 85% | With pyridine for 3h; Ambient temperature; | |
| 85% | In pyridine for 3h; Ambient temperature; | |
| 83% | With pyridine at 20℃; for 16h; | |
| 80% | With pyridine Reflux; | |
| 80% | With pyridine at 20℃; for 46h; Inert atmosphere; | 1.1 (1) Synthesis of Compound 1 Under an argon (Ar) atmosphere, adenosine (3.01 g, 10.1 mmol, 1.0 eq.) was dissolved in pyridine (65 mL) to obtain a mixture, TPDSCl2 (3.2 mL, 10.1 mmol, 1.0 eq.) was added into the mixture, and the mixture thus obtained was stirred at room temperature for 46 hours. The solvent was distilled off under reduced pressure, and the resultant mixture was separated with ethyl acetate and water (0.1 M HCl aq., H2O, sat. NaHCOaq., brine). The drying was performed by the addition of anhydrous sodium sulfate, and then the filtration with a cotton plug was performed, subsequently the solvent was distilled off under reduced pressure. The residue was purified by neutral flash column chromatography (CHCl3 (MeOH 0-4%)) to obtain compound 1 (4.14 g, 80%). The H-NMR information of the obtained compound is as follows. 1H-NMR (400 MHz, CDCl3): δ 1.06-1.13 (m, 28H), 3.31 (s, 1H), 4.01-4.16 (m, 3H), 4.56 (d, J=5.6 Hz, 1H), 5.07-5.11 (m, 1H), 5.79 (s, 2H), 5.97 (d, J=1.2 Hz, 1H), 7.97 (s, 1H), 8.28 (s, 1H). |
| 80% | With pyridine | |
| 77% | With pyridine at 20℃; for 20h; | |
| With pyridine for 2.5h; Ambient temperature; | ||
| With pyridine | ||
| With pyridine | ||
| With pyridine | ||
| With pyridine at 0℃; | 17.1 Example 17. Preparation of (5S,6R,8R,9R)-6-(6-amino-9H-purin-9-yl)-8- (hydroxymethyl)-l,7-dioxaspiro[4.4]nonan-9-oI (94)94 78 88 89MgBr THF/-78°C93 94In the preparation of 94, it is possible to forego protection of the 6-amino- purine, which means that 94 can be prepared from adenine (78) using a seven-step sequence. Step 1: Preparation of compound 88 | |
| With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; | 16.1 Step 1 : (6aR,8R,9R,9aS)-8-(6-amino-9H-purin-9-yl)-2,2,4,4-tetraisopropyltetrahydro- 6H-furo [3 ,2-f] [ 1 ,3 ,5 ,2,4]trioxadisilocin-9-ol 58 To a solution of adenosine (20 g, 74.838 mmol) and imidazole (7.642 g, 1 12.257 mmol) in dry DMF (100 mL) at r.t. was added 1,3-dichloro-l, 1,3,3- tetraisopropyldisiloxane (26.335 mL, 0.986 g/mL, 82.322 mmol) under nitrogen atmosphere. The mixture was stirred at r.t. for 2h. The mixture was poured into a mixture of ice and water (200mL), and then extracted with EtOAc (2x300mL). The organic layer was successively washed with brine (4x300mL), dried over Na2S04, filtered and concentrated to afford crude intermediate 58 as white foam (41.3g) that was used as such for the next step. 'H NMR (400 MHz, DMSC /6) δ ppm 1.01 - 1.09 (m, 28 H), 3.91 - 3.96 (m, 1 H), 4.00 (dt, J=8.5, 2.9 Hz, 1 H), 4.04 (d, J=3.3 Hz, 1 H), 4.52 (t, J=4.5 Hz, 1 H), 4.80 (dd, J=8.5, 5.2 Hz, 1 H), 5.59 (d, J=4.6 Hz, 1 H), 5.87 (d, J=l .l Hz, 1 H), 7.29 (s, 2 H), 8.07 (s, 1 H), 8.20 (s, 1 H) MS (ES+): 560.3, | |
| 8.61 g | With pyridine; dmap at 0 - 20℃; for 5h; | 1.1 Step 1 Preparation of (6aR,8R,9R,9aS)-8-(6-amino-9H-purin-9-yl)-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-9-ol (i18): To a suspension of adenosine (i7, 5.80 g, 21.70 mmol) in pyridine (40 mL) at 0° C. was added DMAP (1.33 g, 10.85 mmol) followed by 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (7.64 mL, 23.87 mmol). The resulting mixture was warmed to rt and allowed to stir 5 h after which time the mixture was concentrated in vacuo to give a yellow oil. A mixture of MeCN and diethyl ether were added to the oil resulting in the formation of a white precipitate. The resulting precipitate was filtered off and collected to give compound i18 as a white solid (8.61 g): 1H (400 MHz, CD3OD) δ 8.28 (s, 1H), 8.16 (s, 1H), 5.97 (d, J 0.8 Hz, 1H), 4.83 (dd, J 8.4, 4.9 Hz, 1H), 4.57 (d, J=4.8 Hz, 1H), 4.22-4.13 (m, 2H), 4.06 (dd, J 12.8, 2.5 Hz, 1H), 1.15-1.05 (m, 28H); LCMS (Method C) Rt 3.20 mins; m/z 510.1 (M+H+). |
| 93 % | With pyridine | |
| 76 % | With pyridine; dmap at 20℃; | 3 TIPDSi-protection of Adenosine To a 100 mL round bottom flask, adenosine 18 (0.3 g, 1.12 mmol) was dissolved in pyridine and coevaporated (3 5 mL) to a white suspension. The co-evaporated substrate 18 was dissolved in pyridine (4 mL) and TIPDSCl2 (0.40 mL, 1.25 mmol) and DMAP (0.0686 g, 0.561 mmol) were added. The reaction was stirred at room temperature for ~23 h and monitored by TLC. Once no starting material was detected, mixture was diluted with CH2Cl2 (25 mL). The resulting solution was transferred to a separatory funnel and washed with water (1 25 mL). The aqueous layer was then extracted with additional CH2Cl2 (2 15 mL). The organic layers were combined and washed with brine and dried over MgSO4 provide crude silyl-protected 19 as a white solid which was purified by silica gel flash chromatography (CH2Cl2/ CH3OH, 5%; 0.05% Et3N) Yield (0.885 g, 76 %). Compound 19 was stored at -20 °C until it was used.1 NMR (300 MHz, DMSO-d6, δ): 8.19 (s, 1H), 8.05 (s, 1H), 5.85 (s, 1H), 5.63 (d, 3J = 4.6 Hz, 1H), 4.79-4.75 (m, 1H), 4.49 (t, 3J = 4.7 Hz, 1H), 4.06-3.88 (m, 3H), 1.02 (s, 28H). MS (ESI+, 100% CH3OH, TOF): m/z calc'd for [C22H40N5O5Si2]+ [M+H]+ 510.2563; found 510.3010. |
| 76 % | With pyridine; dmap at 20℃; | 3 TIPDSi-protection of Adenosine To a 100 mL round bottom flask, adenosine 18 (0.3 g, 1.12 mmol) was dissolved in pyridine and coevaporated (3 5 mL) to a white suspension. The co-evaporated substrate 18 was dissolved in pyridine (4 mL) and TIPDSCl2 (0.40 mL, 1.25 mmol) and DMAP (0.0686 g, 0.561 mmol) were added. The reaction was stirred at room temperature for ~23 h and monitored by TLC. Once no starting material was detected, mixture was diluted with CH2Cl2 (25 mL). The resulting solution was transferred to a separatory funnel and washed with water (1 25 mL). The aqueous layer was then extracted with additional CH2Cl2 (2 15 mL). The organic layers were combined and washed with brine and dried over MgSO4 provide crude silyl-protected 19 as a white solid which was purified by silica gel flash chromatography (CH2Cl2/ CH3OH, 5%; 0.05% Et3N) Yield (0.885 g, 76 %). Compound 19 was stored at -20 °C until it was used.1 NMR (300 MHz, DMSO-d6, δ): 8.19 (s, 1H), 8.05 (s, 1H), 5.85 (s, 1H), 5.63 (d, 3J = 4.6 Hz, 1H), 4.79-4.75 (m, 1H), 4.49 (t, 3J = 4.7 Hz, 1H), 4.06-3.88 (m, 3H), 1.02 (s, 28H). MS (ESI+, 100% CH3OH, TOF): m/z calc'd for [C22H40N5O5Si2]+ [M+H]+ 510.2563; found 510.3010. |
| 76 % | With pyridine; dmap at 20℃; | 3 TIPDSi-protection of Adenosine To a 100 mL round bottom flask, adenosine 18 (0.3 g, 1.12 mmol) was dissolved in pyridine and coevaporated (3 5 mL) to a white suspension. The co-evaporated substrate 18 was dissolved in pyridine (4 mL) and TIPDSCl2 (0.40 mL, 1.25 mmol) and DMAP (0.0686 g, 0.561 mmol) were added. The reaction was stirred at room temperature for ~23 h and monitored by TLC. Once no starting material was detected, mixture was diluted with CH2Cl2 (25 mL). The resulting solution was transferred to a separatory funnel and washed with water (1 25 mL). The aqueous layer was then extracted with additional CH2Cl2 (2 15 mL). The organic layers were combined and washed with brine and dried over MgSO4 provide crude silyl-protected 19 as a white solid which was purified by silica gel flash chromatography (CH2Cl2/ CH3OH, 5%; 0.05% Et3N) Yield (0.885 g, 76 %). Compound 19 was stored at -20 °C until it was used.1 NMR (300 MHz, DMSO-d6, δ): 8.19 (s, 1H), 8.05 (s, 1H), 5.85 (s, 1H), 5.63 (d, 3J = 4.6 Hz, 1H), 4.79-4.75 (m, 1H), 4.49 (t, 3J = 4.7 Hz, 1H), 4.06-3.88 (m, 3H), 1.02 (s, 28H). MS (ESI+, 100% CH3OH, TOF): m/z calc'd for [C22H40N5O5Si2]+ [M+H]+ 510.2563; found 510.3010. |
| 96 % | With pyridine at 0 - 20℃; Inert atmosphere; | 3′,5′-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)adenosine (2) To a stirred suspension of adenosine (2.00 g, 7.48 mmol) in dry pyridine (75.0 mL) was added dropwise 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (2.63 mL, 8.23 mmol) at 0 C under argon atmosphere. The reaction mixture was stirred for 17 hours at room temperature, methanol was added for quench and then evaporated in vacuo. The residue was diluted with dichloromethane. The solution was washed with a saturated aqueous solution of NaHCO3, water and brine and dried over Na2SO4. The filtrate was evaporated in vacuo and purified by column chromatography on silica gel (hexane/ethyl acetate = 10/90) to afford desired compound 2 (3.66 g, 7.19 mmol, 96%) as a white solid. 1H NMR (594 MHz, Chloroform-d1) : δ 8.29 (s, 1H), 8.00, (s, 1H), 6.11 (br s, 2H), 5.98 (d, J = 1.2 Hz, 1H), 5.06 (dd, J = 5.3, 8.1 Hz, 1H), 4.57 (dd, J = 1.2, 5.3 Hz, 1H), 4.16-4.10 (m, 2H), 4.04 (dd, J = 2.4, 12.0 Hz, 1H), 3.38-3.30 (br, 1H), 1.18-0.98 (m, 28H). 13C NMR (149 MHz, Chloroform-d1) : δ 154.95, 151.74, 149.10, 140.01, 120.44, 89.84, 82.33, 75.26, 70.77, 61.75, 17.58, 17.49, 17.48, 17.43, 17.25, 17.15, 17.11, 17.05, 13.42, 13.18, 12.89, 12.73. HRMS (ESI) m/z calculated for C22H39N5O5Si2, [M+H]+: 510.2563, found for [M+H]+: 510.2567. |
| 99 % | In pyridine at 0 - 20℃; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | With 1,4-diaza-bicyclo[2.2.2]octane In various solvent(s) at 140℃; for 0.0833333h; | |
| 62% | With pyridine In N,N-dimethyl-formamide at 0℃; for 12h; | |
| 60% | With triethylamine for 0.025h; Microwave irradiation; neat (no solvent); |
| 54% | In pyridine for 96h; Ambient temperature; | |
| With dmap In N,N-dimethyl-formamide | 23 Example 23; Preparation of 5'-O-DMTr-Adenosine, 2'-OTBDMS-5'-O-DMTr-Adenosine (14A), 2'-O-TBDMS-3'-O-Acetoxy-5'-O-DMTr-Adenosine (16A), and 3'-O-Acetoxy-5'-O-DMTr-Adenosine Adenosine is treated with 4,4'-dimethoxytriphenylmethyl chloride (DMTrCl) and DMAP in DMF to give 5'-O-DMTr-adenosine. 5'-O-DMTr-adenosine is treated with tert-butyldimethylsilyl chloride, silver nitrate and pyridine in THF to give 2'-OTBDMS-5'-O-DMTr-adenosine. 2'-OTBDMS-5'-O-DMTr-adenosine is treated with acetic anhydride in pyridine or DMAP to give 2'-O-TBDMS-3'-O-acetoxy-5'-O-DMTr-adenosine. 2'-O-TBDMS-3'-O-acetoxy-5'-O-DMTr-adenosine is treated with TBAF to give 3'-acetoxy-5'-O-DMTr-adenosine | |
| With pyridine | ||
| With pyridine; dmap at 20℃; for 3.33333h; Inert atmosphere; |

[ 17287-03-5 ]
[ 58-61-7 ]
[ 60037-52-7 ]
[ 57817-83-1 ]
[ 2140-79-6 ]
[ 1867-73-8 ]
[ 10300-22-8 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 19 % Chromat. 2: 7 % Chromat. 3: 18 % Chromat. 4: 12 % Chromat. 5: 4 % Chromat. | In methanol; N,N-dimethyl-formamide at 70℃; for 1h; presence of Mg(acac)2 or Ca(acac)2; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 3% 2: 7 % Chromat. 3: 9% 4: 21% | With magnesium(II) acetylacetonate In N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; | |
| 1: 18% 2: 11% 3: 7% 4: 18% | In N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; | |
| 1: 18 % Spectr. 2: 9% 3: 3% 4: 11% | In methanol; N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 37% 2: 5% 3: 4% 4: 41% | With copper acetylacetonate In N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; | |
| 1: 28% 2: 15% 3: 15% 4: 7% | With bis(acetylacetonate)nickel(II) In N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; | |
| 1: 18 % Spectr. 2: 9% 3: 4 % Spectr. 4: 3% | In methanol; N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 28% 2: 15% 3: 8% 4: 15% | With bis(acetylacetonate)nickel(II) In N,N-dimethyl-formamide at 70℃; for 1h; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 18% 2: 2% 3: 5% 4: 2 % Spectr. | In N,N-dimethyl-formamide at 100℃; for 1h; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 3% 2: 2% 3: 5% 4: 18% | In N,N-dimethyl-formamide at 100℃; for 1h; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 15% 2: 4 % Chromat. 3: 3 % Chromat. 4: 31% | With copper acetylacetonate In methanol; N,N-dimethyl-formamide at 70℃; for 0.5h; Further byproducts given; | |
| 1: 31% 2: 4 % Chromat. 3: 3 % Chromat. 4: 15% | With copper acetylacetonate In N,N-dimethyl-formamide at 70℃; for 0.5h; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With dimethyl amine; sodium iodide 1.) DMF, 80 deg C, 6 h, 2.) MeOH, RT; Yield given. Multistep reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96.3% | With methanesulfonic acid In N,N-dimethyl-formamide; acetone at 60℃; for 6h; Inert atmosphere; | A.A92.1 Preparation of intermediate 418 To a solution of Adenosine (75 g, 2 1 mmol ) in acetone ( 1 200 mL ) and DMF (400 mL ) was added 2,2-dimethoxypropane (35. 1 g, 336.8 mmol ) and methanesulfonic acid (40.5 g, 42 1 mmol ) under N2. The react ion mixture was stirred at 60 C for 6 h. The reaction mixture was treated with aqueous aHCO ; ( PH to 7-8 ) and then concentrated under reduced pressure. The residue was diluted with H20 ( 1 200 mL ) and extracted with ethyl acetate ( 1 500 ml x 3 ). The organic layers were combined, washed with brine (500 mL ), dried and concentrated under reduced pressure to give intermediate 418 (85 g, 96.3% yield ) as a white solid. |
| 95% | With Amberlyst 15H+ resin In DMF (N,N-dimethyl-formamide) at 55℃; for 3h; | 1 EXAMPLES; Example 1. Preparation of 5'-aryl ether derivatives:; 5-Amino-2- {2-benzyl-6- [6- (3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo [3,4- d] [1, 3] dioxol-4-ylmethoxy}-benzoic acid:; Adenosine (10 g, 37 mmol was dissolved in N, N-dimethyl formamide (100 mL) and dimethoxypropane (25 mL) followed by addition of Amberlyst 1 SH+ resin. The mixture was stirred 3h at 55°C. The resin was removed by filtration and the solvents removed in vacuo, affording 2', 3'-di-O-isopropylidene adenosine (11 g, 95%). This product (6 g, 20 mmol) was dissolved in N, N-dimethyl formamide (22 mL) and stirred with triisopropylsilyl chloride and imidazole 16 h at 23°C. The solution was partitioned between ether (200 mL) and brine (100 mL) and the ether phase washed with additional brine (2 x 50 mL). The ether was dried over magnesium sulfate and evaporated, affording 5'-O-triisopropylsilyl-2', 3'-di-O-isopropylidene adenosine. This residue was dissolved in toluene (20 mL) and treated with phenylisocyanate (3.6 g, 30 mmol) for 16 h at 25°C. A solution of sodium bicarbonate (1 mL of 10 M) was added and the mixture evaporated to dryness. The residue was partitioned between ethyl acetate (100 mL) and water (25 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness. The solid was dissolved in tetrahydrofuran (20 mL) and stirred with tetrabutyl ammonium fluoride in tetrahydrofuran (20 mL of a 1 M solution) for 1 h in a dry ice/acetone bath. Removal of the solvent in vacuo followed by washing with hexane afforded the 5'-alcohol (5.3 g). A portion of the above phenylurea product (0.41 g, 0.96 mmol) was suspended in 25 mL of 20% aqueous acetic acid and 5 mL of tetrahydrofuran/dioxane (1 : 1) and was stirred at 50°C for 24 h. The white suspension became a clear yellow solution. The mixture was concentrated and then lyophilized, to give 0.360 g (97% yield) of 1- [9- (3, 4- dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-9H-purin-6-yl]-3-phenyl-urea as a yellow solid. MW calculated for C17Hl8N605 (MH 387, found 387 by LCMS. A small amount of 4A flame dried molecular sieves (cooled down by a flow of argon) wasadded to a vial containing a portion of the product immediately above (0. 131 g, 0.34 mmol). The mixture was capped with a rubber septum and cooled down to 0 °C. To this mixture trifluoroacetic acid (2. 5mL) was added via syringe and the mixture stirred at this temperature for 15 min. Phenyl acetaldehyde dimethylacetal (0.230 ml, 4 eq. ) was added dropwise and the mixture stirred at 0 °C for 2 h. One more equivalent of phenyl acetaldehyde dimethyl acetal was added and stirred an additional five hours. The volatiles were evaporated off and the residue was purified by flash chromatography (hexane: ethyl acetate, 8 : 2, 1% triethylamine) to give 0.095 g of product (60% yield) as a yellow solid. MW calculated for C2sH24N6Os (MH+) 489, found 489 by LCMS.. A portion of this acetal product (0.068 g, 0.14 mmol) was dissolved in dry N, N- dimethyl formamide (2.5 mL) and potassium tert-butoxide (0.084 g, 5 eq) was added to give a yellow solution. To this mixture was added 2-fluoro-5-nitrobenzoic acid (0.046 g, 1.8 eq). After 2.5 h of stirring at room temperature the mixture was concentrated and purified by preparative HPLC to give the nucleoside analog as a white powder. MW calculated for C32H27N709 (MH+) 654, found 654 by LCMS.. The nitro group of the product immediately above was reduced under a hydrogen atmosphere with a catalytic amount of 10% Pd/C in methanol during 6 h. Filtration through Celite followed by HPLC purification yielded 52 mg (62% yield) of the title compound as clear semisolid. |
| 95% | With Amberlyst 15H+ resin In N,N-dimethyl-formamide at 55℃; for 3h; | 1 Adenosine (10 g, 37 mmol was dissolved in N, N-dimethyl formamide (100 mL) and dimethoxypropane (25 mL) followed by addition of Amberlyst 15H+ resin. The mixture was stirred 3h at 55°C. The resin was removed by filtration and the solvents removed in vacuo, affording 2', 3'-di-O-isopropylidene adenosine (11 g, 95%). |
| 90% | With toluene-4-sulfonic acid In acetone at 20℃; for 72h; | Synthesis of [(3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol (2) To a suspension of adenosine (3 g, 11.23 mmol) and p-toluensulfonic acid (2.33 g, 13.55 mmol) in dry acetone (120 mL), 2,2-dimethoxypropane (5.6 mL, 45.6 mmol) was added. After 3 days of vigorous stirring, the solution was neutralized with a saturated solution of Na2CO3 and then extracted with chloroform (3 x 50 mL). The organic layers were mixed and dried using Na2SO4. The solvent was removed under reduced pressure and the remainder solid was suspended with ether and washed with cold water obtaining a white solid (3.11 g, 10.13 mmol, 90 %); mp 202-203 °C; IR (KBr)νmax: 3,271, 3,109, 2,987, 2,938, 1,686, 1,605, 1,476,1,378, 1,300, 1,208, 1,116; 1H NMR (400 MHz, CDCl3) δ = 1.38 (s, 3H, CH3), 1.65 (s, 3H, CH3), 3.81 (dd, 1H,J = 12.6, 2 Hz, H-5'), 3.98 (dd, 1H, J = 12.6, 1.6 Hz, H-5'),4.55 (br, 1H, H-4'), 5,11 (t, 1H, J = 6.4 Hz, H-3'), 5.21 (t,1H, J = 5.6 Hz, H-2'), 5.90 (d, 1H, J = 4.4 Hz, H-1'), 6.23(s, 2H,NH2), 7.91 (s, 1H, H-8), 8.31 (s, 1H, H-2);FABMS m/z 308 [M]+ (88). |
| 89% | With sulfuric acid In acetone at 20℃; for 0.5h; | |
| 87.7% | With toluene-4-sulfonic acid In acetone for 48h; | 1 Example 1-Synthesis of 2', 3'-O-Isopropylideneadenosine [69] A solution of p-toluenesulfonic acid (7.79 g, 0.45 mol) in dry acetone (100 ml) is added dropwise to a solution of adenosine (10 g, 0.037 mol) in dry acetone (300 ml). 2,2-Dimethoxypropane (18.18 ml, d=0.847) is then added to the reaction mixture, and the mixture stirred for 48 hours (TLC methylene chloride/ethanol 9: 1). The solution slowly becomes clear and is made basic with 3 % ammonium hydroxide (800 ml). The solvent is removed at reduced pressure, keeping the temperature below 30° C until formation of a solid that is collected by filtration. This procedure is repeated several times by concentrating the filtrate. A white solid is obtained (10.08 g, 0.0328 mol, 87.7% yield). [70] M. p: 228 °C. LH-NMR (CDCL3) : 8 1.38 (s, 3H); 1.65 (s, 3H); 3.79- 4.02 (m, 2H); 4.55 (s, 1H); 5.10-5. 13 (m, 1H); 5.18-5. 24 (m, 1H); 5.84 (s, 2H); 5.87 (s, 1H) ; 6.57-6. 63 (m, 1H) ; 7.84 (s, 1H) ; 8.32 (s, 1H). Analyzed for C13H17N5O4. |
| 83% | With Bis(p-nitrophenyl) phosphate In acetone | |
| 80% | With perchloric acid In water; acetone at 0 - 25℃; for 18h; | 2',3'-O-Isopropylideneadenosine 9 2,2-Dimethoxypropane(45.8mL, 374 mmol, 10 eq.) and perchloric acid (70% in water, 3.54 mL, 24.7mmol, 0.67 eq.) were slowly added to a suspension of adenosine (10.0 g, 37.4 mmol, 1.0 eq.) in acetone (200 mL)at 0 °C. The mixture was allowed to slowly warm to rt, and stirred for a further 18 h. The reaction was quenched by addition of aqueous ammonia (30%, 20mL) and concentrated. The residue was taken up into DCM (150 mL) and water (100 mL) was added. The phases were separated and the aqueous phase washed with EtOAc (3 × 100 mL) before the organic phases were combined, dried over Na2SO4, and concentrated to a white powder. The powder was suspended in Et2O (200 mL), and filtered before being washed with further Et2O (3 × 100 mL) to give 9 as a white powder (9.16 g, 80%.). Rf = 0.21 (95:5 DCM:MeOH); mp 218-220 °C (DCM); δH(300.0 MHz, d6-DMSO): 8.34(1 H, s, H-8), 8.15 (1 H, s, H-2), 7.36 (2 H, br s, NH2), 6.12 (1 H, d, J 3.1, H-1), 5.34 (1 H, dd, J 6.2,3.1, H-2), 5.25 (1 H, dd, J 6.0, 5.1, C-5 OH), 4.69 (1 H, dd, J 6.2, 2.5, H-3), 4.23-4.19 (1 H, m, H-4),3.60-3.47 (1 H, m, H-5a, H-5b), 1.54 (3 H, s, C(CH3)2), 1.32 (3 H,s, C(CH3)2); δC(125.8 MHz, CDCl3): 156.2 (C-6),152.7 (C-2), 148.8 (C-4), 139.7 (C-8), 119.1 (C-5), 113.1(C(CH3)2), 89.6(C-1), 86.4 (C-4), 83.2 (C-2), 81.4(C-3), 61.6 (C-5), 27.1 (C(CH3)2),25.2 (C(CH3)2);m/z(ES+) 308 ([M+H]+,100%), 330 ([M+Na]+,29). |
| 73% | With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 70℃; for 8h; Inert atmosphere; | |
| 66% | With toluene-4-sulfonic acid In acetone for 2h; | |
| 53% | Stage #1: 2,2-dimethoxy-propane; adenosine With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 70℃; for 7h; Stage #2: In ethyl acetate at 0 - 20℃; for 5.5h; | 1 To a solution of 9β-D-ribofaranosyladenosine (adenosine) (1) (6.68 g, 25 mmol) in anhydrous dimethylformamide (100 ml) was added 2,2-dimethoxypropane (13 g, 125 mmol, 5 mol eq.) and anhydrous p-toluenesulfonic acid (1.19 g, 6.26 mmol). The reaction mixture was heated to 70° C. for 7 hours with stirring in a nitrogen stream, and then concentrated in vacuo at 40° C. to about 30 ml. The concentrate was poured into 5% aqueous sodium hydrogen carbonate (125 ml), and extracted twice with 150 ml of ethyl acetate. The organic layer was washed twice with 50 ml of water and 50 ml of saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo to remove the solvent. The resultant yellow oily residue (ca. 8 g) was dissolved in 150 ml of ethyl acetate with heating. The solution was stirred for 5 hours at room temperature and another 30 minutes at 0° C. to result in precipitation of crystals. The crystals were collected by filtration, and washed with ethyl acetate and diethyl ether to give compound 2 (4.1 g, 13.3 mmol, 53%). IR (Nujol, cm-1) 3350 (sh), 3240, 3180, 1685 (s). 1H NMR (200 mHz, CDCl3) δ: 1.38 (3H, s), 1.65 (3H, s), 3.72-3.86 (1H, m), 3.95-4.02 (1H, m), 4.55 (1H, 8), 5.10-5.25 (2H, m), 5.86 (3H, d, J=4.8 Hz), 6.57 (1H, dd, J=1.8, 11.4 Hz), 7.84 (1H, s), 8.32 (1H, s). |
| 35% | Stage #1: adenosine With toluene-4-sulfonic acid In water; N,N-dimethyl-formamide; acetone for 4h; Stage #2: 2,2-dimethoxy-propane In water; N,N-dimethyl-formamide; acetone for 6h; | 2′,3′-O-Isoprppylideneadenosine (8) Adenosine (20 g, 75 mmol) was dissolved in 800 mL of acetone-DMF (3:1, v/v) and to the mixture was added 14 g of TsOH monohydrate (75 mmol). After 4 h stirring, 19 mL of 2,2-dimethoxypropane (150 mmol) was added and the reaction was allowed to stir for another 6 h. The mixture was partially evaporated and partitioned between EtOAc (200 mL) and sat. Na2CO3 aq. The water layer was washed with CHCl3 and CH2Cl2. Combined organic layer was then washed with brine (100 mL) and dried over anhydrous Na2SO4. After the removal of solvent in vacuo, 2′,3′-Oisoprppylideneadenosine (8) was recovered by trituration with EtOAc-hexane as colorless crystals (8.0 g, 35%). 1H NMR (400 MHz, DMSO-d6) δ 8.32 (1H, s, H, H-2), 8.14 (1H, s, H-8), 7.34 (2H, s, H-6), 6.10 (1H, d, J = 2.8 Hz, H-1′), 5.33 (1H, dd, J = 6.4, 3.2 Hz, H-2′), 4.95 (1H, dd, J = 6.2, 2.5 Hz, H-3′), 4.20 (1H, m, H-4′), 3.52 (2H, m, H-5′), 1.53 (3H, s, Me), 1.31 (3H, s, Me). |
| With toluene-4-sulfonic acid In acetone for 1h; Ambient temperature; | ||
| With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 70℃; for 8h; Inert atmosphere; | 1.1 Step 1:2',3'-O-Isopropylideneadenosine 1c. 1. Add adenosine (0.9 mmol) to anhydrous DMF (6 ml) with constant stirring;2. Add 2,2-dimethoxypropane (0.6 ml, 4.5 mmol) and toluenesulfonic acid (0.04 g, 0.2 mmol) to the continuously stirring solution of step 2;3. Under a nitrogen atmosphere, stir the reactants of the above step 2 at 70 degrees Celsius, and make them react for 8 hours;4. Concentrate the reactant in step 3 in vacuo;5. Add saturated aqueous sodium bicarbonate solution to the concentrated product of step 4, and stir for 6 hours;6. Extract the organic fraction in step 5 with ethyl acetate;7. All organic parts in step 6 are evaporated under reduced pressure;8. Purify the remaining crude residue in step 7 with silica gel. | |
| With toluene-4-sulfonic acid In N,N-dimethyl-formamide | ||
| With toluene-4-sulfonic acid In acetone at 20℃; for 48h; Inert atmosphere; | 1.1 Example 1.1: Synthesis of ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-il)methanol A 5 L glass reactor equipped with a mechanical stirrer was charged with acetone (2 L), adenosine (100.00 g, 274.00 mmol, 1 eq), p-toluenesulfonic acid (77.60 g, 452.00 mmol, 1.21 eq), and 2,2-dimethoxypropane (180.0 mL, 1469.00 mmol, 5.36 eq) under a nitrogen atmosphere. The resulting suspension was stirred at 250 rpm for 48 h at room temperature. After this period, a 10% NaOH solution (200 mL) was added to achieve a pH of about 8. The resulting mixture was concentrated under vacuum to about 10 volumes and filtered under vacuum. The filtered solid was washed with ice-cold water (100 mL). Finally, the solid was dried under vacuum at 40 °C. The product was obtained with a molar yield of 90%, and a purity of 85% (qNMR). |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 27% | With sodium hydride In N,N-dimethyl-formamide at 0℃; for 4h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; | |
| 91% | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; Stage #2: With ammonium hydroxide at 20℃; for 0.5h; | |
| 90% | With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; Inert atmosphere; |
| 90% | Stage #1: adenosine With pyridine In acetonitrile at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With thionyl chloride In acetonitrile at 0 - 20℃; Stage #3: With ammonium hydroxide In methanol for 0.5h; | 25 Preparation of compound 6e: Adenosine 5'e [purchased from Shanghai Bied Pharmaceutical Technology Co., Ltd.] (5.0 g, 18.71 mmol) was suspended in acetonitrile (50 mL).Pyridine (6.02 mL, 74.84 mmol) was added to the suspension under nitrogen.Cool to 0 ° C and stir for 10 minutes.Slowly drip the thionyl chloride (13.6 mL, 187.10 mmol),The reaction was stirred at a temperature of 0 ° C for 4 hours.After the temperature was raised to room temperature, the reaction was stirred overnight, and the reaction mixture was evaporated to dryness. Methanol (100 mL) was added, and the mixture was stirred and the solution became clear. Ammonia water (20 mL) was added and stirred for 30 minutes.TLC check the reaction is complete,The reaction mixture was stirred to give a yellow or red oil. Water (100 mL) was added to the oil. After stirring at room temperature for 5 minutes, a white solid was precipitated, filtered, and the filter cake was vacuum dried to constant weight.The amorphous white solid product 6e (4.8 g, 16.80 mmol) was obtained, yield: 90%. |
| 90% | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; for 19h; Stage #2: With ammonium hydroxide In methanol; water at 20℃; for 0.5h; | |
| 89% | With thionyl chloride In N,N,N,N,N,N-hexamethylphosphoric triamide; water | 2 Preparation of 5'-deoxy-5'-ethylthioadenosine EXAMPLE 2 Preparation of 5'-deoxy-5'-ethylthioadenosine 1 kg of adenosine is dissolved under a nitrogen atmosphere in 10 l of hexamethylphosphoramide, and 7.5 l of thionyl chloride are added under cooling. The mixture is left to react at ambient temperature for 20 hours. 10 l of water are added, and the mixture neutralised with 2 N NaOH. The 5'-deoxy-5'-chloroadenosine which thus forms is allowed to crystallise overnight at 3° C. It is filtered off. 0.950 kg of 5'-deoxy-5'-chloroadenosine are obtained (yield 89%). |
| 88% | With thionyl chloride In N,N,N,N,N,N-hexamethylphosphoric triamide at 0℃; for 2h; r.t., overnight; | |
| 88% | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile Stage #2: With ammonium hydroxide In methanol; water | |
| 88% | With thionyl chloride In pyridine; acetonitrile | |
| 86% | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 0 - 5℃; Stage #2: With ammonium hydroxide In methanol; water; acetonitrile at 20℃; for 0.5h; | 1 Compound 308l-(3-((((2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2- yl)methyl)thio)propyl)-3-(4-(tert-butyI)phenyl)ureaStep 1. (2R,3R,4S,5S)-2-(6-amino-9H-purin-9-yl)-5- (chloromethyl)tetrahydrofuran-3,4-diol To a solution of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5- (hydroxymethyl)tetrahydrofuran-3,4-diol (1 g, 3.47 mmol) in pyridine (593 mg, 0.6 ml, 7.49 mmol) in acetonitrile (10ml) cooled in an ice bath was added SOCl2 (2.22g, 1.36ml,18.65mmol). Stirring was continued at 0-5° C for 3-4 h, and warning to ambient temperature for overnight. The resulting suspension was concentrated in vacuo. To the reaction mixture was added methanol (20 ml), water (2ml), and NH4OH (4 ml), followed by stirring for 0.5 h at room temperature. The reaction mixture was concentrated to dryness. The compound was dissolved in MeOH, silica gel (3g) was added and then solvent was removed. The residue was purified by SGC to elute with EA : MeOH (0%-10%) to obtain the title compound (0.915 g, yield 86%) as yellowish solid. NMR (500 MHz, MeOD): δ 8.24 (s, 1H), 8.02 (s, 1H), 7.27-7.20 (m, 5H), 6.19 (d, J = 2.0 Hz, 1H), 5.48-5.46 (m, 1H), 5.08-5.06 (m, 1H), 4.43 (t, J = 4.0, Hz, 1H), 3.83- 3.81 (m, 2H). |
| 86% | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 0 - 5℃; Stage #2: With ammonium hydroxide In methanol; water; acetonitrile at 20℃; for 0.5h; | 1 ((3aS,4S,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2 dimethyltetrahydro furo[3,4- d][l,3]dioxol-4-yl)methanethiolStep 1. Preparation of (2R,3R,4S,5S)-2-(6-amino-9H-purin-9-yl)-5- (chloromethyl) tetrahydrofuran-3,4-diolTo a solution of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5- (hydroxymethyl)tetrahydrofuran-3,4-diol (1 g, 3.47 mmol) in pyridine (593 mg, 0.6 ml, 7.49 mmol) in acetonitrile (10ml) cooled in an ice bath was added SOCl2 (2.22g, 1.36ml,18.65mmol). Stirring was continued at 0-5° C for 3-4 h, and warning to ambient temperature for overnight. The resulting suspension was concentrated in vacuo. To this reaction mixture was added methanol (20 ml), water (2ml), and NH4OH (4 ml), followed by stirring for 0.5 h at room temperature. The reaction mixture was concentrated to dryness. The compound was dissolved in MeOH, silica gel (3g) was added and then solvent was removed. The residue was purified by SGC to elute with EA : MeOH (0%-10 ) to obtain the target compound (0.915 g, yield 86%) as yellowish solid. NMR (500 MHz, MeOD): δ 8.24 (s, IH), 8.02 (s, IH), 7.27-7.20 (m, 5H), 6.19 (d, / = 2.0 Hz, IH), 5.48-5.46 (m, IH), 5.08-5.06 (m, IH), 4.43 (t, J = 4.0, Hz, IH), 3.83- 3.81 (m, 2H), 3.01-2.99 (br s, 2H), 1.60 (s, 3H), 1.38 (s, 3H) ppm, LCMS (m/z): 395.8 [M+H]+. |
| 85% | With thionyl chloride In N,N,N,N,N,N-hexamethylphosphoric triamide for 16h; Ambient temperature; | |
| 84% | With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; for 18h; | 11.1 first step:(2R, 3R, 4S, 5S)-2-(6-amino-9H- purine-9-yl)-5-(chloromethyl)oxolane-3,4-diolSynthesis of (XI-1): In acetonitrile (100 mL) at 0 ° C,(2R,3R,4S,5R)-2-(6-Amino-9H-indol-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol (I- 1, adenosine, 10.0g, 37.4mmol),Pyridine (5.91 g, 74.8 mmol)And thionyl chloride (22.0 g, 185 mmol),The resulting solution was stirred at room temperature for 18 hours.It was then carefully quenched with ice water (30 mL).After removing the organic solvent under vacuum,Adjust the pH to ~8 with a saturated aqueous solution of sodium carbonate.It was then extracted with ethyl acetate (150 mL×3).Combine the organic phases,Dry with sodium sulfate and filter.The filtrate was concentrated in vacuo.The residue was purified by silica gel column chromatography (eluent:0-10% methanol in ethyl acetate solution) 9.0 g (yield: 84%)(2R,3R,4S,5S)-2-(6-Amino-9H-indol-9-yl)-5-(chloromethyl)oxolane-3,4-diol (XI-1 ),It is a white solid. |
| 76% | With N,N,N,N,N,N-hexamethylphosphoric triamide; thionyl chloride | |
| 69.8% | With pyridine; thionyl chloride In acetonitrile at 0 - 25℃; | |
| 60% | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; Stage #2: With ammonium hydroxide In methanol; water at 20℃; for 0.5h; | 1 4.5.1 5'-Chloro-5'-deoxyadenosine (36) To a cold suspension (0°С) of adenosine (3.0 g, 11.2 mmol) in acetonitrile (35 ml) and pyridine (22.4 mmol, 1.8 ml), thionyl chloride (4.1 ml, 56.1 mmol) was slowly added and the mixture was stirred 4 h under 0°С. The resulting solution was kept at ambient temperature overnight. The precipitate was filtered and dissolved in H2O/MeOH (5:50 ml) and 25% aqueous ammonia (4.7 ml) was added to the mixture. The reaction mixture was kept at ambient temperature for 30 min and evaporated in vacuum. The residue was transferred to a glass filter, washed with cold water (2 * 20 ml) and dried in vacuum desiccator over P2O5. Yield 1.92 g (60%) as white crystals. Rf 0.15 (CH2Cl2-EtOH, 9:1 v/v). 1H NMR (DMSO-d6): δ = 3.84 (dd, 1H, J5'b-4' = 6.3 Hz, J5'ba = -11.6 Hz, H5'b), 3.94 (dd, 1H, J5'a-4' = 5.1 Hz, J5'ab = -11.6 Hz, H5'a), 4.10 (ddd, 1H, J4'-5'b = 6.3 Hz, J4'-5'a = 5.1 Hz, J4'-3' = 4 Hz, H4'), 4.23 (ddd, 1H, J3'-4' = 4 Hz, J3'-OH = 5.1 Hz, J3'-2' = 5 Hz, H3'), 4.75 (dd, 1H, J2'-3' = 5 Hz, J2'-1' = 5.6 Hz, H2'), 5.41 (d, 1H, JOH-3' = 5.1 Hz, 3'OH), 5.56 (d, 1H, JOH-2' = 6.03 Hz, 2'OH), 5.93 (d, 1H, J1'-2' = 5.6 Hz, H1'), 7.26 (s, 2H, NH2), 8.15 (s, 1H, H8), 8.33 (s, 1H, H2). |
| 37% | With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; | |
| With pyridine; thionyl chloride; ammonia 1.) acetonitrile, 2.) MeOH, H2O; Yield given. Multistep reaction; | ||
| With pyridine; thionyl chloride In N,N,N,N,N,N-hexamethylphosphoric triamide | ||
| With thionyl chloride In acetonitrile at 20℃; for 15h; | ||
| With thionyl chloride | ||
| Multi-step reaction with 2 steps 1: thionyl chloride; pyridine / acetonitrile / 18 h / 0 - 20 °C 2: ammonium hydroxide / water; methanol / 1 h / 0 - 5 °C | ||
| Multi-step reaction with 2 steps 1: pyridine; thionyl chloride / acetonitrile / 0 - 20 °C / Inert atmosphere 2: ammonium hydroxide / methanol / 0.5 h / 20 °C | ||
| Multi-step reaction with 2 steps 1: pyridine; thionyl chloride / acetonitrile / 3 - 20 °C 2: ammonium hydroxide; water / methanol | ||
| With thionyl chloride | ||
| Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; for 19h; Inert atmosphere; Stage #2: With ammonia In methanol; water at 20℃; for 0.5h; Inert atmosphere; | Compound 17: Pyridine (610 L, 7.48 mmol) and thionyl chloride (1.4 mL, 18.7 mmol) were addedat 0 C, over 5 min to a solution of adenosine (1 g, 3.74 mmol) in MeCN (10 mL). The reaction mixturewas stirred at 0 C for 3 h before being warmed to room temperature and stirred for 16 h. The resultingprecipitate was filtered and dissolved in water/MeOH (5:1) and aqueous ammonia (25%, 2 mL) wasadded. The reaction mixture was stirred at room temperature for 30 min and the solvent was removedunder reduced pressure to provide 50-chloroadenosine [66]. The resulting 50-chloroadenosine was thensolubilized in DMF (5 mL) and sodium azide (1.2 g, 18.7 mmol) was added. The reaction mixture washeated at 80 C for 5 h, and cooled to room temperature. The excess of sodium azide was removed byfiltration and the filtrate purified by flash chromatography (DCM/MeOH 9:1) to give 17 as a whitefoam (393 mg, 36% over 2 steps). 1H NMR (500 MHz, CD3OD): 8.29 (s, 1H, H8), 8.21 (s, 1H, H2),6.03 (s, 1H, H10), 4.80-4.78 (m, 1H, H20), 4.40-4.36 (m, 1H, H40), 4.27 (q, J = 5 Hz, 0.5H, H30), 4.18 (q,J = 5 Hz, 0.5H, H30), 3.94 (dd, J = 10, 5 Hz, 0.5H, H50), 3.84 (dd, J = 10, 5 Hz, 0.5H, H50), 3.69-3.62 (m,1H, H50). HRMS (ESI) m/z: calcd for C10H13N8O3 [M + H]+: 293.1110; found: 293.1098. Analyticaldata were in accordance with the literature [67]. | |
| Multi-step reaction with 2 steps 1: thionyl chloride; pyridine / acetonitrile / 19 h / 0 - 20 °C / Inert atmosphere 2: ammonium hydroxide / methanol / 1 h / 20 °C | ||
| 1.11 g | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 4 - 20℃; for 19h; Inert atmosphere; Stage #2: With ammonium hydroxide In methanol at 20℃; for 1h; | 5'-Chloro-5'-deoxyadenosine 3 To a suspension of adenosine (2) (1.50 g, 5.61 mmol) in dry acetonitrile (6 ml) under an argon atmosphere was added thionyl chloride (1.2 ml, 16.5 mmol) dropwise cooling in the ice bath and keeping the temperature below 4°C. Pyridine (0.9 ml, 11.1 mmol) was added keeping temperature below 4°C and the mixture was stirred in the ice bath for 3 h, then the mixture was allowed to warm to room temperature and stirred 16 h. The precipitate was dissolved by adding water (15 ml) to the reaction mixture. The solution was neutralized to pH 5 by the slow addition of sodium bicarbonate. [029] The precipitate was collected by vacuum filtration, washed with cold water (2x5 ml), and dried in vacuo to give 1.36 g (77%) of the sulfinyladenosine intermediate. A suspension containing 1.36 g of the sulfinyladenosine in MeOH (15 ml) was treated with 1.5 ml of ammonium hydroxide. Precipitate was formed upon stirring at room temperature for 1 h, the precipitate was filtered, washed with cold MeOH/ammonium hydroxide solution (10:1, 2x5 ml), and dried under vacuum to give 1.11 g (69%) of the product 3 as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.15 (s, 1H), 7.29 (br s, 2H), 5.93 (d, J = 5.6 Hz, 1H), 5.60 (br d, 1H), 5.46 (br d, 1H), 4.75 (q, J = 5.2 Hz, 1H), 4.22 (d, J = 4.5 Hz, 1H), 4.26 - 4.18 (m, 1H), 4.14 - 4.05 (m, 1fH), 3.94 (dd, J = 11.6, 5.0 Hz, 1H), 3.84 (dd, J = 11.6, 6.3 Hz, 1H). Data are consistent with literature values. |
| 1.11 g | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 4 - 20℃; for 19h; Inert atmosphere; Stage #2: With ammonium hydroxide In methanol at 20℃; for 1h; | 5'-Chloro-5'-deoxyadenosine 3 To a suspension of adenosine (2) (1.50 g, 5.61 mmol) in dry acetonitrile (6 ml) under an argon atmosphere was added thionyl chloride (1.2 ml, 16.5 mmol) dropwise cooling in the ice bath and keeping the temperature below 4°C. Pyridine (0.9 ml, 11.1 mmol) was added keeping temperature below 4°C and the mixture was stirred in the ice bath for 3 h, then the mixture was allowed to warm to room temperature and stirred 16 h. The precipitate was dissolved by adding water (15 ml) to the reaction mixture. The solution was neutralized to pH 5 by the slow addition of sodium bicarbonate. [029] The precipitate was collected by vacuum filtration, washed with cold water (2x5 ml), and dried in vacuo to give 1.36 g (77%) of the sulfinyladenosine intermediate. A suspension containing 1.36 g of the sulfinyladenosine in MeOH (15 ml) was treated with 1.5 ml of ammonium hydroxide. Precipitate was formed upon stirring at room temperature for 1 h, the precipitate was filtered, washed with cold MeOH/ammonium hydroxide solution (10:1, 2x5 ml), and dried under vacuum to give 1.11 g (69%) of the product 3 as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.15 (s, 1H), 7.29 (br s, 2H), 5.93 (d, J = 5.6 Hz, 1H), 5.60 (br d, 1H), 5.46 (br d, 1H), 4.75 (q, J = 5.2 Hz, 1H), 4.22 (d, J = 4.5 Hz, 1H), 4.26 - 4.18 (m, 1H), 4.14 - 4.05 (m, 1fH), 3.94 (dd, J = 11.6, 5.0 Hz, 1H), 3.84 (dd, J = 11.6, 6.3 Hz, 1H). Data are consistent with literature values. |
| 1.11 g | Stage #1: adenosine With pyridine; thionyl chloride In acetonitrile at 4 - 20℃; for 19h; Inert atmosphere; Stage #2: With ammonium hydroxide In methanol at 20℃; for 1h; | 5'-Chloro-5'-deoxyadenosine 3 To a suspension of adenosine (2) (1.50 g, 5.61 mmol) in dry acetonitrile (6 ml) under an argon atmosphere was added thionyl chloride (1.2 ml, 16.5 mmol) dropwise cooling in the ice bath and keeping the temperature below 4°C. Pyridine (0.9 ml, 11.1 mmol) was added keeping temperature below 4°C and the mixture was stirred in the ice bath for 3 h, then the mixture was allowed to warm to room temperature and stirred 16 h. The precipitate was dissolved by adding water (15 ml) to the reaction mixture. The solution was neutralized to pH 5 by the slow addition of sodium bicarbonate. [029] The precipitate was collected by vacuum filtration, washed with cold water (2x5 ml), and dried in vacuo to give 1.36 g (77%) of the sulfinyladenosine intermediate. A suspension containing 1.36 g of the sulfinyladenosine in MeOH (15 ml) was treated with 1.5 ml of ammonium hydroxide. Precipitate was formed upon stirring at room temperature for 1 h, the precipitate was filtered, washed with cold MeOH/ammonium hydroxide solution (10:1, 2x5 ml), and dried under vacuum to give 1.11 g (69%) of the product 3 as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.15 (s, 1H), 7.29 (br s, 2H), 5.93 (d, J = 5.6 Hz, 1H), 5.60 (br d, 1H), 5.46 (br d, 1H), 4.75 (q, J = 5.2 Hz, 1H), 4.22 (d, J = 4.5 Hz, 1H), 4.26 - 4.18 (m, 1H), 4.14 - 4.05 (m, 1fH), 3.94 (dd, J = 11.6, 5.0 Hz, 1H), 3.84 (dd, J = 11.6, 6.3 Hz, 1H). Data are consistent with literature values. |
| 85.8 % | With pyridine; thionyl chloride In acetonitrile at 0 - 20℃; | Synthesis of 2R,3R,4S,5S-2-(6-amino-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3,4-diol (17) We followed the reported procedure by Anglin J. L. et. al 2012, to a suspension of adenosine (5g, 18.7mmol) in MeCN (50mL), 13.6mL of SOCl2 (187.1mmol) was added followed by the dropwise addition of pyridine (6mL, 74.8mmol) to the reaction vessel which was placed under an ice-bath and stirred for 1h then allowed to sit at room temperature overnight. Reaction completion after overnight was monitored using TLC. The reaction mixture became yellowish with some precipitate. The resulting precipitate was filtered and dried in vacuo to give a white solid powder, which was suspended in MeOH/H2O (v/v=5:1, 60mL). Then a 25% aqueous ammonium solution (5mL) was added and stirred for 30min at room temperature. Next, the solvents were reduced using a rotary evaporator to obtain a white precipitate, which was then filtered, washed with cold water, and dried in vacuo to give 17 as a white powder (4.59g, 85.8% yield). 1H NMR (300MHz, d6-DMSO): δH 8.33 (s, 1H), 8.15 (s, 1H), 7.28 (s, 2H), 5.92 (d, J=5.7Hz, 1H), 5.62 (d, J=6.0Hz, 1H), 5.48 (d, J=5.1Hz, 1H), 4.77-4.71 (m, 1H), 4.24-4.20 (m, 1H), 4.11-4.06 (m, 1H), 3.93 (dd, J=5.1, 4.8Hz, 1H), 3.83 (dd, J=6.3, 6.3Hz, 1H). |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 95% | With K 10 clay In methanol; water for 20h; Ambient temperature; | |
| 95% | With cerium(IV) triflate; water In acetonitrile at 25℃; for 0.75h; | |
| 87 % Turnov. | With 1,1,1,3',3',3'-hexafluoro-propanol for 1h; Ambient temperature; |
| Multi-step reaction with 6 steps 1: Et3N; DMAP / CH2Cl2 2: dichloroacetic acid; pyrrole / CH2Cl2 3: 87 percent / 2,4,6-triisopropylbenzenesulfonyl chloride; 3-nitro-1,2,4-1H-triazole; pyridine / 1 h / 20 °C 4: Me3SiCl / acetonitrile / 6 h / 60 °C 5: 0.060 g / aq. NH3 / acetonitrile / 0.08 h / 20 °C 6: CD3CO2D; D2O / 23 °C |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Yield given. Multistep reaction. Yields of byproduct given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 10.7% | With sodium hydride In N,N-dimethyl-formamide for 5h; |
[ 17287-03-5 ]
[ 58-61-7 ]
[ 60037-52-7 ]
[ 57817-83-1 ]
[ 20649-46-1 ]
[ 2140-79-6 ]
[ 1867-73-8 ]
[ 10300-22-8 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With copper acetylacetonate In N,N-dimethyl-formamide at 70℃; for 1h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | Stage #1: adenosine With sodium hydride In N,N-dimethyl-formamide Stage #2: bromoacetic acid methyl ester In N,N-dimethyl-formamide | |
| 56% | With sodium hydride In N,N-dimethyl-formamide | |
| 56% | Stage #1: adenosine With sodium hydride In N,N-dimethyl-formamide Stage #2: bromoacetic acid methyl ester In N,N-dimethyl-formamide |
| 47% | With sodium hydride In N,N-dimethyl-formamide at 20℃; for 8h; | |
| 47% | With sodium hydride at 20℃; for 8h; | |
| 47% | With sodium hydride In N,N-dimethyl-formamide at 20℃; for 8h; | |
| 42% | Stage #1: adenosine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1h; Stage #2: bromoacetic acid methyl ester In N,N-dimethyl-formamide; mineral oil at 25℃; for 8h; | |
| With sodium hydride In N,N-dimethyl-formamide at 20℃; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 66.5 percent / NaH / dimethylformamide 2: 80.4 percent / aq. acetic acid; NaNO2 | ||
| Multi-step reaction with 2 steps 1: 34 percent / SnCl2 / methanol; 1,2-dimethoxy-ethane 2: 72 percent / sodium nitrite, 25percent aq. acetic acid / 5 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 6 steps 1.1: pyridine / 14 h / 20 °C 2.1: pyridine / acetonitrile / 1 h / 4 °C 3.1: 91 g / AcOH / methanol / 48 h / -20 °C 4.1: 75 percent / pyridine / 1 h / 20 °C 5.1: iPr2NEt; Bu2SnCl2 / 1,2-dichloro-ethane / 1 h / 20 °C 5.2: 40 percent / CH2Cl2 / 0.33 h / 80 °C 6.1: 93 percent / iPr2NEt / CH2Cl2 / 14 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1: pyridine 2: 1-hydroxybenzotriazole / acetonitrile / 17 h / Ambient temperature 3: pyridine / 5 °C 4: imidazole / pyridine / Ambient temperature 5: diisopropylethylamine / DMAP / tetrahydrofuran / 3 h / Ambient temperature |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1.44 g (85.2%) | With m-chloroperoxybenzoic acid; 3-chloro-benzenecarboperoxoic acid In hydrogenchloride; water; 2,4-dichlorophenoxyacetic acid dimethylamine; toluene | 1 8-Chloroadenine (1) EXAMPLE 1 8-Chloroadenine (1) To a solution of adenosine (2.67 g, 10 mmol) in DMA/HCl (0.5M, 45 mL) was added m-chloroperoxybenzoic acid (MCPBA, 3.22 g, 16 mmol 87%) and stirred at room temperature for 2.5 h. An additional portion of MCPBA (0.9 g, 5 mmol) was added and stirring continued for another 1 h. Toluene (50 mL) was added to the reaction mixture and the solvents evaporated at 60° C. under vacuo to dryness. The residue was dissolved in water (50 mL) and extracted with ether (3*50 mL). The pH of the aqueous phase was adjusted to 5 with 2N NaOH and then diluted with EtOH (100 mL). The solution was stored in the refrigerator overnight. The light yellow solid that separated was collected, washed with cold EtOH (2*25 mL) and dried to give 1.44 g (85.2%) of 1: mp 305°-310° C. (dec.) [Lit. mp>300° C. (dec.)]: IR (KBr): 630 (C-C1), 3100-3300 (NH2) cm-1: UV: λmax (pH 1) 262 nm (ε 8,700): λmax (pH 7) 268 nm (ε 7,900): λmax (pH 11) 269 nm (ε 8,300): 1 H NMR (Me2 SO-d6): δ 7.48 (br s, 2, NH2), 8.10 (s, 1, C2 H) and 13.60 (br s, 1, N9 H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium hydride In N,N-dimethyl-formamide at -50 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium hydroxide In dimethyl sulfoxide at 20℃; for 12h; | ||
| Stage #1: adenosine With potassium hydroxide In N,N-dimethyl-formamide at 20 - 30℃; Stage #2: methyl p-toluene sulfonate In N,N-dimethyl-formamide at 10 - 20℃; | 1.S1; 2-5; 13 S1: Add 100g adenosine (formula I) and 900mL DMF into the reaction bottle, stir,Heat until dissolved and cool to 20-30.Add 35.7g of potassium hydroxide and stir for 10 minutes.Adjust the temperature to 10-15°C, and drop the prepared methyl p-toluenesulfonate DMF solution (the amount of methyl p-toluenesulfonate is 104.5g, DMF is 100mL) into the reaction bottle.Stir the reaction for 3-4 hours at 10-20°C. After the reaction is completed, control the temperature to 5-10°C.Add 50mL of water dropwise, and then add 6N HCl dropwise to adjust the pH=6-8. The reaction solution is decompressed under reduced pressure until there is no obvious fraction, and a light yellow paste is obtained.Add 2L DCM dispersion paste, and the resulting suspension will be used directly for the next step of feeding; |
[ 80-48-8 ]
[ 58-61-7 ]
[ 647834-80-8 ]
[ 1177249-97-6 ]
[ 2140-79-6 ]
[ 647834-87-5 ]
[ 10300-22-8 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 26% | Stage #1: methyl p-toluene sulfonate; adenosine With potassium hydroxide In dimethyl sulfoxide at 20℃; for 12h; Stage #2: O-levulinyl acetonoxime In tetrahydrofuran at 30℃; for 120h; Inert atmosphere; Enzymatic reaction; Stage #3: With ammonium hydroxide In methanol at 20℃; for 2h; regioselective reaction; |
[ 80-48-8 ]
[ 58-61-7 ]
[ 647834-80-8 ]
[ 1177249-97-6 ]
[ 647834-83-1 ]
[ 647834-87-5 ]
[ 647834-88-6 ]
[ 10300-22-8 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: methyl p-toluene sulfonate; adenosine With potassium hydroxide In dimethyl sulfoxide at 20℃; for 12h; Stage #2: O-levulinyl acetonoxime In tetrahydrofuran at 30℃; for 120h; Inert atmosphere; Enzymatic reaction; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With cerium(IV) trifluoromethanesulfonate; diethylazodicarboxylate In acetonitrile at 20℃; for 3h; Molecular sieve; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | With 2-methoxy-ethanol; sodium hydroxide; In N,N-dimethyl-formamide; at 8 - 65℃;Large scale; | 10kg of Adenosine was added to 130L of anhydrous DMF and stirred to dissolve, then 50L anhydrous ethylene glycol monomethyl ether was added controlling the temperature 8-15C , added 6.89Kg of <strong>[16427-44-4]2-methoxyethyl methanesulfonate</strong> and 2.99Kg solid sodium hydroxide, stirred reaction was incubated 60-65C , HPLC monitoring completion of the reaction to the main raw material, then concentrated under reduced pressure at 60 degrees to dryness to give a brown oil as 2'-O-(2-methoxyethyl) adenosine. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 9 h / 20 °C / Cooling with ice; Inert atmosphere 2.1: pyridine; chloro-trimethyl-silane / 1.33 h / Inert atmosphere; Cooling with ice 2.2: 2 h 3.1: pyridine / 0.5 h / 20 °C / Inert atmosphere 3.2: 4 h | ||
| Multi-step reaction with 3 steps 1.1: N,N-dimethyl-formamide; mineral oil / 1 h / 20 - 100 °C 1.2: 16 h / 50 °C 2.1: pyridine; chloro-trimethyl-silane / 0.5 h 2.2: 3 h 3.1: pyridine / methanol / 3.5 h / 0 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 9 h / 20 °C / Cooling with ice; Inert atmosphere 2.1: pyridine; chloro-trimethyl-silane / 1.33 h / Inert atmosphere; Cooling with ice 2.2: 2 h | ||
| Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide; mineral oil / 1 h / 20 - 100 °C 1.2: 16 h / 50 °C 2.1: pyridine; chloro-trimethyl-silane / 0.5 h 2.2: 3 h |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | With Selectfluor; riboflavin In water; acetonitrile for 7h; Inert atmosphere; UV-irradiation; | 12 Ribonucleoside demethylation of N'6,N6-dimethyladenine by using Vitamin B2as photosensitizer under 470nm wavelength blue light and Selectfluor: and then into the reaction tube added the N6,N6-dimethyladenine Ribonucleoside (0.01mmol, 29.5mg), Selectfluor (0.22mmol, 78mg), Vitamin B2 (0.01mmol, 3.8 mg), under nitrogen protection added 2 ml of H20 / CH3CN (1/1) solution, 470nm wavelength of blue light, stirring 7 hours, add the appropriate amount of sodium bicarbonate to the reaction solution at pH 7, spin dry liquid, after column chromatography (CH2Cl2/MeOH=12/1) separation obtained adenine Ribonucleoside 22mg, yield is 78%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 6% 2: 6% | With borax In water; formamide at 50℃; for 18h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1.1: triethylamine / dichloromethane 2.1: pyridine; chloro-trimethyl-silane / 2.5 h / 20 °C 2.2: 2.5 h / 20 °C 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran 4.1: pyridine / 6 h / 20 °C 5.1: triethylamine / dichloromethane |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 69% | With hydrogenchloride; orthoformic acid triethyl ester In 1,4-dioxane; N,N-dimethyl-formamide at 20℃; for 24h; | 2 ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dioctyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (2b, NL 5.9.0.0) Dry adenosine (1, NS_5.0.0.0; 1 g, 3.74 mmol) was dissolved in 15 ml of dry and amine-free dimethylformamide. Heptadecan-9-one (1.018 g, 4 mmol), triethyl orthoformate (0.662 ml, 4 mmol) and 4M HCI in 1,4-dioxane (7.5 ml) were added. The mixture was stirred at room temperature for 24 hours and then distributed between 80 ml of CH2Cl2 and a saturated aqueous solution of sodium hydrogen carbonate. The aqueous phase was extracted 3 times with 12 ml CH2Cl2. The combined organic phases were washed with H2O (3 × 50 ml) and then dried for 30 minutes over MgSO4. The filtered raw product was concentrated at a rotary evaporator an evaporated several times with CH2Cl2 harshly to remove the remaining DMF. The raw product was dried overnight in high vacuum at room temperature. The resulting product was obtained by column chromatography on silica gel (SiO2 60, column: 6.5 cm × 11.5 cm; CH2Cl2/ MeOH 9:1; v/v). The isolated product, freed from the solvent, forms a white solid in high vacuum (1.2997 g, 69 %). TLC (SiO2 60, CH2Cl2/MeOH 9:1; v/v): Rf 0.82. UV/Vis (MeOH): λmax: 260 nm, ε=13704.7 l·mol-1·cm-1. logPOW: 3.86. 1H-NMR (500.13 MHz, DMSO - d6): 8.333 (s, 1H, H-C(2)); 8.146 (s, 1H, H-C(8)); 7.279 (s, 2H, NH2); 6.133 (d, 1H, 3J(H-C(1'), H-C(2')) =2.5, H-C(1')); 5.360 (dd, 1H, 3J(H-C(2'), H-C(1')) =2.5, 3J(H-C(2'), H-C(3')) =6.0, H-C(2')); 5.102 (t, 1H, 3J(HO-C(5'), H2-C(5')) =5.5, HO-C(5')); 4.964 (dd, 1H, 3J(H-C(3'), H-C(2')) =2.5, 3J(H-C(3'), H-C(4')) =6.0, H-C(3')); 4.204 - 4.178 (m, 1H, H-C(4')); 3.545 - 3.473 (m, 2H, H2-C(5')); 1.738- 1.706 (m, 2H, H2C(1a")); 1.558 - 1.543 (m, 2H, H2-C(1b")); 1.429 - 1.420 (m, 2H, H2-C(2a")); 1.297 - 1.237 (m, 22H, H2-C(2b") - H2-C(7b") + H2-C(3a") - H2-C(7a")); 0.873 - 0.820 (m, 6H, H3-C(8a"), H3-C(8b")). 13C-NMR (125.76 MHz, DMSO-d6): 156.025 (C(6)); 152.492 (C(2)); 148.781 (C(4)); 139.584 (C8)); 118.966 (C(5)); 116.626 (C(acetal)); 89.405 (C(1')); 86.809 (C(4')); 83.526 (C(2')); 81.450 (C(3')); 61.503 (C(5')); 36.356 (C(1a")); 36.135 (C(1b")); 31.157 (C(2a")); 31.123 (C(2b")); 30.514 (C(3a")); 29.047 (C(3b")); 28.787 - 28.513 (4 × C, C(4a") - C(7a")); 23.499 - 21.919 (4 × C, C(4b") - C(7b")); 13.778 (C(8a")); 13.746 (C(8b")). ESI - MS: 504.35 [MW+H]+ (calculated: MW=503.68). Elemental analysis calculated for C27H45N5O4 · 0.05 H2O · 0.15 Heptadecan-9-one: C, 65.25 (64.38); H, 9.102 (9.01); N, 12.80 (13.90). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 54% | With hydrogenchloride; orthoformic acid triethyl ester In 1,4-dioxane; N,N-dimethyl-formamide at 20℃; for 24h; | 1 ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-diheptyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (2a, NL 5.7.0.0) Anhydrous adenosine (1, NS_5.0.0.0; 1.0 g; 3.74 mmol) was dissolved in 15 ml of dry and amine-free dimethylformamide. Pentadecan-8-one (0.906 g; 4.0 mmol), triethyl orthoformate (0.662 ml) and 4M HCI in 1.4-dioxane (7.5 ml) were then added. The mixture was stirred at room temperature for 24 hours and then distributed between 60 ml of CH2Cl2 and a saturated aqueous solution of sodium hydrogen carbonate. The aqueous phase was extracted 3 times with 12.5 ml CH2Cl2. The combined organic phases were washed with 120 ml H2O and then dried for 1 h over MgSO4. The filtered raw product was concentrated at a rotary evaporator and evaporated several times with CH2Cl2 harshly to remove the remaining DMF. The raw product was dried overnight in high vacuum at room temperature. The resulting product was obtained by column chromatography on silica gel (SiO2 60, column: 6.5 cm × 7.5 cm; CH2Cl2/ MeOH 9:1; v/v). The isolated product, freed from the solvent, forms a white solid in high vacuum (0.9562 g, 54%). TLC (SiO2 60, CH2Cl2/MeOH 9:1; v/v): Rf 0.80. UV/Vis UV/Vis (MeOH): λmax: 259 nm, ε=14648.0 l·mol-1·cm-1. logPOW: 2.82. 1H-NMR (500.13 MHz, DMSO - d6): 8.335 (s, 1H, H-C(2)); 8.148 (s, 1H, H-C(8)); 7.281 (s, 2H, NH2); 6.132 (d, 1H, 3J(H-C(1'), H-C(2')) =3.0, H-C(1')); 5.364 (dd, 1H, 3J(H-C(2'), H-C(1')) =3.0, 3J(H-C(2'), H-C(3')) =6.5, H-C(2')); 5.099 (t, 1H, 3J(HO-C(5'), H2-C(5')) =5.5, HO-C(5')); 4.964 (dd, 1H, 3J(H-C(3'), H-C(2')) =2.5, 3J(H-C(3'), H-C(4')) =6.0, H-C(3')); 4.203 - 4.178 (m, 1H, H-C(4')); 3.558 - 3.460 (m, 2H, H2-C(5')); 1.740 - 1.708 (m, 2H, H2C(1a")); 1.562 - 1.546 (m, 2H, H2-C(1b")); 1.432 - 1.423 (m, 2H, H2-C(2a")); 1.311 - 1.243 (m, 18H, H2-C(2b"), (H2-C(3a"), (H2-C(3b"), (H2-C(4a"-6a"), (H2-C(4b"-6b")); 0.884 - 0.825 (m, 6H, H3-C(7a"), H3-C(7b")). 13C-NMR (125.76 MHz, DMSO-d6): 156.043 (C(6)); 152.527 (C(2)); 148.806 (C(4)); 139.613 (C8)); 118.978 (C(5)); 116.654 (C(acetal)); 89.410 (C(1')); 86.832 (C(4')); 83.542 (C(2')); 81.478 (C(3')); 61.518 (C(5')); 36.376 (C(1a")); 36.198 (C(1b")); 31.134 (C(2a")); 31.076 (C(2b")); 28.518 (C(3a")); 28.450 (C(3b")); 21.976 (C(4a"-6a")); 21.938 (C(4b"-6b")); 13.822 (C(7a")); 13.784 (C(7b")). ESI - MS: 476.26 [MW+H]+ (calculated: MW=475.62). Elemental analysis calculated for C25H41N5O4 · 0.15 H2O: C, 62.95 (62.78); H, 8.89 (8.7); N, 14.36 (14.64). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: potassium hydroxide / N,N-dimethyl-formamide / 16 h / 60 °C 1.2: 3 h / 0 - 20 °C 2.1: N-ethyl-N,N-diisopropylamine / ethyl acetate / 1 h / 0 - 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | With hydrogenchloride; orthoformic acid triethyl ester In 1,4-dioxane; N,N-dimethyl-formamide at 20℃; for 24h; | 3 ((2R/2S,3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2-methyl-2-tridecyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (2c, NL 5.72.0.0, diastereoisomeric mixture, (1R) + (1S)) Anhydrous adenosine (1, NS_5.0.0.0; 1.0 g; 3.74 mmol) was dissolved in dry and amine-free dimethylformamide (10 ml). Thereupon, pentadecan-2-one (0.906 g; 4 mmol), triethyl orthoformate (0.662 ml, 4 mmol) and 4M HCI in 1.4-dioxane (4 ml) were added. The reaction mixture was stirred for 24 h at room temperature and then partitioned between CH2Cl2 (80 ml) and a saturated, aqueous NaHCO3 solution (40 ml). The aqueous phase was extracted thrice with CH2Cl2 (15 ml, each). The combined organic phases were washed three times with 50 ml H2O and then dried over MgSO4 for 30 minutes, filtered and evaporated at a rotary evaporator. Residual DMF was removed by repeated co-evaporation from CH2Cl2 and drying in high vacuum overnight. Column chromatography (SiO2 60, column: 5 × 7 cm; CH2Cl2/MeOH, 9:1 v/v) gave the title compound as a white solid upon evaporation of the main fractions and drying in high vacuum (1.1918 g, 67%). TLC (SiO2 60, CH2Cl2/MeOH 9:1; v/v): Rf0.80. UV/Vis (MeOH): λmax: 260 nm, ε=14260.4 l·mol-1·cm-1. logPOW: 2.83. 1H-NMR (500.13 MHz, DMSO - d6): 8.333 (s, H-C(2), (1R) + (1S)); 8.149 (s, H-C(8), (1R) + (1S)); 7.282 (s, NH2); 6.139 (d, 3J(H-C(1'), H-C(2'))=3.0; H-C(1'), (1S)); 6.115 (d, 3J(H-C(1'), H-C(2'))=3.0; H-C(1'), (1R)); 5.367 (dd, 3J(H-C(2'), H-C(1'))= 3.0; 3J(H-C(2'), H-C(3'))=6.5, H-C(2'), (1R); 5.287 (dd, 3J(H-C(2'), H-C(1'))= 3.5; 3J (H-C(2'), H-C(3'))= 6.5, HC(2'), (1S); 5.158 - 5.129 (m, 2H, HO-C(5'), (1R) + (1S)); 4.980 (dd, 3J(H-C(3'), H-C(2'))= 2.5; 3J(H-C(3'), H-C(4'))=6.5, H-C(3'), (1R); 4.947 (dd, 3J(H-C(3'), H-C(2'))= 2.5; 3J(H-C(3'), H-C(4'))=6.0, H-C(3'), (1S); 4.217 - 4.182 (m, 1H, H-C(4'), (1R) + (1S)); 3.571 - 3.479 (m, 2H, H-C(5'), (1R) + (1S)); 1.766 - 1.734 (m, 2H, H2-C(a1), (1R)); 1.573 - 1.404 (m, 5H, H2-C(a1') + H3-C(b1'), (1S)); 1.296 - 1.223 (m, 25H, H-C(b1) + H2-C(a2) - H2-C(a12), (1R) + H2-C(a2') - H2-C(a12'), (1S)); 0.859 - 0.832 (m, 3H, H-C(a13) + H-C(a13'), (1R) + (1S)). 13C-NMR (125.76 MHz, DMSO-d6): 156.049 (C(6), (1R) + (1S)); 152.543 (C(2), (1R) + (1S)); 148.819 (C(4), (1R) + (1S)); 139.618 (C(8), (1R) + (1S)); 119.006 (C(5), (1R) + (1S)); 115.018 (C(acetal), (1S)); 114.643 (C(acetal), (1S)); 89.611 (C(1'), (1S)); 89.370 (C(1'), (1R)); 86.628 (C(4'), (1S)); 86.482 (C(4'), (1R)); 83.570 (C(2'), (1S)); 83.140 (C(2'), (1R)); 81.607 (C(3'), (1S)); 81.105 (C(3'), (1R)); 61.515 (C(5'), (1R) + (1S)); 31. 199 (C(a11), (1R) + (1S)); 29.060 - 28.587 (10 × C, C(a1) - C(a10), (1R) + (1S)); 23.310 (C(b1), (1R)); 23.180 (C(b1'), (1S)); 21.980 (C(a12), (1R) + (1S)); 13.820 (C(a13), (1R) + (1S)). ESI - MS: 476.32 [MW+H]+ (calculated: MW=475.62). Elemental analysis calculated for C25H41N5O4 · 0.35 H2O: C, 62.62 (62.31); H, 8.71 (8.72); N, 14.17 (14.53). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: potassium hydroxide / N,N-dimethyl-formamide / 16 h / 60 °C 1.2: 3 h / 0 - 20 °C 2.1: pyridine / 6 h / 20 °C 3.1: N-ethyl-N,N-diisopropylamine / ethyl acetate / 1 h / 0 - 20 °C |
Tags: Adenosine | Adenine riboside | D-Adenosine | Nucleoside Antimetabolite/Analog | Autophagy | Apoptosis | Endogenous Metabolite | GPCR | endogenous | nadenine riboside | purine nucleoside | cellular energy | ATP | ADP | AMP | neurotransmitter | anti-inflammatory | vasodilation | 58-61-7
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| H229 | Pressurized container: may burst if heated |
| H230 | May react explosively even in the absence of air |
| H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
| H240 | Heating may cause an explosion |
| H241 | Heating may cause a fire or explosion |
| H242 | Heating may cause a fire |
| H250 | Catches fire spontaneously if exposed to air |
| H251 | Self-heating; may catch fire |
| H252 | Self-heating in large quantities; may catch fire |
| H260 | In contact with water releases flammable gases which may ignite spontaneously |
| H261 | In contact with water releases flammable gas |
| H270 | May cause or intensify fire; oxidizer |
| H271 | May cause fire or explosion; strong oxidizer |
| H272 | May intensify fire; oxidizer |
| H280 | Contains gas under pressure; may explode if heated |
| H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
| H290 | May be corrosive to metals |
Health hazards | |
| Code | Phrase |
| H300 | Fatal if swallowed |
| H301 | Toxic if swallowed |
| H302 | Harmful if swallowed |
| H303 | May be harmful if swallowed |
| H304 | May be fatal if swallowed and enters airways |
| H305 | May be harmful if swallowed and enters airways |
| H310 | Fatal in contact with skin |
| H311 | Toxic in contact with skin |
| H312 | Harmful in contact with skin |
| H313 | May be harmful in contact with skin |
| H314 | Causes severe skin burns and eye damage |
| H315 | Causes skin irritation |
| H316 | Causes mild skin irritation |
| H317 | May cause an allergic skin reaction |
| H318 | Causes serious eye damage |
| H319 | Causes serious eye irritation |
| H320 | Causes eye irritation |
| H330 | Fatal if inhaled |
| H331 | Toxic if inhaled |
| H332 | Harmful if inhaled |
| H333 | May be harmful if inhaled |
| H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
| H335 | May cause respiratory irritation |
| H336 | May cause drowsiness or dizziness |
| H340 | May cause genetic defects |
| H341 | Suspected of causing genetic defects |
| H350 | May cause cancer |
| H351 | Suspected of causing cancer |
| H360 | May damage fertility or the unborn child |
| H361 | Suspected of damaging fertility or the unborn child |
| H361d | Suspected of damaging the unborn child |
| H362 | May cause harm to breast-fed children |
| H370 | Causes damage to organs |
| H371 | May cause damage to organs |
| H372 | Causes damage to organs through prolonged or repeated exposure |
| H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
| Code | Phrase |
| H400 | Very toxic to aquatic life |
| H401 | Toxic to aquatic life |
| H402 | Harmful to aquatic life |
| H410 | Very toxic to aquatic life with long-lasting effects |
| H411 | Toxic to aquatic life with long-lasting effects |
| H412 | Harmful to aquatic life with long-lasting effects |
| H413 | May cause long-lasting harmful effects to aquatic life |
| H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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