Home Cart 0 Sign in  

[ CAS No. 7481-89-2 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 7481-89-2
Chemical Structure| 7481-89-2
Structure of 7481-89-2 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 7481-89-2 ]

Related Doc. of [ 7481-89-2 ]

Alternatived Products of [ 7481-89-2 ]

Product Details of [ 7481-89-2 ]

CAS No. :7481-89-2 MDL No. :MFCD00012188
Formula : C9H13N3O3 Boiling Point : -
Linear Structure Formula :- InChI Key :WREGKURFCTUGRC-POYBYMJQSA-N
M.W : 211.22 Pubchem ID :24066
Synonyms :
2',3'-Dideoxycytidine;ddC;dideoxycytidine, Brand name: Hivid.;2′-3′-dideoxycytidine;2’,3’-Dideoxycytidine;Ro 24-2027/000;NSC 606170;Dideoxycytidine
Chemical Name :4-Amino-1-((2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one

Calculated chemistry of [ 7481-89-2 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.56
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 53.52
TPSA : 90.37 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.51 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.05
Log Po/w (XLOGP3) : -1.3
Log Po/w (WLOGP) : -0.82
Log Po/w (MLOGP) : -0.3
Log Po/w (SILICOS-IT) : -0.47
Consensus Log Po/w : -0.37

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.49
Solubility : 67.6 mg/ml ; 0.32 mol/l
Class : Very soluble
Log S (Ali) : -0.1
Solubility : 168.0 mg/ml ; 0.794 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.6
Solubility : 52.9 mg/ml ; 0.251 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.25

Safety of [ 7481-89-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H351-H361 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 7481-89-2 ]

* 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.

  • Downstream synthetic route of [ 7481-89-2 ]

[ 7481-89-2 ] Synthesis Path-Downstream   1~88

  • 1
  • [ 10400-19-8 ]
  • [ 7481-89-2 ]
  • 5',4N-bisnicotinyl-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% With pyridine at 40℃;
  • 2
  • [ 129151-50-4 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
70% With ammonia In methanol Heating;
  • 3
  • (5-O-benzoyl-2,3-dideoxy-β-D-glycero-pentofuranosyl)cytosine [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
With ammonia In methanol Yield given;
  • 4
  • [ 125612-00-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
98% With ammonia In methanol for 18h; Ambient temperature;
  • 5
  • [ 120885-66-7 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
79% With ammonia In methanol Ambient temperature;
  • 7
  • [ 4637-24-5 ]
  • [ 7481-89-2 ]
  • N4-<(dimethylamino)methylene>-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% In N,N-dimethyl-formamide Ambient temperature;
  • 8
  • [ 120885-60-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
75% With ammonia In methanol for 22h; Ambient temperature; pH 12;
  • 10
  • [ 126430-21-5 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
62% With N-benzyl-trimethylammonium hydroxide In methanol Ambient temperature;
  • 11
  • [ 7481-88-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
93% With hydrogen In ethanol for 2h; Ambient temperature;
With hydrogen Yield given;
  • 12
  • [ 5211-86-9 ]
  • [ 7481-89-2 ]
  • N4-(piperidinomethylene)-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% In N,N-dimethyl-formamide Ambient temperature;
  • 13
  • [ 4432-76-2 ]
  • [ 7481-89-2 ]
  • N4-<(diethylamino)methylene>-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% In N,N-dimethyl-formamide Ambient temperature;
  • 14
  • [ 19449-28-6 ]
  • [ 7481-89-2 ]
  • N4-<(diisopropylamino)methylene>-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% In N,N-dimethyl-formamide Ambient temperature;
  • 15
  • [ 5211-95-0 ]
  • [ 7481-89-2 ]
  • N4-<(dipropylamino)methylene>-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% In N,N-dimethyl-formamide Ambient temperature;
  • 16
  • [ 5564-73-8 ]
  • [ 7481-89-2 ]
  • N4-(pyrrolidinomethylene)-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% In N,N-dimethyl-formamide Ambient temperature;
  • 17
  • [ 7481-89-2 ]
  • [ 19449-31-1 ]
  • N4-(morpholinomethylene)-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% In N,N-dimethyl-formamide Ambient temperature;
  • 18
  • [ 7481-89-2 ]
  • [ 114748-57-1 ]
YieldReaction ConditionsOperation in experiment
85.8% With iodine In methanol; dichloromethane 5.A A. A. Preparation of 5-Iodo-2',3'-dideoxycytidine (1) A solution of 2',3'-dideoxycytidine (500 mg, 2.36 mmol), and mercuric acetate (800 mg, 2.5 mmol) in methanol (25 mL) was refluxed for 10 h. The white suspension was diluted with methanol (15 mL) in dichloromethane (25 mL). Iodine (750 mg, 2.95 mmol) was added and the suspension was stirred at room temperature until a clear purple solution resulted (in about 4 h). The free base form of AG 3X4A resin (3.5 g, Bio-Rad, a weakly basic polystyrene resin) was added and hydrogen sulfide was bubbled into the reaction mixture for 10 min. The reaction mixture was filtered through a filter aid, which was washed with 1:1 methanol and dichloromethane. The filtrate was concentrated and the resultant solid was collected through filtration, washed with diethyl ether, and dried to give 670 mg of pure product (85.8%). The Rf on a silica gel plate using 10% methanol in dichloromediane was 0.2. 1 H NMR (DMSO-d6); 1.79-2.3 (m, 4H, H2" and H3,), 3.5 5(dt, 1H, H5", b), 3.73 (dd, 1H, H5", a), 4.05 (m, 1H, H4"), 5.2 (t, 1H, 5"--OH), 5.86 (dd, 1H, H1"), 6.55 (broad s, 1H, NH2 b), 7.75 (broad s, 1H, NH2 a) and 8.5 (s, 1H, H6).
With mercury(II) diacetate; iodine Multistep reaction;
2.79 g (83%) With iodine In methanol; dichloromethane 1.B B. B. Preparation of 5-Iodo-2',3'-Dideoxycytidine (44) A solution of 2',3'-dideoxycytidine (2.11 g, 10 mmol, Raylo) and mercuric acetate (3.35 g, 10.5 mmol, Fisher) in 50 mL of methanol was refluxed for 19 h. The resulting white suspension was diluted with methanol (50 mL) and dichloromethane (100 mL). Iodine (3.05 g, 12 mmol) was added and the suspension was stirred at 25° until a clear purple solution was present. After 4 h, the free base form of AG3 X4A resin (20 mL, 38 meq, Bio-Rad; a weakly basic polystyrene resin) was added and hydrogen sulfide was bubbled into the reaction for 15 min. Complete precipitation of mercury(II) was verified by TLC. The reaction was filtered though filter aid and the filter aid was washed with 1:1 methanol-dichloromethane. The filtrate was evaporated onto silica gel 10 g) and the loaded silica gel was placed on top of a 150 g silica gel column. Elution with 5%, 10% and 20% methanol in dichloromethane afforded 2.79 g (83%) of iodide 44 as a colorless crystalline solid. Two recrystallizations from boiling water afforded, after vacuum-drying at 50°, large, analytically-pure prisms (mp: d 178°). 1 H-NMR (DMSO-d6): 8.50 (s, 1H, H6), 7.73 (broad s, 1H, --NH2 a), 6.53 (broad s, 1H, --NH2 b), 5.86 (dd, J=6.5 and 2.1, 1H, H1'), 5.19 (t, 1H, 5'OH), 4.04 (m, 1H, H4'), 3.75 (ddd, J=12.1, 5.2, and 2.9, 1H, H5'a), 3.53 (dt, J=12.1 and 3.8, 1H, H5'b), and 2.3-1.7 (m, 4H, H2' and H3'). Calculated for C9 H12 N3 O3 I: C 32.07%, H 3.59%, N12.46%. Found: C 32.05%, H 3.80%, N 12.46%.
2.79 g (83%) With iodine In methanol; dichloromethane 1.B B. B. PREPARATION OF 5-IODO-2',3'-DIDEOXYCYTIDINE (44) A solution of 2',3'-dideoxycytidine (2.11 g, 10 mmol, Raylo) and mercuric acetate (3.35 g, 10.5 mmol, Fisher) in 50 mL of methanol was refluxed for 19 h. The resulting white suspension was diluted with methanol (50 mL) and dichloromethane (100 mL). Iodine (3.05 g, 12 mmol) was added and the suspension was stirred at 25° until a clear purple solution was present After 4 h, the free base form of AG3 X4A resin (20 mL, 38 meq, Bio-Rad; a weakly basic polystyrene resin) was added and hydrogen sulfide was bubbled into the reaction for 15 min. Complete precipitation of mercury(II) was verified by TLC. The reaction was filtered though filter aid and the filter aid was washed with 1:1 methanol-dichloromethane. The filtrate was evaporated onto silica gel (10 g) and the loaded silica gel was placed on top of a 150 g silica gel column. Elution with 5%, 10% and 20% methanol in dichloromethane afforded 2.79 g (83%) of iodide 44 as a colorless crystalline solid. Two recrystallizations from boiling water afforded, after vacuum-drying at 50°, large, analytically-pure prisms (mp: d 178°). 1 H--NMR (DMSO-d6): 8.50 (s, 1H, H6), 7.73 (broad s, 1H, --NH2 a), 6.53 (broad s, 1H, --NH2 b), 5.86 (dd, J=6.5 and 2.1, 1H, H1'), 5.19 (t, 1H, 5'OH), 4.04 (m, 1H, H4'), 3.75 (ddd, J=12.1, 5.2, and 2.9, 1H, H5'a), 3.53 (dt, J=12.1 and 3.8, 1H, H5'b), and 2,3-1.7 (m, 4H, H2' and H3'). Calculated for C9 H12 N3 O3 I: C 32.07%, H 3.59%, N12.46%. Found: C 32.05%, H 3.80%, N 12.46%.
2.79 g (83%) With iodine In methanol; dichloromethane 5.B B. B. PREPARATION OF 5-IODO-2',3'-DIDEOXYCYTIDINE (19) A solution of 2',3'-dideoxycytidine (2.11 g, 10 mmol, Raylo) and mercuric acetate (3.35 g, 10.5 mmol, Fisher) in 50 mL of methanol was refluxed for 19 hours. The resulting white suspension was diluted with methanol (50 mL) and dichloromethane (100 mL). Iodine (3.05 g, 12 mmol) was added and the suspension was stirred at 25°. After 4 hours, the free base form of AG3 X4A resin (20 mL, 38 meq, Bio-Rad) was added and hydrogen sulfide was bubbled into the reaction for 15 minutes. Complete precipitation of mercury(II) was verified by TLC. The reaction was filtered through filter aid and the filter aid was washed with 1:1 methanol-dichloromethane. The filtrate was evaporated onto silica gel (10 g) and the loaded silica gel was placed on top of a 150 g silica gel column. Elution with 5%, 10% and 20% methanol in dichloromethane afforded 2.79 g (83%) of iodide 19 as a colorless crystalline solid. Two recrystallizations from boiling water afforded, after vacuum-drying at 50°, large, analytically-pure prisms (mp: d 178°). 1 H-NMR (DMSO-d6): 8.50 (s, 1H, H6), 7.73 (broad s, 1H, --NH2 a), 6.53 (broad s, 1H, --NH2 b), 5.86 (dd, J=6.5 and 2.1, 1H, H1'), 5.19 (t, 1H, 5'OH), 4.04 (m, 1H, H4'), 3.75 (ddd, J=12.1, 5.2, and 2.9, 1H, H5'a), 3.53 (dt, J=12.1 and 3.8, 1H, H5'b), and 2.3-1.7 (m, 4H, H2' and H3'). Calculated for C9 H12 N3 O3 I: C 32.07%, H 3.59%, N 12.46%. Found: C 32.05%, H 3.80%, N 12.46%.

  • 19
  • [ 7481-89-2 ]
  • [ 107036-57-7 ]
YieldReaction ConditionsOperation in experiment
57% With N-Bromosuccinimide In N,N-dimethyl-formamide
With pyridine; bromine In N,N-dimethyl-formamide 4 Preparation of [79 Br]2',3'-Dideoxy-5-Bromocytidine EXAMPLE 4 Preparation of [79 Br]2',3'-Dideoxy-5-Bromocytidine To a solution of 2',3'-dideoxycytidine (60 mg, 0.3 mmol) in dry DMF (1 ml) was added 0.1 ml pyridine and then [79 Br] bromine (42 mg, 0.3 mmol), and the mixture agitated for 12 hr. The solvent was evaporated, and the residue chromatographed on silica gel (ethyl acetate:methanol:triethylamine 90:10:1) to give 46 mg of the title product as a white solid. This material could be converted to the triphosphate via the monophosphate as in Example 2. The monophosphate was prepared by reaction with cyanoethyl phosphate and dicyclohexylcarbodiimide followed by LiOh deblocking.
0.097 g (57%) With N-Bromosuccinimide In N,N-dimethyl-formamide 2',3'-Dideoxy-5-bromocytidine (17) To a solution of 2',3'-Dideoxy-5-bromocytidine (17) To a solution of 2',3'-dideoxycytidine (0.127 g, 0.6 mmol) in dry DMF (1.5 mL) was added N-bromosuccinimide (0.117 g, 0.65 mmol) and the mixture was stirred under nitrogen overnight. Solvent was removed in vacuo and the residue was chromatographed on a preparative TLC plate (ethyl acetate/methanol/triethylamine=90/10/1) to give 0.097 g (57%) of white solid, mp 188°-190° C. (dec) after recrystallization from acetone-hexane. NMR (D2 O); δ 1.94 (m, 2H), 2.02 (m, 1H), 2.45 (m, 1H), 3.74 (dd, 1H), 4.01 (dd, 1H), 4.23 (m, 1H), 6.01 (dd, 1H), 8.70 (s, 1H). FAB mass spectrum; m/z (relative intensity) 112 (b+3H-Br, 99), 190 ([79 Br]b+2H, 68), 192 ([81 Br]b+2H, 70), 212 (M+2H-Br, 100), 290 ([79 Br]MH+, 35), 292 ([81 Br]MH+, 35). Anal. C9 H12 N3 BrO3; C, H, N, Br.
  • 20
  • [ 58479-61-1 ]
  • [ 7481-89-2 ]
  • [ 143840-02-2 ]
YieldReaction ConditionsOperation in experiment
72% In pyridine
  • 21
  • [ 7481-89-2 ]
  • (suberyl-Trp-Val-Sta-CH(Ph)-CH2Ph) acid [ No CAS ]
  • N4-(1,8-dioxooctyl-Trp-Val-Sta-CH(Ph)-CH2Ph)-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
24% With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 7h; Ambient temperature;
  • 22
  • [ 501-53-1 ]
  • [ 7481-89-2 ]
  • [ 120885-64-5 ]
YieldReaction ConditionsOperation in experiment
74% With dmap In pyridine; N,N-dimethyl-formamide for 18h; Ambient temperature;
  • 23
  • [ 1609-47-8 ]
  • [ 7481-89-2 ]
  • [1-((2R,5S)-5-Hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-carbamic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% In methanol for 4h; Heating;
  • 24
  • [ 1609-47-8 ]
  • [ 7481-89-2 ]
  • Carbonic acid (2S,5R)-5-(4-ethoxycarbonylamino-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With dmap In pyridine for 18h; Ambient temperature;
  • 25
  • N-[1-((S)-5-Hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-acetamide [ No CAS ]
  • [ 116561-09-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In methanol Yield given. Yields of byproduct given;
  • 26
  • [ 75178-96-0 ]
  • [ 7481-89-2 ]
  • 4-N-{3-[(tert-butoxy)carbonyl]amino}propyl}-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; sodium hydrogensulfite In water at 55℃; for 5h;
  • 27
  • [ 7481-89-2 ]
  • β-D-2',3'-dideoxycytidine monophosphate [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% With sodium acetate buffer; tris(p-nitrophenyl)phosphate at 35℃; for 12h;
With trimethyl phosphite; trichlorophosphate at 0℃; for 2h;
With recombinant human deoxycytidine kinase (EC 2.7.1.74); ATP In various solvent(s) at 37℃;
  • 28
  • [ 7481-89-2 ]
  • [ 152406-75-2 ]
  • S-[1-(N4-deoxycytidinyl)methyl]glutathione [ No CAS ]
YieldReaction ConditionsOperation in experiment
In water at 20℃; for 1h;
  • 29
  • [ 7481-89-2 ]
  • [ 199003-54-8 ]
  • 4-N-(N,N-dibenzylformamidinyl)-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
25 mg In N,N-dimethyl-formamide at 70℃;
  • 30
  • [ 5381-99-7 ]
  • [ 7481-89-2 ]
  • [ 688804-54-8 ]
YieldReaction ConditionsOperation in experiment
With pyridine In N,N-dimethyl-formamide at 0℃; for 0.25h;
  • 31
  • difluoromethylenebisphosphonic acid bis(tri-n-butylammonium) salt [ No CAS ]
  • [ 7481-89-2 ]
  • 2',3'-dideoxycytidine 5'-α-P-borano-β,γ-(difluoromethylene)triphosphate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2`,3`-dideoxycytidine With bis(diisopropylamino)chlorophosphine; N-ethyl-N,N-diisopropylamine In chloroform; N,N-dimethyl-formamide at 0℃; for 2h; Stage #2: difluoromethylenebisphosphonic acid bis(tri-n-butylammonium) salt In chloroform; N,N-dimethyl-formamide at 20℃; for 4h; Stage #3: With dimethylsulfide borane complex In chloroform; N,N-dimethyl-formamide at 20℃; for 14h;
  • 32
  • [ 3416-05-5 ]
  • [ 65-46-3 ]
  • [ 7481-89-2 ]
  • [ 1463-10-1 ]
YieldReaction ConditionsOperation in experiment
at 37℃; Enzymatic reaction; Aqueous citrate buffer; 2.4; 2.5 The cells are then centrifuged for 15' at 4000 rpm at 4° C. , washed in 50 ml of phosphate buffer then the pellet obtained after centrifugation is preserved overnight at -20° C. The bacterial pellet resuspended in 20 ml of phosphate buffer is then lysed by passage through a French press at 14000 psi. The lysate is centrifuged for 90' at 50,000 rpm. The supernatant containing the soluble proteins is then precipitated with ammonium sulphate (40% saturation). The precipitate obtained after centrifugation at 13900 rpm (20,000 g) for 30' at 4° C. is resuspended in 1 ml of 100 mM phosphate buffer, pH 7.5, 1.5 M NaCl, then deposited on a Sephacryl S200 gel filtration column (Amersham-Pharmacia). The fractions are then analyzed by SDS-PAGE gel and the enzymatic activity determined. The most active and purest fractions are dialysed overnight at 4° C. against the same buffer at pH=6.0. The protein concentration is determined by measuring the OD at 280 nm.The measurement of the enzymatic activities is carried out as described in paragraph 4.2.5) ResultsThe transforming clones of the E. coli strain PAK9, expressing the mutated ntd gene of L. fermentans were selected in glucose mineral medium with dideoxyuracil (ddR-U) and cytosine (C) added.Several transformants were obtained and are capable of carrying out the exchange: ddR-Pyr+Pur The nucleotide sequences of the different variants of ntd are identical and only differ from the wild-type gene by one mutation (indicated in bold type in Table 2 below). In both cases (L. leichmannii and L. fermentum) a neutral amino acid (glycine and alanine) is replaced by a nucleophilic amino acid (serine and threonine respectively). The conversion of N-deoxyribosyl transferase to N-dideoxyribosyl transferase or N-didehydroribosyl transferase therefore seems to require the substitution of a neutral amino acid by a nucleophilic amino acid which must contribute to the positioning of the sugar promoting its catalysis. It is interesting to note in Table 2 that all the N-deoxyribosyl transferases as well as a certain number of homologous proteins (of unknown function) possess a glycine or an alanine in this position.The enzymatic activities of the native and mutant N-deoxyribosyl transferases of L. leichmannii (LL and LL G9S) and of L. fermentum (LF and LFA15T) in the exchange reactions dT+CThe results reported in Table 3 below show that the specific activity of the mutant LFA15T is less than that of the native enzyme (LF) for the transfer of deoxyribose but that the latter is greater for the transfer of dideoxyribose or didehydroribose. For the transfer of deoxyribose, the activity is reduced by a factor of 7, whereas the latter is increased by 3 in the case of the transfer of dideoxyribose and by 35 in the case of didehydroribose.Table 4 below shows in detail the results of enzymatic activity tests for the native enzyme and the mutated enzyme of B. fermentum for each of the dT+C, ddT+C and d4T+C reactions. The first column of the table shows the affinity constant values (Km), the second the maximum reaction speed (Vmax), the third, the catalysis constant (Kcat), and the last the ratio of the affinity and catalysis constants (Km/Kcat) taking account of the effectiveness of the enzymes tested. These different values were measured according to the protocol described in the literature [P A Kaminski (2002) “Functional cloning, heterologous expression and purification of two different N-deoxyribosyl transferases from Lactobacillus helveticus” J. Biol. Chem; vol. 277; 14400-14407]. The enzyme mutated according to the method of the invention shows a better catalytic activity on d4T and on ddT than the native enzyme. The activities are increased respectively by 60% and 54%. Moreover, the mutated enzyme LFA15T is 60 times more effective than the native enzyme LF in the ddT+X exchange and 7.5 times more effective in the d4T+X exchange.The selected enzyme is therefore used in the enzymatic synthesis of 2',3'-dideoxynucleosides and 2',3'-dideoxy, 2',3'-didehydronucleosides from natural bases ddC, ddA, ddl, d4T, d4C, d4G (Ray et al. 2002; Stuyver et al. 2002) or modified bases (Pokrovsky et al. 2001 Chong et al., 2002) such as (1β-3'-fluoro) 2',3'-dideoxy, 2',3'-didehydro-4'-thio-Nucleosides comprising or not comprising radioelements.
at 37℃; Enzymatic reaction; Aqueous citrate buffer; 2.4; 2.5 The cells are then centrifuged for 15' at 4000 rpm at 4° C. , washed in 50 ml of phosphate buffer then the pellet obtained after centrifugation is preserved overnight at -20° C. The bacterial pellet resuspended in 20 ml of phosphate buffer is then lysed by passage through a French press at 14000 psi. The lysate is centrifuged for 90' at 50,000 rpm. The supernatant containing the soluble proteins is then precipitated with ammonium sulphate (40% saturation). The precipitate obtained after centrifugation at 13900 rpm (20,000 g) for 30' at 4° C. is resuspended in 1 ml of 100 mM phosphate buffer, pH 7.5, 1.5 M NaCl, then deposited on a Sephacryl S200 gel filtration column (Amersham-Pharmacia). The fractions are then analyzed by SDS-PAGE gel and the enzymatic activity determined. The most active and purest fractions are dialysed overnight at 4° C. against the same buffer at pH=6.0. The protein concentration is determined by measuring the OD at 280 nm.The measurement of the enzymatic activities is carried out as described in paragraph 4.2.5) ResultsThe transforming clones of the E. coli strain PAK9, expressing the mutated ntd gene of L. fermentans were selected in glucose mineral medium with dideoxyuracil (ddR-U) and cytosine (C) added.Several transformants were obtained and are capable of carrying out the exchange: ddR-Pyr+Pur The nucleotide sequences of the different variants of ntd are identical and only differ from the wild-type gene by one mutation (indicated in bold type in Table 2 below). In both cases (L. leichmannii and L. fermentum) a neutral amino acid (glycine and alanine) is replaced by a nucleophilic amino acid (serine and threonine respectively). The conversion of N-deoxyribosyl transferase to N-dideoxyribosyl transferase or N-didehydroribosyl transferase therefore seems to require the substitution of a neutral amino acid by a nucleophilic amino acid which must contribute to the positioning of the sugar promoting its catalysis. It is interesting to note in Table 2 that all the N-deoxyribosyl transferases as well as a certain number of homologous proteins (of unknown function) possess a glycine or an alanine in this position.The enzymatic activities of the native and mutant N-deoxyribosyl transferases of L. leichmannii (LL and LL G9S) and of L. fermentum (LF and LFA15T) in the exchange reactions dT+CThe results reported in Table 3 below show that the specific activity of the mutant LFA15T is less than that of the native enzyme (LF) for the transfer of deoxyribose but that the latter is greater for the transfer of dideoxyribose or didehydroribose. For the transfer of deoxyribose, the activity is reduced by a factor of 7, whereas the latter is increased by 3 in the case of the transfer of dideoxyribose and by 35 in the case of didehydroribose.Table 4 below shows in detail the results of enzymatic activity tests for the native enzyme and the mutated enzyme of B. fermentum for each of the dT+C, ddT+C and d4T+C reactions. The first column of the table shows the affinity constant values (Km), the second the maximum reaction speed (Vmax), the third, the catalysis constant (Kcat), and the last the ratio of the affinity and catalysis constants (Km/Kcat) taking account of the effectiveness of the enzymes tested. These different values were measured according to the protocol described in the literature [P A Kaminski (2002) “Functional cloning, heterologous expression and purification of two different N-deoxyribosyl transferases from Lactobacillus helveticus” J. Biol. Chem; vol. 277; 14400-14407]. The enzyme mutated according to the method of the invention shows a better catalytic activity on d4T and on ddT than the native enzyme. The activities are increased respectively by 60% and 54%. Moreover, the mutated enzyme LFA15T is 60 times more effective than the native enzyme LF in the ddT+X exchange and 7.5 times more effective in the d4T+X exchange.The selected enzyme is therefore used in the enzymatic synthesis of 2',3'-dideoxynucleosides and 2',3'-dideoxy, 2',3'-didehydronucleosides from natural bases ddC, ddA, ddl, d4T, d4C, d4G (Ray et al. 2002; Stuyver et al. 2002) or modified bases (Pokrovsky et al. 2001 Chong et al., 2002) such as (1β-3'-fluoro) 2',3'-dideoxy, 2',3'-didehydro-4'-thio-Nucleosides comprising or not comprising radioelements.
at 37℃; Enzymatic reaction; Aqueous citrate buffer; 2.4; 2.5 The cells are then centrifuged for 15' at 4000 rpm at 4° C. , washed in 50 ml of phosphate buffer then the pellet obtained after centrifugation is preserved overnight at -20° C. The bacterial pellet resuspended in 20 ml of phosphate buffer is then lysed by passage through a French press at 14000 psi. The lysate is centrifuged for 90' at 50,000 rpm. The supernatant containing the soluble proteins is then precipitated with ammonium sulphate (40% saturation). The precipitate obtained after centrifugation at 13900 rpm (20,000 g) for 30' at 4° C. is resuspended in 1 ml of 100 mM phosphate buffer, pH 7.5, 1.5 M NaCl, then deposited on a Sephacryl S200 gel filtration column (Amersham-Pharmacia). The fractions are then analyzed by SDS-PAGE gel and the enzymatic activity determined. The most active and purest fractions are dialysed overnight at 4° C. against the same buffer at pH=6.0. The protein concentration is determined by measuring the OD at 280 nm.The measurement of the enzymatic activities is carried out as described in paragraph 4.2.5) ResultsThe transforming clones of the E. coli strain PAK9, expressing the mutated ntd gene of L. fermentans were selected in glucose mineral medium with dideoxyuracil (ddR-U) and cytosine (C) added.Several transformants were obtained and are capable of carrying out the exchange: ddR-Pyr+Pur The nucleotide sequences of the different variants of ntd are identical and only differ from the wild-type gene by one mutation (indicated in bold type in Table 2 below). In both cases (L. leichmannii and L. fermentum) a neutral amino acid (glycine and alanine) is replaced by a nucleophilic amino acid (serine and threonine respectively). The conversion of N-deoxyribosyl transferase to N-dideoxyribosyl transferase or N-didehydroribosyl transferase therefore seems to require the substitution of a neutral amino acid by a nucleophilic amino acid which must contribute to the positioning of the sugar promoting its catalysis. It is interesting to note in Table 2 that all the N-deoxyribosyl transferases as well as a certain number of homologous proteins (of unknown function) possess a glycine or an alanine in this position.The enzymatic activities of the native and mutant N-deoxyribosyl transferases of L. leichmannii (LL and LL G9S) and of L. fermentum (LF and LFA15T) in the exchange reactions dT+CThe results reported in Table 3 below show that the specific activity of the mutant LFA15T is less than that of the native enzyme (LF) for the transfer of deoxyribose but that the latter is greater for the transfer of dideoxyribose or didehydroribose. For the transfer of deoxyribose, the activity is reduced by a factor of 7, whereas the latter is increased by 3 in the case of the transfer of dideoxyribose and by 35 in the case of didehydroribose.Table 4 below shows in detail the results of enzymatic activity tests for the native enzyme and the mutated enzyme of B. fermentum for each of the dT+C, ddT+C and d4T+C reactions. The first column of the table shows the affinity constant values (Km), the second the maximum reaction speed (Vmax), the third, the catalysis constant (Kcat), and the last the ratio of the affinity and catalysis constants (Km/Kcat) taking account of the effectiveness of the enzymes tested. These different values were measured according to the protocol described in the literature [P A Kaminski (2002) “Functional cloning, heterologous expression and purification of two different N-deoxyribosyl transferases from Lactobacillus helveticus” J. Biol. Chem; vol. 277; 14400-14407]. The enzyme mutated according to the method of the invention shows a better catalytic activity on d4T and on ddT than the native enzyme. The activities are increased respectively by 60% and 54%. Moreover, the mutated enzyme LFA15T is 60 times more effective than the native enzyme LF in the ddT+X exchange and 7.5 times more effective in the d4T+X exchange.The selected enzyme is therefore used in the enzymatic synthesis of 2',3'-dideoxynucleosides and 2',3'-dideoxy, 2',3'-didehydronucleosides from natural bases ddC, ddA, ddl, d4T, d4C, d4G (Ray et al. 2002; Stuyver et al. 2002) or modified bases (Pokrovsky et al. 2001 Chong et al., 2002) such as (1β-3'-fluoro) 2',3'-dideoxy, 2',3'-didehydro-4'-thio-Nucleosides comprising or not comprising radioelements.
at 37℃; Enzymatic reaction; Aqueous citrate buffer; 2.4; 2.5 The cells are then centrifuged for 15' at 4000 rpm at 4° C. , washed in 50 ml of phosphate buffer then the pellet obtained after centrifugation is preserved overnight at -20° C. The bacterial pellet resuspended in 20 ml of phosphate buffer is then lysed by passage through a French press at 14000 psi. The lysate is centrifuged for 90' at 50,000 rpm. The supernatant containing the soluble proteins is then precipitated with ammonium sulphate (40% saturation). The precipitate obtained after centrifugation at 13900 rpm (20,000 g) for 30' at 4° C. is resuspended in 1 ml of 100 mM phosphate buffer, pH 7.5, 1.5 M NaCl, then deposited on a Sephacryl S200 gel filtration column (Amersham-Pharmacia). The fractions are then analyzed by SDS-PAGE gel and the enzymatic activity determined. The most active and purest fractions are dialysed overnight at 4° C. against the same buffer at pH=6.0. The protein concentration is determined by measuring the OD at 280 nm.The measurement of the enzymatic activities is carried out as described in paragraph 4.2.5) ResultsThe transforming clones of the E. coli strain PAK9, expressing the mutated ntd gene of L. fermentans were selected in glucose mineral medium with dideoxyuracil (ddR-U) and cytosine (C) added.Several transformants were obtained and are capable of carrying out the exchange: ddR-Pyr+Pur The nucleotide sequences of the different variants of ntd are identical and only differ from the wild-type gene by one mutation (indicated in bold type in Table 2 below). In both cases (L. leichmannii and L. fermentum) a neutral amino acid (glycine and alanine) is replaced by a nucleophilic amino acid (serine and threonine respectively). The conversion of N-deoxyribosyl transferase to N-dideoxyribosyl transferase or N-didehydroribosyl transferase therefore seems to require the substitution of a neutral amino acid by a nucleophilic amino acid which must contribute to the positioning of the sugar promoting its catalysis. It is interesting to note in Table 2 that all the N-deoxyribosyl transferases as well as a certain number of homologous proteins (of unknown function) possess a glycine or an alanine in this position.The enzymatic activities of the native and mutant N-deoxyribosyl transferases of L. leichmannii (LL and LL G9S) and of L. fermentum (LF and LFA15T) in the exchange reactions dT+CThe results reported in Table 3 below show that the specific activity of the mutant LFA15T is less than that of the native enzyme (LF) for the transfer of deoxyribose but that the latter is greater for the transfer of dideoxyribose or didehydroribose. For the transfer of deoxyribose, the activity is reduced by a factor of 7, whereas the latter is increased by 3 in the case of the transfer of dideoxyribose and by 35 in the case of didehydroribose.Table 4 below shows in detail the results of enzymatic activity tests for the native enzyme and the mutated enzyme of B. fermentum for each of the dT+C, ddT+C and d4T+C reactions. The first column of the table shows the affinity constant values (Km), the second the maximum reaction speed (Vmax), the third, the catalysis constant (Kcat), and the last the ratio of the affinity and catalysis constants (Km/Kcat) taking account of the effectiveness of the enzymes tested. These different values were measured according to the protocol described in the literature [P A Kaminski (2002) “Functional cloning, heterologous expression and purification of two different N-deoxyribosyl transferases from Lactobacillus helveticus” J. Biol. Chem; vol. 277; 14400-14407]. The enzyme mutated according to the method of the invention shows a better catalytic activity on d4T and on ddT than the native enzyme. The activities are increased respectively by 60% and 54%. Moreover, the mutated enzyme LFA15T is 60 times more effective than the native enzyme LF in the ddT+X exchange and 7.5 times more effective in the d4T+X exchange.The selected enzyme is therefore used in the enzymatic synthesis of 2',3'-dideoxynucleosides and 2',3'-dideoxy, 2',3'-didehydronucleosides from natural bases ddC, ddA, ddl, d4T, d4C, d4G (Ray et al. 2002; Stuyver et al. 2002) or modified bases (Pokrovsky et al. 2001 Chong et al., 2002) such as (1β-3'-fluoro) 2',3'-dideoxy, 2',3'-didehydro-4'-thio-Nucleosides comprising or not comprising radioelements.

  • 33
  • [ 7481-89-2 ]
  • [ 5983-09-5 ]
  • 34
  • [ 62396-80-9 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: DIBAL-H / CH2Cl2; toluene / 2 h / -90 °C 2: molecular sieves (4 Angstroem), BF3*OEt2 / diethyl ether / 0.5 h 3: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl4, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h 4: TBAF / tetrahydrofuran / 8 h 5: K2CO3 / methanol
Multi-step reaction with 4 steps 1: Dibal / toluene / 0.08 h / -78 - -68 °C 2: 69 percent / Triethylamine (Et3N) / 1.) 0 deg, 20 min, 2.) RT, overnight 3: 41 percent / EtAlCl3 / CH2Cl2; toluene / 0.67 h / Ambient temperature 4: 95 percent / p-toluenesulfonic acid monohydrate, Bio-Rex 9 / methanol; H2O / 7 h / Ambient temperature
Multi-step reaction with 3 steps 1.1: diisobutylaluminium hydride / dichloromethane; toluene / 0.75 h / Inert atmosphere; Cooling 1.2: 16 h / 0 - 20 °C 2.1: ethylaluminum dichloride / toluene; 1,2-dichloro-ethane / 16 h / 0 - 20 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 °C
  • 35
  • [ 32780-06-6 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: 90 percent / imidazole / CH2Cl2 / 3 h 2: DIBAL-H / CH2Cl2; toluene / 2 h / -90 °C 3: molecular sieves (4 Angstroem), BF3*OEt2 / diethyl ether / 0.5 h 4: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl4, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h 5: TBAF / tetrahydrofuran / 8 h 6: K2CO3 / methanol
Multi-step reaction with 9 steps 1: 98 percent / imidazole / dimethylformamide / 1 h / Ambient temperature 2: 1) lithium hexamethyldisilazide / 1) THF, -78 deg C, 1h, 2) room temperature, 30 min 3: tetrahydrofuran / -78 °C 4: DIBAL-H / toluene / 2 h / -78 °C 5: 96 percent / pyridine, DMAP / CH2Cl2 / 2 h / 0 °C 6: 1) hexamethyldisilazane (HMDS), ammonium sulfate, 2) trimethylsilyl triflate (TMSOTf) / 1) reflux, 3 h, 2) 1,2-dichlorethane, a) 5 deg C, 10 min, b) room temperature, 35 min 7: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 8: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 9: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
Multi-step reaction with 5 steps 1: imidazole / CH2Cl2 / 1.) 0 deg, 15 min, 2.) RT, 2 h 2: Dibal / toluene / 0.08 h / -78 - -68 °C 3: 69 percent / Triethylamine (Et3N) / 1.) 0 deg, 20 min, 2.) RT, overnight 4: 41 percent / EtAlCl3 / CH2Cl2; toluene / 0.67 h / Ambient temperature 5: 95 percent / p-toluenesulfonic acid monohydrate, Bio-Rex 9 / methanol; H2O / 7 h / Ambient temperature
Multi-step reaction with 4 steps 1.1: 1H-imidazole / dichloromethane / 0 - 20 °C 2.1: diisobutylaluminium hydride / dichloromethane; toluene / 0.75 h / Inert atmosphere; Cooling 2.2: 16 h / 0 - 20 °C 3.1: ethylaluminum dichloride / toluene; 1,2-dichloro-ethane / 16 h / 0 - 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 °C

  • 36
  • [ 221459-89-8 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: molecular sieves (4 Angstroem), BF3*OEt2 / diethyl ether / 0.5 h 2: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl4, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h 3: TBAF / tetrahydrofuran / 8 h 4: K2CO3 / methanol
Multi-step reaction with 3 steps 1: 69 percent / Triethylamine (Et3N) / 1.) 0 deg, 20 min, 2.) RT, overnight 2: 41 percent / EtAlCl3 / CH2Cl2; toluene / 0.67 h / Ambient temperature 3: 95 percent / p-toluenesulfonic acid monohydrate, Bio-Rex 9 / methanol; H2O / 7 h / Ambient temperature
  • 37
  • [ 57501-72-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: aq. NaIO4, SiO2 / CH2Cl2 / 0.25 h 2: NaBH4 / methanol / 1.5 h / -30 - -15 °C 3: 90 percent / imidazole / CH2Cl2 / 3 h 4: DIBAL-H / CH2Cl2; toluene / 2 h / -90 °C 5: molecular sieves (4 Angstroem), BF3*OEt2 / diethyl ether / 0.5 h 6: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl4, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h 7: TBAF / tetrahydrofuran / 8 h 8: K2CO3 / methanol
  • 38
  • [ 75629-74-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: NaBH4 / methanol / 1.5 h / -30 - -15 °C 2: 90 percent / imidazole / CH2Cl2 / 3 h 3: DIBAL-H / CH2Cl2; toluene / 2 h / -90 °C 4: molecular sieves (4 Angstroem), BF3*OEt2 / diethyl ether / 0.5 h 5: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl4, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h 6: TBAF / tetrahydrofuran / 8 h 7: K2CO3 / methanol
  • 39
  • [ 185303-79-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl4, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h 2: TBAF / tetrahydrofuran / 8 h 3: K2CO3 / methanol
  • 40
  • N-{1-[(S)-5-(tert-Butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-acetamide [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: TBAF / tetrahydrofuran / 8 h 2: K2CO3 / methanol
  • 41
  • [ 7481-89-2 ]
  • 2',3'-dideoxy-5'-O-ethoxycarbonylcytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 74 percent / 4-dimethylaminopyridine / dimethylformamide; pyridine / 18 h / Ambient temperature 2: 94 percent / 4-dimethylaminopyridine / pyridine / 2 h / Ambient temperature 3: 65 percent / hydrogen / 10percent palladium on charcoal / ethanol / 1 h
  • 42
  • [ 7481-89-2 ]
  • 2,2-Dimethyl-propionic acid (2S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxymethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 74 percent / 4-dimethylaminopyridine / dimethylformamide; pyridine / 18 h / Ambient temperature 2: 36 percent / 60percent sodium hydride in oil / dimethylformamide / 18 h / Ambient temperature 3: 84 percent / hydrogen / 10percent palladium on charcoal / ethanol / 0.17 h
  • 43
  • phenyl 2,3-dideoxy-1-thio-D-glycero-pentofuranoside [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / NaH / dimethylformamide / 0 °C 2: dimethyl(methylthio)sulfonium tetrafluoroborate, MS 4A / acetonitrile / 5 h / -20 °C 3: 1 M NaOH / acetonitrile / 2.5 h / 0 °C 4: 70 percent / NH3 / methanol / Heating
  • 44
  • phenyl 2,3-dideoxy-5-O-(4-methoxy-2-pyrimidyl)-1-thio-D-glycero-pentofuranoside [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dimethyl(methylthio)sulfonium tetrafluoroborate, MS 4A / acetonitrile / 5 h / -20 °C 2: 1 M NaOH / acetonitrile / 2.5 h / 0 °C 3: 70 percent / NH3 / methanol / Heating
  • 45
  • [ 153864-68-7 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 85 percent / t-BuOK / 2-methyl-propan-2-ol / 2 h / Ambient temperature 2: 93 percent / H2 / 10 percent Pd/C / ethanol / 2 h / 760 Torr / Ambient temperature
  • 46
  • [ 153864-69-8 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 85 percent / t-BuOK / 2-methyl-propan-2-ol / 20 h / Ambient temperature 2: 93 percent / H2 / 10 percent Pd/C / ethanol / 2 h / 760 Torr / Ambient temperature
  • 47
  • [ 153864-64-3 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 322 mg / NH3 / CHCl3 / 48 h / Ambient temperature 2: 85 percent / t-BuOK / 2-methyl-propan-2-ol / 2 h / Ambient temperature 3: 93 percent / H2 / 10 percent Pd/C / ethanol / 2 h / 760 Torr / Ambient temperature
  • 48
  • [ 153864-65-4 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 31 mg / NH3 / CHCl3 / 48 h / Ambient temperature 2: 85 percent / t-BuOK / 2-methyl-propan-2-ol / 20 h / Ambient temperature 3: 93 percent / H2 / 10 percent Pd/C / ethanol / 2 h / 760 Torr / Ambient temperature
  • 49
  • [ 57846-84-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 293 mg / triphenylphosphine, CCl4 / Heating 2: 322 mg / NH3 / CHCl3 / 48 h / Ambient temperature 3: 85 percent / t-BuOK / 2-methyl-propan-2-ol / 2 h / Ambient temperature 4: 93 percent / H2 / 10 percent Pd/C / ethanol / 2 h / 760 Torr / Ambient temperature
Multi-step reaction with 4 steps 1: 6 percent / triphenylphosphine, CCl4 / Heating 2: 31 mg / NH3 / CHCl3 / 48 h / Ambient temperature 3: 85 percent / t-BuOK / 2-methyl-propan-2-ol / 20 h / Ambient temperature 4: 93 percent / H2 / 10 percent Pd/C / ethanol / 2 h / 760 Torr / Ambient temperature
  • 50
  • [ 7481-89-2 ]
  • 4N-<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>-2',3'-dideoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: pyridine, N,N'-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) / 72 h / Ambient temperature 2: aq. NaOH (pH 7.5) / 2 h / 37 °C 3: aq. NaHCO3, Na2S2O4 / CH2Cl2 / 0.33 h / Ambient temperature
  • 51
  • (3R,5S)-5-(tert-Butyl-diphenyl-silanyloxymethyl)-3-phenylselanyl-tetrahydro-furan-2-ol [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 96 percent / pyridine, DMAP / CH2Cl2 / 2 h / 0 °C 2: 1) hexamethyldisilazane (HMDS), ammonium sulfate, 2) trimethylsilyl triflate (TMSOTf) / 1) reflux, 3 h, 2) 1,2-dichlorethane, a) 5 deg C, 10 min, b) room temperature, 35 min 3: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 4: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 5: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 52
  • [ 149656-26-8 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 1) hexamethyldisilazane (HMDS), ammonium sulfate, 2) trimethylsilyl triflate (TMSOTf) / 1) reflux, 3 h, 2) 1,2-dichlorethane, a) 5 deg C, 10 min, b) room temperature, 35 min 2: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 3: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 4: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 53
  • [ 102717-29-3 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: 1) lithium hexamethyldisilazide / 1) THF, -78 deg C, 1h, 2) room temperature, 30 min 2: tetrahydrofuran / -78 °C 3: DIBAL-H / toluene / 2 h / -78 °C 4: 96 percent / pyridine, DMAP / CH2Cl2 / 2 h / 0 °C 5: 1) hexamethyldisilazane (HMDS), ammonium sulfate, 2) trimethylsilyl triflate (TMSOTf) / 1) reflux, 3 h, 2) 1,2-dichlorethane, a) 5 deg C, 10 min, b) room temperature, 35 min 6: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 7: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 8: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 54
  • [ 125440-13-3 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: tetrahydrofuran / -78 °C 2: DIBAL-H / toluene / 2 h / -78 °C 3: 96 percent / pyridine, DMAP / CH2Cl2 / 2 h / 0 °C 4: 1) hexamethyldisilazane (HMDS), ammonium sulfate, 2) trimethylsilyl triflate (TMSOTf) / 1) reflux, 3 h, 2) 1,2-dichlorethane, a) 5 deg C, 10 min, b) room temperature, 35 min 5: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 6: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 7: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 55
  • [ 115728-44-4 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: DIBAL-H / toluene / 2 h / -78 °C 2: 96 percent / pyridine, DMAP / CH2Cl2 / 2 h / 0 °C 3: 1) hexamethyldisilazane (HMDS), ammonium sulfate, 2) trimethylsilyl triflate (TMSOTf) / 1) reflux, 3 h, 2) 1,2-dichlorethane, a) 5 deg C, 10 min, b) room temperature, 35 min 4: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 5: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 6: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 56
  • [ 119794-42-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / H2 / 10percent Pd/C / methanol; tetrahydrofuran / 0.58 h 2: tetrabutylammonium fluoride trihydrate / tetrahydrofuran / 3.5 h / Ambient temperature 3: methanol, triethylamine / 5 h / 47 °C
Multi-step reaction with 3 steps 1: 85 percent / 1 M tetra-n-butylammonium fluoride / tetrahydrofuran 2: 77.5 percent / H2 / 10percent Pd/C / ethanol / 775.7 Torr 3: 80 percent / ammonia / methanol / Heating
  • 57
  • [ 141171-32-6 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrabutylammonium fluoride trihydrate / tetrahydrofuran / 3.5 h / Ambient temperature 2: methanol, triethylamine / 5 h / 47 °C
  • 58
  • [ 126430-19-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 970 mg / H2 / 10percent Pd/C / methanol; dimethylformamide / 760 Torr / Ambient temperature 2: 62 percent / 40percent benzyltrimethylammonium hydroxide / methanol / Ambient temperature
  • 59
  • N4-acetyl-1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pentofuranosyl>cytosine [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 2: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 60
  • [ 141684-80-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94.74 percent / n-Bu3SnH, Et3B / benzene; hexane / Ambient temperature 2: 99.5 percent / TBAF / tetrahydrofuran / Ambient temperature 3: 88.73 percent / sodium methoxide / methanol / 1 h / Ambient temperature
  • 62
  • [ 114827-12-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: Mg(OMe)2, NaBH4 / benzene; methanol / 1.5 h / 65 °C 2: 87 percent / pyridine / Ambient temperature 3: 95 percent / NaH / tetrahydrofuran / Ambient temperature 4: 1.) t-BuOK; 2.) NH3 / 1.) t-BuOH; 2.) MeOH 5: H2 / 10 percent palladium on carbon
  • 63
  • [ 114827-17-7 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 95 percent / NaH / tetrahydrofuran / Ambient temperature 2: 1.) t-BuOK; 2.) NH3 / 1.) t-BuOH; 2.) MeOH 3: H2 / 10 percent palladium on carbon
  • 64
  • [ 58526-07-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 87 percent / pyridine / Ambient temperature 2: 95 percent / NaH / tetrahydrofuran / Ambient temperature 3: 1.) t-BuOK; 2.) NH3 / 1.) t-BuOH; 2.) MeOH 4: H2 / 10 percent palladium on carbon
  • 65
  • [ 21461-84-7 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: borane-dimethyl sulfide (BH3-SMe2) / tetrahydrofuran / 2 h / Ambient temperature 2: imidazole / CH2Cl2 / 1.) 0 deg, 15 min, 2.) RT, 2 h 3: Dibal / toluene / 0.08 h / -78 - -68 °C 4: 69 percent / Triethylamine (Et3N) / 1.) 0 deg, 20 min, 2.) RT, overnight 5: 41 percent / EtAlCl3 / CH2Cl2; toluene / 0.67 h / Ambient temperature 6: 95 percent / p-toluenesulfonic acid monohydrate, Bio-Rex 9 / methanol; H2O / 7 h / Ambient temperature
Multi-step reaction with 5 steps 1.1: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 2.1: 1H-imidazole / dichloromethane / 0 - 20 °C 3.1: diisobutylaluminium hydride / dichloromethane; toluene / 0.75 h / Inert atmosphere; Cooling 3.2: 16 h / 0 - 20 °C 4.1: ethylaluminum dichloride / toluene; 1,2-dichloro-ethane / 16 h / 0 - 20 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 °C
  • 66
  • [ 56-86-0 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: 56 percent / sodium nitrite, HCl / H2O / 1.) 15-20 deg C, 5 h, 2.) RT, overnight 2: borane-dimethyl sulfide (BH3-SMe2) / tetrahydrofuran / 2 h / Ambient temperature 3: imidazole / CH2Cl2 / 1.) 0 deg, 15 min, 2.) RT, 2 h 4: Dibal / toluene / 0.08 h / -78 - -68 °C 5: 69 percent / Triethylamine (Et3N) / 1.) 0 deg, 20 min, 2.) RT, overnight 6: 41 percent / EtAlCl3 / CH2Cl2; toluene / 0.67 h / Ambient temperature 7: 95 percent / p-toluenesulfonic acid monohydrate, Bio-Rex 9 / methanol; H2O / 7 h / Ambient temperature
Multi-step reaction with 6 steps 1.1: sodium nitrite; hydrogenchloride / water / 16 h / 0 - 20 °C 2.1: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 3.1: 1H-imidazole / dichloromethane / 0 - 20 °C 4.1: diisobutylaluminium hydride / dichloromethane; toluene / 0.75 h / Inert atmosphere; Cooling 4.2: 16 h / 0 - 20 °C 5.1: ethylaluminum dichloride / toluene; 1,2-dichloro-ethane / 16 h / 0 - 20 °C / Inert atmosphere 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 °C
  • 67
  • [ 187458-07-7 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 41 percent / EtAlCl3 / CH2Cl2; toluene / 0.67 h / Ambient temperature 2: 95 percent / p-toluenesulfonic acid monohydrate, Bio-Rex 9 / methanol; H2O / 7 h / Ambient temperature
Multi-step reaction with 2 steps 1: ethylaluminum dichloride / 1,2-dichloro-ethane; toluene / 16 h / 20 °C / Inert atmosphere; Cooling with ice 2: tetrabutyl ammonium fluoride / tetrahydrofuran
Multi-step reaction with 2 steps 1: ethylaluminum dichloride / toluene; 1,2-dichloro-ethane / 16 h / 0 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 °C
  • 68
  • [ 127073-27-2 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / triethylamine / Pd/C / 1,2-dimethoxy-ethane / 1.25 h / 1810.02 Torr 2: 90 percent / HCl-EtOH / ethyl acetate / 0.5 h / 10 - 15 °C 3: 75 percent / ammonia / methanol / 22 h / Ambient temperature; pH 12
  • 69
  • [ 108895-51-8 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 63 percent / LiI / ethyl acetate / 2.5 h / Heating 2: 94 percent / triethylamine / Pd/C / 1,2-dimethoxy-ethane / 1.25 h / 1810.02 Torr 3: 90 percent / HCl-EtOH / ethyl acetate / 0.5 h / 10 - 15 °C 4: 75 percent / ammonia / methanol / 22 h / Ambient temperature; pH 12
  • 70
  • [ 105862-10-0 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 87 percent / pyridine / 1.5 h / Ambient temperature 2: 63 percent / LiI / ethyl acetate / 2.5 h / Heating 3: 94 percent / triethylamine / Pd/C / 1,2-dimethoxy-ethane / 1.25 h / 1810.02 Torr 4: 90 percent / HCl-EtOH / ethyl acetate / 0.5 h / 10 - 15 °C 5: 75 percent / ammonia / methanol / 22 h / Ambient temperature; pH 12
  • 71
  • [ 4836-13-9 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: 72 percent / pyridine / 70 h / Ambient temperature 2: 87 percent / pyridine / 1.5 h / Ambient temperature 3: 63 percent / LiI / ethyl acetate / 2.5 h / Heating 4: 94 percent / triethylamine / Pd/C / 1,2-dimethoxy-ethane / 1.25 h / 1810.02 Torr 5: 90 percent / HCl-EtOH / ethyl acetate / 0.5 h / 10 - 15 °C 6: 75 percent / ammonia / methanol / 22 h / Ambient temperature; pH 12
  • 72
  • [ 951-77-9 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: 85 percent / ethanol / 2 h / Heating 2: 72 percent / pyridine / 70 h / Ambient temperature 3: 87 percent / pyridine / 1.5 h / Ambient temperature 4: 63 percent / LiI / ethyl acetate / 2.5 h / Heating 5: 94 percent / triethylamine / Pd/C / 1,2-dimethoxy-ethane / 1.25 h / 1810.02 Torr 6: 90 percent / HCl-EtOH / ethyl acetate / 0.5 h / 10 - 15 °C 7: 75 percent / ammonia / methanol / 22 h / Ambient temperature; pH 12
  • 73
  • [ 40156-61-4 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 90 percent / tBuOOH, D-(-)-diisopropyl tartrate, Ti(OiPr)4 2: 63 percent / DIBAL / toluene; hexane / 1.) -78 deg C, 2 h, then to 25 deg C over 1 h, 2.) reflux, 0.5 h 3: 100 percent / 1.5 percent methanolic HCl / CH2Cl2 / 0.08 h / 25 °C 4: 100 percent / pyridine, DMAP / 0.25 h / 25 °C 5: 1.) tert-butyldimethylsilyl triflate, 2.) methanolic ammonia / 1.) CH3CN, 25 deg C, 12 h, 2.) 25 deg C, 3 h
Multi-step reaction with 4 steps 1: 90 percent / tBuOOH, D-(-)-diisopropyl tartrate, Ti(OiPr)4 2: 10 percent / DIBAL / toluene; hexane / 1.) -78 deg C, 2 h, then to 25 deg C over 1 h, 2.) reflux, 0.5 h 3: 100 percent / pyridine, DMAP / 0.25 h / 25 °C 4: 1.) tert-butyldimethylsilyl triflate, 2.) methanolic ammonia / 1.) CH3CN, 25 deg C, 12 h, 2.) 25 deg C, 3 h
  • 74
  • [ 132747-40-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 63 percent / DIBAL / toluene; hexane / 1.) -78 deg C, 2 h, then to 25 deg C over 1 h, 2.) reflux, 0.5 h 2: 100 percent / 1.5 percent methanolic HCl / CH2Cl2 / 0.08 h / 25 °C 3: 100 percent / pyridine, DMAP / 0.25 h / 25 °C 4: 1.) tert-butyldimethylsilyl triflate, 2.) methanolic ammonia / 1.) CH3CN, 25 deg C, 12 h, 2.) 25 deg C, 3 h
Multi-step reaction with 3 steps 1: 10 percent / DIBAL / toluene; hexane / 1.) -78 deg C, 2 h, then to 25 deg C over 1 h, 2.) reflux, 0.5 h 2: 100 percent / pyridine, DMAP / 0.25 h / 25 °C 3: 1.) tert-butyldimethylsilyl triflate, 2.) methanolic ammonia / 1.) CH3CN, 25 deg C, 12 h, 2.) 25 deg C, 3 h
  • 75
  • ((1E,3Z)-5,5-Dimethoxy-penta-1,3-dienyloxy)-trimethyl-silane [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: 75 percent / DIBAL / diethyl ether 2: 90 percent / tBuOOH, D-(-)-diisopropyl tartrate, Ti(OiPr)4 3: 63 percent / DIBAL / toluene; hexane / 1.) -78 deg C, 2 h, then to 25 deg C over 1 h, 2.) reflux, 0.5 h 4: 100 percent / 1.5 percent methanolic HCl / CH2Cl2 / 0.08 h / 25 °C 5: 100 percent / pyridine, DMAP / 0.25 h / 25 °C 6: 1.) tert-butyldimethylsilyl triflate, 2.) methanolic ammonia / 1.) CH3CN, 25 deg C, 12 h, 2.) 25 deg C, 3 h
Multi-step reaction with 5 steps 1: 75 percent / DIBAL / diethyl ether 2: 90 percent / tBuOOH, D-(-)-diisopropyl tartrate, Ti(OiPr)4 3: 10 percent / DIBAL / toluene; hexane / 1.) -78 deg C, 2 h, then to 25 deg C over 1 h, 2.) reflux, 0.5 h 4: 100 percent / pyridine, DMAP / 0.25 h / 25 °C 5: 1.) tert-butyldimethylsilyl triflate, 2.) methanolic ammonia / 1.) CH3CN, 25 deg C, 12 h, 2.) 25 deg C, 3 h
  • 76
  • [ 119794-43-3 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 77.5 percent / H2 / 10percent Pd/C / ethanol / 775.7 Torr 2: 80 percent / ammonia / methanol / Heating
  • 77
  • [ 119794-51-3 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 2: 59 percent / tri-n-butyltin hydride, azobisisobutyronitrile / toluene / Heating 3: 85 percent / 1 M tetra-n-butylammonium fluoride / tetrahydrofuran 4: 77.5 percent / H2 / 10percent Pd/C / ethanol / 775.7 Torr 5: 80 percent / ammonia / methanol / Heating
  • 78
  • [ 119794-41-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 59 percent / tri-n-butyltin hydride, azobisisobutyronitrile / toluene / Heating 2: 85 percent / 1 M tetra-n-butylammonium fluoride / tetrahydrofuran 3: 77.5 percent / H2 / 10percent Pd/C / ethanol / 775.7 Torr 4: 80 percent / ammonia / methanol / Heating
  • 79
  • [ 62805-52-1 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 91 percent / H2, Et3N / 5percent Pd/C / ethanol / 25 °C / 760 Torr 2: 79 percent / NH3(gas) / methanol / Ambient temperature
  • 80
  • [ 52482-84-5 ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 84 percent / tetrabutylammonium tosylate, oxalic acid / acetonitrile / 2 h / 10 - 20 °C / electrolysis 2: 91 percent / H2, Et3N / 5percent Pd/C / ethanol / 25 °C / 760 Torr 3: 79 percent / NH3(gas) / methanol / Ambient temperature
  • 81
  • [ 1336-21-6 ]
  • S-(cytosine-1-yl)-4' R-carboethoxytetrahydrofuran [ No CAS ]
  • ethyl (R)-tetrahydrofuran-2-carboxylate [ No CAS ]
  • [ 7481-89-2 ]
YieldReaction ConditionsOperation in experiment
28 mg (84%) With sodium borohydrid In ethanol 5 β-L-2' 3' -DIDEOXYCYTIDINE STR21 EXAMPLE 5 β-L-2' 3' -DIDEOXYCYTIDINE STR21 A mixture of 1' S-(N-4-acetylcytosin-1-yl)- 4' R-carboethoxytetrahydrofuran (49 mg, 0.158 mmol, contains ca. 4% of the corresponding 1' R isomer) and trifluoroacet:ic acid (24 μL, 2 equivalents) in ethanol (1 mL) was refluxed under an argon atmosphere for 2 hours and 40 minutes. The resultant mixture consisting of 1' S-(cytosine-1-yl)-4' R-carboethoxytetrahydrofuran and its 1' epimer was cooled to room temperature and then was diluted with ethanol (0.5 mLT). Sodium borohydride (18 mg, 3 equivalents) was introduced and the reaction mixture was stirred for 1.5 hours. More reducing agent (6 mg) was added and stirring was continued for another 1 hour 20 minutes. The reaction was quenched by the addition of 2 drops of concentrated ammonium hydroxide followed by rigorous stirring for 15 minutes. The solvent was evaporated under reduced pressure and the crude product obtained was subjected to column chromatography (30% MeOH-EtOAc) to provide 28 mg (84%) of the title compound. The IH NMR spectrum of this material indicated the presence of ca. 3% of the corresponding 1' R isomer. This material was dissolved in a minimum amount of methanol.
  • 82
  • [ 7481-89-2 ]
  • 2',3'-Dideoxy-N-[(dimethylamino)methylene]cytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
13 2',3'-Dideoxy-N-[(dimethylamino)methylene]cytidine EXAMPLE 13 2',3'-Dideoxy-N-[(dimethylamino)methylene]cytidine To a solution of 1.05 g (5 mmol) of 2',3'-dideoxycytidine in 5 ml of dimethylforamide was added 2 ml (15 mmol) of N,N-dimethylforamide dimethylacetal. After stirring at ambient temperature for 15 hours, the reaction solution was evaporated in vacuo to give 1.2 (93%) of a pale yellow solid. NMR (CDCl3): 1.8-2.6 (m, 4H, H-2's and H-3's), 3.76 (dd, J=4 and 12 Hz, 1H, H-5'a), 4.02 (dd, J=3 and 12 Hz, 1H, H-5'b), 4.24 (m, 1H, H-4'), 6.07 (d, J=8 Hz, H-5), 6.12 (dd, J=4 and 7 Hz, 1H, H-1'), 7.98 (d, J=8 Hz, 1H, H-6), 8.84 (s, 1H,=CH).
  • 83
  • [ 760974-67-2 ]
  • [ 7481-89-2 ]
  • 6a-ddc [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2`,3`-dideoxycytidine With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 2h; Stage #2: N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)-{4-[1,5-bis(4-N,N-dimethylaminophenyl)-5-(4-N-ethyl-N-(2,3-dihydro-1,4-phthalazinedion-6-yl)aminophenyl)-2,4-pentadienylidene]-2,5-cyclohexadien-1-ylidene}ammonium perchlorate In dimethyl sulfoxide; mineral oil at 20℃; for 2h; A mixture of 2',3'-dideoxycytidine (19.2 mg, 0.091 mmol), sodium hydride (60% in mineral oil, 3.7 mg, 0.093 mmol), and freshly distilled DMSO (4.5 mL) were stirred under argon at room temperature for 2 hours. An aliquot (1.84 mL) of this resulting clear solution was added via a syringe to a solution containing 29.8 mg (0.0308 mmol) of 5a and 0.35 mL of freshly distilled DMSO in an argon atmosphere. The resulting mixture was stirred under the same atmosphere at room temperature for 2 hours yielding a dark green solution of 6a (0.0141 M). This solution was used for the in vitro test against HIV without further purification.
  • 84
  • C8H10O8Pol [ No CAS ]
  • [ 7481-89-2 ]
  • C26H32N6O12Pol [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 60℃; for 7h; solid phase reaction;
  • 85
  • cyanoethyl (methyl stearate)-2-yl-N,N-diisopropylphosphoramidite [ No CAS ]
  • [ 7481-89-2 ]
  • [ 1542227-30-4 ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; O-cyanoethyl, O-(methyl stearate)-2-yl, 2’,3'-dideoxycytidin-5'-phosphate (17): To a stirred solution of ddC (0.1 g, 0.47 mmol) and 0.5M solution of 1H-Tetrazole (4.7 mmol, 10.5 mL) in dry DCM (10 mL) was added phosphoramidite 6 (0.5 g, 0.94 mmol) in dry DCM drop wise at 0°C and the reaction mixture was stirred at rt for 12 h. The reaction mixture is oxidized with 0.02M solution of I2 in THF/H2O until the reaction mixture turned pale yellow. Excess of Iodine is quenched with 10% sodium thiosulfate until the pale yellow color disappeared. The reaction mixture is diluted with DCM and washed with 1M phosphoric acid, dilute sodium bicarbonate and with brine, dried over sodium sulfate, filtered, concentrated in vacuo, and purified by column chromatography using 5% methanol in DCM as eluent (Rf:0.1) to give the desired product as colorless solid (0.25g, 82%).
  • 86
  • [ 7481-89-2 ]
  • zalcitabine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2`,3`-dideoxycytidine In isopropyl alcohol at 34.84℃; for 0.0833333h; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 24.84℃; for 0.0833333h;
  • 87
  • [ 134678-17-4 ]
  • [ 7481-89-2 ]
  • C8H11N3O3S*C9H13N3O3*2ClH [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: lamivudine; 2`,3`-dideoxycytidine In isopropyl alcohol at 34.84℃; for 0.0833333h; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 24.84℃; for 0.0833333h;
  • 88
  • [ 93-97-0 ]
  • [ 7481-89-2 ]
  • [ 120885-60-1 ]
YieldReaction ConditionsOperation in experiment
98% In N,N-dimethyl-formamide at 20℃; for 24h; 4.2. Synthesis of nucleoside derivatives N4-Benzoyl-1-(20,30-dideoxy-30-thia-b-L-ribofuranosyl)-cytosine (3) and N4-benzoyl-20,30-dideoxycytidine (4) General procedure: For selective N-acylation of cytosine nucleosides (1 or 2,Scheme 1) the procedure described in15 was used. To a suspensionof lamivudine (1-(20,30-dideoxy-30-thia-b-L-ribofuranosyl)cytosine)1 or zalcitabine (20,30-dideoxycytidine) 2 (0.322 mmol, 1 equiv.) inDMF (2 mL) benzoic anhydride (81 mg, 0.354 mmol, 1.1 equiv.)was added, and the mixture was stirred at ambient temperaturefor 24 h. After removal of DMF under reduced pressure, the residuewas triturated with diethyl ether. The crystalline products werecollected by filtration, washed thoroughly with diethyl ether andair-dried. Yield of compound 3 was 98%. 1H NMR (DMSO-d6,400 MHz, d, ppm): 8.48 (d, 1H, H6 (Cyt), J = 7.3 Hz); 8.01 (d, 2H,Bz, J = 7.17 Hz); 7.62 (t, 1H, Bz, J = 7.5 Hz); 7.51 (t, 2H, Bz, J = 7.5,7.8 Hz); 7.36 (d, 1H, H5 (Cyt), J = 6.8 Hz); 6.26 (dd, 1H, H10 ,J = 3.0, 5.4 Hz); 5.28 (t, 1H, H40 , J = 4.1 Hz); 3.86 (m, 2H, H50);3.60 (m, H, H20); 3.26 (m, H, H20). Yield of compound 4 was 98%.1H NMR (DMSO-d6, 400 MHz, d, ppm): 8.55 (d, 1H, H6 (Cyt),J = 7.4 Hz); 7.99 (d, 2H, Bz, J = 7.4 Hz); 7.82 (t, 1H, Bz, J = 7.4 Hz);7.50 (t, 2H, Bz, J = 7.4, 7.9 Hz); 7.33 (d, 1H, H5 (Cyt), J = 5.6 Hz);5.95 (dd, 1H, H10 , J = 2.1, 6.9 Hz); 4.12 (m, 1H, H40); 3.79-3.57(m, 2H, H50); 2.44-2.34 (m, H, H20); 2.02-1.96 (m, H, H20); 1.88-1.75 (m, 2H, H30).
Same Skeleton Products
Historical Records