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CAS No. : | 505-95-3 | MDL No. : | MFCD00002739 |
Formula : | C12H24O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZDHCZVWCTKTBRY-UHFFFAOYSA-N |
M.W : | 216.32 | Pubchem ID : | 79034 |
Synonyms : |
12-hydroxy Lauric Acid;G12;NSC 664211;NSC 159293;ω-hydroxy Lauric Acid
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.92 |
Num. rotatable bonds : | 11 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 62.73 |
TPSA : | 57.53 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.08 cm/s |
Log Po/w (iLOGP) : | 2.64 |
Log Po/w (XLOGP3) : | 3.58 |
Log Po/w (WLOGP) : | 2.96 |
Log Po/w (MLOGP) : | 2.27 |
Log Po/w (SILICOS-IT) : | 2.95 |
Consensus Log Po/w : | 2.88 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 1.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -2.71 |
Solubility : | 0.421 mg/ml ; 0.00195 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.47 |
Solubility : | 0.00726 mg/ml ; 0.0000336 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -3.14 |
Solubility : | 0.157 mg/ml ; 0.000726 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 3.0 |
Synthetic accessibility : | 1.91 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
76% | With hydrotalcite; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In tetrahydrofuran; chloroform for 18h; Reflux; Inert atmosphere; | |
57% | With 18-crown-6 ether; potassium carbonate; 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; cesium fluoride In acetonitrile at 70℃; for 48h; | |
56% | With pyridine; pyridine hydrochloride; triphenylphosphine; iodosodilactone In toluene for 12h; Reflux; |
55% | With hafnium tetrakis(trifluoromethanesulfonate) In toluene at 110℃; for 24h; | |
55% | With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 20℃; | Dodecan-12-olide This compound was synthesized as illustrated in FIGS. 1 and 2. FIG. 1 illustrates the synthesis via Mitsunobu cyclization using the method reported by Boden et al. in 1993 (Boden C D, et al (1993) A concise, efficient and flexible strategy for the synthesis of the pheromones of Oryzaephilus and Cryptolestes grain beetles. Synthesis 4: 411-420). This method involves the Mitsunobu esterification of w-hydroxyacid using PPh3 and DIAD (dii sopropyl azodicarboxylate) in toluene at RT. This method provided the dodecan- 12-olide in a 55% yield and one step from the hydroxyacid. |
54% | With 2,3,5-trimethyl-pyridine; oxalyl dichloride; tetramethylurea In diethyl ether; acetonitrile for 51h; Ambient temperature; | |
52% | With dmap; polymer bound carbodiimide; 4-(dimethylamino)pyridine hydrochloride In tetrahydrofuran; chloroform Heating; | |
32% | With dmap; 4-(dimethylamino)pyridine hydrochloride; dicyclohexyl-carbodiimide In tetrahydrofuran; chloroform Heating; | |
22% | With di(n-butyl)tin oxide In 1,3,5-trimethyl-benzene for 21h; Heating; | |
22% | Stage #1: 12-hydroxydodecanoic acid With 1-ethoxyacetylene In toluene Stage #2: With camphor-10-sulfonic acid In toluene at 20℃; Further stages.; | |
10% | In toluene for 72h; Heating; | |
With benzenesulfonic acid; benzene | ||
10 % Chromat. | With diphenylphosphinopolystyrene; diethylazodicarboxylate In tetrahydrofuran at 25℃; for 4h; | |
With TEA; toluene-4-sulfonic acid; 3-(5-nitro-2-oxo-1,2-dihydro-1-pyridyl)-1,2-benzisothiazole 1,1,-dioxide 1) 1,2-dichloroethane, 1 h, 2) 2 h, reflux; Yield given. Multistep reaction; | ||
Multi-step reaction with 2 steps 1: Boc2O; i-Pr2NEt / 20 °C 2: 4-pyrrolidinopyridine / toluene / 16 h / 90 °C | ||
Multi-step reaction with 2 steps 1: triethylamine / toluene / 2 h / Ambient temperature 2: 44 percent / 4-dimethylaminopyridine / toluene / 15 h / 90 - 95 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / concd. HCl / 18 h / Heating 2: 82 percent / imidazole / dimethylformamide / 19 h 3: 98 percent / aq. NaOH / methanol / 24 h / Ambient temperature 4: 99.8 percent / N,N'-dicyclohexylcarbodiimide, 4-(dimethylamino)pyridine / tetrahydrofuran / 22 h / Ambient temperature 5: 85 percent / aq. CF3COOH / tetrahydrofuran / 1 h / Ambient temperature 6: 23 percent / mercuric trifluoroacetate / acetonitrile / 0.6 h / Ambient temperature; other reagents, solvents and time | ||
Multi-step reaction with 2 steps 2: 68 percent / KHCO3, phosphonium mesylate resin / toluene; H2O / 20 h / 90 °C / triphase catalytic lactonization | ||
Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C 2: recombinant DcsB protein from Beauvera bassiana ARSEF 2860 / aq. phosphate buffer / 30 °C / pH 7.4 / Enzymatic reaction |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; In water; for 8h;Reflux; Inert atmosphere; | 12-bromodecanoic acid was synthesized according to the method of Okada.4 To a 10 mL round bottom flask under argon equipped with a magnetic stirring bar was added solid 12-hydroxydodecanoic acid (500 mg, 2.31 mmol, 1.00 eq.) and 47% aqueous hydrobromic acid solution (500 muL, 4.33 mmol, 1.87 eq.). The flask was equipped with a water-cooled condenser, and the reaction mixture was heated to reflux for four hours. After this time, an additional portion of 47% aqueous hydrobromic acid solution (500 muL, 4.33 mmol, 1.87 eq.) was added, and heating at reflux was continued for a further four hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted three times with CH2Cl2 before the combined organics were dried over anhydrous Na2SO4. TLC (2:1 hexanes / EtOAc, UV / anisaldehyde) showed complete consumption of the starting material (Rf = 0.10) and formation of the product of Rf = 0.38. The solvent was removed under reduced pressure, and the residue was dried under high vacuum to give crude 12-bromododecanoic acid as a yellow solid. This material was used directly in the next step without purification. | |
With hydrogen bromide; acetic acid; at 60℃; for 2h; | The hydroxy dodecanoic acid and 6g of hydrogen bromide acetic acid solution was added 20mL 50mL round bottom flask, 60 2 hours the reaction, The mixture was concentrated in vacuo and purified by available bromo dodecanoic acid; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sodium iodide at 85 - 100℃; Green chemistry; | |
With phosphorus; iodine | ||
With hydrogen iodide; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With hydrogenchloride; calcium hypochlorite In tetrachloromethane; <i>tert</i>-butyl alcohol for 7h; | |
46% | With oleate hydratase from S. maltophilia In aq. buffer at 35℃; for 2h; Enzymatic reaction; | |
With chromium(VI) oxide; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In decane for 24h; Heating; | |
With benzenesulfonic acid; benzene | ||
Multi-step reaction with 2 steps 1: Boc2O; i-Pr2NEt / 20 °C 2: 4-pyrrolidinopyridine / toluene / 16 h / 90 °C |
Multi-step reaction with 6 steps 1: 97 percent / concd. HCl / 18 h / Heating 2: 82 percent / imidazole / dimethylformamide / 19 h 3: 98 percent / aq. NaOH / methanol / 24 h / Ambient temperature 4: 99.8 percent / N,N'-dicyclohexylcarbodiimide, 4-(dimethylamino)pyridine / tetrahydrofuran / 22 h / Ambient temperature 5: 85 percent / aq. CF3COOH / tetrahydrofuran / 1 h / Ambient temperature 6: 30 percent / mercuric trifluoroacetate / acetonitrile / 0.6 h / Ambient temperature; other reagents, solvents and time |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.9% | With potassium hydroxide In ethanol for 2h; Heating; | |
63% | With sodium hydroxide | |
With sodium hydroxide In dimethyl sulfoxide for 0.416667h; ΔH; |
With potassium hydroxide | ||
hydrolysis; | ||
Multi-step reaction with 2 steps 1: 57 percent / hydrazine / ethanol / 5 h / Heating 2: CH2Cl2 / 6 h | ||
With water; sodium hydroxide In 1,4-dioxane at 20℃; for 2.5h; Cooling with ice; | ||
10.16 g | Stage #1: oxacyclotridecan-2-one With sodium hydroxide In tetrahydrofuran; methanol; water Reflux; Stage #2: With hydrogenchloride In water | |
4.326 g | With potassium hydroxide In methanol for 3h; Reflux; | 1; 1.c.i 1. Compound 2 (crude, 5.418 g) was refluxed in 19 KOH (1.5 M in 18 MeOH, 40 ml, 60 mmol) for 3 hours. The reaction solution was allowed to warm to room temperature, and then poured into H2O. This mixture was washed with EtOAc twice, and the aqueous layer was then acidified with 2 M HCl, and was extracted with EtOAc twice. The combined organic layer was washed with a saturated aqueous NaCl solution, and was dried over Na2SO4. After evaporation of the solvent, precipitated crude crystals were recrystallized from a mixed solvent of acetone:hexane = 1:5 to yield the corresponding 25 carboxylic acid (4.326 g, 72% for 2 steps). Mp. 82-83°C. 1H-NMR (400 MHz, CDCl3) δ 3.65 (2H, t, J= 6.6 Hz, CH2OH), 2.35 (2H, t, J= 7.5 Hz, CH2CO2H), 1.67-1.53 (4H, m, CH2CH2OH and CH2CH2CO2Et), 1.28 {16H, br, CH2OH, COOH & (CH2)}. |
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol 2: sulfuric acid / water | ||
4.326 g | With methanol; potassium hydroxide for 3h; Reflux; | 1 Compound 2 (crude, 5.418 g) was refluxed in KOH (1.5 M in MeOH, 40 ml, 60 mmol) for 3 hours. After returning to room temperature, the reaction mixture was poured into H2O and washed twice with EtOAc, and the aqueous layer was then acidified with 2 M HCl and extracted twice with EtOAc. The combined organic layers were washed with sat. aq. NaCl and dried over Na2SO4. After the solvent was distilled off, the precipitated crude crystals were recrystallized from a mixed solvent of acetone:hexane = 1:5 to give the corresponding carboxylic acid (4.326 g, 72% for 2 steps). Mp. 82-83°C. [0055] 1H-NMR (400 MHz, CDCl3) δ 3.65 (2H, t, J= 6.6 Hz, CH2OH), 2.35 (2H, t, J = 7.5 Hz, CH2CO2H), 1.67-1.53 (4H, m, CH2CH2OH and CH2CH2CO2Et), 1.28 {16H, br, CH2OH, COOH & (CH2)7}. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 10-Undecen-1-ol; carbon monoxide With acetylacetonatodicarbonylrhodium(l); hydrogen; 6,6′-[(3,3′-di-tert-butyl-5,5′-dimethoxy-1,1′-biphenyl-2,2′-diyl)bis(oxy)]bis(di-benzo[d,f][1,3,2]dioxaphosphepin) In isopropyl alcohol at 150℃; for 1h; Stage #2: With dodecacarbonyl-triangulo-triruthenium; 2,3,4,5-tetraphenylcyclopenta-2,4-dienone In isopropyl alcohol at 150℃; | |
Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridine at 20℃; for 12h; | |
With sodium acetate | ||
With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With toluene-4-sulfonic acid In tetrahydrofuran at 5℃; for 4.5h; | |
94% | With toluene-4-sulfonic acid In tetrahydrofuran for 16h; Ambient temperature; | |
80% | With toluene-4-sulfonic acid In tetrahydrofuran for 2h; Ambient temperature; |
With toluene-4-sulfonic acid In tetrahydrofuran for 4h; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogenchloride for 12h; Ambient temperature; | |
99.6% | With hydrogenchloride In dichloromethane for 1h; Ambient temperature; | |
98% | With hydrogenchloride at 20℃; for 12h; |
97% | With hydrogenchloride for 18h; Heating; | |
96% | With chloro-trimethyl-silane In diethyl ether; hexane at 22℃; | |
96% | With hydrogenchloride Heating; | |
96% | With sulfuric acid at 20℃; for 72h; | Preparation of HO-(CH2)11-CO2Me; A suspension of HO-(CH2)11-CO2H (45 g, 0.21 mol) and concd sulfuric acid (1 mL) in methanol (1 L) was stirred at room temperature for 3 days. Sodium bicarbonate (8.4 g, 0.1 mol) was then added and the mixture was concentrated by rotary evaporation. To the resulting crude was added dichloromethane (50 mL). The solution was filtered through 150 ml silica gel, and the silica gel was further eluted with dichloromethane (500 mL). The combined organics were concentrated by rotary evaporation to give 46 g (96%) of the title compound. |
94% | With chloro-trimethyl-silane In hexane | |
89.2% | With chloro-trimethyl-silane for 16h; Ambient temperature; | |
82% | With sulfuric acid for 4h; Reflux; | Synthesis of methyl 12-hydroxyllaurate To a solution of 12-hydroxyllauric acid (1.0g, 4.6mmol) in methanol (40mL) was slowly added concentrated H2SO4 (200μL, 18.4M) and refluxed for 4h. Then the reaction cooled to room temperature and the methanol was then concentrated in vacuo. The mixture was diluted with EtOAc (20mL) and was rinsed with brine, dried over Na2SO4, and concentrated in vacuo. The crude was purified by semi-preparative HPLC on an ODS column (MeOH/H2O containing 0.15% TFA, 70:30, v/v, 4mL/min) to provide methyl 12-hydroxyllaurate as a white oil (0.871g, 82% yield, tR 18.2min): 1H NMR (CDCl3, 600MHz) δ 3.62 (s, 3H), 3.58 (t, J=6.7Hz, 2H), 2.26 (t, J=7.5Hz, 2H), 1.58-1.55 (m, 2H), 1.53-1.50 (m, 2H), 1.31-1.29 (m, 2H), 1.26-1.20 (m, 12H). 13C NMR (150MHz, CDCl3) δ 174.5, 62.9, 51.5, 34.2, 32.8, 29.6, 29.5×3, 29.3, 29.2, 25.8, 25.0; ESIMS m/z 253.2 [M+Na]+. |
80% | With sulfuric acid for 8h; Reflux; | 4.11.2. 12-Hydroxydodecanoic acid methyl ester (13) 12-Hydroxydodecanoic acid (1.10 g, 5.09 mmol) was stirred with CH3OH (30 mL, 0.74 mol) in the presence of a catalytic amount of concentrated H2SO4 (20 drops) under reflux for 8 h. Volatile materials were removed via rotary evaporation, the residue was dissolved in Et2O (200 mL), and successively washed with 10% NaHCO3 (3 × 100 mL) and H2O (3 × 100 mL). The organic layer was then dried (anhydr. Na2SO4) and concentrated to yield 12-hydroxydodecanoic acid methyl ester (13, 0.81 g, 80%): a white solid; |
50% | With hydrogenchloride; 2,2-dimethoxy-propane In water monomer at 20℃; for 24h; | |
With sulfuric acid for 16h; Ambient temperature; | ||
5.2 g | With hydrogenchloride Heating; | |
With acetyl chloride at 20℃; for 3h; | ||
With sulfuric acid In benzene for 12h; Heating; | ||
With hydrogenchloride at 70℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | for 4h; Heating; | |
87.2% | In <i>tert</i>-butyl alcohol at 65℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium hydroxide for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With chloro-trimethyl-silane In tetrahydrofuran at 66℃; for 64h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With pyridine; carbon tetrabromide; triphenylphosphine In dichloromethane at -20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 91% 2: 3% | With p-nitrobenzoic anhydride; scandium tris(trifluoromethanesulfonate) In tetrahydrofuran; acetonitrile Heating; | |
1: 88% 2: 5% | With dmap; 2-methyl-6-nitrobenzoic anhydride In dichloromethane at 20℃; for 15h; | |
1: 88% 2: 5% | With dmap; 2-methyl-6-nitrobenzoic anhydride In dichloromethane at 20℃; for 1h; |
1: 86% 2: 3% | With dmap; di-2-thienyl carbonate In toluene; acetonitrile for 6h; Heating; | |
1: 10% 2: 83% | With chloro-trimethyl-silane; TiCl2(OTf)2; 4-(trifluoromethyl)benzoic anhydride In dichloromethane at 50℃; | |
1: 83% 2: 10% | With chloro-trimethyl-silane; TiCl2(OTf)2; 4-(trifluoromethyl)benzoic anhydride In dichloromethane at 50℃; other Ti(IV)-sats, other anhydrides; other temp., var. conc. of reagents; | |
1: 83% 2: 5% | With chloro-trimethyl-silane; TiCl2(OTf)2; 4-(trifluoromethyl)benzoic anhydride In dichloromethane at 50℃; for 5h; | |
1: 77% 2: 14% | With dmap; iodine; di-2-thienyl carbonate In toluene; acetonitrile for 10h; Heating; | |
1: 72% 2: 12% | With pentafluorobenzoylchloride; triethylamine In toluene at 110℃; for 24h; | |
1: 55% 2: 16% | With chloro-trimethyl-silane; TiCl2(OTf)2; 4-(trifluoromethyl)benzoic anhydride In dichloromethane at 60℃; | |
With RhCl(PPh3)3; bis(trifluoromethanesulfonyloxy)dimethylsilane; 1,2-bis(dimethylsilyl)benzene 1) benzene, RT, 6 h, 2) benzene, 80 deg C, 3 h, 3) benzene, 80 deg C, 9 h; Yield given. Multistep reaction. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N(Et)4(1+)*(2-pyrrolidone-anion) In N,N-dimethyl-formamide for 1h; Ambient temperature; | |
82.9% | With potassium hydrogencarbonate In N,N-dimethyl-formamide for 20h; | C.2.77e 77e: benzyl 12-hydroxydodecanoate 5,0 g (22,4 mmol) 12-hydroxydodecanoic acid were dissolved in 100 ml DMF. After adding 4,5 g (3,15 ml, 25,8 mmol) benzylbromide and 3,37 g (33,6 mmol) potassium bicarbonate, the mixture was stirred for 20 h. The solvent was removed i. vac. and the residue was dissolved in diethyl ether. After washing with H20, the aqueous phase was separated and extracted with diethyl ether. The combined organic layers were dried with MgS04 and purified by silicagel chromatography (0 to 30 % EtOAc in n-heptane), yielding 5,70 g (82,9 %) of the desired benylester. LCMS-Method A: UV -wavelength [nm] = 220: Rt[min] = 2,04 Ionization method: ES+: [M+H]+ = 307,2 |
82.9% | With potassium hydrogencarbonate In N,N-dimethyl-formamide for 20h; | C 79e: Benzyl 12-hydroxydodecanoate 5,0 g (22,4 mmol) 12-hydroxydodecanoic acid were dissolved in 100 ml DMF. After adding 4,5 g (3,15 ml, 25,8 mmol) benzylbromide and 3,37 g (33,6 mmol) potassium bicarbonate, the mixture was stirred for 20 h. The solvent was removed in vacuo and the residue was dissolved in diethyl ether. After washing with H2O, the aqueous phase was separated and extracted with diethyl ether. The combined organic layers were dried with MgSO4 and purified by silicagel chromatography (0 to 30 % EtOAc in n-heptane), yielding 5,70 g (82,9 %) of the desired benylester 79e. LCMS-Method A: UV-wavelength [nm] = 220: Rt[min] = 2,04 Ionization method: ES+: [M+H]+ = 307,2 |
70% | With potassium hydrogencarbonate In N,N-dimethyl-formamide for 18h; Ambient temperature; | |
8.50 g | With potassium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 24h; | |
8.50 g | With potassium hydrogencarbonate In N,N-dimethyl-formamide for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethylamine In ethyl acetate for 12h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In tetrahydrofuran for 3h; Ambient temperature; | ||
With triethylamine In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 24h; | |
With 1H-imidazole In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With pyridine; chloro-trimethyl-silane In dichloromethane at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With pyridine In tetrahydrofuran for 12h; Ambient temperature; | |
40.5% | With pyridine; 2,6-di-tert-butyl-4-methyl-phenol In tetrahydrofuran Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
542 mg | With 1H-imidazole In N,N-dimethyl-formamide for 12h; Ambient temperature; | |
With 1H-imidazole In N,N-dimethyl-formamide Ambient temperature; | ||
With 1H-imidazole In dichloromethane at 20℃; for 48h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium hydroxide In dimethyl sulfoxide at 65℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sulfuric acid for 4h; Heating; | |
96% | With acetyl chloride for 24h; Reflux; Inert atmosphere; | 4.a a) Synthesis of ethyl 12-hydroxydodecanoate In a 100 mL two-neck flask with a reflux condenser and magnetic anchor, under a static flux of nitrogen, 12-hydroxy-dodecanoic acid (5.0 g, 23.2 mmol) is weighed, ethanol (20 mL) and acetyl chloride (1.62 mmol, 0.09ml, 0.1 eq.) are added. The mixture is left stirring, in reflux conditions for 24 hours. It is concentrated in the Rotavapor and in the high vacuum pump and the product is purified with column chromatography on silica gel with eluant mixture petroleum ether/ethyl acetate 5/4. 3.30 g of ethyl 12-hydroxydodecanoate are isolated as a light yellowish oil for a yield of 96%. |
96% | With acetyl chloride for 24h; Inert atmosphere; Reflux; | 4.a; 5 a) Synthesis of ethyl 12-hydroxydodecanoate a) Synthesis of ethyl 12-hydroxydodecanoate In a 100 mL two-neck flask with a reflux condenser and magnetic anchor, under a static flux of nitrogen, 12-hydroxy-dodecanoic acid (5.0 g, 23.2 mmol) is weighed, ethanol (20 mL) and acetyl chloride (1.62 mmol, 0.09 ml, 0.1 eq.) are added. The mixture is left stirring in reflux conditions for 24 hours. It is concentrated in the Rotavapor and in the high vacuum pump and the product is purified with column chromatography on silica gel with eluant mixture petroleum ether/ethyl acetate 5/4. 3.30 g of ethyl 12-hydroxydodecanoate are isolated as a light yellowish oil for a yield of 96%. Spectroscopic Data: IR: 3662, 2926, 2853, 1731. 1H-NMR (400 MHz, CDCl3): 1.05-1.25 (m, 17H), 1.40-1.60 (m, 4H), 2.17 (t, J=7.2 Hz, 2H), 2.34 (s, 1H), 3.49 (t, J=6.8 Hz, 2H), 4.01 (1, J=7.2 Hz, 2H). 13C-NMR (75.3 MHz, CDCl3): 14.0, 24.7, 25.6, 28.9, 29.0, 29.2, 29.2, 29.3, 29.4, 32.6, 34.2, 59.98, 62.6, 173.8. MS: 234 (M+) |
With acetyl chloride Heating; | ||
With sulfuric acid for 5h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With recombinant human cytochrome P450 or CYP enzymes; all-trans-retinoic-acid Enzymatic reaction; | ||
With glucose-6-phosphate dehydrogenase; α-D-glucose 6-phosphate; NADPH In phosphate buffer at 30℃; for 1h; | ||
With putidaredoxin reductase; CYP153A monooxygenase from marinobacter aquaeolei; putidaredoxin aq. phosphate buffer; |
With oxygen; NADPH In aq. phosphate buffer; dimethyl sulfoxide at 30℃; for 2h; Enzymatic reaction; | ||
With glucose-6-phosphate dehydrogenase; DL-dithiothreitol; human cytochrome P450 4A11; NADP; 1,2-dilauroyl-sn-glicero-3-phosphatidylcholine; NADPH-P450 reductase In aq. phosphate buffer at 37℃; for 0.0333333h; Enzymatic reaction; | Enzymatic assays Assays were done as described previously (4) with minorchanges. Typical incubations included 0.2 M P450 4A11, 0.4M NADPH-P450 reductase, 0.4 M b5, 150 M L--dilauroylsn-glycero-3-phosphocholine (DLPC; Sigma-Aldrich), 100 mMpotassium phosphate buffer (pH 7.4), and the indicated concentrationof lauric acid ([1-14C]lauric acid, usually added as anaqueous 10 mM solution of sodium laurate) in a final volume of0.25 ml. b5 was included because it stimulates the catalyticactivity (4). Following temperature equilibration to 37 °C for 5min, reactions were initiated by the addition of an NADPHregeneratingsystem consisting of 0.5 mM NADP, 10 mM glucose6-phosphate, and 1 IU ml1 yeast glucose 6-phosphate dehydrogenase (66). Reactions generally proceeded at 37 °C for2 min and were terminated with 1.0 ml of ethyl acetate containing0.1% CH3CO2H (v/v), and, following mixing with a vortexdevice, the mixtures were centrifuged (103 g for 10 min). A0.8-ml aliquot of the ethyl acetate layer (upper phase) was transferredto a clean tube, and the solvent was removed under anN2stream.The dried extracts were dissolved in 200l of a 1:1 mixture ofH2O/CH3CN containing 0.1% CH3CO2H (v/v) and 10 Mbutylated hydroxytoluene, and aliquots were analyzed on areversed-phase (octadecylsilane, C18) HPLC column (5 m,2.1 100 mm (Waters, Milford, MA)) coupled with a radioactivitydetector (-RAM, IN/US Systems, Tampa, FL). Reactionproducts and substrate were eluted at a flow rate of 0.6 mlmin1 using an increasing linear gradient ofCH3CN(including0.1% (v/v) HCO2H) from 35 to 95% (v/v) over 30 min.Assays with P450s other than P450 4A11 were performed asdescribed previously, with the modification of either preincubationwith DTT (1 mM) for 10 min or not (the DTT remainedin the reactions): P450 2C8-paclitaxel as substrate (67), P4502C9-tolbutamide as substrate (68), P450 2D6-bufuralol assubstrate (69), P450 3A4-nifedipine as substrate (70), P45019A1-testosterone as substrate (71), P450 21A2-progesteroneas substrate (72), P450 2A6-coumarin as substrate (73), andP450s 1B1-, 1A1-, and 1A2-7-ethoxyresorufin as substrate(74). | |
With cytochrome P450 monooxygenase CYP153A<SUB>M.aq</SUB>; NADH In aq. phosphate buffer; dimethyl sulfoxide for 1h; Enzymatic reaction; | ||
With cytochrome P450 monooxygenase CYP153A<SUB>M.aq</SUB> In dimethyl sulfoxide for 1h; Enzymatic reaction; | ||
31 %Chromat. | With cytochrome P450 monooxygenase CYP153A7, D258E/I83A mutant; NADH In aq. phosphate buffer; dimethyl sulfoxide for 4h; Heating; Enzymatic reaction; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.7% | With pyridine In chloroform at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With dmap; 3-(3-dimethylaminopropyl)-1-carbodiimide In dichloromethane at 0 - 25℃; for 12h; | |
97% | With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 2,2-dimethylpropanoic anhydride; triphenylphosphine In tetrahydrofuran; water at 60℃; for 16h; | |
78% | Stage #1: 12-hydroxydodecanoic acid With di(succinimido) carbonate; sodium carbonate; tricyclohexylphosphine In tetrahydrofuran at 60℃; Stage #2: phenylboronic acid In tetrahydrofuran at 60℃; for 20h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In o-xylene for 24h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylsilane In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dmap; tri(4-chlorophenyl)phosphine In toluene at 60℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifuran-2-yl-phosphane; sodium carbonate In chloroform at 50℃; for 16h; Title compound not separated from byproducts.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In nitromethane at 40℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With N,N'-dimethylaminopyridine; di-<i>tert</i>-butyl dicarbonate In nitromethane at 50℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With pyridine In tetrahydrofuran at 0 - 20℃; | |
With triethylamine In tetrahydrofuran at 4℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sulfuric acid Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With triethylsilane; bismuth(III) chloride In chloroform at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 90 percent / 50percent HBr / acetic acid / 5 h / Heating 2: EtONa / ethanol / 0.5 h / Heating 3: Li2CuCl4 / tetrahydrofuran / 4 h / -10 - -5 °C 4: LiAlH4 / tetrahydrofuran / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 90 percent / 50percent HBr / acetic acid / 5 h / Heating 2: EtONa / ethanol / 0.5 h / Heating 3: Li2CuCl4 / tetrahydrofuran / 4 h / -10 - -5 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 8.50 g / KHCO3 / dimethylformamide / 24 h / 20 °C 2: 3.15 g / pyridinium chlorochromate / CH2Cl2 / 1.5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 8.50 g / potassium bicarbonate / dimethylformamide / 24 h 2: 3.15 g / pyridinium chlorochromate / CH2Cl2 / 1.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 8.50 g / KHCO3 / dimethylformamide / 24 h / 20 °C 2.1: 3.15 g / pyridinium chlorochromate / CH2Cl2 / 1.5 h / 20 °C 3.1: NaH / tetrahydrofuran / 0 °C 3.2: 9.80 g / tetrahydrofuran / 24 h 4.1: 3.95 g / p-toluenesulfonic acid / toluene | ||
Multi-step reaction with 4 steps 1.1: 8.50 g / potassium bicarbonate / dimethylformamide / 24 h 2.1: 3.15 g / pyridinium chlorochromate / CH2Cl2 / 1.5 h / 20 °C 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 3.2: 9.80 g / tetrahydrofuran / 24 h / 0 °C 4.1: 3.95 g / p-toluenesulfonic acid / toluene / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 8.50 g / KHCO3 / dimethylformamide / 24 h / 20 °C 2.1: 3.15 g / pyridinium chlorochromate / CH2Cl2 / 1.5 h / 20 °C 3.1: NaH / tetrahydrofuran / 0 °C 3.2: 9.80 g / tetrahydrofuran / 24 h | ||
Multi-step reaction with 3 steps 1.1: 8.50 g / potassium bicarbonate / dimethylformamide / 24 h 2.1: 3.15 g / pyridinium chlorochromate / CH2Cl2 / 1.5 h / 20 °C 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 3.2: 9.80 g / tetrahydrofuran / 24 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: acetyl chloride / Heating 2: N-bromosuccinimide; PPh3 / CH2Cl2 / Heating | ||
Multi-step reaction with 3 steps 1: acetyl chloride / 24 h / Inert atmosphere; Reflux 2: triphenylphosphine; N-Bromosuccinimide / dichloromethane / 24 h / Inert atmosphere; Reflux 3: 24 h / 150 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 97 percent / EDC; 4-DMAP / CH2Cl2 / 12 h / 25 °C 2: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 12 h / 25 °C | ||
Multi-step reaction with 2 steps 1: 97 percent / 3-(3-dimethylaminopropyl)-1-carbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 12 h / 0 - 25 °C 2: 100 percent / 1-hydroxy-1,2-benziodoxol-3(1H)-one-1-oxide / dimethylsulfoxide / 12 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 97 percent / EDC; 4-DMAP / CH2Cl2 / 12 h / 25 °C 2.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 12 h / 25 °C 3.1: n-BuLi; HMPA / tetrahydrofuran; hexane / 0.33 h / -78 °C 3.2: 72 percent / tetrahydrofuran; hexane / 12 h / -78 - 25 °C 4.1: 29 percent / Dess-Martin periodinane; H2O / CH2Cl2 / 22 h / 0 °C 5.1: 63 percent / xylene / 24 h / 145 °C | ||
Multi-step reaction with 5 steps 1.1: 97 percent / 3-(3-dimethylaminopropyl)-1-carbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 12 h / 0 - 25 °C 2.1: 100 percent / 1-hydroxy-1,2-benziodoxol-3(1H)-one-1-oxide / dimethylsulfoxide / 12 h / 25 °C 3.1: nBuLi; HMPA / tetrahydrofuran / 0.33 h / -78 °C 3.2: 72 percent / tetrahydrofuran / 12 h / -78 - 25 °C 4.1: 29 percent / Dess-Martin periodinane; water / CH2Cl2 / 22 h / 0 °C 5.1: 63 percent / xylene / 24 h / 145 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With molecular sevies 4A In o-xylene for 24h; Heating / reflux; | 6 Example 6 [Composition of Polyester] By using the effect of the hafnium (IV) compound as an esterification catalyst, the synthesis of polyester shown in Table 3 was studied (S. R. Sandler and W. Karo, Polymer Synthesis, 2nd ed. (Academic Press: San Diego, 1992) Vol.1, Chapter 2). A Soxhlet tube filled with dried molecular sieves 4A (about 1.5 g) was connected to the top of a 5 ml eggplant flask contained with a teflon coated magnetic stirrer, and a cooling tube was further attached over said Soxhlet tube. 10 mmol of hydroxycarboxylic acid, 2 ml of o-xylene and 0.2 mol % of hafnium chloride (IV)•(THF)2were added and heating reflux was conducted in the argon for 24 hours. After the reaction, a solution wherein the mixture solution was dissolved into 30 ml of chloroform was poured into 150 ml of acetone while being stirred. The white precipitation that was produced, was collected by filtration, and dried under reduced pressure. Furthermore, by the same method, 10 mmol of dicarboxylic acid, 10 mmol of diol, 2 ml of o-xylene and 0.2 mol % of hafnium chloride (IV)•(THF)2 were added and heating reflux was conducted in the argon for 24 hours. After the reaction, the mixture solution was dissolved in 200 ml of chloroform, and 30 ml of methanol was added. The mixture solution was concentrated, the white precipitation thus produced was collected by filtration, and dried under reduced pressure. [0028] The results are shown in Table 3. In Table 3, the following are shown: the yield represents isolated yield; DP stands for the degree of polymerization; DP and the number average molecular weight (Mn) are values obtained by 1H NMR; the weight-average molecular weight (Mw) is the value wherein gel permeation column chromatography (two columns of Two linear TSK-gel-GMXXL (Tosoh Corporation) connected in series were used) is conducted to 0.2% by weight of the generated polymer in THF at 40° C., with polystyrene as a standard; the value in parenthesis for HO [CO(CH2)11O]nH is a value of thermal polymerization condensation in the absence of catalyst; the various values for polyester in the bottom line are the values obtained by using 1 mol % of hafnium chloride (IV)•(THF)2 and conducting the reaction for 4 days. These results revealed that the hafnium chloride (IV)•(THF)2 is useful as a catalyst for polycondensation reaction in the method for preparing polyester using ω-hydroxycarboxylic acid or the method for preparing polyester using α,ω-aliphatic dicarboxylic acid and α, ω-aliphatic diol. [TABLE-US-00003] TABLE 3 isolated yield polyester (%) DPMn × 104 Mw × 104 HO[CO(CH2)9O]nH 95 >200 1.82 3.40 [>3.40]HO[CO(CH2)11O]nH 97 >200 2.77 7.24 [>3.96] (88) (45) -[0.89)] -HO[CO(CH2)2CO2(CH2)6O]nH 98 >200 2.24 3.87 [>4.00]HO[CO(CH2)7CO2(CH2)10O]nH 97 >200 2.69 5.83 [>6.52] 96 >200 1.34 6.51 [>6.09] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 18h; | 25.C A solution of 12-hydroxydodecanoic acid (0.135 g, 0.6 mmol), N-Boc- ethylenediamine (0.100 g, 0.6 mmol), HOAT (0.170 g, 1.2 mmol), and diisopropylethylamine (0.22 ML, 1.2 mmol) in anhydrous N, N-dimethylformamide (1 ML) was treated with DIC (0.19 mL, 1.2 mmol) and the reaction was stirred at room temperature under nitrogen for 18 hours. The reaction was diluted with ethyl acetate (25 mL), washed consecutively with 1N HCl (25 ML), 0. 5N NAOH (25 mL), and brine (25 mL), dried (MGS04), and concentrated. The resulting residue was purified by flash chromatography on silica gel, eluting with ethyl acetate to give the title compound as a colorless solid (0.237 g, contaminated with 1,3-diisopropylurea according to LC/MS [1] ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 6h; | 20 A solution of 12-hydroxydodecanoic acid (25 mg, 0.12 mmol), the product of Experiment 13, Part D (52 mg, 0.12 mmol), and HOAT (30. 8 mg, 0.23 mmol) in anhydrous N, N-dimethylformamide (0.2 mL) was treated with diisopropylethylamine (100 GEL, 0. 57 MMOL) and DIC (35. 5 {IL, 0.24 mmol), and stirred at room temperature under nitrogen for 3 hours. Additional product of Experiment 13, Part D (8 mg, 0.02 mmol) was added and the reaction was stirred for another 3 hours. The reaction was purified by HPLC on a Phenomenex Luna C18 (2) column (21.2 x 250 mm) using a 0.9%/minute gradient of 18 to 45% acetonitrile containing 0.1% trifluoroacetic acid at a flow rate of 20 ML/MIN. The main product peak eluting at 21 minuteswas lyophilized to give the title compound as a colorless solid (29 mg, 39%, HPLC purity 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; wild-type CYP119; dihydrogen peroxide In ethanol; water at 50℃; Enzymatic reaction; regiospecific reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-(4'-methoxyphenyl)propenoic acid With thionyl chloride In dimethyl sulfoxide Stage #2: 12-hydroxydodecanoic acid In dimethyl sulfoxide at 60℃; for 5h; | 4; 8 Reaction sceme (8) EXAMPLE 4 11-carboxyundecyl-4'-methoxycinnamate was synthesised according to reaction scheme (8) below. A 250-ML round-bottomed flask equipped with a reflux condenser was charged with 150 ML of DMSO and 9 g of 4-methoxycinnamic acid. 6 g of thionyl chloride was added into the flask in a nitrogen atmosphere and stirred. 5 g of 12-hydroxydodecanoic acid was slowly added into the mixture, heated slowly to about 60° C. while stirring it, and reacted for 5 hours.The reaction mixture was cooled to room temperature, and the reaction product was poured into excess distilled water to precipitate it.The resulting precipitates were filtered, washed several times with distilled water, and recrystallized using a solvent mixture of chloroform and ethanol to provide 14.7 g of 11-carboxyundecyl-4'-methoxycinnamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 86% 2: 8% | With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In tetrahydrofuran; chloroform for 18h; Reflux; Inert atmosphere; | |
1: 30% 2: 19% | With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In chloroform for 18h; Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide for 1h; Inert atmosphere; Reflux; | |
68% | With potassium <i>tert</i>-butylate In toluene at 0℃; for 1.25h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 12-hydroxydodecanoic acid With lithium hydroxide monohydrate In 4-methyl-2-pentanone at 92℃; Azeotropic removal of water; Stage #2: (2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononyl)oxirane With boron trifluoride diethyl etherate In 4-methyl-2-pentanone at 85℃; for 5.5h; | 14 Example 14; The following product is synthesized: [Show Image] The same apparatus of Example 1 is loaded with: a) 21.63 g (0.1 mol) of 12-hydroxydodecanoic acid; b) 4.19 g of lithium hydroxide monohydrate c) 50 g of methyl isobutyl ketone. Under agitation, distillation is performed with a Marcusson-type apparatus at the azeotropic temperature of 92°C to remove the water that is present in the system. Drop by drop, at the temperature of 85°C, 200 ul of BF3 etherate are introduced together with b) 47.6 g (0.1 mol) of fluorinated epoxide (IV). Dripping lasts one hour, continuing subsequently with the reaction for another 4.5 hours at 85°C, adding two 200 µl doses of BF3 etherate. 200 g of water are added and then the solvent is distilled with part of the water added at 92°C with a flow of nitrogen. Finally, 231 g of 2-propanol are loaded and the quantity of water removed during distillation is restored. The result is a pale yellow homogeneous product with 15%-16% dry material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In dichloromethane at 20℃; for 60h; | 4.2.2. Preparation of amides from dicarboxylic acids mono-esters (general procedure B) General procedure: The solution of dicarboxylic acid mono-ester in CH2Cl2, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) and N-deacetylcolchicine were stirred together at room temperature for 12-60 h. The mixture was concentrated and the residue was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00131] A mixture of 20 g (0.087 mole) 1 ,12-dodecandioic acid, 32 g methanol, 18 g water and 5 g of 5% Ru on carbon catalyst containing 1% Sn are was charged to a 300 mL Stainless Steel autoclave containing a thermocouple, cooling coil, baffle and stirrer. The vessel was flushed first with nitrogen followed by hydrogen, and pressurized to 2500psig with hydrogen. Stirring at 1800 rpm was commenced and the reactor was heated to 230C. The hydrogenation was run for 22 hr. Analysis of the product showed a 98.4 wt% conversion of DDDA with 30.7% molar selectivity to C12LD. Also produced was 1-dodecanol (1.8 molar%) along with the intermediate 12-hydroxydodecanoic acid (14.4 molar%) and the mono methyl ester of 1,12-dodecanedioic acid (38 molar%). It can be seen from the low molar yield to C12LD, the un-reacted intermediate 12-hydroxydodecanoic acid and mono methyl ester of 1 ,2-dodecanedioic acid that the absence of Re had a dramatic effect on the reduction rate to C12LD. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49.3% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 72h; Inert atmosphere; | 3 Example 3 Compounds in which lauroyl group introduced with one hydroxyl group at the end was bound to the 1-position or the 4-position were synthesized as follows.12-Hydroroxylauric acid (225 mg, 1.04 mmol) was added with dichloromethane (10 ml), and the mixture was added with EDCI (200 mg, 1.04 mmol) and DMAP (127 mg, 1.04 mmol) under a nitrogen gas atmosphere, and the mixture was stirred until all the substances were dissolved. The solution was added with 1N,8N-diBoc-spermidine (300 mg, 0.870 mmol) dissolved in dichloromethane (5 ml), and the mixture was stirred at room temperature for 3 days under a nitrogen gas atmosphere. [0074] After completion of the stirring, the reaction mixture was added with aqueous citric acid (10%, w/w, 10 ml), the mixture was stirred for 5 minutes to terminate the reaction, and extracted with dichloromethane (10 ml×3). The organic layer was dehydrated over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a crude product (0.62 g) as colorless oil. The crude product was purified by silica gel column chromatography (ethyl acetate:n-hexane=4:1) to obtain 1N,8N-diBoc-4N-(12-hydroroxylauroyl)-spermidine (155 mg, 32.8%) as colorless oil. 1H NMR (500 MHz, CDCl3), δ 1.28 (16H, s, H2-4′-11′), 1.44 (20H, m, 2× Boc, H2-3′), 1.56-1.69 (6H, m, H2.2, 6, 7), 2.34 (2H, t, JH,H=7.5 Hz, H2-2′), 3.07-3.40 (9H, m, H2-1, 3, 5, 8, -OH), 3.62 (2H, t, JH,H=6.5 Hz, H2-12′) [0075] The above product was stirred in trifluoroacetic acid/ dichloromethane (20% v/v, 10 ml) for 1 hour, trifluoroacetic acid was evaporated under reduced pressure by azeotropy with methanol, and the residue was added with 1 M NaOH (5 ml). The mixture was transferred to a separating funnel, and extracted with dichloromethane (5 ml×4), and the organic layer was washed with distilled water (5 ml), and dehydrated over sodium sulfate. Then, the solvent was evaporated under reduced pressure to obtain 4N-(12-hydroroxylauroyl)-spermidine (73 mg, 24.5%) as amorphous white crystals. [0076] 12-Hydroroxylauric acid (300 mg, 1.39 mmol) was added with dichloromethane (15 ml), the mixture was added with EDCI (275 mg, 1.39 mmol) and DMAP (170 mg, 1.39 mmol) under a nitrogen gas atmosphere, and the mixture was stirred until all the substances were dissolved. The solution was added with 4N,8N-diBoc-spermidine (400 mg, 1.16 mmol) dissolved in dichloromethane (5 ml), and the mixture was stirred at room temperature for 3 days under a nitrogen gas atmosphere. [0077] After completion of the stirring, the reaction mixture was added with aqueous citric acid (10%, w/w, 10 ml), and the mixture was stirred for 5 minutes to terminate the reaction, and extracted with dichloromethane (10 ml×3). The organic layer was dehydrated over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a crude product (0.68 g) as colorless oil. The crude product was purified by silica gel column chromatography (ethyl acetate:n-hexane=4:1) to obtain 4N,8N-diBoc-1N-(12-hydroroxylauroyl)-spermidine (311 mg, 49.3%) as colorless oil. [0078] 1H NMR (500 MHz, CDCl3), δ 1.27 (16H, s, H2-4′-11′), 1.44 (20H, m, 2× Boc, H2-3′), 1.51-1.64 (6H, m, H2-2,6,7), 2.18 (2H, t, JH,H=7.8 Hz, H2-2′), 3.13-3.28 (9H, m, H2-1, 3, 5, 8, -OH), 3.63 (2H, m, H2-12′) [0079] The above product was stirred in trifluoroacetic acid/ CH2Cl2 (20% v/v, 10 ml) for 1 hour, trifluoroacetic acid was evaporated under reduced pressure by azeotropy with methanol, then the residue was added with 1M NaOH (5 ml), and the mixture was transferred to a separating funnel, and extracted with dichloromethane (5 ml×4). The organic layer was washed with distilled water (5 ml), and dehydrated over sodium sulfate, and then the solvent was evaporated under reduced pressure to obtain 1-N-(12-hydroroxylauroyl)-spermidine (160 mg, 40.2%) as amorphous white crystals. [0080] YIS12OH1N (compound formed by binding -CO-(CH2)10CH2-OH to the amino group at the 1-position of spermidine) [0081] 1H NMR (500 MHz, CDCl3), δ 1.28 (16H, m, H2-4′-11′), 1.44-1.67 (9H, m, H2-2,6,7,3′, -OH), 2.30 (2H, m, H2-2′), 2.64-2.76 (4H, m, H2-1,8), 3.00-3.47 (4H, m, H2-3,5), 3.62 (2H, t, JH,H=6.5 Hz, H2-1′) [0082] YIS12OH4N (compound formed by binding -CO-(CH2)10CH2-OH to the amino group at the 4-position of spermidine) [0083] 1H NMR (500 MHz CDCl3) δ 1.28 (16H, m, H2-4′-11′), 1.50-1.67 (9H, m, H2-2,6,7,3′, -OH), 2.14 (2H, t, JH,H=7.5 Hz, H2-2′), 2.61 (2H, t, JH,H=6.8 Hz, H2-8), 2.71 (4H, m, H2-3,5), 3.35 (2H, dt, JH,H=6.0 Hz, 6.0 Hz, H2-1), 3.63 (2H, t, JH,H=6.5 Hz, H2-12), 6.73 (1H, s, -NHCO) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32.8% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 72h; Inert atmosphere; | 3 Example 3 Compounds in which lauroyl group introduced with one hydroxyl group at the end was bound to the 1-position or the 4-position were synthesized as follows.12-Hydroroxylauric acid (225 mg, 1.04 mmol) was added with dichloromethane (10 ml), and the mixture was added with EDCI (200 mg, 1.04 mmol) and DMAP (127 mg, 1.04 mmol) under a nitrogen gas atmosphere, and the mixture was stirred until all the substances were dissolved. The solution was added with 1N,8N-diBoc-spermidine (300 mg, 0.870 mmol) dissolved in dichloromethane (5 ml), and the mixture was stirred at room temperature for 3 days under a nitrogen gas atmosphere. [0074] After completion of the stirring, the reaction mixture was added with aqueous citric acid (10%, w/w, 10 ml), the mixture was stirred for 5 minutes to terminate the reaction, and extracted with dichloromethane (10 ml×3). The organic layer was dehydrated over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a crude product (0.62 g) as colorless oil. The crude product was purified by silica gel column chromatography (ethyl acetate:n-hexane=4:1) to obtain 1N,8N-diBoc-4N-(12-hydroroxylauroyl)-spermidine (155 mg, 32.8%) as colorless oil. 1H NMR (500 MHz, CDCl3), δ 1.28 (16H, s, H2-4′-11′), 1.44 (20H, m, 2× Boc, H2-3′), 1.56-1.69 (6H, m, H2.2, 6, 7), 2.34 (2H, t, JH,H=7.5 Hz, H2-2′), 3.07-3.40 (9H, m, H2-1, 3, 5, 8, -OH), 3.62 (2H, t, JH,H=6.5 Hz, H2-12′) [0075] The above product was stirred in trifluoroacetic acid/ dichloromethane (20% v/v, 10 ml) for 1 hour, trifluoroacetic acid was evaporated under reduced pressure by azeotropy with methanol, and the residue was added with 1 M NaOH (5 ml). The mixture was transferred to a separating funnel, and extracted with dichloromethane (5 ml×4), and the organic layer was washed with distilled water (5 ml), and dehydrated over sodium sulfate. Then, the solvent was evaporated under reduced pressure to obtain 4N-(12-hydroroxylauroyl)-spermidine (73 mg, 24.5%) as amorphous white crystals. [0076] 12-Hydroroxylauric acid (300 mg, 1.39 mmol) was added with dichloromethane (15 ml), the mixture was added with EDCI (275 mg, 1.39 mmol) and DMAP (170 mg, 1.39 mmol) under a nitrogen gas atmosphere, and the mixture was stirred until all the substances were dissolved. The solution was added with 4N,8N-diBoc-spermidine (400 mg, 1.16 mmol) dissolved in dichloromethane (5 ml), and the mixture was stirred at room temperature for 3 days under a nitrogen gas atmosphere. [0077] After completion of the stirring, the reaction mixture was added with aqueous citric acid (10%, w/w, 10 ml), and the mixture was stirred for 5 minutes to terminate the reaction, and extracted with dichloromethane (10 ml×3). The organic layer was dehydrated over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a crude product (0.68 g) as colorless oil. The crude product was purified by silica gel column chromatography (ethyl acetate:n-hexane=4:1) to obtain 4N,8N-diBoc-1N-(12-hydroroxylauroyl)-spermidine (311 mg, 49.3%) as colorless oil. [0078] 1H NMR (500 MHz, CDCl3), δ 1.27 (16H, s, H2-4′-11′), 1.44 (20H, m, 2× Boc, H2-3′), 1.51-1.64 (6H, m, H2-2,6,7), 2.18 (2H, t, JH,H=7.8 Hz, H2-2′), 3.13-3.28 (9H, m, H2-1, 3, 5, 8, -OH), 3.63 (2H, m, H2-12′) [0079] The above product was stirred in trifluoroacetic acid/ CH2Cl2 (20% v/v, 10 ml) for 1 hour, trifluoroacetic acid was evaporated under reduced pressure by azeotropy with methanol, then the residue was added with 1M NaOH (5 ml), and the mixture was transferred to a separating funnel, and extracted with dichloromethane (5 ml×4). The organic layer was washed with distilled water (5 ml), and dehydrated over sodium sulfate, and then the solvent was evaporated under reduced pressure to obtain 1-N-(12-hydroroxylauroyl)-spermidine (160 mg, 40.2%) as amorphous white crystals. [0080] YIS12OH1N (compound formed by binding -CO-(CH2)10CH2-OH to the amino group at the 1-position of spermidine) [0081] 1H NMR (500 MHz, CDCl3), δ 1.28 (16H, m, H2-4′-11′), 1.44-1.67 (9H, m, H2-2,6,7,3′, -OH), 2.30 (2H, m, H2-2′), 2.64-2.76 (4H, m, H2-1,8), 3.00-3.47 (4H, m, H2-3,5), 3.62 (2H, t, JH,H=6.5 Hz, H2-1′) [0082] YIS12OH4N (compound formed by binding -CO-(CH2)10CH2-OH to the amino group at the 4-position of spermidine) [0083] 1H NMR (500 MHz CDCl3) δ 1.28 (16H, m, H2-4′-11′), 1.50-1.67 (9H, m, H2-2,6,7,3′, -OH), 2.14 (2H, t, JH,H=7.5 Hz, H2-2′), 2.61 (2H, t, JH,H=6.8 Hz, H2-8), 2.71 (4H, m, H2-3,5), 3.35 (2H, dt, JH,H=6.0 Hz, 6.0 Hz, H2-1), 3.63 (2H, t, JH,H=6.5 Hz, H2-12), 6.73 (1H, s, -NHCO) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sulfuric acid at 70℃; for 20h; | 1; 1.c.ii H2SO4(0.5 ml) was added to a solution of this carboxylic acid (0.803 g, 3.71 mmol) in iPrOH (50 ml) at room temperature , and the mixture was stirred at 70°C for 20 hours. The reaction solution was allowed to warm to room temperature, and then the solvent was evaporated to about half its volume. The residue was poured into H2O. After extraction with EtOAc twice, the combined organic layer was washed with saturated aqueous NaCO3 and a saturated aqueous NaCl solution, and was dried over Na2SO4. After evaporation of the solvent, the residue was purified by column chromatography on silica gel (Hexane:EtOAc = 4:1 to 1:1) to prepare the corresponding isopropyl ester (Compound 4) (0.680 g, 71%). 1H-NMR (400 MHz, CDCl3) δ 5.00 {2H, sep, J= 6.2 Hz, OCH(CH3)2}, 3.64 (2H, t, J = 5.9 Hz, CH2OH), 2.29 (2H, t, J= 7.5 Hz, CH2CO2Et), 1.68-1.53 (4H, m, CH2CH2OH and CH2CO2Et), 1.42 (1H, br, OH),1.27 {14H, m, (CH2)7}, 1.22 {6H, d, J= 6.2 Hz, OCH(CH3)2}. |
71% | With sulfuric acid at 70℃; for 20h; | 1 To a solution of this carboxylic acid (0.803 g, 3.71 mmol) in iPrOH (50 ml), H2SO4 (0.5 ml) was added at room temperature and stirred at 70°C for 20 hours. After returning to room temperature, the reaction mixture was evaporated to distill off about half of the solvent, and then poured into H2O. This mixture was extracted twice with EtOAc, and the combined organic layers were washed with sat. aq. NaCO3 and sat. aq. NaCl, and then dried over Na2SO4. After the solvent was distilled off, the residue was purified by silica gel column chromatography (hexane:EtOAc = 4:1 → 1:1) to prepare the corresponding isopropyl ester (compound 4) (0.680 g, 71%). 1H-NMR (400 MHz, CDCl3) δ 5.00 {2H, sep, J= 6.2 Hz, OCH(CH3)2}, 3.64 (2H, t, J= 5.9 Hz, CH2OH), 2.29 (2H, t, J = 7.5 Hz, CH2CO2Et), 1.68-1.53 (4H, m, CH2CH2OH and CH2CH2CO2Et), 1.42 (1H, br, OH),1.27 {14H, m, (CH2)7}, 1.22 {6H, d, J= 6.2 Hz, OCH(CH3)2}. |
70% | With sodium iodide for 4h; Reflux; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With dicarbonylacetylacetonato rhodium (I); N-(3-diphenylphosphanylbenzoyl)guanidine; hydrogen In dichloromethane at 40℃; for 29h; Autoclave; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With dmap; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 6.5h; | 14 Preparation of 16-hydroxy-hexadecanoic acid 3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved in dimethylformaldehyde (100 mL). After addingdicyclohexylcarbodiimide (34 g, 2 eq) and 4-dimethylaminopyridine (4.03 g, 0.2 eq), 16-hydroxydodecanoic acid (44.9g, 2 eq) was slowly added dropwise for 30 minutes while stirring at room temperature. After stirring for 6 hours, uponcompletion of reaction, the mixture was diluted with ethyl acetate (200 mL) and washed with 1 N HCl solution (200 mL)and distilled water (200 mL). The organic layer was dried with anhydrous magnesium sulfate, filtered and concentratedunder reduced pressure. Then, 17 g of white solid (45%) was obtained using a silica column. The obtained white solidwas 16-hydroxy-hexadecanoic acid 3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester representedby Chemical Formula 15. 1H NMR analysis result of the white solid is as follows.[0088] 1H NMR (300 MHz, CDCl3) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H), 3.69-3.64 (m, 6H), 3.60-3.52 (m, 2H),3.53-3.48 (m, 2H), 2.37 (t, J = 7.5 Hz, 2H), 2.22 (t, J = 7.5 Hz, 2H), 1.60-1.54 (m, 12H), 1.30-1.20 (m, 40H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; Inert atmosphere; | (5) hydroxydodecanamidoglycine-4,4′-dimethoxytrityloxydodecanamide (Compound 5) (5) hydroxydodecanamidoglycine-4,4'-dimethoxytrityloxydodecanamide (Compound 5) Compound 4 (3.15 g, 5.62 mmol) was dried three times by azeotropic distillation with anhydrous pyridine, 12-hydroxydodecanoic acid (3.41 g, 6.74 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.29 g, 6.74 mmol), 1-hydroxybenzotriazole monohydrate (2.06 g, 13.48 mmol) and anhydrous dichloromethane (50 ml) were added at room temperature under an argon atmosphere, and the mixture was stirred for 10 min. To the thus-obtained mixture was added triethylamine (2.05 g, 20.22 mmol), and the mixture was stirred at room temperature overnight under an argon atmosphere. To the obtained reaction mixture was added dichloromethane (200 ml), and the mixture was washed three times with saturated aqueous sodium hydrogen carbonate, and further washed once with saturated brine. The organic layer was fractionated, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: dichloromethane-methanol (95:5)+0.05% pyridine) to give hydroxydodecanamidoglycine-4,4'-dimethoxytrityloxydodecanamide (5) (2.97 g, 70%) as a colorless syrup. The instrumental analysis values of hydroxydodecanamidoglycine-4,4'-dimethoxytrityloxydodecanamide (5) are shown below. hydroxydodecanamidoglycine-4,4′-dimethoxytrityloxydodecanamide (5) (0147) 1H-NMR (CDCl3): δ=7.42-7.40 (2H, m), 7.33-7.26 (6H, m), 7.22-7.21 (1H, m), 6.83-6.80 (4H, m), 3.84 (2H, s), 3.79 (6H, s), 3.64-3.61 (2H, t, J=6.3 Hz), 3.26-3.24 (2H, t, J=6.1 Hz), 3.08-3.06 (2H, t, J=5.6 Hz), 2.28-2.24 (2H, t, J=6.8 Hz), 1.69-1.52 (12H, m), 1.44-1.39 (26H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 20h; | Ethyl 12-((2-(12-hydroxydodecanamido)ethyl)amino)-12-oxododecanoate (4-CH2OH) A mixture of 11 (3.00 g, 10 mmol), 12-hydroxydodecanoic acid 13 (2.16 g, 10 mmol), EDC (3.83 g, 20 mmol) and HOBt (1.63 g, 12 mmol) in CH2Cl2 (100 mL) was stirred for 20 h at room temperature. The resulting mixture was diluted with CH2Cl2 (100 mL), washed with 1M HCl (50 mL) and brine, and then dried over Na2SO4. Concentration gave colorless solids (1.78 g). Recrystallization from CHCl3 (19 mL) gave 4-CH2OH (313 mg, 6%) as colorless solids of mp 131-132 °C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: pellynol M With ozone In dichloromethane at -78℃; for 0.0166667h; Stage #2: With sodium tetrahydroborate In dichloromethane at 25℃; for 1h; | 3.4. Ozonolysis of 1-3 General procedure: Solutions of 1-3 (0.5mg each) in CH2Cl2 (1mL) were treated with O3 for 1 min at-78°C, respectively. After added NaBH4 (0.5mg), the reaction mixtures were stirred for 1 h at room temperature (25°C).20 The crude products were concentrated and subjected to LC-MS analysis without further separation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: pellynol N With ozone In dichloromethane at -78℃; for 0.0166667h; Stage #2: With sodium tetrahydroborate In dichloromethane at 25℃; for 1h; | 3.4. Ozonolysis of 1-3 General procedure: Solutions of 1-3 (0.5mg each) in CH2Cl2 (1mL) were treated with O3 for 1 min at-78°C, respectively. After added NaBH4 (0.5mg), the reaction mixtures were stirred for 1 h at room temperature (25°C).20 The crude products were concentrated and subjected to LC-MS analysis without further separation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42 %Chromat. | With sodium phosphite; phosphite dehydrogenase; OleT<SUB>JE </SUB>decarboxylase/P450BM3 reductase domain fusion protein; oxygen; NADPH; catalase In water at 20℃; for 12h; Green chemistry; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With copper(l) iodide In dichloromethane at 20℃; for 24h; | 2 Example 2, General procedure: Add alkyne amide (0.22mmol), 12-hydroxyalkanoic acid (0.2mmol) to a clean 4mL reaction tube, add 10mol% CuI, add 2mL CH2Cl2 as solvent, react at room temperature for 24h, detect by TLC dot plate, solvent after reaction Concentrated and column chromatography to obtain a pure product. White solid, yield 93%. |
87% | With copper(l) chloride In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 5h; | 8.2 Synthesis of 7-(((((2R, 3R, 5R)-5-(4-amino-2-oxopyrimidin-l (2H)-yl)-4, 4- difluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)carbonyl)oxy)heptanoic acid (6) To a DCM (10 mL) solution of 4 ( lg, 4.6 mmol), 4-nitrophenyl chloroformate (2.79g, 13.8 mmol), DIPEA (2.38g, 18.4 mmol) and a catalytic amount of pyridine were added at 0°C and stirred for 5h at room temperature. Then the reaction mixture was concentrated in vacuo. The crude residue was dissolved in DMF (10 mL). To this solution, GMC hydrochloride (4.1g, 13.8 mmol) in DMF (5mL) and TEA (2 mL) were added and continued to stir for 24 h. The progress of the reaction was monitored by GC-MS analysis of the crude reaction mixture. After completion of reaction, excess diethyl ether (200 mL) was added to the reaction mixture. The yellowish oil thus obtained was separated and purified by flash chromatography using MeOH/CHCl3 (5%, v/v) as eluent. Compound 6 was isolated as a sticky yellow liquid. (1.5g, Yield = 64.3%). (0363) NMR (DMSO-d6): δ 10.5 (brs, 1H, -COOH), 7.63 (d, J = 7.5 Hz, 1H, -CH), 7.41 (brs, 2H, -NH2), 6.20 (d, J = 7.5 Hz, 1H, -CH), 5.18 (brs, 1H, -CH), 3.71-3.55 (m, 5H,- CH2 X2, -CHX1), 2.36 (brs, 2H, -CH2), 1.23-1.17 (m, 18H, -CH2 X 9). (0364) I3C NMR (DMSO-d6): 172.1, 166.0, 155.1, 154.9, 153.6, 123.5, 95.2, 95.0, 80.8, 69.1, 68.8, 33.6, 29.4, 29.3,29.2, 28.9, 28.8, 25.5, 25.4. (0365) ESI-MS: cald for C22H33F2N3Og, 504.2; found 527.0 (M +Na salt). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,3,4,5,6-pentahydroxy-hexanal; cytochrome b5; glucose dehydrogenase from Bacillus megaterium; human cytochrome P450 monooxygenase; rat cytochrome P450 reductase; 1,2-dilauroyl-sn-glicero-3-phosphatidylcholine; NADPH; superoxide dismutase; catalase from bovine liver In aq. phosphate buffer; dimethyl sulfoxide at 30℃; Enzymatic reaction; | 2.4 Fatty acid and fatty alcohol conversion by CYP4B1 General procedure: Conversions of fatty acids 1-8 and fatty alcohols 9-12 were carried out in 50mM potassium phosphate buffer, pH 7.5 and a total reaction volume of 100μL. Reaction mixtures contained 0.25μM CYP4B1, 0.5μM CPR, 0.25μM cytochrome b5, 100 U mL-1 superoxide dismutase, 1000 UmL-1 catalase, 25 U mL-1 GDH, 20mM glucose, 25μgmL-1 DLPC, 200μM substrate (from a 10mM stock solution dissolved in DMSO) and 200μM NADPH. Samples were incubated at 30°C for 90min; this reaction time was chosen as an almost complete substrate conversion (as achieved for C12 4 after 120min) was not desirable, so as to allow comparison of the conversion values for the individual substrates and also between the two CYP4B1 isoforms. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,3,4,5,6-pentahydroxy-hexanal; cytochrome b5; glucose dehydrogenase from Bacillus megaterium; rabbit cytochrome P450 monooxygenase; rat cytochrome P450 reductase; 1,2-dilauroyl-sn-glicero-3-phosphatidylcholine; NADPH; superoxide dismutase; catalase from bovine liver In aq. phosphate buffer; dimethyl sulfoxide at 30℃; Enzymatic reaction; | 2.4 Fatty acid and fatty alcohol conversion by CYP4B1 General procedure: Conversions of fatty acids 1-8 and fatty alcohols 9-12 were carried out in 50mM potassium phosphate buffer, pH 7.5 and a total reaction volume of 100μL. Reaction mixtures contained 0.25μM CYP4B1, 0.5μM CPR, 0.25μM cytochrome b5, 100 U mL-1 superoxide dismutase, 1000 UmL-1 catalase, 25 U mL-1 GDH, 20mM glucose, 25μgmL-1 DLPC, 200μM substrate (from a 10mM stock solution dissolved in DMSO) and 200μM NADPH. Samples were incubated at 30°C for 90min; this reaction time was chosen as an almost complete substrate conversion (as achieved for C12 4 after 120min) was not desirable, so as to allow comparison of the conversion values for the individual substrates and also between the two CYP4B1 isoforms. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.3% | Stage #1: 12-hydroxydodecanoic acid; 4-Nitrophenyl chloroformate With pyridine; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 5h; Stage #2: gemcitabine hydrochloride With triethylamine In N,N-dimethyl-formamide for 24h; | 9.9.2 9.2 Synthesis of 7-(((((2R, 3R, 5R)-5-(4-amino-2-oxopyrimidin-1( 2H)-yl)-4 , 4- difluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)carbonyl)oxy)heptanoic acid (6) : To a DCM (10 mL) solution of 4 ( lg, 4.6 mmol), 4-nitrophenyl chloroformate (2.79g, 13.8 mmol), DIPEA (2.38g, 18.4 mmol) and a catalytic amount of pyridine were added at 0°C and stirred for 5h at room temperature. Then the reaction mixture was concentrated in vacuo. The crude residue was dissolved in DMF (10 mL). To this solution, GMC hydrochloride (4.1g, 13.8 mmol) in DMF (5mL) and TEA (2 mL) were added and continued to stir for 24 h. The progress of the reaction was monitored by GC-MS analysis of the crude reaction mixture. After completion of reaction, excess diethyl ether (200 mL) was added to the reaction mixture. The yellowish oil thus obtained was separated and purified by flash chromatography using MeOH/CHCL (5%, v/v) as eluent. Compound 6 was isolated as a sticky yellow liquid. (1.5g, Yield = 64.3%).1H NMR (DMSO-d6): d 10.5 (brs, 1H, -COOH), 7.63 (d, J = 7.5 Hz, 1H, -CH), 7.41 (brs, 2H, -NH2), 6.20 (d, J = 7.5 Hz, 1H, -CH), 5.18 (brs, 1H, -CH), 3.71-3.55 (m, 5H,- CHz X2, -CHX1), 2.36 (brs, 2H, -CH2), 1.23-1.17 (m, 18H, -CH2X 9).13C NMR (DMSO-d6): 172.1, 166.0, 155.1, 154.9, 153.6, 123.5, 95.2, 95.0, 80.8, 69.1, 68.8, 33.6, 29.4, 29.3,29.2, 28.9, 28.8, 25.5, 25.4.ESI-MS: cald for C22H33F2N3O8, 504.2; found 527.0 (M +Na salt). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water monomer; sodium hydroxide In ethanol for 5h; Reflux; | 4.4.6 Hydrolysis of 2a-5a To a solution of 2a (2.6mg, 0.003mmol) in ethanol (1mL) was added aqueous NaOH solution (20μL, 2.25M) and refluxed for 5h. Then the reaction was quenched and extracted under the same conditions as hydrolysis of 1a, then obtained two main peaks at m/z 413.12286 [M-H]- (calcd. for C22H21O8, 413.12309) and m/z 215.16408 [M-H]- (calcd. for C12H23O3, 215.16417) in the HPLC-HRESIMS (Fig. S54), corresponding to the desired products 1b and 1c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water monomer; sodium hydroxide In ethanol for 5h; Reflux; | 4.4.6 Hydrolysis of 2a-5a To a solution of 5a (2.9mg, 0.004mmol) in ethanol (1mL) was added aqueous NaOH solution (20μL, 2.25M) and refluxed for 5h. Then the reaction was quenched and extracted under the same conditions as hydrolysis of 1a, then obtained two main peaks at m/z 395.07703 [M-H]- (calcd. for C21H15O8, 395.07614) and m/z 215.16458 [M-H]- (calcd. for C12H23O3, 215.16417) in the HPLC-HRESIMS (Fig. S57), corresponding to the desired products 5b and 1c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With water monomer; sodium hydroxide In ethanol for 5h; Reflux; | 4.4.5 Hydrolysis of 1a To a solution of 1a (8.0mg, 0.01mmol) in ethanol (1mL) was added aqueous NaOH solution (20μL, 2.25M) and refluxed for 5h. Then the reaction cooled to room temperature and was adjusted to pH 3.0 with 0.1M hydrochloric acid, and the ethanol was then evaporated off in vacuo. The mixture was diluted with H2O (10mL) and extracted with EtOAc (20mL) and the organic layer was rinsed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product was analyzed by HPLC-HRESIMS, which showed two main peaks at m/z 413.12442 [M-H]- (calcd. for C22H21O8, 413.12309) and m/z 215.16484 [M-H]- (calcd. for C12H23O3, 215.16417) respectively (Fig. S53), corresponding to the desired products 1b and 1c. The mixture was further purified by semi-preparative HPLC on an ODS column (MeOH/H2O, 45:55, v/v, 4mL/min) to give 1b as a yellow oil (3.4mg, 0.008mmol, 80% yield, tR 10.2min). The racemic 1b was further separated on Cellulose-5 chiral column eluting with MeOH/H2O containing 0.05% TFA (55:45, v/v, 0.8mL/min) to give the optically-pure (+)-1b (1.1mg, tR 19.4min) and (-)-1b (1.0mg, tR 26.8min). 1H NMR (600MHz, CDCl3) δ 7.77 (s, 1H, H-7), 6.88 (s, 1H, H-6), 6.66 (s, 1H, H-3), 6.65 (d, J=8.2Hz, 1H, H-5′), 6.57 (s, 1H, H-2′), 6.37 (d, J=8.2Hz, 1H, H-6′), 4.64 (s, 1H, H-7′), 3.93 (s, 1H, H-8′), 3.90/3.83/3.78/3.76 (s, 3H each, 4/5/3'/4′-OCH3); 13C NMR (150MHz, CDCl3) δ 178.5 (C-9′), 172.4 (C-9), 151.6 (C-4), 149.1 (C-3′), 148.5 (C-5), 148.2 (C-4′), 140.2 (C-7), 135.0 (C-1′), 130.5 (C-2), 124.1 (C-1), 121.2 (C-8), 119.6 (C-6′), 112.3 (C-6), 112.2 (C-3), 111.3 (C-5′), 110.8 (C-2′), 56.2/56.1/56.0/56.0 (4/5/3'/4′-OCH3), 47.1 (C-8′), 45.4 (C-7′); HRESIMS m/z 413.12408 [M-H]- (calcd. for C22H21O8, 413.12309); (+)-1b: [α]D25 +138.4 (c 0.10, MeOH); (-)-1b: [α]D25 -139.6 (c 0.10, MeOH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In toluene at 90℃; | 5 Hydroxydodecanoic add succinate (HDDAS) A solution of 12-hydroxydodecanoic acid (HDD A) (5.0 g, 23 mmol, 1.0 equiv.) and succinic anhydride (2.8 g, 28 mmol, 1.2 equiv.) in toluene (25 mL) was stirred at 90°C. The reaction was monitored by TLC using hexane/ethyl acetate/acetic acid (80/30/1 v/v/v) as an eluent, and vanillin stain was used to identify the spots. After the full conversion of HDD A, the reaction mixture was cooled to RT, and toluene was removed using an evaporator. Then, water was added to the residue and stirred for 15 min. Ethyl acetate was used for the extraction, and the organic layer was washed three times with distilled water. Then, the organic layer was dried over anhydrous Na2SO4 and evaporated to dryness. HDDAS was obtained with 91% yield (6.7 g) as a white solid. 12-((3- Carboxypropanoyl)oxy)dodecanoic acid; ^H NMR (300 MHz, CDC13) 6 4.12 (t, J = 6.4 Hz, 2H), 2.75 - 2.66 (m, 2H), 2.66 - 2.57 (m, 2H), 2.36 (t, J = 6.9 Hz, 2H), 1.73 - 1.55 (m, 4H), 1.45 - 1.19 (m, 14H). |
Tags: 505-95-3 synthesis path| 505-95-3 SDS| 505-95-3 COA| 505-95-3 purity| 505-95-3 application| 505-95-3 NMR| 505-95-3 COA| 505-95-3 structure
[ 533-87-9 ]
rel-(9R,10S)-9,10,16-Trihydroxyhexadecanoic acid
Similarity: 0.84
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
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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