|
【结 构 式】 
|
【分子编号】16813 【品名】(3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate 【CA登记号】604-35-3 |
【 分 子 式 】C29H48O2 【 分 子 量 】428.69892 【元素组成】C 81.25% H 11.29% O 7.46% |
合成路线1
该中间体在本合成路线中的序号：(II)Prasterone can be obtained by two related ways: 1) The acetylation of cholesterol (I) with refluxing acetic anhydride gives the corresponding acetate (II), which is brominated with Br2 in acetic acid to the dibromide (III). The oxidation of (III) with CrO3 in acetic acid followed by debromination with Zn in the same solvent and treatment with semicarbazide and sodium acetate in ethanol/water affords 3beta-acetoxyandrost-5-en-17-one semicarbazone (IV), which is finally hydrolyzed with 5N H2SO4 in refluxing ethanol. 2) The partial silylation of androst-5-ene-3beta,17beta-diol (V) with tert-butyldimethylsilyl chloride and imidazole in DMF yields the 3beta-silyloxy derivative (VI), which is oxidized with CrO3-pyridine complex in pyridine affording 3-(tert-butyldimethylsilyloxy)androst-5-en-17-one (VII). Finally, this compound is deprotected with hot acetic acid/water/THF or with tetrabutylammonium fluoride in THF.
| 【1】 Fernholz, E.; Wallis, E.S.; The preparation of dehydroandrosterone from cholesterol. J Am Chem Soc 1935, 57, 1504-6. |
| 【2】 Castañer, J.; Mealy, N.; Rabasseda, X.; Prasterone. Drugs Fut 1995, 20, 6, 575. |
| 【3】 Ruzicka, L.; Wettstein, A.; Sexual hormones: Synthetic preparation of the male sexual hormones trans-dehydroandrosterone and androstene-3,17-dione. Helv Chim Acta 1935, 18, 986-95. |
| 【4】 Fernholz, E.; Wallis, E.S.; The constitution of dehydro-androsterone and its preparation from cholesterol. J Am Chem Soc 1935, 57, 1379-80. |
| 【5】 Hosoda, H.; Fishman, J.; Fukushima, D.K.; Convenient, high yield conversion of androst-5-ene-3beta,17beta-diol to dehydroisoandrosterone. J Org Chem 1973, 38, 24, 4209-11. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 32057 | tert-butyl(chloro)dimethylsilane | 18162-48-6 | C6H15ClSi | 详情 | 详情 | |
| (I) | 16812 | (+)-Cholesterol; (+)-(3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol | 14868-17-8 | C27H46O | 详情 | 详情 |
| (II) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (III) | 16814 | (3S,8S,9S,10R,13R,14S,17R)-5,6-dibromo-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C29H48Br2O2 | 详情 | 详情 | |
| (IV) | 16815 | (3S,8R,9S,10R,13S,14S)-17-[(E)-2-(aminocarbonyl)hydrazono]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H33N3O3 | 详情 | 详情 | |
| (V) | 16816 | (3S,8R,9S,10R,13S,14S,17S)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol; 3beta,17beta-Dihydroxyandrost-5-ene; 5-Androstene-3beta,17beta-diol | 521-17-5 | C19H30O2 | 详情 | 详情 |
| (VI) | 16817 | (3S,8R,9S,10R,13S,14S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol | C25H44O2Si | 详情 | 详情 | |
| (VII) | 16818 | (3S,8R,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C25H42O2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Ozonolysis of chloesteryl acetate (I) produced keto acid (II), which was converted to the B-homo-6-oxacholestenone (III) upon treatment with SOCl2. Subsequent displacement of the 3beta-acetate group of (III) by NaN3 afforded azide (IV). Pyrolysis of (IV) over silica gel at 180 C yielded a mixture of cleavage products, from which the title nitrile was isolated by column chromatography.
| 【1】 Peng, H.; Zalkow, L.H.; Abraham, R.T.; Powis, G.; Novel CDC25A phosphatase inhibitors from pyrolysis of 3-alpha-azido-B-homo-6-oxa-4-cholesten-7-one on silica gel. J Med Chem 1998, 41, 24, 4677. |
| 【2】 Peng, H.; Zalkow, L.H. (Georgia Technology Research Corp.); Seco-cholestane derivs. and methods of making the same. US 6011058 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (II) | 29439 | 2-[(1R,3aS,4S,5S,7aR)-5-[(1R,4S)-4-(acetoxy)-1-methyl-2-oxocyclohexyl]-1-[(1R)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-yl]acetic acid | C29H48O5 | 详情 | 详情 | |
| (III) | 29440 | (1R,3aS,3bS,8S,10aR,10bS,12aR)-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-5-oxo-2,3,3a,3b,4,5,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-indeno[4,5-d][1]benzoxepin-8-yl acetate | C29H46O4 | 详情 | 详情 | |
| (IV) | 29441 | (1R,3aS,3bS,8R,10aR,10bS,12aR)-8-azido-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-1,2,3,3a,3b,4,8,9,10,10a,10b,11,12,12a-tetradecahydro-5H-indeno[4,5-d][1]benzoxepin-5-one | C27H43N3O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Ozonolysis of chloesteryl acetate (I) produced keto acid (II), which was converted to the B-homo-6-oxacholestenone (III) upon treatment with SOCl2. Subsequent displacement of the 3-beta-acetate group of (III) by NaN3 afforded azide (IV). Pyrolysis of (IV) over silica gel at 180 C yielded a mixture of cleavage products, from which the title nitrile was isolated by column chromatography.
| 【1】 Peng, H.; Zalkow, L.H.; Abraham, R.T.; Powis, G.; Novel CDC25A phosphatase inhibitors from pyrolysis of 3-alpha-azido-B-homo-6-oxa-4-cholesten-7-one on silica gel. J Med Chem 1998, 41, 24, 4677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (II) | 29439 | 2-[(1R,3aS,4S,5S,7aR)-5-[(1R,4S)-4-(acetoxy)-1-methyl-2-oxocyclohexyl]-1-[(1R)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-yl]acetic acid | C29H48O5 | 详情 | 详情 | |
| (III) | 29440 | (1R,3aS,3bS,8S,10aR,10bS,12aR)-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-5-oxo-2,3,3a,3b,4,5,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-indeno[4,5-d][1]benzoxepin-8-yl acetate | C29H46O4 | 详情 | 详情 | |
| (IV) | 29441 | (1R,3aS,3bS,8R,10aR,10bS,12aR)-8-azido-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-1,2,3,3a,3b,4,8,9,10,10a,10b,11,12,12a-tetradecahydro-5H-indeno[4,5-d][1]benzoxepin-5-one | C27H43N3O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)Ozonolysis of chloesteryl acetate (I) produced keto acid (II), which was converted to the B-homo-6-oxacholestenone (III) upon treatment with SOCl2. Subsequent displacement of the 3-beta-acetate group of (III) by NaN3 afforded azide (IV). Pyrolysis of (IV) over silica gel at 180 C yielded a mixture of cleavage products, from which the required nitrile (V) was isolated by column chromatography. Finally, selective hydrogenation of the conjugated double bond using Pd/C furnished the title compound.
| 【1】 Peng, H.; Xie, W.; Otterness, D.M.; et al.; Synthesis and biological activities of a novel group of steroidal derived inhibitors for human CDC25A protein phosphatase. J Med Chem 2001, 44, 5, 834. |
| 【2】 Peng, H.; Zalkow, L.H.; Abraham, R.T.; Powis, G.; Novel CDC25A phosphatase inhibitors from pyrolysis of 3-alpha-azido-B-homo-6-oxa-4-cholesten-7-one on silica gel. J Med Chem 1998, 41, 24, 4677. |
| 【3】 Peng, H.; Zalkow, L.H. (Georgia Technology Research Corp.); Seco-cholestane derivs. and methods of making the same. US 6011058 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (II) | 29439 | 2-[(1R,3aS,4S,5S,7aR)-5-[(1R,4S)-4-(acetoxy)-1-methyl-2-oxocyclohexyl]-1-[(1R)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-yl]acetic acid | C29H48O5 | 详情 | 详情 | |
| (III) | 29440 | (1R,3aS,3bS,8S,10aR,10bS,12aR)-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-5-oxo-2,3,3a,3b,4,5,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-indeno[4,5-d][1]benzoxepin-8-yl acetate | C29H46O4 | 详情 | 详情 | |
| (IV) | 29441 | (1R,3aS,3bS,8R,10aR,10bS,12aR)-8-azido-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-1,2,3,3a,3b,4,8,9,10,10a,10b,11,12,12a-tetradecahydro-5H-indeno[4,5-d][1]benzoxepin-5-one | C27H43N3O2 | 详情 | 详情 | |
| (V) | 29442 | 2-[(1R,3aS,4R,5S,7aR)-5-[(Z)-5-cyano-1-methylene-4-pentenyl]-1-[(1R)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-yl]acetic acid | C27H43NO2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(I)Nitration of cholesteryl acetate (I) with nitric acid in acetic acid gave the 6-nitro derivative (II). Reduction of the D5 double bond of (II) with ethanolic NaBH4 at reflux temperature provided the 6-alpha-nitro compound (III). Finally, reduction of the nitro group of (III) with concomitant deacetylation using hydrazine and Pd/C in EtOH yielded the title compound.
| 【1】 Beuchet, P.; el Kihel, L.; Dherbomez, M.; Charles, G.; Letourneux, Y.; Synthesis of 6(alpha,beta)-aminocholestanols as ergosterol biosynthesis inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3627. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (II) | 29597 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-6-nitro-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C29H47NO4 | 详情 | 详情 | |
| (III) | 29598 | (3S,5S,6S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-6-nitrohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C29H49NO4 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)Nitration of cholesteryl acetate (I) with nitric acid in acetic acid gave the 6-nitro derivative (II). Reduction of the D5 double bond of (II) with ethanolic NaBH4 at room temperature provided the 6-beta-nitro compound (III). Finally, reduction of the nitro group of (III) with concomitant deacetylation using LiAlH4 in refluxing Et2O yielded the title compound.
| 【1】 Beuchet, P.; el Kihel, L.; Dherbomez, M.; Charles, G.; Letourneux, Y.; Synthesis of 6(alpha,beta)-aminocholestanols as ergosterol biosynthesis inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3627. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (II) | 29597 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-6-nitro-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C29H47NO4 | 详情 | 详情 | |
| (III) | 29599 | (3S,5S,6R,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-6-nitrohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C29H49NO4 | 详情 | 详情 |