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【结 构 式】 
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【分子编号】32178 【品名】(5S,8R,9S,10S,13S,14S)-10,13-dimethyl-1,4,5,6,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one 【CA登记号】 |
【 分 子 式 】C19H28O 【 分 子 量 】272.43072 【元素组成】C 83.77% H 10.36% O 5.87% |
合成路线1
该中间体在本合成路线中的序号：(I)The enol acylation of 5alpha-androst-2-en-17-one (I) with isopropenyl acetate (A) using H2SO4 as catalyst gives 17-acetoxyandrost-2,16-diene (II), which is epoxidized by treatment with m-chloroperbenzoic acid in ether yielding 2alpha,3alpha:16alpha,17alpha-diepoxy-17beta-acetoxy-5alpha-androstane (III). The hydrolytic rearrangement of (III) with KOH affords 2alpha,3alpha-epoxy-5alpha-androstan-17beta-ol-16-one (IV), which is condensed with refluxing aqueous piperidine (B) to give 2beta,16beta-dipiperidino-5alpha-androstan-3alpha-ol-17-one (V). The reduction of (V) with NaBH4 in methylene chloride - methanol yields 2beta,16beta-dipiperidino-5alpha-androstan-3alpha,17beta-diol (VI), which is acetylated by reaction with acetyl chloride as usual to afford the corresponding diacetate (VII). Finally, this compound is quaternized by reaction with methyl bromide in ether.
| 【1】 Buckett, W.R.; et al.; Pancuronium bromide and other steroidal neuromuscular blocking agents containing acetylcholine fragments. J Med Chem 1973, 16, 10, 1116-24. |
| 【2】 Serradell, M.N.; Castaner, J.; Blancafort, P.; Hillier, K.; ORG-NC-45. Drugs Fut 1981, 6, 5, 287. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
| (A) | 21178 | isopropenyl acetate | 108-22-5 | C5H8O2 | 详情 | 详情 |
| (I) | 32178 | (5S,8R,9S,10S,13S,14S)-10,13-dimethyl-1,4,5,6,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H28O | 详情 | 详情 | |
| (II) | 32179 | (5S,8R,9S,10S,13S,14S)-10,13-dimethyl-4,5,6,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl acetate | C21H30O2 | 详情 | 详情 | |
| (III) | 32180 | (1aS,2aS,2bS,4aS,5aR,6aS,6bR,8aS,9aS)-2a,4a-dimethylhexadecahydro-4bH-oxireno[2'',3'':4',5']cyclopenta[1',2':7,8]phenanthro[2,3-b]oxiren-4-yl acetate | C21H30O4 | 详情 | 详情 | |
| (IV) | 32181 | (1R,3aS,3bR,5aS,6aS,7aS,8aS,8bS,10aS)-1-hydroxy-8a,10a-dimethylhexadecahydro-2H-cyclopenta[7,8]phenanthro[2,3-b]oxiren-2-one | C19H28O3 | 详情 | 详情 | |
| (V) | 16465 | (2S,3S,5S,8R,9S,10S,13S,14S,16S)-3-hydroxy-10,13-dimethyl-2,16-di(1-piperidinyl)hexadecahydro-17H-cyclopenta[a]phenanthren-17-one | C29H48N2O2 | 详情 | 详情 | |
| (VI) | 32182 | (2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-10,13-dimethyl-2,16-di(1-piperidinyl)hexadecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol | C29H50N2O2 | 详情 | 详情 | |
| (VII) | 32183 | (2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-17-(acetoxy)-10,13-dimethyl-2,16-di(1-piperidinyl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C33H54N2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The reaction of 5alpha-androst-2-ene-17-one (I) with isopropenyl acetate (II) by means of H2SO4 as catalyst gives 17beta-acetoxy-5alpha-androsta-2,16-diene (III), which is epoxidized by means of perbenzoic acid (A) in benezene yielding 2alpha, 3alpha:16alpha,17alpha-diepoxy-17beta-acetoxy-5alpha-androstane (IV). The reaction of (IV) with N-methylpiperazine (V) in refluxing water affords 2beta,16beta-bis(4-methyl-1-piperazino)-3alpha-hydroxy-5alpha-androstane-17-one (VI), which is reduced with NaBH4 in THF methanol to give 2,16-bis(4-methyl-1-piperazino)-3alpha,17beta-dihydroxy-5alpha-androstane (VII). The acetylation of (VII) with acetic anhydride by means of ZnCl2 in acetic acid yields 2beta,16beta-bis(4-methyl-1-piperazino)-3alpha, 17beta-diacetoxy-5alpha-androstane (VIII), which is finally treated with methyl bromide in acetone.
| 【1】 US 312398 . |
| 【2】 Tuba, Z.; et al.; GB 1398050 . |
| 【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hopkins, S.J.; Pipecuronium bromide. Drugs Fut 1980, 5, 12, 621. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 39215 | benzenecarboperoxoic acid | 93-59-4 | C7H6O3 | 详情 | 详情 |
| (I) | 32178 | (5S,8R,9S,10S,13S,14S)-10,13-dimethyl-1,4,5,6,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H28O | 详情 | 详情 | |
| (II) | 21178 | isopropenyl acetate | 108-22-5 | C5H8O2 | 详情 | 详情 |
| (III) | 32179 | (5S,8R,9S,10S,13S,14S)-10,13-dimethyl-4,5,6,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl acetate | C21H30O2 | 详情 | 详情 | |
| (IV) | 13647 | (1aR,2aS,2bS,4aS,5aR,6aS,6bR,8aS,9aS)-2a,4a-dimethylhexadecahydro-4bH-oxireno[2'',3'':4',5']cyclopenta[1',2':7,8]phenanthro[2,3-b]oxiren-4-yl acetate | C21H30O4 | 详情 | 详情 | |
| (V) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (VI) | 39216 | (2S,3S,5S,8R,9S,10S,13S,14S,16S)-3-hydroxy-10,13-dimethyl-2,16-bis(4-methyl-1-piperazinyl)hexadecahydro-17H-cyclopenta[a]phenanthren-17-one | C29H50N4O2 | 详情 | 详情 | |
| (VII) | 39217 | (2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-10,13-dimethyl-2,16-bis(4-methyl-1-piperazinyl)hexadecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol | C29H52N4O2 | 详情 | 详情 | |
| (VIII) | 39218 | (2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-17-(acetoxy)-10,13-dimethyl-2,16-bis(4-methyl-1-piperazinyl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C33H56N4O4 | 详情 | 详情 |