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【结 构 式】 
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【分子编号】53754 【品名】(3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-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】n/a |
【 分 子 式 】C25H38O4 【 分 子 量 】402.57432 【元素组成】C 74.59% H 9.51% O 15.9% |
合成路线1
该中间体在本合成路线中的序号：(LX)In a synthetic route starting from dehydroepiandrosterone (LXVI), Wittig reaction of ketone (LXVI) with ethyl triphenylphosphonium bromide (LXVII) and potassium tert-butoxide gave the C-17 ethylidene derivative (LXVIII). Condensation of (LXVIII) with isopropyl vinyl ketone (LXIX) in the presence of dimethylaluminum chloride, followed by catalytic hydrogenation over Pt/C, yielded (LV), which was then converted into ethylene ketal (LVI). Catalytic hydrogenation of (LVI) gave compound (LXX), whose acetate ester was hydrolyzed to afford alcohol (LXXI). Oxidation of (LXXI) by means of chromic acid furnishes ketone (LXXII), from which intermediate (LX) was obtained by introduction of the 7-alpha hydroxyl group by means of microbiological oxidation employing several microorganism strains.
| 【1】 Moriarty, R.M.; Guo, L.; Tuladhar, S.M. (Genaera Corp.); Chemical synthesis of squalamine. WO 9419366 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LV) | 53712 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethyl-4-oxohexyl]-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 | n/a | C29H46O3 | 详情 | 详情 |
| (LVI) | 53739 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-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 | n/a | C31H50O4 | 详情 | 详情 |
| (LX) | 53754 | (3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C25H38O4 | 详情 | 详情 |
| (LXVI) | 20083 | Prasterone acetate;3b-Hydroxy-5-androstene-17-one acetate；Dehydroisoandrosterone acetate;Dehydroepiandrosterone 3-acetate;Dehydroepiandrosterone acetate;(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 853-23-6 | C21H30O3 | 详情 | 详情 |
| (LXVII) | 11717 | Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide | 1530-32-1 | C20H20BrP | 详情 | 详情 |
| (LXVIII) | 53749 | (3S,8S,9S,10R,13S,14S)-17-[(E)ethylidene]-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 | n/a | C23H34O2 | 详情 | 详情 |
| (LXIX) | 53750 | 4-methyl-1-penten-3-one | 1606-47-9 | C6H10O | 详情 | 详情 |
| (LXX) | 53751 | (3S,5S,8R,9S,10S,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C31H52O4 | 详情 | 详情 |
| (LXXI) | 53752 | (3S,5S,8R,9S,10S,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol | n/a | C29H50O3 | 详情 | 详情 |
| (LXXII) | 53753 | (5S,8R,9S,10S,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C29H48O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXXIV)In another synthetic route from pregnenolone acetate (LXXIII), its ketalization to (LXXIV) followed by allylic oxidation led to enone (LXXV). Sequential reduction of (LXXV) with lithium in liquid ammonia and then with K-Selectride gave alcohol (LXXVI), which was further protected as the methoxymethyl derivative (LXXVII). Selective deprotection of the C-20 ketal of (LXXVII) yielded ketone (LXXVIII). Ylide (LXXX) was prepared by condensation of bromide (LXXIX) with triphenylphosphine, followed by deprotonation with n-BuLi. Wittig condensation of ketone (LXXVIII) with phosphorane (LXXX) furnished olefin (LXXXI). Then, double-bond hydrogenation and deprotection of the 7-hydroxyl group of (LXXXI) gave rise to the intermediate (XI).
| 【1】 Moriarty, R.M.; Guo, L.; Tuladhar, S.M. (Genaera Corp.); Chemical synthesis of squalamine. WO 9419366 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 53697 | (3S,5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C35H64O4Si | 详情 | 详情 |
| (LXXIII) | 35173 | (3S,8S,9S,10R,13S,14S,17S)-17-acetyl-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 | 1778-02-5 | C23H34O3 | 详情 | 详情 |
| (LXXIV) | 53754 | (3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C25H38O4 | 详情 | 详情 |
| (LXXV) | 53755 | (3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-7-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C25H36O5 | 详情 | 详情 |
| (LXXVI) | 53756 | (3S,5S,7R,8R,9S,10S,13S,14S,17S)-7-hydroxy-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C25H40O5 | 详情 | 详情 |
| (LXXVII) | 53757 | (3S,5S,7R,8R,9S,10S,13S,14S,17S)-7-(methoxymethoxy)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C27H44O6 | 详情 | 详情 |
| (LXXVIII) | 53758 | (3S,5S,7R,8R,9S,10S,13S,14S,17S)-17-acetyl-7-(methoxymethoxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C25H40O5 | 详情 | 详情 |
| (LXXIX) | 53759 | 1-(2-bromoethyl)-2-methylpropyl tert-butyl(dimethyl)silyl ether; [1-(2-bromoethyl)-2-methylpropoxy](tert-butyl)dimethylsilane | n/a | C12H27BrOSi | 详情 | 详情 |
| (LXXX) | 53760 | (3-{[tert-butyl(dimethyl)silyl]oxy}-4-methylpentylidene)(triphenyl)phosphorane; tert-butyl(dimethyl)silyl 2-methyl-1-[2-(triphenylphosphoranylidene)ethyl]propyl ether | n/a | C30H41OPSi | 详情 | 详情 |
| (LXXXI) | 53761 | (3S,5S,7R,8R,9S,10S,13S,14S,17R)-17-((Z)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethyl-1-hexenyl)-7-(methoxymethoxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C37H66O5Si | 详情 | 详情 |