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【结 构 式】 
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【分子编号】53697 【品名】(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 【CA登记号】n/a |
【 分 子 式 】C35H64O4Si 【 分 子 量 】576.97626 【元素组成】C 72.86% H 11.18% O 11.09% Si 4.87% |
合成路线1
该中间体在本合成路线中的序号：(XI)Allylic oxidation of (VIII) by means of t-butyl hydroperoxide and chromium hexacarbonyl produced enone (IX). Subsequent Birch reduction of (IX) employing lithium metal in liquid ammonia gave the saturated ketone (X), which was further reduced to alcohol (XI) with K-Selectride in cold THF. Removal of the acetate ester of (XI) was achieved by treatment with NaCN in MeOH, giving diol (XII). The 3-beta hydroxyl group of (XII) was then selectively oxidized to ketone (XIII) under Oppenauer conditions. Ketone (XIII) was converted to the primary amine (XV) via formation of the O-benzyl oxime (XIV), which was reduced by LiAlH4.
| 【1】 Moriarty, R.M.; et al.; Synthesis of squalamine. A steroidal antibiotic from the shark. Tetrahedron Lett 1994, 35, 44, 8103. |
| 【2】 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 |
|---|---|---|---|---|---|---|
| (VIII) | 53694 | (3S,8S,9S,10R,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-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 | n/a | C35H62O3Si | 详情 | 详情 |
| (IX) | 53695 | (3S,8S,9S,10R,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethyl-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 | C35H60O4Si | 详情 | 详情 |
| (X) | 53696 | (3S,5R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C35H62O4Si | 详情 | 详情 |
| (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 |
| (XII) | 53698 | (3S,5R,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol | n/a | C33H62O3Si | 详情 | 详情 |
| (XIII) | 53699 | (5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C33H60O3Si | 详情 | 详情 |
| (XIV) | 53700 | (5R,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one O-benzyloxime | n/a | C40H67NO3Si | 详情 | 详情 |
| (XV) | 53701 | (3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-amino-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol | n/a | C33H63NO2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)In a different synthesis of intermediate (XI), compound (LIV) (prepared by acetylation of fucosterol (LIII)) was subjected to ozonolysis to produce ketone (LV). Protection of the keto group by ketalization yielded (LVI), which was allylically oxidized to the conjugated ketone (LVII). Double bond reduction in (LVII) by lithium in ammonia, followed by stereoselective reduction of resulting ketone with K-Selectride, yielded alcohol (LVIII). Acid-catalyzed hydrolysis of the ethylene ketal group of (LVIII) gave ketone (LIX). This was converted to intermediate (XI) by reduction with Ca(BH4)2 and subsequent silylation of the resulting alcohol.
| 【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 |
| (LIII) | 53737 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,4Z)-4-isopropyl-1-methyl-4-hexenyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol | n/a | C29H48O | 详情 | 详情 |
| (LIV) | 53738 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,4Z)-4-isopropyl-1-methyl-4-hexenyl]-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 | C31H50O2 | 详情 | 详情 |
| (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 |
| (LVII) | 53740 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethyl-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 | C31H48O5 | 详情 | 详情 |
| (LVIII) | 53741 | (3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C31H52O5 | 详情 | 详情 |
| (LIX) | 53742 | (3S,5S,7R,8R,9S,10S,13R,14S,17R)-17-[(1R)-1,5-dimethyl-4-oxohexyl]-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C29H48O4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XI)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 |