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【结 构 式】 
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【分子编号】53741 【品名】(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 【CA登记号】n/a |
【 分 子 式 】C31H52O5 【 分 子 量 】504.75088 【元素组成】C 73.77% H 10.38% O 15.85% |
合成路线1
该中间体在本合成路线中的序号：(LVIII)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2
该中间体在本合成路线中的序号：(LVIII)Optionally, acetate ester hydrolysis of intermediate (LVIII), followed by regioselective alcohol oxidation with Collin's reagent, yielded ketone (LX). The 7-hydroxyl group of (LX) was then protected by benzylation to afford (LXI). Reductive amination of ketone (LXI) with the di-Boc-protected spermidine (XL) provided the polyamino sterol (LXII). After hydrolysis of the ethylidene ketal group of (LXII), the resultant ketone was reduced by NaBH4 to give alcohol (LXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (XL) | 53724 | tert-butyl 3-aminopropyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate | n/a | C17H35N3O4 | 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 |
| (LX) | 53743 | (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-3H-cyclopenta[a]phenanthren-3-one | n/a | C29H48O4 | 详情 | 详情 |
| (LXI) | 53744 | (5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C36H54O4 | 详情 | 详情 |
| (LXII) | 53745 | tert-butyl 3-({(3S,5R,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl}amino)propyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate | n/a | C53H89N3O7 | 详情 | 详情 |
| (LXIII) | 53746 | tert-butyl 3-({(3S,5R,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-17-[(1R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl}amino)propyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate | n/a | C51H87N3O6 | 详情 | 详情 |