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【结 构 式】 
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【分子编号】53720 【品名】(6R)-6-[(3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methyl-3-heptanol 【CA登记号】n/a |
【 分 子 式 】C39H62O4 【 分 子 量 】594.91888 【元素组成】C 78.74% H 10.5% O 10.76% |
合成路线1
该中间体在本合成路线中的序号：(XXXVI)In a different method, protection of alcohol (III) as the tert-butyldimethylsilyl ether (XXX), followed by allylic oxidation by means of CrO3 in the presence of 3,5-dimethylpyrazole (DMP), gave enone (XXXI). Hydrogenation of (XXXI) using Adams catalyst resulted in the formation of the saturated ketone (XXXII). Some undesired 7-beta alcohol byproduct was reoxidized to ketone (XXXII) by means of Collin's reagent. Stereoselective reduction of ketone (XXXII) with K-Selectride afforded the 7-alpha alcohol (XXXIII), which was protected as the benzyl ether (XXXIV) by treatment with benzyl bromide and NaH. After desilylation of (XXXIV) with Bu4NF, the deprotected alcohol was subjected to Swern oxidation to provide aldehyde (XXXV). Addition of isopropylmagnesium chloride to aldehyde (XXXV) gave alcohol (XXXVI) as a mixture of epimers.
| 【1】 Pechulis, A.D.; et al.; Synthesis of 24xi-squalamine, an anti-infective steroidal polyamine. J Org Chem 1995, 60, 16, 5121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 53689 | (4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-pentanol | n/a | C29H48O3 | 详情 | 详情 |
| (XXX) | 53714 | tert-butyl(dimethyl)silyl (4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentyl ether; tert-butyl({(4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentyl}oxy)dimethylsilane | n/a | C35H62O3Si | 详情 | 详情 |
| (XXXI) | 53715 | (3S,8S,9S,10R,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methylbutyl)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-1,2,3,4,8,9,10,11,12,13,14,15,16,17-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one | n/a | C35H60O4Si | 详情 | 详情 |
| (XXXII) | 53716 | (3S,5R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methylbutyl)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-7H-cyclopenta[a]phenanthren-7-one | n/a | C35H62O4Si | 详情 | 详情 |
| (XXXIII) | 53717 | (3S,5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methylbutyl)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-7-ol | n/a | C35H64O4Si | 详情 | 详情 |
| (XXXIV) | 53718 | benzyl (3S,5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methylbutyl)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-7-yl ether; ({(4R)-4-[(3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentyl}oxy)(tert-butyl)dimethylsilane | n/a | C42H70O4Si | 详情 | 详情 |
| (XXXV) | 53719 | (4R)-4-[(3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanal | n/a | C36H54O4 | 详情 | 详情 |
| (XXXVI) | 53720 | (6R)-6-[(3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methyl-3-heptanol | n/a | C39H62O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVI)After silylation of alcohol (XXXVI) to silyl ether (XXXVII), its tetrahydropyranyl protecting group was selectively removed by treatment with magnesium bromide in Et2O. The resultant 3-beta alcohol (XXXVIII) was oxidized to ketone (XXXIX) employing Collin's reagent. The polyamino side-chain was then introduced in (XXXIX) by reductive amination with the di-Boc-protected spermidine (XL) in the presence of NaBH3CN, giving (XLI) as a mixture of 3-alpha and 3-beta isomers.
| 【1】 Pechulis, A.D.; et al.; Synthesis of 24xi-squalamine, an anti-infective steroidal polyamine. J Org Chem 1995, 60, 16, 5121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXVI) | 53720 | (6R)-6-[(3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methyl-3-heptanol | n/a | C39H62O4 | 详情 | 详情 |
| (XXXVII) | 53721 | ({(4R)-4-[(3S,5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-isopropylpentyl}oxy)(tert-butyl)dimethylsilane; benzyl (3S,5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)hexadecahydro-1H-cyclopenta[a]phenanthren-7-yl ether | n/a | C45H76O4Si | 详情 | 详情 |
| (XXXVIII) | 53722 | (3S,5R,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol | n/a | C40H68O3Si | 详情 | 详情 |
| (XXXIX) | 53723 | (5S,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C40H66O3Si | 详情 | 详情 |
| (XL) | 53724 | tert-butyl 3-aminopropyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate | n/a | C17H35N3O4 | 详情 | 详情 |
| (XLI) | 53725 | tert-butyl 3-{[(5R,7R,8R,9S,10S,13R,14S,17R)-7-(benzyloxy)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]amino}propyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate | n/a | C57H101N3O6Si | 详情 | 详情 |