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【结 构 式】 
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【分子编号】53701 【品名】(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 【CA登记号】n/a |
【 分 子 式 】C33H63NO2Si 【 分 子 量 】533.95426 【元素组成】C 74.23% H 11.89% N 2.62% O 5.99% Si 5.26% |
合成路线1
该中间体在本合成路线中的序号：(XV)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：(XV)The condensation between 4-bromobutyronitrile (XVI) and 3-amino-1-propanol (XVII) gave the hydroxy amino nitrile (XVIII), which was further converted to the N,O-bis-tosylated derivative (XIX). Displacement of the tosylate ester group of (XIX) with NaI in boiling acetone afforded the alkyl iodide (XX). Alkylation of amine (XV) with iodide (XX) provided the secondary amine adduct (XXI). The p-toluenesulfonamido group of (XXI) was reductively removed by sodium in liquid ammonia, yielding diamine (XXII). Subsequent nitrile reduction by means of LiAlH4 furnished triamine (XXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (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 |
| (XVI) | 34789 | 4-bromobutanenitrile | 5332-06-9 | C4H6BrN | 详情 | 详情 |
| (XVII) | 18522 | 3-amino-1-propanol | 156-87-6 | C3H9NO | 详情 | 详情 |
| (XVIII) | 53702 | 4-[(3-hydroxypropyl)amino]butanenitrile | n/a | C7H14N2O | 详情 | 详情 |
| (XIX) | 53703 | 3-{(3-cyanopropyl)[(4-methylphenyl)sulfonyl]amino}propyl 4-methylbenzenesulfonate | n/a | C21H26N2O5S2 | 详情 | 详情 |
| (XX) | 53704 | N-(3-cyanopropyl)-N-(3-iodopropyl)-4-methylbenzenesulfonamide | n/a | C14H19IN2O2S | 详情 | 详情 |
| (XXI) | 53705 | N-(3-{[(3S,5R,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]amino}propyl)-N-(3-cyanopropyl)-4-methylbenzenesulfonamide | n/a | C47H81N3O4SSi | 详情 | 详情 |
| (XXII) | 53706 | 4-[(3-{[(3S,5R,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]amino}propyl)amino]butanenitrile | n/a | C40H75N3O2Si | 详情 | 详情 |
| (XXIII) | 53707 | (3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol | n/a | C40H79N3O2Si | 详情 | 详情 |