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【结 构 式】

【分子编号】53707

【品名】(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

【CA登记号】n/a

【 分 子 式 】C40H79N3O2Si

【 分 子 量 】662.17178

【元素组成】C 72.56% H 12.03% N 6.35% O 4.83% Si 4.24%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXIII)

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

合成路线2

该中间体在本合成路线中的序号:(XXII)

After protection of triamine (XXIII) as the tris-benzyloxycarbonyl derivative (XXIV), its 7-hydroxyl was acetylated by means of Ac2O and DMAP. Further hydrogenolysis of the benzyloxycarbonyl groups in ethanolic HCl also removed the O-silyl group, yielding (XXV). Treatment of alcohol (XXV) with sulfur trioxide in pyridine generated the pyridinium sulfate salt (XXVI). The 7-acetate ester of (XXVI) was finally hydrolyzed with NaOH to furnish the title compound.

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
(XXII) 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
(XXIV) 53708 benzyl 4-{[(benzyloxy)carbonyl]amino}butyl(3-{[(benzyloxy)carbonyl][(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)carbamate n/a C64H97N3O8Si 详情 详情
(XXV) 53709 (3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-[(1R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-yl acetate n/a C36H67N3O3 详情 详情
(XXVI) 53710 pyridinium (3S,5R,7R,8R,9S,10S,13R,14S,17R)-7-(acetyloxy)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-[(1R)-1,5-dimethyl-4-(sulfonatooxy)hexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene n/a C41H72N4O6S 详情 详情
Extended Information