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【结 构 式】

【分子编号】53724

【品名】tert-butyl 3-aminopropyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate

【CA登记号】n/a

【 分 子 式 】C17H35N3O4

【 分 子 量 】345.48272

【元素组成】C 59.1% H 10.21% N 12.16% O 18.52%
与该中间体有关的原料药合成路线共 4 条
合成路线1合成路线2合成路线3合成路线4

合成路线1

该中间体在本合成路线中的序号：(XL)

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.

参考文献 中间体
合成目标
【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

合成路线2

该中间体在本合成路线中的序号：(XL)

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).

参考文献 中间体
合成目标
【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

合成路线3

该中间体在本合成路线中的序号：(XL)

Reductive amination of ketone (CII) with the deprotected spermidine (XL) in the presence of NaBH3CN provided the triamino derivative (CIII). The Boc protecting groups of (CIII) were then removed by acidic treatment to furnish the target precursor (CIV).

参考文献 中间体
合成目标
【1】 Moriarty, R.M.; et al.; Stereoselective synthesis of squalamine dessulfate. Tetrahedron Lett 1995, 36, 29, 5139.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(CII) 53780 (5S,7R,8R,9S,10S,13R,14S,17R)-17-[(1R,4R)-4-(acetyloxy)-1,5-dimethylhexyl]-10,13-dimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-7-yl acetate C31H50O5 详情 详情
(CIII) 53781 (1R,4R)-4-((3S,5R,7R,8R,9S,10S,13R,14S,17R)-7-(acetyloxy)-3-{[3-((tert-butoxycarbonyl){4-[(tert-butoxycarbonyl)amino]butyl}amino)propyl]amino}-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-1-isopropylpentyl acetate C48H85N3O8 详情 详情
(CIV) 53782 (3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol C34H65N3O2 详情 详情
(XL) 53724 tert-butyl 3-aminopropyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate n/a C17H35N3O4 详情 详情

合成路线4

该中间体在本合成路线中的序号：(XIV)

The reductocondensation of (XIII) with protected amine (XIV) by means of NaBH4 in methanol gives a mixture of the 3-beta and 3-alpha steroids, easily separated by flash chromatography. The desired 3-beta isomer (XV) is deprotected by means of HCl in methanol, yielding intermediate (XVI), which is finally treated with SO3 and pyridine to afford the target 24(R)-O-sulfate steroid

参考文献 中间体
合成目标
【1】 Zhou, X.D.; et al.; A stereoselective synthesis of squalamine. Tetrahedron 2002, 58, 52, 10293.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIII) 62205 (5R,7R,10S,13R,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one C27H46O3 详情 详情
(XIV) 53724 tert-butyl 3-aminopropyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate n/a C17H35N3O4 详情 详情
(XV) 62206 tert-butyl 4-[(tert-butoxycarbonyl)amino]butyl[3-({(3S,5S,7R,10S,13R,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl}amino)propyl]carbamate C44H81N3O6 详情 详情
(XVI) 62207 (3S,5S,7R,10S,13R,17R)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol C34H65N3O2 详情 详情
Extended Information