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【结 构 式】 
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【分子编号】52186 【品名】(2R,3S,4R)-3-{[tert-butyl(dimethyl)silyl]oxy}-N-methoxy-2,4-dimethyl-5-oxohexanamide 【CA登记号】 |
【 分 子 式 】C15H31NO4Si 【 分 子 量 】317.50098 【元素组成】C 56.74% H 9.84% N 4.41% O 20.16% Si 8.85% |
合成路线1
该中间体在本合成路线中的序号：(III)The Grignard reaction of the chiral pentanamide (I) with methylmagnesium bromide in ether gives the hydroxyhexanamide (II), which is oxidized with SO3/pyridine in DMSO to yield the oxohexanamide (III). The aldol condensation of the oxohexanamide (III) with the chiral aldehyde (IV) by means of (+)-beta-chlorodiisopinocampheylborane and TEA in ethyl ether affords the aldol (V), which is reduced with tetramethylammonium triacetoxyborohydride in acetonitrile/acetic acid to provide the dihydroxyamide (VI). Finally, this compound is deprotected and lactonized by treatment with HCl in THF/water to furnish the target discodermolide.
| 【1】 Kinder, F.R. (Novartis AG; Novartis-Erfindungen VmbH); Process for preparing discodermolide and analogues thereof. WO 0212220 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 52184 | (2R,3S,4R)-3-{[tert-Butyl(dimethyl)silyl]oxy}-N-methoxy-2,4-dimethyl-5-oxopentanamide | C14H29NO4Si | 详情 | 详情 | |
| (II) | 52185 | (2R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-N-methoxy-2,4-dimethylhexanamide | C15H33NO4Si | 详情 | 详情 | |
| (III) | 52186 | (2R,3S,4R)-3-{[tert-butyl(dimethyl)silyl]oxy}-N-methoxy-2,4-dimethyl-5-oxohexanamide | C15H31NO4Si | 详情 | 详情 | |
| (IV) | 42650 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-13-oxo-6,11-tridecadienyl carbamate | C37H69NO5Si2 | 详情 | 详情 | |
| (V) | 52187 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z,13S,16R,17S,18R)-3,9,17-tris{[tert-butyl(dimethyl)silyl]oxy}-13-hydroxy-19-(methoxyamino)-2,4,6,8,10,16,18-heptamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-15,19-dioxo-6,11-nonadecadienyl carbamate | C52H100N2O9Si3 | 详情 | 详情 | |
| (VI) | 52188 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z,13S,15S,16S,17S,18R)-3,9,17-tris{[tert-butyl(dimethyl)silyl]oxy}-13,15-dihydroxy-19-(methoxyamino)-2,4,6,8,10,16,18-heptamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-19-oxo-6,11-nonadecadienyl carbamate | C52H102N2O9Si3 | 详情 | 详情 |