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【结 构 式】 
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【分子编号】64743 【品名】3-[5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,4-dimethyl-3-{[(methyloxy)methyl]oxy}-8-({[4-(methyloxy)phenyl]methyl}oxy)octanoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C36H55NO8Si 【 分 子 量 】657.92014 【元素组成】C 65.72% H 8.43% N 2.13% O 19.45% Si 4.27% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Mono-protection of 1,4-butanediol (XI) by means of 4-methoxybenzyl chloride, followed by Swern oxidation with DMSO/SO3-Pyr, leads to the aldehyde (XII). Condensation of (XII)with the boron enolate of the N-propionyl oxazolidinone (III) and subsequent silylation with tert-butyldimethylsilyl triflate furnishes the N-acyl oxoazolidinone (XIII), which is reduced by LiBH4 to the primary alcohol (XIV), which is then subjected to Swern oxidation to produce the aldehyde (XV). Further condensation of (XV) with acyl oxazolidinone (III) leads to adduct (XVI). The free hydroxyl group of (XVI) is alkylated with chloromethyl methyl ether to produce the O-methoxymethyl derivative (XVII), which under desilylation conditions with HF-pyridine cyclizes to the lactone (XVIII).
| 【1】 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846. |
| 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) | 25713 | (4S)-4-benzyl-3-propionyl-1,3-oxazolidin-2-one | C13H15NO3 | 详情 | 详情 | |
| (XI) | 46190 | (1R,2R,6S)-1-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-hydroxy-2,6-dimethyl-7-octenyl methanesulfonate | C26H47NO5S2Si | 详情 | 详情 | |
| (XII) | 64738 | 4-({[4-(methyloxy)phenyl]methyl}oxy)butanal | C12H16O3 | 详情 | 详情 | |
| (XIII) | 64739 | 3-[3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-6-({[4-(methyloxy)phenyl]methyl}oxy)hexanoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one | C31H45NO6Si | 详情 | 详情 | |
| (XIV) | 64740 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-6-({[4-(methyloxy)phenyl]methyl}oxy)-1-hexanol | C21H38O4Si | 详情 | 详情 | |
| (XV) | 64741 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-6-({[4-(methyloxy)phenyl]methyl}oxy)hexanal | C21H36O4Si | 详情 | 详情 | |
| (XVI) | 64742 | C34H51NO7Si | 详情 | 详情 | ||
| (XVII) | 64743 | 3-[5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,4-dimethyl-3-{[(methyloxy)methyl]oxy}-8-({[4-(methyloxy)phenyl]methyl}oxy)octanoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one | C36H55NO8Si | 详情 | 详情 | |
| (XVIII) | 64744 | 3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-one | C20H30O6 | 详情 | 详情 |