【结 构 式】 |
【分子编号】62856 【品名】methyl (2R,3S,4S)-3-hydroxy-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanoate 【CA登记号】 |
【 分 子 式 】C16H24O5 【 分 子 量 】296.36356 【元素组成】C 64.84% H 8.16% O 26.99% |
合成路线1
该中间体在本合成路线中的序号:(VIII)Synthesis of the chiral 5-oxopentanoic ester intermediate (XI): The reaction of 3-hydroxy-2(S)-methylpentanoic acid methyl ester (I) with 4-methoxybenzyl trichloroacetimidate gives the aryl ether (II), which is treated with ethylmagnesium bromide to yield the ketone (III). The condensation of (III) with formaldehyde by means of (c-Hex)2B-Cl and H2O2 affords the hydroxypentanone (IV), which is reduced by means of NaBH(OAc)3 in THF/AcOH to provide the diol (V). The regioselective oxidation of the primary alcohol of (V) with TEMPO and BAIB in dichloromethane gives the beta-hydroxyaldehyde (VI), which is further oxidized with NaClO2 yielding the carboxylic acid (VII). The esterification of (VII) by means of Me-I and K2CO3, or with TMS-CHN2 affords the methyl ester (VIII), which is treated with Tbdms-OTf and lutidine to provide the silyl ether (IX). The selective deprotection of (IX) by means of DDQ in dichloromethane furnishes the omega-hydroxyester (X), which is finally submitted to a Swern oxidation to yield the chiral 5-oxopentanoic ester intermediate (XI).
【1】 Paterson, I.; Delgado, O.; Florence, G.J.; Lyothier, I.; Scott, J.P.; Sereinig, N.; 1,6-asymmetric induction in boron-mediated aldol reactions: Application to a practical total synthesis of (+)-discodermolide. Org Lett 2003, 5, 1, 35. |
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) | 17128 | Methyl (2S)-3-hydroxy-2-methylpropanoate | 72657-23-9 | C5H10O3 | 详情 | 详情 |
(II) | 42654 | methyl (2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropanoate | C13H18O4 | 详情 | 详情 | |
(III) | 42614 | (2S)-1-[(4-methoxybenzyl)oxy]-2-methyl-3-pentanone | C14H20O3 | 详情 | 详情 | |
(IV) | 62852 | (2S,4S)-1-hydroxy-5-[(4-methoxybenzyl)oxy]-2,4-dimethyl-3-pentanone | C15H22O4 | 详情 | 详情 | |
(V) | 62853 | (2S,3R,4S)-5-[(4-methoxybenzyl)oxy]-2,4-dimethyl-1,3-pentanediol | C15H24O4 | 详情 | 详情 | |
(VI) | 62854 | (2R,3S,4S)-3-hydroxy-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C15H22O4 | 详情 | 详情 | |
(VII) | 62855 | (2R,3S,4S)-3-hydroxy-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanoic acid | C15H22O5 | 详情 | 详情 | |
(VIII) | 62856 | methyl (2R,3S,4S)-3-hydroxy-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanoate | C16H24O5 | 详情 | 详情 | |
(IX) | 62857 | methyl (2R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanoate | C22H38O5Si | 详情 | 详情 | |
(X) | 62858 | methyl (2R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-2,4-dimethylpentanoate | C14H30O4Si | 详情 | 详情 | |
(XI) | 62859 | methyl (2R,3S,4R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2,4-dimethyl-5-oxopentanoate | C14H28O4Si | 详情 | 详情 |