STEREOSPECIFIC SYNTHESIS OF N-PROTECTED STATINE AND ITS ANALOGS VIA CHIRAL TETRAMIC ACID
STEREOSPECIFIC SYNTHESIS OF N-PROTECTED STATINE AND ITS ANALOGS VIA CHIRAL TETRAMIC ACID
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DOI：
10.1039/p19870001177
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发表时间：
1987-06-01
期刊：
影响因子：
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通讯作者：
NISATO, D
中科院分区：
文献类型：
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作者：
JOUIN, P;CASTRO, B;NISATO, D
研究了手性N-保护氨基酸在氯甲酸异丙烯和4-N，N-二甲氨基吡啶(DMAP)存在下与麦德鲁姆‘S酸的缩合反应。反应产物在有机溶剂中加热环化，得到N保护的四酸衍生物(4a.sbd.i)，还原后得到相应的苏氨酸-4-羟基吡咯烷酮-2-酮(5a.sbd.i)。N-保护的吡咯烷基-2-酮的区域选择性碱或酸水解导致N-Boc-他汀类化合物(6a)及其类似物(6b.sbd.i)以40-60%的产率得到对映体纯N-Boc-他汀类化合物。相应的他汀类甲酯(7a.sbd.i)也可以高产率合成。
The condensation of a chiral N-protected amino acid with Meldrum''s acid in the presence of isopropenyl chloroformate (IPCF) and of 4-N,N-dimethylaminopyridine (DMAP) has been examined. The cyclisation of the reaction product, by heating in an organic solvent, gave the N-protected tetramic acid derivatives (4a.sbd.i) which, after reduction, afforded the corresponding threo-4-hydroxypyrrolidin-2-ones (5a.sbd.i). The regioselective alkaline or acid hydrolysis of the N-protected pyrrolidin-2-ones led to enantiomeric pure N-Boc-statine (6a) and its analogues (6b.sbd.i) in 40-60% yield from the N-protected amino acids. The corresponding statine methyl esters (7a.sbd.i) could also be synthesized in high yield.