以D-苯丙氨酸为原料,经过硼氢化钠/碘还原后与三光气在碱性条件下环合得到Evans手性助剂(R)-4-苄基-2-噁唑烷酮(2),然后将其与丙酰氯缩合,经过LDA偶联、反式Aldol等反应,合成了天然环酯肽Stereocalpin A中含有的独特结构片段,该片段对3种人实体瘤细胞系(HT-29,B16/F10,HepG2)具有中等细胞毒性,总收率为30.6%.结果表明,合成路线简便可行,反应产率高,立体选择性好.是制备该化合物的有效途径.
(R)-4-Benzyl-2-oxazolidinone, an Evans chiral auxiliary reagent, was synthesized from D-phenylalanine as a starting material, which was reduced by sodium borohydride/iodine followed by reacting with bis(trichloromethyl) carbonate under alkaline condition. Then the (R)-4-benzyl-2-oxazolidinone was condensated with propionyl chloride and coupled with lithium diisopropylamide(LDA). After the anti-Aldol reaction, a unique segment of Stereocalpin A was obtained in an overall yield of 30.6% which has moderate cytotoxicity against three human solid tumor cell lines(HT-29, B16/F10, HepG2). The developed method is efficient to synthesize this compound with high yield and selectivity.
参考文献
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