天然产物Divergolide A手性甲基酮片段(C4-C10)的合成

Synthesis of Chiral Methyl Ketone Fragment(C4-C10)of Natural Product Divergolide A

手性甲基酮片段(C4-C10)是天然产物Divergolide A的重要组成部分。分别采用3种方法实现了该片段的合成。第一种方法包含手性丁酸衍生物的常规不对称烷基化反应及后续反应等8步反应,总收率42%;第二种方法包含手性辅基诱导的手性丁酸衍生物的迈克尔加成反应和选择性维悌希反应等4步反应,总收率58%;第三种方法包含二苯基脯氨醇甲醚催化的甲基乙烯基酮的迈克尔加成反应和选择性维悌希反应等两步反应,总收率67%。产物结构经1H NMR,13C NMR和HR-MS(EI)确证。

Chiral methyl ketone fragment(C4-C10)is an important component of natural product Divergolide A.In this work,three methods were developed to synthesize the fragment separately.In the first method,eight steps including conventional asymmetric alkylation of a chiral butyric acid derivative and subsequent reactions were carried out to obtain the target fragment compound in 42%overall yield.The second method,consisting of four steps,among of which were the Michael addition reaction of chiral butyric acid derivative induced by chiral auxiliary and selective Wittig reaction,produced the wanted compound in 58%overall yield,while the third method involved two steps including the classical Michael addition reaction of methyl vinyl ketone catalyzed by diphenylprolinol methyl ether and selective Wittig reaction,getting the same compound in 67%overall yield.The structure is confirmed by 1H NMR,13C NMR and HR-MS(EI).The successful synthesis of the fragment compound has effectively promoted the total synthesis of natural product Divergolide A.