Tsuruda Takeshi, Ebine Makoto, Umeda Aya, Oishi Tohru
Department of Chemistry, Faculty and Graduate School of Sciences, Kyushu University , 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
J Org Chem. 2015 Jan 16;80(2):859-71. doi: 10.1021/jo502322m. Epub 2015 Jan 7.
Stereoselective synthesis of the C1-C29 part of amphidinol 3 (AM3) was achieved. The C1-C20 part was assembled from three building blocks via regioselective cross metathesis to form the C4-C5 double bond and addition of an alkenyllithium and a lithium acetylide to two Weinreb amides followed by asymmetric reduction to form the C9-C10 and C14-C15 bonds, respectively. The C21-C29 part was synthesized via successive cross metathesis and oxa-Michael addition sequence to construct the 1,3-diol system at C25 and C27 and Brown asymmetric crotylation to introduce the stereogenic centers at C23 and C24. Coupling of the C1-C20 and C21-C29 parts was achieved by Julia-Kocienski olefination and regio- and stereoselective dihydroxylation of the C20-C21 double bond in the presence of the C4-C5 and C8-C9 double bonds to afford the C1-C29 part of AM3.
实现了两性霉素3（AM3）C1 - C29部分的立体选择性合成。C1 - C20部分由三个结构单元通过区域选择性交叉复分解反应组装而成，形成C4 - C5双键，然后将烯基锂和乙炔锂加成到两个Weinreb酰胺上，接着进行不对称还原反应，分别形成C9 - C10和C14 - C15键。C21 - C29部分通过连续的交叉复分解反应和氧杂 - 迈克尔加成序列合成，在C25和C27构建1,3 - 二醇体系，并通过布朗不对称巴豆酰化反应在C23和C24引入手性中心。C1 - C20和C21 - C29部分通过Julia - Kocienski烯化反应以及在C4 - C5和C8 - C9双键存在下对C20 - C21双键进行区域和立体选择性二羟基化反应实现偶联，得到AM3的C1 - C29部分。
