Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
J Org Chem. 2012 Oct 19;77(20):9260-7. doi: 10.1021/jo301803h. Epub 2012 Oct 4.
We describe a simple and convenient synthesis of the western zone of caprazamycin B using two catalytic asymmetric reactions as key elements of our approach. Desymmetrization of 3-methylglutaric anhydride with the (S)-Ni(2)-(Schiff base) complex as a catalyst furnished the chiral hemiester, and a thioamide-aldol reaction with mesitylcopper, (R,R)-Ph-BPE, and 2,2,5,7,8-pentamethylchromanol as a catalyst furnished the β-hydroxy thioamide in good yield and enantioselectivity. On further transformation, the thioamide functionality was converted to the corresponding β-hydroxy ester. Finally, a convergent synthesis of the western zone of caprazamycin B was achieved by connecting the hemiester, the β-hydroxy ester, and the 2,3,4-tri-O-methyl-l-rhamnose fragments.
我们描述了一种使用两种催化不对称反应作为关键步骤的简单便捷的方法，来合成卡泊沙苷 B 的西部区域。（S）-Ni(2)-(Schiff 碱)络合物作为催化剂对 3-甲基戊二酸酐进行去对称化，得到手性半酯，然后与Mesitylcopper、(R,R)-Ph-BPE 和 2,2,5,7,8-五甲基-2,3-环戊二醇作为催化剂进行硫代酰胺-羟醛缩合反应，以良好的收率和对映选择性得到β-羟基硫代酰胺。进一步转化后，硫代酰胺官能团转化为相应的β-羟基酯。最后，通过连接半酯、β-羟基酯和 2,3,4-三-O-甲基-L-岩藻糖片段，实现了卡泊沙苷 B 的西部区域的收敛性合成。
