Department of Pharmaceutical Sciences, University of Connecticut , 69 N. Eagleville Road, Storrs, Connecticut 06269, United States.
J Am Chem Soc. 2014 Mar 19;136(11):4309-15. doi: 10.1021/ja413106t. Epub 2014 Mar 10.
The asymmetric total syntheses of the natural products (+)- and (-)-frondosin B and (+)-frondosin A are reported based on a diastereoselective cycloaddition between tetrabromocyclopropene and an annulated furan to provide a highly functionalized common building block. The bridged bicyclic intermediate could be stereo- and chemoselectively manipulated to produce the two structurally distinct members of the frondosins. Both syntheses feature regioselective palladium-coupling reactions and an unprecedented phosphine-mediated ether bridge cleavage. Surprisingly, the planned enantioselective synthesis of frondosin B led to the opposite epimer of the natural product, suggesting an unusual late stage stereoinversion at C8. Frondosin A, but not frondosin B, was shown to have selective antiproliferative activity against several B-cell lines.
报道了天然产物 (+)-和 (-)-frondosin B 以及 (+)-frondosin A 的不对称全合成，其基于四溴环丙烯和稠合呋喃之间的立体选择性环加成，提供了一个高度官能化的通用构建块。桥环双环中间体可以进行立体和化学选择性操作，从而产生 frondosins 两个结构不同的成员。两个合成都具有区域选择性钯偶联反应和前所未有的膦介导的醚键断裂。令人惊讶的是，计划中的 frondosin B 的对映选择性合成导致了与天然产物相反的差向异构体，表明 C8 处存在不寻常的晚期立体反转。Frondosin A（而非 frondosin B）显示出对几种 B 细胞系的选择性抗增殖活性。
