Larrosa Igor, Da Silva Marianne I, Gómez Patricio M, Hannen Peter, Ko Eunjung, Lenger Steven R, Linke Simon R, White Andrew J P, Wilton Donna, Barrett Anthony G M
Department of Chemistry, Imperial College London, London SW7 2AZ, England.
J Am Chem Soc. 2006 Nov 1;128(43):14042-3. doi: 10.1021/ja0662671.
The first total synthesis of (+)-clavilactone B, a potent antifungal agent and novel tyrosine kinase inhibitor, is described. The absolute configuration of clavilactones has been unambiguously established by using Sharpless asymmetric epoxidation to generate the enantiomerically pure substrate. The strategy highlights the use of a powerful and convergent three-component benzyne coupling with a methylallyl Grignard and a chiral epoxy-aldehyde to generate two C-C bonds and install the carbon skeleton of clavilactone. Oxidative lactonization, ten-membered ring construction by ring closing metathesis, and oxidation gave clavilactone B.
本文描述了强效抗真菌剂及新型酪氨酸激酶抑制剂（+）-克拉维内酯B的首次全合成。通过使用夏普莱斯不对称环氧化反应生成对映体纯的底物，明确确定了克拉维内酯的绝对构型。该策略的亮点在于使用强大且收敛的三组分苯炔偶联反应，与甲基烯丙基格氏试剂和手性环氧醛反应，生成两个C-C键并构建克拉维内酯的碳骨架。氧化内酯化、通过闭环复分解反应构建十元环以及氧化反应得到了克拉维内酯B。
