Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
J Am Chem Soc. 2011 May 18;133(19):7260-3. doi: 10.1021/ja200034b. Epub 2011 Jan 31.
Lomaiviticins A and B are complex antitumor antibiotics that were isolated from a strain of Micromonospora. A confluence of several unusual structural features renders the lomaiviticins exceedingly challenging targets for chemical synthesis. We report an 11-step, enantioselective synthetic route to lomaiviticin aglycon. Our route proceeds by late-stage, stereoselective dimerization of two equivalent monomeric intermediates, a transformation that may share parallels with the natural products' biosyntheses. The route we describe is scalable and convergent, and it lays the foundation for determination of the mode of action of these natural products.
洛马维丁 A 和 B 是从一株 Micromonospora 中分离得到的复杂抗肿瘤抗生素。多种不寻常结构特征的融合使得洛马维丁类化合物成为化学合成极具挑战性的目标。我们报告了洛马维丁苷元的 11 步对映选择性合成路线。我们的路线通过两个等效的单体中间体的晚期立体选择性二聚化进行，该转化可能与天然产物的生物合成具有相似之处。我们描述的路线是可扩展的和收敛的，为确定这些天然产物的作用模式奠定了基础。
