Ghosh Arun K, Swanson Lisa
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA.
J Org Chem. 2003 Dec 12;68(25):9823-6. doi: 10.1021/jo035077v.
A highly enantioselective and convergent synthesis of cryptophycin 52 (2), an exceedingly potent cytotoxic agent, is described. Cryptophycin 52, a synthetic variant of the cryptophycin family, is currently undergoing clinical trials. The synthesis is convergent and involves assembly of three fragments, phenyl hexenal 3, d-tyrosine phosphonate 4, and protected beta-amino acid derivative 5. The synthesis of fragment 3 involves an efficient and stereocontrolled construction of both stereogenic centers at C-3 and C-4 by cleavage of a substituted tetrahydrofuran ring via an acyloxycarbenium ion intermediate. Both of these stereogenic centers were derived from optically active 4-phenylbutyrolactone, synthesized enantioselectively by Corey-Bakshi-Shibata reduction.
描述了一种对映体高度选择性且汇聚式的隐藻素52（2）的合成方法，隐藻素52是一种极其有效的细胞毒性剂。隐藻素52是隐藻素家族的一种合成变体，目前正在进行临床试验。该合成是汇聚式的，涉及三个片段的组装，即苯基己烯醛3、d-酪氨酸膦酸酯4和受保护的β-氨基酸衍生物5。片段3的合成涉及通过酰氧基碳鎓离子中间体裂解取代的四氢呋喃环，高效且立体控制地构建C-3和C-4处的两个立体中心。这两个立体中心均源自光学活性的4-苯基丁内酯，通过Corey-Bakshi-Shibata还原对映选择性合成。
