Synthesis and complete stereochemical assignment of psymberin/irciniastatin A
Synthesis and complete stereochemical assignment of psymberin/irciniastatin A
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DOI：
10.1021/ja0537068
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发表时间：
2005-08-17
影响因子：
15
通讯作者：
De Brabander, JK
中科院分区：
文献类型：
--
作者：
Jiang, X;García-Fortanet, J;De Brabander, JK
我们描述了一种简洁而灵活的合成途径，用于制备具有与新型海洋来源的差异性细胞毒素psymberin和irciniastatin A的结构相关的结构的化合物。我们的努力导致他们的完整的立体化学分配和概念，Psymberin和irciniastatin A是相同的化合物。我们的全合成的特点是一个有趣的终端分化lactolization从aC 2-对称的双烯烃前体，一个温和的铂催化水解的epimerizable腈，一个新的协议，以制备敏感的甲基亚胺酯，和一锅转换这些亚胺到N-酰基胺醛得到的二醛。从片段5 - 7（每步7 - 8步制备，总收率30 - 49%）开始，以额外的9步和30%的收率（17步最长的线性序列，总收率8.9%）完成了Psymberin/irciniastatin A的合成。
We describe a concise and flexible synthetic avenue for the preparation of compounds with structures relevant to those proposed for the novel marine-derived differential cytotoxins psymberin and irciniastatin A. Our efforts led to their complete stereochemical assignment and the notion that psymberin and irciniastatin A are identical compounds. Our total synthesis features an interesting termini-differentiating lactolization of a dialdehyde obtained from aC2-symmetrical bis-olefin precursor, a mild platinum-catalyzed hydrolysis of an epimerizable nitrile, a novel protocol to prepare sensitive methyl imidates, and a one-pot conversion of these imidates toN-acyl aminals. Starting from fragments5−7(prepared in 7−8 steps each, 30−49% overall yield) the synthesis of psymberin/irciniastatin A was completed in an additional 9 steps and 30% yield (17 steps longest linear sequence, 8.9% overall).