Stereospecific synthesis of the CP-263,114 core structure
Stereospecific synthesis of the CP-263,114 core structure
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DOI：
10.1021/ja982581m
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发表时间：
1998-10-21
影响因子：
15
通讯作者：
Shair, MD
中科院分区：
文献类型：
--
作者：
Chen, C;Layton, ME;Shair, MD
CP-263，114（1）是一种真菌代谢产物，作为鉴定Ras法尼基转移酶3和角鲨烯合酶4抑制剂计划的一部分而被分离1，2（图1）。有人提出，1是一个成员的nonadride类的天然产物;特别是，它的结构相似的蓝桉酸（2）指出。1b，5两种结构的检查表明，C10和C26之间的跨环键形成以产生1的核心骨架可能是可行的，从九元环中间体。本文详细介绍了一种新的双环成环反应，该反应涉及跨环环化，导致CP-263，114核心结构的快速立体特异性合成。组装九元环烯醇化物及其跨环酰化的合成方案概述于方案1中。设想将乙烯基有机金属（4）加成到β-酮酯3上将生成醇盐5，其在阴离子加速的氧-Cope重排之后将导致九元环烯醇化物6。中间体6的跨环烯醇化物酰化得到7（1的核心结构）将代表类似于所提出的C10 → C26生物合成环化的反应。1b通过用Pb（OAc）4（CHCl 3，25 ℃）处理乙烯基锡烷96，然后将中间体乙烯基铅试剂暴露于β-酮酯8来开始合成（方案2
CP-263,114 (1) is a fungal metabolite that was isolated1, 2 as part of a program to identify inhibitors of Ras farnesyltransferase3 and squalene synthase4 (Figure 1). It has been proposed that 1 is a member of the nonadride class of natural products; in particular, its structural similarity to glaucanic acid (2) was noted. 1b, 5 Inspection of the two structures suggests that transannular bond formation between C10 and C26 to generate the core skeleton of 1 may be feasible from a nine-membered-ring intermediate. This paper details a new bicyclic ring-forming reaction involving a transannular cyclization that has resulted in a rapid, stereospecific synthesis of the CP-263,114 core structure.The synthetic plan for assembling the nine-membered-ring enolate and its transannular acylation is outlined in Scheme 1. It was envisaged that addition of a vinyl organometallic (4) to β-ketoester 3 would generate alkoxide 5 that, following an anionaccelerated oxy-Cope rearrangement, would lead to nine-memberedring enolate 6. Transannular enolate acylation of intermediate 6 to afford 7, the core structure of 1, would represent a reaction similar to the proposed C10 f C26 biosynthetic cyclization. 1b The synthesis was initiated (Scheme 2) by treatment of vinylstannane 96 with Pb (OAc) 4 (CHCl3, 25 C) followed by exposure of the intermediate vinyllead reagent to β-ketoester 8