A cycloaddition cascade approach to the total synthesis of (-)-FR182877
A cycloaddition cascade approach to the total synthesis of (-)-FR182877
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DOI：
10.1021/ja037643
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发表时间：
2003-11-05
影响因子：
15
通讯作者：
Starr, JT
中科院分区：
文献类型：
--
作者：
Evans, DA;Starr, JT
已实现细胞毒性天然产物 (-)-FR182877 (1) 的不对称合成。使用两个 (4R)-4-苄基-2-恶唑烷酮介导的硼羟醛反应确定了整个结构的手性。通过使用区域选择性 Suzuki 偶联 (17 + 23 --> 26; 84%) 偶联两个片段以及 β-酮酯大环化 (30 - 31; 77%) 合成 19 元大碳环。 31 的氧化引发了一系列立体选择性跨环狄尔斯-阿尔德反应 (32 --> 34; 63%)，在关键的构建事件中形成四个新环和七个新立体中心。随后将该五环中间体转化为(-)-FR182877。对跨环狄尔斯-阿尔德环加成级联进行半经验计算以确定不对称诱导的起源。
An asymmetric synthesis of the cytotoxic natural product, (-)-FR182877 (1), has been achieved. Chirality for the entire structure was established using two (4R)-4-benzyl-2-oxazolidinone-mediated boron aldol reactions. A 19-membered macrocarbocycle was synthesized by the coupling of two fragments using a regioselective Suzuki coupling (17 + 23 --> 26; 84%) and macrocyclization of a beta-keto ester (30 - 31; 77%). Oxidation of 31 triggered a sequence of stereoselective transannular Diels-Alder reactions (32 --> 34; 63%) forming four new rings and seven new stereocenters in the pivotal construction event. This pentacyclic intermediate was subsequently transformed to (-)-FR182877. Semiempirical calculations of the transannular Diels-Alder cycloaddition cascade were carried out to determine the origins of asymmetric induction.