Total synthesis of hybocarpone and analogues thereof. A facile dimerization of naphthazarins to pentacyclic systems
Total synthesis of hybocarpone and analogues thereof. A facile dimerization of naphthazarins to pentacyclic systems
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DOI：
10.1021/ja030497n
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发表时间：
2004-01-21
影响因子：
15
通讯作者：
Gray, DLF
中科院分区：
文献类型：
--
作者：
Nicolaou, KC;Gray, DLF
描述了地衣衍生的抗肿瘤药物氢卡波酮(1)及其相关化合物的全合成。一种新颖的基于自由基二聚化/水合的级联反应，以立体控制的方式生成分子的桥接受阻的碳-碳键，一步完成四个连续立体中心的相对构型。推测这一过程可能与自然界中导致羟基卡波酮形成的生物合成途径没有太大不同。所开发的这些分子骨架的序列还包括第一个合成有用的Diels-Alder捕获具有1，1-二取代烯烃的光化学生成的羟基-邻奎诺二甲烷物种以形成四元中心的例子，并且包括一条由天然产物的单体亚单位代表的羟基萘并苯型结构的有效途径。
The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and related compounds is described. The successful route to hybocarpone features a novel radical-based dimerization/hydration cascade which generates the bridging hindered carbon-carbon bond of the molecule in a stereocontrolled manner, setting the relative configurations of the four contiguous stereocenters in a single step. The conjecture is made that this process may not be so dissimilar to the biosynthetic pathway leading to the formation of hybocarpone in nature. The developed sequence to these molecular frameworks also features the first example of a synthetically useful Diels-Alder trapping of a photochemically generated hydroxy-o-quinodimethane species with a 1,1-disubstituted olefin to form a quaternary center, and includes an efficient route to hydroxynaphthoquinone-type structures represented by the monomeric subunit of the natural product.