Nicolaou K C, Gray David L F
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2004 Jan 21;126(2):607-12. doi: 10.1021/ja030497n.
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.
本文描述了地衣衍生的抗肿瘤药物扁蒴藤素（1）及相关化合物的全合成。成功合成扁蒴藤素的路线具有一种新型的基于自由基的二聚化/水合级联反应，该反应以立体控制的方式生成分子中的桥连受阻碳-碳键，一步确定了四个相邻立体中心的相对构型。据推测，这个过程可能与自然界中导致扁蒴藤素形成的生物合成途径并无太大差异。这些分子骨架的合成路线还首次展示了一种合成上有用的狄尔斯-阿尔德反应，即利用光化学产生的羟基邻醌二甲烷物种与1,1-二取代烯烃捕获形成一个季碳中心，并且包括一条通向以天然产物单体亚基为代表的羟基萘醌型结构的有效路线。
