Total Synthesis of Hybocarpone and Analogues Thereof. A Facile Dimerization of Naphthazarins to Pentacyclic Systems

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• 作者：K. C. Nicolaou and David L. F. Gray
• 刊名：Journal of the American Chemical Society
• 出版年：2004
• 出版时间：January 21, 2004
• 年：2004
• 卷：126
• 期：2
• 页码：607 - 612
• 全文大小：189K
• 年卷期：v.126,no.2(January 21, 2004)
• ISSN：1520-5126

文摘

The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and related compoundsis described. The successful route to hybocarpone features a novel radical-based dimerization/hydrationcascade which generates the bridging hindered carbon-carbon bond of the molecule in a stereocontrolledmanner, setting the relative configurations of the four contiguous stereocenters in a single step. Theconjecture is made that this process may not be so dissimilar to the biosynthetic pathway leading to theformation of hybocarpone in nature. The developed sequence to these molecular frameworks also featuresthe 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 efficientroute to hydroxynaphthoquinone-type structures represented by the monomeric subunit of the naturalproduct.