Pentacyclic Furanosteroids: The Synthesis of Potential Kinase Inhibitors Related to Viridin and Wortmannolone

A regiocontrolled intermolecular Diels−Alder reaction of an o-benzoquinone followed by an intramolecular nitrile oxide cyclization is employed to prepare the BCD fragment of viridin. The AE segment is attached to it by means of an intramolecular Diels−Alder reaction of an o-benzoquinone monoketal generated in situ from tricycle 15 and 5-trimethylsilyl-2E,4E-pentadienol 20. The silyl substituent at C-1 of the pentacyclic product directs the dihydroxylation of the C2−C3 double bond to its β-face. Various transformations of the 1α-trimethylsilyl-2β,3β-dihydroxy pentacycle into several others with oxygen substituents in ring A are described. One of these products 40 possesses the same structure and relative stereochemistry in rings A, B, and E as that of the natural product wortmannolone 3.

本研究通过先进行区域选择性分子间邻苯醌（o-benzoquinone）狄尔斯-阿尔德（Diels−Alder）反应，再实施分子内腈氧化物环化，成功制备了绿黄菌素（viridin）的BCD片段。随后通过由三环15与5-三甲基硅基-2E,4E-戊二烯醇20原位生成的邻苯醌单缩酮的分子内狄尔斯-阿尔德反应，将AE片段连接至该BCD片段之上。该五环产物C1位的硅基取代基可引导C2-C3双键的二羟基化反应优先发生于β面。本文还报道了1α-三甲基硅基-2β,3β-二羟基五环化合物向多种A环带有氧取代基的五环衍生物的各类转化反应。其中产物40的A、B、E环的结构与相对立体化学，与天然产物渥曼青霉素酮（wortmannolone）3完全一致。