Catalytic Asymmetric Formal Total Synthesis of (-)-Triptophenolide and (+)-Triptolide.

Wen-Dan Xu,Hui-Chun Geng,Hong-Bo Qin,Liang-Qun Li,Ming-Ming Li

doi:10.1007/s13659-016-0100-z

Abstract

Catalytic asymmetric formal synthesis of (−)-Triptophenolide and (+)-Triptolide have been achieved. Key reaction involves Palladium catalyzed asymmetric conjugate addition of aryl boronic acid to 3-methyl cyclohexe-1-none to form quaternary carbon. Claisen rearrangement and subsequent aldol reaction furnished trans-decaline key intermediate, which assured a formal total synthesis of (−)-Triptophenolide and (+)-Triptolide.Graphical Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-016-0100-z) contains supplementary material, which is available to authorized users.

Highlights

Catalytic asymmetric formal synthesis of (-)-Triptophenolide and (?)-Triptolide have been achieved
Preliminary enantioselective synthesis of vinyl iodide was performed and we regard it as a racemic synthesis and will report the first catalytic asymmetric formal total synthesis of (-)-Triptophenolide and (?)-TP, which features a palladium catalyzed conjugate addition of arylboronic acid to cyclic enone to construct all-carbon quaternary stereocenter, followed by new cyclization strategy involving claisen rearrangement [26] and aldol reaction
As illustrated in scheme 1, TP and triptophenolide could be synthesized from tetracycle 3, [28] the butenolide installation could be accomplished from key intermediate tricyclic ketone 4,1 [35,36,37,38] which is accessible by a 3-step transformation including Claisen rearrangement, alkene oxidation and aldol cyclization

Summary

Introduction

Catalytic asymmetric formal synthesis of (-)-Triptophenolide and (?)-Triptolide have been achieved. Keywords Total synthesis Á Catalytic asymmetric Á Triptophenolide Á Triptolide Geng University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China Reports of its total synthesis were available from 1980, [18, 19] and the maximum productivity was reached around 2000 [20,21,22,23].

Results

Conclusion