Synthetic Studies toward (−)-Cleistenolide: Highly Stereoselective Synthesis of New γ-Lactone Subunits

Journal of the Brazilian Chemical Society

article

Sartori, Suélen K.¹  Miranda, Izabel L.²  Matos, Davi A. de²  Kohlhoff, Markus³  Diaz, Marisa A. N.⁴  Diaz-Muñoz, Gaspar² 

[1] Laboratório de Aditivos Poliméricos para Produção de Petróleo, Universidade Federal do Rio de Janeiro;Departamento de Química, Universidade Federal de Minas Gerais;Instituto René Rachou;Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa

关键词: (−)-cleistenolide;    γ-lactone;    diacetonide diol;    d-mannitol;   

DOI  :  10.21577/0103-5053.20200227

学科分类：内科医学

来源: SciELO

【 摘 要 】

This study describes the stereoselective synthesis of two new γ-lactones in 6 and 3 steps and 19 and 32% yield, respectively, directed toward the total synthesis of the natural product (−)-cleistenolide. The starting material was an enantiomerically pure diacetonide diol, derived from d-mannitol with the required stereocenters for (−)-cleistenolide synthesis. γ-Lactone syntheses were based on highly selective protection and deprotection of hydroxyls from d-mannitol. The formation of γ-lactone rings was the culmination of this approach, made possible by a Horner-Wadsworth-Emmons Z -olefination between diacetal aldehyde and ethyl 2-(bis( o -tolyloxy)phosphoryl)acetate to produce an unsaturated ester. The Z -isomer ester was highly favored in relation to the E -isomer ( Z/E ratio of 94:6), allowing the formation of the γ-lactone ring under acid catalysis. This strategy precluded the use of chiral auxiliaries or catalysts for the control of stereocenters in the novel γ-lactones.

【 授权许可】

CC BY