Open AccessSynthetic Studies toward (−)-Cleistenolide: Highly Stereoselective Synthesis of New γ-Lactone Subunits
Author(s) -
Suélen K. Sartori,
Izabel L. Miranda,
Davi A. de Matos,
Markus Kohlhoff,
Marisa Alves Nogueira Diaz,
Gaspar Diaz-Muñoz
Publication year - 2021
Publication title -
journal of the brazilian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.337
H-Index - 70
eISSN - 1678-4790
pISSN - 0103-5053
DOI - 10.21577/0103-5053.20200227
Subject(s) - stereocenter , lactone , stereoselectivity , chemistry , aldehyde , d mannitol , catalysis , diol , stereochemistry , yield (engineering) , organic chemistry , enantioselective synthesis , mannitol , materials science , metallurgy
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.