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

• Autor(a) principal: Sartori,Suélen K.
• Data de Publicação: 2021
• Outros Autores: Miranda,Izabel L., Matos,Davi A. de, Kohlhoff,Markus, Diaz,Marisa A. N., Diaz-Muñoz,Gaspar
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532021000400757
• topic: (−)-cleistenolide; γ-lactone; diacetonide diol; d-mannitol

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.