Biomimetic-inspired synthesis of sporochartines through Diels–Alder reaction between enantiopure (−)-sporothriolide and (+)-trienylfuranol A

Abstract

A biomimetic-inspired synthesis of sporochartines A–D involving a [4 + 2] Diels–Alder cycloaddition between (−)-sporothriolide and (+)-trienylfuranol A is described. For this study, we have realized the first enantiopure total synthesis of (+)-trienylfuranol A, containing an unusual and very sensitive terminal trienyl moiety. In this synthetic study, we have performed for the first time baker's yeast-mediated reduction of α-oxo-γ-butyrolactone derivatives with high stereoselectivities. To improve the enantioselectivity level, an enzymatic kinetic resolution with Amano lipase PS, from Burkholderia cepacia, allowed us to prepare (+)-trienylfuranol A with excellent enantiomeric excess (>99%). A Diels–Alder reaction between the two secondary metabolites (−)-sporothriolide and (+)-trienylfuranol A allowed us to observe the formation of sporochartines in 39% isolated yield. The relative distribution of the sporochartines formed showed a spectacular correlation with that obtained from the fermentation culture of Hypoxylon monticulosum CLL-205 and allowed us to confirm that a Diels–Alder reaction is involved in the biosynthetic pathway for the formation of spiranic backbones of sporochartines.