Total Syntheses of (+)-Ineleganolide and (-)-Sinulochmodin C

Described herein are the first total syntheses of the nor-furanocembranoid natural products (+)-ineleganolide (1) and (-)-sinulochmodin C (2). The synthetic strategy is predicated on a transannular Michael reaction that provides both natural products from a common macrocyclic intermediate and leverages a diastereoselective radical cyclization to furnish a key bicyclic lactone. The latter is further advanced to a macrocyclic precursor via a Nozaki-Hiyama-Kishi cyclization and a one-pot furan oxidation/oxa-Michael cascade. Unexpected stereochemical nuances that guided the evolution and eventual completion of the total synthesis are discussed.

Automated summary

This article describes the first total syntheses of the nor-furanocembranoid natural products (+)-ineleganolide and (-)-sinulochmodin C. The synthetic strategy is based on a transannular Michael reaction and a diastereoselective radical cyclization, and discusses the unexpected stereochemical nuances during the evolution and completion of the total synthesis.