Beta-Lactones as Synthetic Vehicles in Natural Product Synthesis: Total Syntheses of Schulzeines B & C and Omphadiol, and Studies toward the Total Syntheses of Scabrolides A & B and Sinulochmodin C

Abstract

β-Lactones are a class of structurally unique compounds. The versatile reactivity patterns offered by β-lactones have enable chemists to utilize them as powerful synthetic vehicles in complex molecule synthesis. In the total syntheses of the naturally occurring, α-glucosidase inhibitors schulzeines B & C, a readily available trichloromethyl β-lactone was used as a versatile masked surrogate for bishomoserine aldehyde, which led to a highly efficient construction of the core structures through a pivotal Pictet-Spengler condensation and a Corey-Link reaction. The first total synthesis of (+)-omphadiol was achieved in ten steps from (R)-carvone. This synthesis features a three-step synthesis of a bicyclic β-lactone, which constitutes the key intermediate for the highly stereocontrolled introduction of the six contiguous stereogenic centers in the natural product. In efforts toward the total syntheses of scabrolides A & B and sinulochmodin C via transannular C-H insertions, β-lactones served as the key intermediates for the synthesis of complex macrocyclic model substrates. These model studies provided valuable insights into the reactivity and selectivity issues for transannular C-H insertion reactions.