ABSTRACT
Radical and transition metal-catalyzed cascade cyclization strategies were investigated with respect to the synthesis of the tetracyclic core of the augustamine-type Amaryllidaceae alkaloids. These studies resulted in the synthesis of noraugustamine and the development of an oxidative Heck/aza-Wacker cascade forming two rings, a C-N bond, and an all-carbon quaternary center in a single step.
Subject(s)
Amaryllidaceae Alkaloids , Amaryllidaceae Alkaloids/chemistry , Cyclization , Molecular Structure , Oxidation-Reduction , Oxidative StressABSTRACT
An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI2-mediated cyclization to establish the eight-membered ring and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.