Enantioselective Total Synthesis of (-)-Napyradiomycin A1 via Asymmetric Chlorination of an Isolated Olefin

摘要

Halogenated natural products are currently recognized to be a large class of agents dispersed throughout Nature, often possessing unique structures and potent biological activity. One such group is the napyradiomycins (1-3, Figure 1), compounds isolated from terrestrial strains of Streptomyces bacteria and characterized by spectroscopic, degradative, and X-ray crystallographic means. Indeed, apart from the synthetic challenges that their polycyclic frameworks are likely to provide, especially in light of their halogenation pattern, these agents have intriguing biological profiles, including activity as nonsteroidal estrogen antagonists. More recently, Fenical et al. described the isolation and characterization of a group of compounds, such as 4, from a marine source of Streptomyces bacteria that possess the napyradiomycin architecture plus an added aryl methyl group.