Stereoselective Total Syntheses of Chlorosulfolipids

Chlorosulfolipids (CSLs) represent an unusual family of natural products that were first isolated from the freshwater alga Ochromonas danica in the 1960s. They have drawn considerable attention as substances of toxicological concern, because some of them display modest cytotoxic activity and are associated with seafood poisoning. CSLs are unique in featuring hydrocarbon framework which possess chlorine-substituted multiple stereogenic centers. Due to the unprecedented structure and interesting biological activity of CSLs, this fascinating class of natural products has recently garnered interest as targets of total synthesis and inspired methodology for stereoselective chlorination. In 2009, Carreira accomplished the total synthesis of hexachlorosulfolipid. After this total synthesis, other three groups including our group have achieved total syntheses of CSLs: Malhamensilipin A and danicalipin A by Vanderwal, hexachlorosulfolipid and danicalipin A by Yoshimitsu and Tanaka, and danicalipin A by authors. This review deals with these total syntheses of CSLs, focusing the development of synthetic methods to stereoselectively incorporate acyclic polychlorinated arrays into hydrocarbon skeletons of CSLs.