Total synthesis of a chlorosulpholipid cytotoxin associated with seafood poisoning.
Each year, there are many cases of seafood poisoning in humans worldwide. Among the various toxins isolated that contribute to these poisonings, the chlorosulpholipids are particularly intriguing because of their structural and stereochemical complexity. The mechanism of biological activity remains unknown and, although chlorosulpholipids are associated with membranes in the organisms from which they are isolated, little is understood about their role within biological membranes. The lack of availability of the natural products has impaired more in-depth biochemical studies. So far, none of the chlorosulpholipids have been obtained from total synthesis, and efficient routes to their synthesis would be desirable for the preparation of material for pharmacological characterization and proper evaluation of the risk to human health. Despite the notable advances in the science of organic synthesis, reliable methods for stereoselective construction of polychlorinated acyclic substrates are lacking, although some preliminary investigations have appeared. Here we report the synthesis of a chlorosulpholipid cytotoxin, leading to confirmation of the proposed structure and the discovery of unanticipated reactivity of polychlorinated hydrocarbons. The concise synthetic approach should enable the preparation of material in sufficient quantities to facilitate biological studies.
Nilewski
Christian
C
Laboratorium für Organische Chemie, ETH Zürich, CH-8093 Zürich, Switzerland.
Geisser
Roger W
RW
Carreira
Erick M
EM
D000438:Alcohols / Q000737:chemistry; D002713:Chlorine / Q000737:chemistry; D036841:Ciguatera Poisoning / Q000139:chemically induced*; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry; D056890:Eukaryota / Q000737:chemistry / Q000166:cytology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D015394:Molecular Structure
D000438:Alcohols; D003603:Cytotoxins; D004852:Epoxy Compounds; D006843:Hydrocarbons, Chlorinated; D008055:Lipids; D002713:Chlorine