title: Total synthesis of tetrahydrolipstatin and stereoisomers via a highly regio- and diastereoselective carbonylation of epoxyhomoallylic alcohols.
abstract: A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid](+)[Co(CO)4](-) catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone. The success of this route to THL and its stereoisomers also demonstrated the practicality of the carbonylation catalyst for complex molecule synthesis as well as its functional group compatibility.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Mulzer
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Tiegs
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Coates
authors.forename: George A
authors.initials: GA
authors.lastname: O'Doherty
mesh_terms: D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D000077403:Orlistat; D020005:Propanols / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D007783:Lactones; D020005:Propanols; C006463:allyl alcohol; D000077403:Orlistat