title: A tandem metal carbene cyclization-cycloaddition approach to the pseudolaric acids.
abstract: An approach toward the synthesis of the antifungal and cytotoxic pseudolaric acids based on the tandem metal carbene cyclization-cycloaddition reaction is described. Using this strategy, the advanced intermediate 3a bearing three of the four stereocenters of the target molecules has been synthesized. The substrate-controlled diastereoselectivity of the tandem carbene cyclization-cycloaddition was preferential for the undesired diastereomer, but reagent control through the use of Hashimoto's chiral rhodium catalyst Rh(2)(S-BPTV)(4) reversed the selectivity in favor of 3a. Ring opening of the oxabicyclic nucleus to give a hydroxycycloheptene has been demonstrated in a model study.
authors.affiliation: Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Rebecca Y Y
authors.initials: RY
authors.lastname: Ko
authors.forename: Mabel S M
authors.initials: MS
authors.lastname: Yuen
authors.forename: Kin-Fai
authors.initials: KF
authors.lastname: Cheng
authors.forename: Pauline
authors.initials: P
authors.lastname: Chiu
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D006838:Hydrocarbons; D007202:Indicators and Reagents; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry*; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004224:Diterpenes; D006838:Hydrocarbons; D007202:Indicators and Reagents; C030011:carbene; C058391:pseudolaric acid B; C058390:pseudolaric acid A; D008697:Methane