A tandem metal carbene cyclization-cycloaddition approach to the pseudolaric acids.
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.
Chen
Bin
B
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.
Ko
Rebecca Y Y
RY
Yuen
Mabel S M
MS
Cheng
Kin-Fai
KF
Chiu
Pauline
P
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
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