pseudolaric-acid-a and carbene

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.

Topics: Antifungal Agents; Antineoplastic Agents; Catalysis; Combinatorial Chemistry Techniques; Cyclization; Diterpenes; Hydrocarbons; Indicators and Reagents; Methane; Models, Molecular; Stereoisomerism