Asymmetric Synthesis of Synargentolide A and Its 3-Epimer Using the RAMP-Hydrazone Methodology

Abstract

Synargentolide A was synthesized in 11 steps starting from the commercially available 2,2-dimethyl-1,3-dioxan-5-one, employing the SAMP/RAMP-methodology via an α,α′-bis-alkylation to generate the first two stereogenic centers with virtually complete asymmetric induction (de, ee >99%). After the asymmetric synthesis of the triol fragment of the molecule, the δ-lactone moiety was constructed using an asymmetric allylation, esterification, and ring-closing metathesis sequence.

Key words

total synthesis - natural products - metathesis - hydrazones - asymmetric synthesis

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