摘要：

A stereocontrolled and asymmetric synthesis of 5-O-carbamoylpolyoxamic acid (2), the major acyclic component of the polyoxin family of antifungal antibiotics, is reported. The sequence began with an erythro-selective addition of vinylmagnesium bromide to the oxazolidine aldehyde 6 (prepared from D-serine) to give the secondary allylic alcohols 7/8. The derived urethane 12 underwent clean allylic rearrangement upon exposure to PdCl2(MeCN)2, yielding the primary allylic urethane 13. Mild acidic methanolysis then gave the homoallylic alcohol 14, which was shown to be configurationally pure by a Mosher ester analysis. Oxidation of 14 with KMnO4 under CO2-buffered conditions gave a mixture of lactols 19/20. Further oxidation of these lactols with N-bromourea yielded a (2.5:1) mixture of γ-lactones 21 and 22 which was purified by chromatography and crystallization. Treatment of 21 with trifluoroacetic acid resulted in quantitative formation of lactone salt 23, whereas hydrolysis of 21 with aqueous HCl gave 25 (=2·HCl) directly.

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