Stereoselective Syntheses of trans-Anhydromevalonic Acid and trans-Anhydromevalonyl Group-Containing Natural Products

Abstract

Collective total syntheses of trans-anhydromevalonic acid (tAHMA) and trans-anhydromevalonyl (tAHM) groupcontaining natural products (pestalotiopin A, pestalotiopamide C, pestalotiopamide D, farinomalein E, eleutherazine B, and trichocyclodipeptide A) were achieved using tAHMA esters as key intermediates. To this end, tAHMA tert-butyl ester was newly prepared by Z-vinyltosylation of tert-butyl 3-oxo-5-((triisopropylsilyl)oxy)pentanoate followed by the Negishi cross-coupling reaction with Me 2 Zn. tAHMA esters were converted to the target natural products via esterification or amidation. Comparison of the spectroscopic data of synthetic and natural products confirmed the E-configuration of the tAHM moieties in the natural products.

Confirmation of the structure of (±)-preisomide by total synthesis

“…A simple disconnection yields tetrahydro-1,2-oxazine 2 and E -anhydromevalonic acid 3 (Scheme 1). The reported syntheses of acid 3 and its derivatives are long 5 or proceed with poor control of alkene stereochemistry. 6 We, therefore, developed a shorter and completely stereocontrolled method (Scheme 2).…”