Total synthesis of myxothiazols, novel bis-thiazole β-methoxyacrylate-based anti-fungal compounds from myxobacteria

Abstract

Convergent total syntheses of myxothiazols A and Z are described. The syntheses are based on elaboration of the (S)-E,E-diene thioamide 22, conversion of 22 into the bis-thiazole 27 and Wittig reactions between 27c and the aldehyde 30. The substituted β-methoxyacrylate aldehyde 30 was produced via an Evans asymmetric aldol protocol or via the 2H-pyran-2-one 31. An E-selective Wittig reaction between the ylide derived from the phosphonium salt 27c and the (+)-aldehyde 30 led to (+)-myxothiazol Z (1b), and a corresponding reaction with the (±)-acrylamide aldehyde 44 gave (±)-myxothiazol A (1a). Complementary studies led to synthesis of the ester 47b, corresponding to myxothiazol R and myxothiazol S.