Melithiazols A–N: New Antifungal β‐Methoxyacrylates from Myxobacteria

Abstract

From cultures of Melittangium lichenicola, Archangium gephyra and Myxococcus stipitatus, thirteen new β-methoxyacrylate (MOA) fungicides related to myxothiazols (1) have been isolated. Melithiazols A (2a), D (2b), K (2c), and L (2d) are characterized by a thiazoline–thiazole system, whereas melithiazols B (3a), E (3b), F (3c), G (3d), H (3e), I (3f), M (3g), and N (3h) are bis(thiazoles). Melithiazol C (4), as the first representative of this class of compounds, contains only one thiazole ring. The structures were established on the basis of spectroscopic data, and confirmed in the case of melithiazol E (3b), including its relative configuration, by an X-ray structure analysis. The absolute configuration of melithiazols A (2a) and B (3a) was determined by degradation and CD spectroscopy. Antifungal and cytotoxic activities, inhibition of NADH oxidation, and lipophilicities of melithiazols 2–4, myxothiazols 1, and strobilurin-type compounds are compared.