Cladocladosin A, an unusual macrolide with bicyclo 5/9 ring system, and two thiomacrolides from the marine mangrove-derived endophytic fungus, Cladosporium cladosporioides MA-299

Abstract

A simple but previously undescribed macrolide with unprecedented bicyclo 5/9 ring system, namely, cladocladosin A (1), along with two new sulfur-containing macrolides, namely, thiocladospolides F and G (2 and 3), were characterized from the mangrove-derived endophytic fungus Cladosporium cladosporioides MA-299. The structures of these compounds were established on the basis of spectroscopic interpretation, and the absolute configurations of compounds 1–3 were determined by X-ray crystallographic analysis, Mosher’s method, and by a biogenetic point of view. The possible biogenetic pathway for compounds 1–3 as well as their congeners thiocladospolides A–D and pandangolide 3 was proposed, providing a role in distinguishing the position of sulfur substitution in thiomacrolides. Compounds 1–3 were evaluated for antimicrobial activities against human-, aquatic-, and plant-pathogenic microbes.