Asperflavipines C–E and aspermichalasine A: three cytochalasan heterotetramers and an unusual cytochalasan monomer from Aspergillus micronesiensis

Abstract

Asperflavipines C–E (1–3), three new cytochalasan heterotetramers, and aspermichalasine A (4), an unusual cytochalasan monomer, along with other four new cytochalasan monomers (5–8) were isolated from solid cultures of the fungus Aspergillus micronesiensis, and their structures, including absolute configurations, were determined based on HRESIMS, NMR spectra, ECD comparison, molecular modeling analysis, and single-crystal X-ray diffraction techniques. Asperflavipines C–E (1–3), possessing highly complex tetradecacyclic ring systems with continuous bridged ring systems, represent the second examples of cytochalasan heterotetramers besides the previously reported asperflavipine A. Single crystal X-ray diffraction analysis of asperflavipine C (1) in this study provided solid evidence for the intriguing skeleton of the 5/6/11/5/6/5/6/5/6/5/5/11/6/5 ring system in asperflavipines A and C–E for the first time. Aspermichalasine A (4) represents the first example of an aspochalasin possessing an unusual 5/6/5/8 ring system. Compounds 1–3 and 5–8 showed moderate cytotoxicity against four human cancer cell lines, and compound 1 could induce apoptosis in HL60 cells.