Cytochalasins from an Australian marine sediment-derived Phomopsis sp. (CMB-M0042F) : acid-mediated intramolecular cycloadditions enhance chemical diversity

Chemical analysis of an Australian coastal marine sediment-derived fungus, Phomopsis sp. (CMBM0042F), yielded the known cytochalasins J (1) and H (2), together with five new analogues, cytochalasins J1−J3 (3−5) and H1 and H2 (6 and 7). Structures of 1−7 were assigned on the basis of detailed spectroscopic analysis, chemical interconversion, and biosynthetic and mechanistic considerations. Of note, 1 and 2 proved to be highly sensitive to acid-mediated transformation, with 1 affording 3−5 and 2 affording 6 and 7. Whereas 1, 2, 4, and 5 were detected as natural products in crude culture extracts, 3, 6, and 7 were designated as acid-mediated handling artifacts. We propose novel stereoand regiospecific intramolecular cycloadditions, under tight functional group control, that facilitate selective conversion of 1 and 2 to the rare 5/6/6/7/5- and 5/6/5/8-fused heterocycles 5 and 7, respectively. Knowledge of acid sensitivity within the cytochalasin family provides a valuable cautionary lesson that has the potential to inform our analysis of past and future investigations into this structure class and inspire novel biomimetic transformations leading to new chemical diversity.