Two new highly oxygenated hexacyclic cyclopiazonic acid (CPA) alkaloids, speradines B and C (1 and 2), together with one new related tetracyclic oxindole alkaloid, speradine D (3), were isolated from the sponge derived fungus Aspergillus flavus MXH-X104. Among them, speradine C (2) possesses unprecedented 6/5/6/5/5/6 hexacyclic ring system and 4-oxo-1, 3-oxazinane ring. The structures including absolute configurations of 1-3 were deduced from the spectroscopic data, X-ray diffraction analysis and the computational method including the calculation of the chemical shifts and the electronic circular dichroism (ECD) spectra. (C) 2015 Elsevier Ltd. All rights reserved.