New alkaloids from the diversity-enhanced extracts of an endophytic fungus Aspergillus flavus GZWMJZ-288

Three new alkaloids (1-3) together with four previously reported compounds (4-7) were identified from the extracts and the diversity-enhanced extracts of the fermentation broth of the endophytic fungus, Aspergillus flavus GZWMJZ-288 associated with Garcinia muldflora. The structures of new compounds were respectively determined as 19-amino-19-dehydroxy 5-epi-alpha-cyclopiazonic acid (1), 2-hydroxymethyl-5-(3-oxobutan-2-yl)aminopyran-4(4H)-one (2) and 4-amino-2-hydroxymethylpyridin-5-ol (3) by spectroscopic analysis, ECD calculation and X-ray single crystal diffraction. Compounds 1 and 4 with 19-enamine were dynamic equilibrium of Z- and E-isomers in the solution but favored in Z- isomers in the solid state, while compound 7 with 19-enol was favored in Z- isomer in the solution but a mixture of Z- and E- isomers in solid state. This phenomenon could be explained by the quantum-mechanical energies calculations. Among the isolated compounds 1-7, compounds 1,4 and 7 with a rare 1,3,4,5-tetrahydro-1-azaacenaphtho [3,4-c] pyrrolizidine skeleton showed alpha-glucosidase inhibitory activity with the IC50 values of 41.97 +/- 0.97, 232.57 +/- 11.45 and 243.95 +/- 3.36 mu M, respectively, and the binding modes were performed by silico docking studies.