Biotransformation of natural compounds. Oxido-reduction of Sch-642305 by Aspergillus ochraceus ATCC 1009

Sch-642305 is the major compound produced by the endophytic fungi Phomopsis sp. CMU-LMA . Incubation of Sch-642305 with Aspergillus ochraceus ATCC 1009 resting cells leads to three new derivatives through an oxido-reduction of the six-membered ring of the molecule. Reduction of the double bound leads to compound ( 1 ), which subsequently undergoes carbonyl reduction to ( 2 ) and ring hydroxylation to ( 3 ). According to the previously solved crystal structure of Sch-642305 coupled with 1 H NMR NOE correlation and the crystal structure of compound 1 , the absolute configurations of the new derivatives were established. In contrast to the parent compound Sch-642305, compound ( 1 ) exhibits antimicrobial activity against Gram-negative bacteria. Furthermore, while all derivatives exhibit cytotoxic activity against various cancer cell lines, compound ( 2 ) achieved an IC 50 of 4 nM against human myelogenous leukemia K 562, compared to 20 nM for the parent Sch-642305.