Iso-Migrastatin Congeners from Streptomyces platensis and Generation of a Glutarimide Polyketide Library Featuring the Dorrigocin, Lactimidomycin, Migrastatin, and NK30424 Scaffolds

Abstract

Iso-Migrastatin (10) has been shown to be the main natural product of Streptomyces platensis, which undergoes a facile, H₂O-mediated rearrangement into dorrigocin A (2), 13-epi-dorrigocin A (11), dorrigocin B (3), and migrastatin (1). Eight new congeners (12−19) of 10 were characterized. They can undergo the same H₂O-mediated rearrangement into the corresponding 1, 2, 3, and 11 analogues (20−43) or 1,4-Michael addition with cysteine to afford the corresponding analogues (44−51) of NK30424 A and B (5, 6). This study generated a 47-member library of glutarimide polyketides, setting the stage to investigate the SAR for this family of natural products. These results also established the absolute stereochemistry of 5 and 6 and shed new light into the post-polyketide synthase steps for 10 biosynthesis.