Total Synthesis and Bioactivity Profile of (+)-Ieodomycins A and B and their Stereoisomers.

Herein, we report the first- and second-generation syntheses of (+)-ieodomycins A and B and their stereoisomers via the late-stage elaboration of their conjugated -diene side chains. Key steps for successful synthesis included Keck asymmetric allylation to introduce a hydroxyl group at the C5 position, consecutive Wipf's carboalumination modification, iodination, Sharpless asymmetric dihydroxylation, one-carbon homologation via cyanation, Mukaiyama lactonization, and Stille cross-coupling to form the conjugated -diene moiety. Further, the preliminary bioactivity profile against various disease-related molecular targets and cell lines was investigated. Results indicated that compounds and , diastereoisomers of (+)-ieodomycin B (), serve as α-glucosidase inhibitors, while compounds and inhibit the angiotensin-converting enzyme.