First Total Synthesis of Pamamycin-621D

Pamamycin-621D, a member of a large family of macrodiolides with antimycobacterial properties, has been synthesized and fully characterized for the first time. A convergent and flexible strategy based on a key aldol coupling delivered this less abundant pamamycin congener. Furthermore, the synthesis of a new unsaturated precursor using cross-metathesis was developed in order to suppress regioselectivity issues in the aldol coupling step.