Convergent Strategy for the Pamamycin Macrodiolides: Total Synthesis of Pamamycin-607, Pamamycin-593, and Pamamycin-621D Precursors

A convergent total synthesis of pamamycin‐607 (1), isolated from Streptomyces alboniger, was achieved by an E–Z isomerization of a tetrahydrofuran alkylidene and a regio‐ and diastereoselective solvent‐dependent cyclo‐C6H11BCl/Et3N‐mediated aldol reaction as the key steps. The second key step was extended to other ketones, opening the route to new pamamycin macrodiolides, for example, pamamycin‐593 and pamamycin‐621D.