Total synthesis of LC-KA05, the proposed structure of LC-KA05-2, and 2,18-seco-lankacidinol B: A quest to revisit lankacidin biosynthesis

Abstract

Abstract We described here the evolution of an iterative aldolization/late-stage cross-coupling strategy for the construction of the polyketide backbones of several non-macrocyclic lankacidins. Selective functionalization of C7-triethylsilyl ether and an end-game fluoride-mediated global desilylation under oxygen-free conditions enabled the first total synthesis of biosynthetic intermediate LC-KA05 (1). A synthesis of its C7-deacetylated congener, originally reported to be LC-KA05-2 (2), was also accomplished. However, the discrepancy of the 1H NMR spectrum in the C1–C7 lactonic portions between our synthetic material and the reported data indicated a need for structural revision. Moreover, the syntheses of the revised structure of 2,18-seco-lankacidinol B (5) and its C4,C5,C7-tris-epimer 54 were also conducted. The NMR spectra of these two compounds were found to be essentially indistinguishable, while the observed specific optical rotations of both synthetic 5 and 54 were different from that recorded in the original isolation paper.