Total Synthesis of Spirastrellolide A Methyl Ester—Part 2: Subunit Union and Completion of the Synthesis

Authors


  • This work was supported by the EPSRC (GR/C541677/1), Merck Research Laboratories, Homerton College, Cambridge (E.A.A.), SK Corporation (J.H.L.), and the German Academic Exchange Service (C.M.). We thank Prof. R. J. Andersen (University of British Columbia) for an authentic sample of spirastrellolide A methyl ester and for helpful discussions, as well as Dr. J. Davies (Cambridge) for solving the X-ray crystal structure of pentaol 12.

Abstract

original image

Succumbing to synthesis: The stereocontrolled total synthesis of spirastrellolide A methyl ester is reported. The union of two key C1–C16 and C17–C40 subunits is followed by macrolactonization and late-stage side chain attachment by a cross-metathesis reaction and a π-allyl Stille coupling reaction with a C43–C47 stannane, thus confirming the 46R configuration. The full configuration and conformation of the 38-membered macrolide is revealed by single-crystal X-ray analysis of an advanced pentaol intermediate.

Ancillary