The Formosalides: Structure Determination by Total Synthesis

Abstract

Total synthesis allowed the constitution of the cytotoxic marine macrolides of the formosalide family to be confirmed and their previously unknown stereostructure to be assigned with confidence.T he underlying blueprint was inherently modular to ensure that each conceivable isomer could be reached. This flexibility derived from the use of strictly catalyst controlled transformations to set the stereocenters,e xcept for the anomeric position, whichi su nder thermodynamic control;a sa ne xtra safety measure,a ll stereogenic centers were set prior to ring closure to preclude any interference of the conformation adopted by the macrolactone rings of the different diastereomers.Late-stage macrocyclization by ring-closing alkyne metathesis was followed by ap latinum-catalyzed transannular 6-exo-dig hydroalkoxylation/ketalization to craft the polycyclic frame.T he side chain featuring avery labile unsaturation pattern was finally attached to the core by Stille coupling.

Stereoselective Synthesis of Volicitin and 9-D 1-Volicitin

“…Protection of the hydroxy group of but-3-yn-1-ol ( 7 ) with TBSCl afforded the silyl ether 8 , the anion of which was coupled with paraformaldehyde to produce the propargylic alcohol 9 . 8 A Z -selective hydrogenation of 9 with P2-Ni (borohydride-reduced nickel) 9 afforded allylic alcohol 10 10 in a 99% yield. The E -isomer was not observed in this reduction.…”