TOTAL SYNTHESIS OF IONOPHORE ANTIBIOTIC X-14547A (INDANOMYCIN)

A convergent, enantioselective total synthesis of ionophore antibiotic X-14547A (indanomycin, 1) is described. The dioxanone-to-dihydropyran variant of the lactonic Ireland-Claisen rearrangement establishes the hydropyran nucleus of the ''left wing'' fragment 2. Elaboration to th e target synthon utilizes a new methodology for the preparation of ste reodefined vinylsilanes (24 --> 25 --> 26) via net S(N)2' coupling of [alpha-(mesyloxy)allyl]silanes with Grignard reagents catalyzed by CuC N. Salient features in the construction of the ''right wing'' subunit 3 include a modification of the Noyori three-component coupling proced ure (32 --> 33) and the application,of a retro hetero Diels-Alder/intr amolecular Diels-Alder (''mock Claisen'') process (5 --> 39), Palladiu m-mediated cross Coupling of ''left wing'' and ''right wing'' synthons using Stille's method tolerates a free carboxylic acid and an unprote cted acyl pyrrole, affording indanomycin directly in its natural absol ute configuration.