Total Synthesis of Ionophore Antibiotic X-14547A (Indanomycin)

Article abstract of DOI:10.1021/jo00081a010

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 the target synthon utilizes a new methodology for the preparation of stereodefined vinylsilanes (24 -> 25 -> 26) via net S_N2' coupling of <α-(mesyloxy)allyl>silanes with Grignard reagents catalyzed by CuCN.Salient features in the construction of the "right wing" subunit 3 include a modification of the Noyori three-component coupling procedure (32 -> 33) and the application of a retro hetero Diels-Alder/intramolecular Diels-Alder ("mock Claisen") process (5 -> 39).Palladium-mediated cross coupling of "left wing" and "right wing" synthons using Stille's method tolerates a free carboxylic acid and an unprotected acyl pyrrole, affording indanomycin directly in its natural absolute configuration.