STUDIES TOWARDS THE TOTAL SYNTHESIS OF VIRIDENOMYCIN

Abstract

Viridenomycin is a very important antibiotic, which showed strong inhibitory activity against gram-positive bacteria and an active agent against B16 melanoma. In this work we confirmed the asymmetric and stereoselective synthesis of tert-butyl(1R,3Z,5E,7E,10RS)-10-hydroxy-1-phenylundeca-3,5,7-trienylcarbamate as the key building block towards the synthesis of the southern polyene section of viridenomycin. In this synthesis, a series of reactions were carried out, including Heck-Mizoroki couplings, Suzuki-Myuara couplings, deprotection of the silyl ethers, selective oxidation and enol-acetylation. In addition, the full explanation for regeoselectivity of hydroboration with catecholborane on terminal alkynes was introduced. Also, our efficient iododeboroation methodology was applied to the alkenyl hindered boronate ester and led to the terminal (E)-alkenyl isomer which was the only isomer obtained. Therefore, this iododeboronation will be a very important method for practical use to prepare highly stereoselective terminal (E)-alkenyl iodide. Moreover, selective cleavage of tert-butoxycarbonyl (Boc) for the deprotection of the corresponding triene was studied. In addition, two mild cleavage protecting groups (TFAA, phthalimide) are studied. In conclusion, we have demonstrated an efficient methodology and a flexible approach to the synthesis of conjugated (Z,E,E)-triene core of viridenomycin.