Total Synthesis of the Broad-Spectrum Antibiotic Amycolamicin.

The total synthesis of the antibiotic amycolamicin with a hybrid molecular architecture composed of five ring systems, which exhibits potent antibacterial activity against a wide range of drug-resistant bacteria, has been achieved in a convergent manner. A protecting-group-free intramolecular Diels-Alder reaction of a hydroxy tetraenal intermediate promoted by two equivalents of EtAlCl, which proceeds highly diastereoselectively via an -equatorial transition state, has been utilized to construct the -decalin moiety of the molecule. The full structure of amycolamicin was assembled by a completely stereoconvergent N-acylation of a northern -glycoside unit (α-anomer/β-anomer = 1:1.1) with a southern β-keto thioester segment followed by installation of the central tetramic acid moiety.