Asymmetric synthesis of the benzoquinoid ansamycin antitumor antibiotics: total synthesis of (+)-macbecin

Abstract

A convergent asymmetric synthesis of the antitumor antibiotic macbecin I has been achieved. Six of the seven stereogenic centers within the target structure were controlled using asymmetric aldol methodology, while the final stereogenic center was established through internal asymmetric induction. Fragment coupling was accomplished using a mild, titanium tetrachloride mediated aldol reaction. The C 1 -C 5 unsaturated dienic ester was stereoselectively incorporated through a kinetically controlled Horner-Emmons olefination. Macrolactamization and subsequent refunctionalization afforded macbecin I