Novel tetracycline analogues. Part 1. Development of a potential synthetic route

Abstract

A new type of tetracycline analogue has been designed to incorporate those features of the tetracycline molecule essential for antibacterial activity but with a reduction in structural complexity. These novel analogues are derivatives of 4-dimethylamino-1,4,4a,5,10,10a-hexahydro-3,10a-dihydroxy-1,10-dioxoanthracene-2-carboxamide. An overall synthetic route has been developed involving preparation of 1,2,3,4-tetrahydro-5,8-dimethoxy-4-oxo-2-naphthylacetic acid (3; R¹= OMe, R²= R³= R⁵= H, R⁴= Me); variation of the starting material should allow a range of tetracycline analogues to be prepared.