Rifamycin antibiotics—new compounds and synthetic methods. Part 3: Study of the reaction of 3-formylrifamycin SV with primary amines and ketones

In the third stage of our study concerning the search for new antibacterial rifamycin antibiotics, the reactions of 3-formylrifamycin SV (1) with a range of primary alkylamines and ketones of general structure R1–CH2–CO–R2 (R1double bond; length as m-dashH or alkyl and R2double bond; length as m-dashalkyl or aryl) has been investigated. A new synthetic method for the preparation of a new group of rifamycin derivatives with an α,β-unsaturated imine substituent at C-3 has been developed. These compounds showed a tendency to reversibly isomerise in organic solvents and, in the presence of water, to rapidly hydrolyse. The structures of four isolated microcrystalline compounds 2, 3, 4, 5 and a reactionʹs mechanism have been proposed on the basis of mass spectrometry results as well as (1D) and (2D) 1H and 13C NMR analysis. The new synthetic route reported herein is a promising pathway to new reactive rifamycins displaying broader capabilities than the plain 3-formylrifamycin SV.