Study of the Reaction of 3‐Formylrifamycin SV with Gaseous Ammonia and Acetone

Abstract

In the second stage of our study concerning the search for new antibacterial rifamycin antibiotics, reaction of the aldehydes 3‐formylrifamycin SV (1) and 25‐O‐deacetyl‐3‐formylrifamycin SV with ammonia and acetone has been investigated. A new synthetic method for the preparation of a new group of rifamycin derivatives with a cyclic substituent at C‐3 having a 4‐piperidone structure, represented by compounds 6a, 6b, and 7a, has been developed. The structures of the compounds and a reaction mechanism have been proposed on the basis of mass spectrometry results as well as 1D and 2D 1H and 13C NMR analysis. The results of the in vitro tests confirm the antituberculous activity of the synthesized compounds. Furthermore, 6a, which is isolated in good yield, is a promising substrate for a new class of rifamycin derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Rifamycin antibiotics—new compounds and synthetic methods. Part 4: Study of the reaction of 3-formylrifamycin SV with secondary amines and ketones

“…This mechanism, partly inspired from the findings of our last investigation with 3-formylrifamycin SV, primary alkylamines and various ketones, 18,19 implies the use of acetic acid to fulfil the reaction. The in situ formed a-amino-alcohol A affords, after abstraction of a water molecule, the violet-blue pyrrolidinium compound B, observed via TLC.…”

“…16 In the first part of our work, we investigated the products of the reaction of 3-formylrifamycin SV (1) with ammonia or primary alkylamines 17 whereas in the second part, we characterized the derivatives obtained from the reaction of 1 with ammonia and acetone. 18 The third part of the study widened the scope and addressed the reaction with primary alkylamines and various ketones, which leads to new derivatives with 'C3-grafted' a,b-unsaturated imines. 19 In essence, the key stage in the synthesis of these compounds turned out to be an 'acid-catalysed' aldol-type condensation of two imines.…”