Chemical modifications in the tetracycline series

Abstract

New tetracycline analogs modified at position 5, 6 and 2 were synthetized. The 5-deoxy-5-oxo-derivatives, 2a and 3a, were obtained by DMSO/acetic anhydride oxidation of doxycycline (2) and methacycline (3), respectively; the 6-demethyl-6-hydroxymethyl-6-alpha-hydroxy-oxytetracycline (3b) by methacycline oxidation with the KC103/0s04 system and the 6-hydroxyanhydrooxytetracycline (4) treating 3b with periodic acid. The 2-ethoxycarbonyl-2-decarboxamidodoxycycline (2b), was synthetized by treating doxycycline nitrile (2c) with EtOH and anhydrous HC1, 2-thiocarboxamide-2-decarboxamidodoxycycline (2d) by reaction of doxycycline with P2S6 in dioxane and 2-aminomethyl-2-decarboxamidodoxycycline (2e) by RANEY-Nickel reduction of 2d. All the synthetized compounds proved to be almost inactive on agar plates both on Gram-positive and Gram-negative bacteria. © 1981, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.