2-carbamimidoyl-6-substituted-1-carbadethiapen-2-em-3-carboxylic acids, a process for preparing and an antibiotic composition comprising the same

Claim 1

A process for preparing a compound of the structural formula: and the pharmaceutically acceptable salt, ester and amide derivatives thereof known in the β-lactam antibiotic art; wherein: R 6 and R 7 , are independently selected from the group consisting of hydrogen; substituted and unsubstituted: alkyl, alkenyl, and alkynyl having 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl having 3―6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moiety; aryl, aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and aliphatic portion has 1-6 carbon atoms; R 6 and R 7 may be joined to form a cyclicalkyl having, together with the carbon atom to which they are attached, 3―6 carbon atoms; wherein the substituent or substituents on R 6 , and R 7 are independently selected from chloro, fluoro, hydroxy, bromo, carboxyl, cyano, azido, amino, mono- and dialkylamino (each alkyl having 1-6 carbon atoms), ureido, alkylthio having 1-6 carbon atoms, and alkoxyl having 1-6 carbon atoms; and R B is a carbamimidoyl selected from the group consisting of: wherein: A is a single, direct bond with the exception that A is not a single, direct bond with such compounds wherein the group ―C=N(NR 1 R 2 ) is not quarternary, or is a divalent cyclic or acyclic connector selected from the group consisting of alkylene, alkenylene, and alkynylene having 1-10 carbon atoms which may be interrupted by a hetero atom selected from 0, S or N, or by phenylene cycloalkylene, cycloalkenylene having 3-6 carbon atoms; heterocyclylene or heteroarylene wherein such cyclic interruptions comprise 3―6 ring atoms selected from C, 0, S an N; cycloalkylene, cycloalkenylene having 3―6 carbon atoms; heterocyclylene or hetereoarylene each having 5-10 ring atoms and one or more hetero atoms selected from 0, N and S; an phenylene; R' and R 2 are independently selected from hydrogen and the previously defined, but monovalent, values for the group A; and wherein the dotted lines indicate provision for cyclic structures formed by the joinder of the indicated nitrogen atom and the connector group A and by the joinder of the indicated nitrogen atoms, with the exception of compounds wherein wherein R'/R 2 are H, H; CH 3 , H; or R 7 is H and wherein n is 1 or 2 and (c) R 6 is (CH 3 ) 2 CH-CH(OH)-R 7 is H and comprising the step of treating: with HSR 8 ; wherein X a is a leaving group and R 5 is a protecting group.