Deprotection processes

A deprotection process for converting the acylmercaptoalkanoylamino lactam acid or ester of the formula

• to the mercaptoalkanoylamino lactam acid or ester of the formula
• or for converting the mercaptoalkanoylamino lactam ester of formula I to the corresponding lactam acid of formula I wherein:
• X1 is a lactam of the formula
• R4 and R5 are both hydrogen;
• R6 and R7 are both methyl;
• R10 an R11 are both hydrogen;
• b is zero;
• q is two;
• m is zero or an integer from 1 to 6;
• n is zero or one;
• R1 and R2 are independently selected from straight or branched chain alkyl of 1 to 6 carbons, —(CH2)m-aryl, —(CH2)m-substituted aryl, or —(CH2)m-heteroaryl;
• and
• R12 is hydrogen or an acid protecting group selected from methyl, ethyl, propyl, phenyl or benzyl;
• which comprises
• a) when R12 in the definition of X1 in formula II is hydrogen, treating the acylmercaptoalkanoylamino lactam acid of formula II with an alkali metal or alkaline earth metal hydroxide or carbonate or with an amine in a suitable solvent containing a sufficient amount of an agent that minimizes the amount of the disulfides of the formula
• which, in turn, minimizes the formation of the undesired epimer of the pharmaceutically active compounds of formula I followed by treatment with an aqueous acid to precipitate the desired lactam acid of formula I;
• or
• b) when R12 in the definition of X1 in formula II is an acid protecting group, treating the acylmercaptoalkanoylamino lactam ester of formula II under aqueous conditions with an alkali metal or alkaline earth metal hydroxide or carbonate in a suitable solvent containing a sufficient amount of an agent that minimizes the amount of the disulfides of formula III which, in turn, minimizes the formation of the undesired epimer of the pharmaceutically active compound of formula I followed by treatment with an aqueous acid to precipitate the desired lactam acid of formula I;
• or
• c) when R12 in the definition of X1 in formula II is an acid protecting group, treating the acylmercaptoalkanoylamino lactam ester of formula II under non-aqueous conditions with an alkali metal or alkaline earth metal hydroxide or carbonate in a suitable solvent containing a sufficient amount of an agent that minimizes the amount of the disulfides of formula III which, in turn, minimizes the formation of the undesired epimer of the pharmaceutically active compound of formula I or treating the acylmercaptoalkanoylamino lactam ester of formula II under aqueous conditions with an amine in a suitable solvent containing a sufficient amount of an agent that minimizes the amount of the disulfides of formula III which, in turn, minimizes the formation of the undesired epimer of the pharmaceutically active compound of formula I thus removing the acyl protecting group R2—C(O)— to give the mercaptoalkanoylamino lactam ester of formula I;
• or
• d) treating the mercaptoalkanoylamino lactam ester of formula I under aqueous conditions with an alkali metal or alkaline earth metal hydroxide or carbonate in a suitable solvent containing a sufficient amount of an agent that minimizes the amount of the disulfides of formula III, which, in turn, minimizes the formation of the undesired epimer of the pharmaceutically active compound of formula I followed by treatment with an aqueous acid to precipitate the desired mercaptoalkanoylamino lactam acid of formula I.