The selective opening of the thiazolidine ring of penicillins between the sulphur and carbon atom 5 without affecting the B-lactam ring may be effected by the use of electrophilic agents, preferably agents capable of functioning as a source of positive halogen, as described in Eli Lilly British Pat. No. 1,346,744, published Feb. 13, 1974. Similar ring openings have also been carried out with penicillin sulfoxides, and a comprehensive review of those reactions is found in "Cephalosporins and Penicillins", E. H. Flynn, Ed., Academic Press, New York and London, 1972, chapter 5. The opening of the thiazolidine ring of anhydropenicillin by means of chlorine has been described by Wolfe et al. in Can. J. Chem. 50, 2902 (1972). Depending upon the reaction conditions selected there were obtained either compounds analogous to the compounds of formula 1 of this Application and their respective stereoisomers at C-4, or compounds analogous to the compounds of formulae 2A or 2B of this Application having R.sup.3 and R.sup.4 in both cases as hydrogen only. Baldwin et al., J.C.S. Chem. Comm. 1976,667, have prepared a compound of formula 1 which differs significantly from the compounds of formula 1 of this invention in having a free hydroxy group as the substituent Z. The transformation of the compounds of the type represented by formula 1 in which R.sup.3 and R.sup.4 are both hydrogen to the corresponding compounds of the type represented by formulae 2A and 2B by means of triethylamine has been described e.g. by Kukolja et al., J. Am. Chem. Soc. 93,6267(1971), in U.S. Pat. No. 3,840,556 issued Oct. 8, 1974, and in British Patent No. 1,346,744 cited above. Compounds of the formula 1 in which R.sup.3 and R.sup.4 are both hydrogen have also been described in British patent No. 1,523,885 issued from British patent application 16582/75 which also discloses an alternate method for their preparation. However, all the procedures disclosed in the above references have the disadvantage that the compounds of the type represented by formula 1 in which R.sup.3 and R.sup.4 are both hydrogen are obtained as mixtures of stereoisomers at C-4, and that such mixtures have to be separated by laborious and expensive chromatographic methods before the individual stereoisomers may be used as starting materials for further syntheses.
USPTO Backgrounds
USPTO Backgrounds