Benzylpenicillin methyl ester

Before interest developed in the structure of penicillin, the imidazo[5,1-b ]thiazole ring system was unknown, and even today, almost all of the examples which have been described are those prepared in connection with penicillin studies. Very mild acidic hydrolysis converts benzylpenicillin methyl ester (293) into benzylpenicillic acid (294) by a mechanism suggested... 

Penicillenic acid and methyl benzylpenicillenate are formed during the degradation of benzylpenicillin and benzylpenicillin methyl ester, respectively (Proctor et al., 1982 Bundgaard, 1980). The mechanism of penicillin degradation could involve intramolecular participation by the C(3) carboxyl group or the 6-amido side chain. 

The second-order rate constant k for the catalysed degradation of penicillin with an ionised carboxyl at C(3) is 0.354M s at 30°C compared with 8.2 x 10 M s for benzylpenicillin methyl ester. This rate difference of 4-fold is insignificant. The calculated first-order rate constant Atq for undissociated benzylpenicillin degradation is 10-fold greater than that for the methyl ester of benzylpenicillin. This is also probably too small to be indicative of intramolecular catalysis by the carboxyl group. 

Benzylpenicillinic Acid. 3,3>Dimerhyf-7-oxo-6-[tphenylacetyllamino]-4-th ia-l-azabicyclo 3.2.0]heptane-2-carboxylic acid free benzyl penicillin free penicillin G free penicillin II. C,jHI8Nj04S mol wt 334.38, C 57.47%, H 5.43%, N 8.38%, O 19.14%, S9,59%. Obtained by extraction at ice temp of the acidified (pH 2) aq soln of sodium benzyl -penicillin with ether Or chloroform. Shows correct analytical composition only it moisture is excluded completely during iis isoln from the ether extract (by lyophilizing from benzene). When kept dry the acid retains its antibiotic potency for limited periods, bui it is rapidly inactivated by small amounts of water. The product formed on slow inactivation by moisture seems to be benzylpenicilloic acid, cf. Clarke et [., The Chemistry of Penicillin (Princeton, 1949). Prepn of methyl ester Dan. pet. 85,976 (1958 to Leo Pharm.). Pharmacokinetics in humans M. Barza, L. Weinstein, Clin. 

Pcnamecillilt. 3,3-Di methyl-7-oxo-6-[(phenylace-tyl)amino]-4-thla-l-azabicyclo[3.2.0]heptane-2-ca rboxy lie acid (acetyloxyfmeihyl ester penicillin G hydroxymethyl ester acetate acetoxymethyl benzylpenicillinate benzylpenicillin acetoxymethyl ester Wy-20788 Havapen. C.,HKN,06S mol wt 406.48. C 56.14%. H 5.46%, N 6.89%, 6 23.62%, S 7.89%. Semi-synthetic antibiotic related to penicillin. Prepn Jansen, Russell. J. Chem. Soc. 1965, 2127 eidem, Brit. pat. 1,083,479 corresp to U,S. pet. 3,250,679 (1965, 1966 to John Wyeth A Brother). 

Copper(II) ion coordinates to the carboxylate group and the P-lactam nitrogen of benzylpenicillin as shown in [26] (Gensmantel et al., 1980). Coordination occurring to the carboxylate group is indicated because esterification of this group decreases the rate enhancement by a factor of ca 5 X 10. Nonetheless, the rate of the hydroxide-ion catalysed hydrolysis of the copper(II)-bound methyl ester of benzylpenicillin is still 1.5 x 10 -fold faster than the rate of hydrolysis of the uncoordinated ester, although the product of the reaction is not known. 

The hypothesis was not seriously tested until 1971, when Bohme and his colleagues synthesized the methyl esters of 6a- and 6p-methyl-benzylpenicillin. 

The activities of these compounds against Staphylococcus aureus and Streptococcus pyogenes were compared with those of the methyl ester of benzylpenicillin. Both methyl isomers were inactive at a concentration of 500 JLg/ml, whereas penicillin G methyl ester was active at p-g/ml. This group also synthesized a 7a-methylcephalosporin which was inactive compared to its parent compound. The results of these studies were... 

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