文献一覧: 宮内正雄 (著者)

1 0 0 0 OA Studies on Orally Active Cephalosporin Esters. II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution

著者: 宮内正雄笹原邦宏藤本光一川本勲井手純也中尾英雄
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.37, no.9, pp.2369-2374, 1989-09-25 (Released:2008-03-31)
参考文献数: 21
被引用文献数: 10 9

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.

2018-05-30 05:24:32
1 + 0 Twitter

1 0 0 0 Studies on orally active cephalosporin esters. II. Chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

著者: 宮内正雄笹原邦宏藤本光一川本勲井手純也中尾英雄
出版者: 公益社団法人日本薬学会
雑誌: CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)
巻号頁・発行日: vol.37, no.9, pp.2369-2374, 1989
被引用文献数: 9

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.

2018-05-30 05:23:39
1 + 0 Twitter

1 0 0 0 OA Studies on Orally Active Cephalosporin Esters. III. : Effect of the 3-Substituent on the Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution

著者: 宮内正雄栗原英志藤本光一川本勲井手純也中尾英雄
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.37, no.9, pp.2375-2378, 1989-09-25 (Released:2008-03-31)
参考文献数: 17
被引用文献数: 1 2

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of Δ3 cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the Δ2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the Δ2 ester (log k12) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the Δ3 ester (Δδ(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the Δ3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the Δ3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated π-bond system (C3=C4-C4=O) and consequently affects the feasibility of isomerization to the Δ2 ester, i.e., the stability to degradation.

2018-05-30 05:23:14
1 + 0 Twitter

1 0 0 0 Studies on orally active cephalosporin esters. III. Effect of the 3-substituent on the chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

著者: 宮内正雄栗原英志藤本光一川本勲井手純也中尾英雄
出版者: 公益社団法人日本薬学会
雑誌: CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)
巻号頁・発行日: vol.37, no.9, pp.2375-2378, 1989
被引用文献数: 2

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of Δ3 cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the Δ2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the Δ2 ester (log k12) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the Δ3 ester (Δδ(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the Δ3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the Δ3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated π-bond system (C3=C4-C4=O) and consequently affects the feasibility of isomerization to the Δ2 ester, i.e., the stability to degradation.

2018-05-30 05:22:49
1 + 0 Twitter