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

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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.

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

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The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of &Delta;<SUP>3</SUP> cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the &Delta;<SUP>2</SUP> ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the &Delta;<SUP>2</SUP> ester (log k<SUB>12</SUB>) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the &Delta;<SUP>3</SUP> ester (&Delta;&delta;(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the &Delta;<SUP>3</SUP> esters also correlated with log k<SUB>12</SUB>. 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 &Delta;<SUP>3</SUP> ester (log k<SUB>21</SUB>) 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 &pi;-bond system (C<SUB>3</SUB>=C<SUB>4</SUB>-C<SUB>4</SUB>=O) and consequently affects the feasibility of isomerization to the &Delta;<SUP>2</SUP> ester, i.e., the stability to degradation.