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.