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The Reversible Proxibarbal‐Valofan Isomerisation. Part II. Kinetic studies in a biphasic octanol/water system
Author(s) -
Wittekind H. Harald,
Testa Bernard,
Estreicher Jurek
Publication year - 1988
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19880710534
Subject(s) - chemistry , lipophilicity , isomerization , reaction rate constant , octanol , aqueous solution , partition coefficient , kinetic energy , equilibrium constant , kinetics , medicinal chemistry , computational chemistry , stereochemistry , organic chemistry , catalysis , physics , quantum mechanics
The tautomerisation between proxibarbal (I) and the two diasterloisomers of valofan ( IIX and IIY ) was investigated at pH 7.4 in a biphasic octanol/H 2 O system. The rate constants of isomerisation and the equilibrium constants of (partition coefficients) were calculated by compartmental analysis. The rate constants of isomerisation were comparable with those determined in monophasic aqueous solutions, whereas at pH 7.4 and 37° the duration necessary for a global equilibrium to be reached was 4–6 times longer in the biphasic system. These reduced rates and the higher lipophilicity of IIX and IIY as compared to I may be of pharmacokinetic and pharmacodynamic significance. They may also have relevance for a number of drugs known or suspected to form lactonic or lactamic metabolites.