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Cited by 23Chemical Reaction MechanismsAnalytical Methods in PharmaceuticalsSynthesis of β-Lactam Compounds

Degradation of Clavulanic Acid in Aqueous Alkaline Solution : Isolation and Structural Investigation of Degradation Products

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HAGINAKA, JUN, YASUDA, HIROYUKI, UNO, TOYOZO, NAKAGAWA, TERUMICHI·1985·CHEMICAL & PHARMACEUTICAL BULLETIN
DOI 10.1248/cpb.33.218
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Abstract

The degradation of potassium clavulanate in a weakly alkaline aqueous solution has been investigated. Potassium clavulanate was degraded in 0.1 M Na2HPO4 solution at various temperatures. Four degradation products were isolated and their structures were elucidated as 2, 5-bis-(2-hydroxyethyl) pyrazine (I), 3-methyl-2, 5-bis-(2-hydroxyethyl) pyrazine (II), 3-(2-carboxyethyl)-2, 5-bis-(2-hydroxyethyl) pyrazine (III). and 3-ethyl-2.5-bis-(2-hydroxyethyl) pyrazine (IV) by mass spectroscopy and nuclear magnetic resonance spectroscopy. High-performance liquid chromatographic analysis of the reaction solution indicated that the reaction at 60°C yielded all four pyrazine derivatives, whereas II was not formed at 35°C and III was not formed at 100°C. A reaction mechanism is proposed which involves 4-amino-3-oxobutanol (IX) as a key intermediate.

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  • The kinetic approach is consequent with a feasible chemical mechanism of reaction for CA in aqueous solutions characterized by several equilibrium steps.

    “This kinetic approach is consequent with a feasible chemical mechanism of reaction for CA in aqueous solutions, characterized by several equilibrium steps (Figure 4) [28,29].”

    From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [28]

    The Degradation Mechanism section (p. 6) proposes a multistep mechanism for clavulanate degradation, supporting the claim that a feasible chemical mechanism exists. It does not characterize those steps as equilibria or establish that the proposed mechanism follows from the citing paper’s kinetic approach; the study concerns weakly alkaline aqueous solution, not aqueous solutions generally. (LLM, conf=0.86)

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Research works printed but not linked: 18

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Authors
HAGINAKA, J., YASUDA, H., UNO, T., & NAKAGAWA, T.
ORCID
Venue
CHEMICAL & PHARMACEUTICAL BULLETIN
Publisher
Pharmaceutical Society of Japan
Published
1985
Volume
33
Issue
1
Pages
218-224
ISSN
  • 0009-2363 (ISSN-L)
  • 1347-5223
DOI
10.1248/cpb.33.218
OpenAlex
W2491268877
Cited by
23
References
0
Citations by year
2026: 1 · 2024: 2 · 2022: 3 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
FWCI
0.57
Type
journal article
Language
en
Open access
Locations
Chemical and Pharmaceutical Bulletin (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis of β-Lactam Compounds
Keywords
clavulanic acid, potassium clavulanate, alkaline hydrolysis, degradation products, pyrazine derivatives, reaction mechanism, temperature dependence, structure elucidation

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