Influence ofL-Cysteine on the Oxidation Chemistry of (-)-Epinephrine: Formation of Cysteinyl Conjugates and Novel Dihydrobenzothiazines
✍ Scribed by Xue-Ming Shen; Glenn Dryhurst
- Publisher
- Elsevier Science
- Year
- 1996
- Tongue
- English
- Weight
- 286 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0045-2068
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✦ Synopsis
Oxidation of epinephrine (EPI) in aqueous solution at pH 7.4 generates an ortho-quinone (1) that normally deprotonates and undergoes a rapid intramolecular cyclization and secondary reactions, ultimately leading to an indolic melanin polymer. In this investigation, it is demonstrated that L-cysteine (CySH) can intervene in this reaction by scavenging o-quinone 1 to give 5-S-cysteinylepinephrine (5-S-CyS-EPI) and 2-S-cysteinylepinephrine (2-S-CyS-EPI). Subsequent oxidation (2e, 2H ϩ ) of the latter cysteinyl conjugates gives o-quinones that can either react further with free CySH to give the 2,5-bi-S-and 2,5,6-tri-S-cysteinyl conjugates of EPI or cyclize to give 7-[(2-methylamino)ethyl]-3,4-dihydro-5-hydroxy-2H-1,4benzothiazine-3-carboxylic acid (DHBT-E1) and 8-[(2-methylamino)ethyl]-3,4-dihydro-5hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-E2), respectively, Oxidations of 2,5bi-S-CyS-EPI and 2,5,6-tris-S-CyS-EPI and of DHBT-E1 and DHBT-E2 in the presence of CySH provide routes to a number of other dihydrobenzothiazines (DHBTs). Four new cysteinyl conjugates of EPI and seven DHBTs have been isolated and their structures elucidated by spectroscopic methods. Based upon a number of lines of converging evidence, it is suggested that these compounds might include unusual metabolites of EPI formed in adrenergic neurons under certain pathological brain conditions.