In vitro metabolism of chloroprene: Species differences, epoxide stereochemistry and a de-chlorination pathway
Cottrell, L; Golding, BT; Munter, T; Watson, WP
HERO ID
157445
Reference Type
Journal Article
Year
2001
Language
English
PMID
| HERO ID | 157445 |
|---|---|
| In Press | No |
| Year | 2001 |
| Title | In vitro metabolism of chloroprene: Species differences, epoxide stereochemistry and a de-chlorination pathway |
| Authors | Cottrell, L; Golding, BT; Munter, T; Watson, WP |
| Journal | Chemical Research in Toxicology |
| Volume | 14 |
| Issue | 11 |
| Page Numbers | 1552-1562 |
| Abstract | Chloroprene (1) was metabolized by liver microsomes from Sprague-Dawley rats, Fischer 344 rats, B6C3F1 mice, and humans to the monoepoxides, (1-chloro-ethenyl)oxirane (5a/5b), and 2-chloro-2-ethenyloxirane (4a/4b). The formation of 4a/4b was inferred from the identification of their degradation products. With male Sprague-Dawley and Fischer 344 rat liver microsomes, there was a ca. 3:2 preference for the formation of (R)-(1-chloroethenyl)oxirane (5a) compared to the (S)-enantiomer (5b). A smaller but distinct enantioselectivity in the formation of (S)-(1-chloro-ethenyl)oxirane occurred with liver microsomes from male mouse (R:S, 0.90:1) or male human (R:S, 0.86:1). 2-Chloro-2-ethenyloxirane was very unstable in the presence of the microsomal mixture and was rapidly converted to 1-hydroxybut-3-en-2-one (11) and 1-chlorobut-3-en-2-one (12). An additional rearrangement pathway of 2-chloro-2-ethenyloxirane gave rise to 2-chlorobut-3-en-1-al (14) and 2-chlorobut-2-en-1-al (15). Further reductive metabolism of these metabolites occurred to form 1-hydroxybutan-2-one (17) and 1-chlorobutan-2-one (18). In the absence of an epoxide hydrolase inhibitor, the microsomal incubations converted (1-chloroethenyl)oxirane to 3-chlorobut-3-ene-1,2-diol (21a/21b). When microsomal incubations were supplemented with glutathione, 1-hydroxybut-3-en-2-one was not detected because of its rapid conjugation with this thiol scavenger. |
| Doi | 10.1021/tx0155404 |
| Pmid | 11712914 |
| Wosid | WOS:000172396000012 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |