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由细胞色素P450c作用于7,12-二甲基苯并[a]蒽形成的5,6-氧化物的绝对构型

Absolute configuration of the 5,6-oxide formed from 7,12-dimethylbenz[a]anthracene by cytochrome P450c.

作者信息

Balani S K, Yeh H J, Ryan D E, Thomas P E, Levin W, Jerina D M

出版信息

Biochem Biophys Res Commun. 1985 Jul 31;130(2):610-6. doi: 10.1016/0006-291x(85)90460-7.

DOI:10.1016/0006-291x(85)90460-7
PMID:3927907
Abstract

The absolute configurations of the enantiomeric 5,6-arene oxides of 7,12-dimethylbenz[a]anthracene (DMBA) were recently assigned such that the late eluting enantiomer from a chiral HPLC column has 5R,6S absolute configuration. [Mushtaq et al. (1984) BBRC 125, 539]. The authors further concluded that the 5R,6S-enantiomer predominates on metabolism of DMBA by cytochrome P450c in liver microsomes from 3-methylcholanthrene-treated rats. Their chemical assignment of absolute configuration is incorrect. Thus, metabolism of DMBA by these microsomes as well as by homogeneous cytochrome P450c produces 5,6-oxide highly enriched (95%) in the 5S,6R-enantiomer in accord with theoretical predictions.

摘要

最近确定了7,12-二甲基苯并[a]蒽(DMBA)对映体5,6-芳烃氧化物的绝对构型,使得手性高效液相色谱柱上洗脱较晚的对映体具有5R,6S绝对构型。[Mushtaq等人(1984年)《生物化学与生物物理研究通讯》125, 539]。作者进一步得出结论,在经3-甲基胆蒽处理的大鼠肝微粒体中,细胞色素P450c对DMBA进行代谢时,5R,6S-对映体占主导。他们对绝对构型的化学指定是错误的。因此,这些微粒体以及均一的细胞色素P450c对DMBA的代谢产生的5,6-氧化物中,5S,6R-对映体高度富集(95%),这与理论预测一致。

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引用本文的文献

1
Stereoselective formation and hydration of 12-methylbenz[a]anthracene 5,6-epoxide enantiomers by rat liver microsomal enzymes.大鼠肝微粒体酶对12-甲基苯并[a]蒽5,6-环氧化物对映体的立体选择性形成及水化作用。
Biochem J. 1987 Jul 1;245(1):191-204. doi: 10.1042/bj2450191.
2
Stereoselective fungal metabolism of 7,12-dimethylbenz[a]anthracene: identification and enantiomeric resolution of a K-region dihydrodiol.7,12-二甲基苯并[a]蒽的立体选择性真菌代谢:一种K区域二氢二醇的鉴定及对映体拆分
Appl Environ Microbiol. 1987 Oct;53(10):2560-6. doi: 10.1128/aem.53.10.2560-2566.1987.