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Enantioselective aliphatic hydroxylations of racemic 1‐hydroxy‐3‐methylcholanthrene by rat liver microsomes
Author(s) -
Shou Magang,
Yang Shen K.
Publication year - 1990
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530020304
Subject(s) - chemistry , enantiomer , hydroxylation , stereochemistry , diol , enantiomeric excess , chirality (physics) , enantioselective synthesis , organic chemistry , enzyme , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
Enantiomeric pairs of 1‐hydroxy‐3‐hydroxymethylcholanthrene (1‐OH‐3‐OHMC), 3‐methylcholanthrene (3MC) trans ‐ and cis ‐1,2‐diols, and 1‐hydroxy‐3‐methylcholanthrene (1‐OH‐3MC) were resolved by HPLC using a covalently bonded (R)‐ N ‐(3,5‐dinitrobenzoyl)phenylglycine chiral stationary phase (Pirkle type 1A) column. The absolute configuration of an enantiomeric 3MC trans ‐1,2‐diol was established by the exciton chirality CD method following conversion to a bis‐ p ‐ N , N ‐dimethylaminobenzoate. Incubation of an enantiomeric 1‐OH‐3MC with rat liver microsomes resulted in the formation of enantiomeric 3MC trans ‐ and cis ‐1,2‐diols; the absolute configurations of the enantiomeric 1‐OH‐3MC and 3MC cis ‐1,2‐diol were established on the basis of the absolute configuration of an enantiomeric 3MC trans ‐1,2‐diol. Absolute configurations of enantiomeric 1‐OH‐3‐OHMC were determined by comparing their CD spectra with those of enantiomeric 1‐OH‐3MC. The relative amount of three aliphatic hydroxylation products formed by rat liver microsomal metabolism of racemic 1‐OH‐3MC was 1‐OH‐3‐OHMC > 3MC cis ‐1,2‐diol > 3MC trans ‐1,2‐diol. Enzymatic hydroxylation at C 2 of racemic 1‐OH‐3MC was enantioselective toward the 1S‐enantiomer over the 1R‐enantiomer (∼3/1); hydroxylation at the C 3 ‐methyl group was enantioselective toward the 1R‐enantiomer over the 1S‐enantiomer (∼58/42). Rat liver microsomal C 2 ‐hydroxylation of racemic 1‐OH‐3MC resulted in a 3MC trans ‐1,2‐diol with a (1S,2S)/(1R,2R) ratio of 63/37 and a 3MC cis ‐1,2‐diol with a (1S,2R)/(1R,2S) ratio of 12/88, respectively.