Chiral HPLC separation and absolute configuration of novel S ‐DABO derivatives

Chiral 2‐( sec ‐butylthio)‐6‐[1‐(2,6‐dichlorophenyl)propyl]‐5‐methylpyrimidin‐4( 3H )‐one (compound 1 ) was synthesized to serve as a model compound for structural elucidation of novel S ‐DABO (dihydroalkoxybenzyloxopyrimidine) derivatives endowed with potential HIV‐1 reverse transcriptase inhibitory activity. Stereochemical characterization of four stereoisomers of 1 was achieved by an experimental approach based on the following steps: (a) direct HPLC enantio‐ and diastereoseparation at semipreparative scale; (b) determination of elution order of stereomeric mixture by using chiroptical detection (polarimeter or circular dichroism (CD)); (c) X‐ray crystallography of two diastereoisomers isolated at semipreparative scale. The CD analysis of 1 and its two analogues (compounds 2 and 3) , both having a single stereogenic center located in two different alkyl side chains of the dihydropyrimidinone structure, was carried out. The results of this study indicated a correlation between the absolute configuration at C‐1 of alkyl side chain of the dihydropyrimidinone structure and the sign of the CD band at around 245 nm. Chirality, 2008. © 2009 Wiley‐Liss, Inc.