Premium
Chiral HPLC separation and absolute configuration of novel S ‐DABO derivatives
Author(s) -
Cirilli Roberto,
Ferretti Rosella,
La Torre Francesco,
Borioni Anna,
Fares Vincenzo,
Camalli Mercedes,
Faggi Cristina,
Rotili Dante,
Mai Antonello
Publication year - 2009
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.20654
Subject(s) - chemistry , stereocenter , diastereomer , circular dichroism , absolute configuration , chirality (physics) , high performance liquid chromatography , cotton effect , stereochemistry , alkyl , chiral column chromatography , side chain , chromatography , enantioselective synthesis , organic chemistry , polymer , catalysis , nambu–jona lasinio model , physics , quantum mechanics , quark , chiral symmetry breaking
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.