title: Chiral HPLC separation and absolute configuration of novel S-DABO derivatives.
abstract: 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.
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Rome, Italy. rcirilli@iss.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Rosella
authors.initials: R
authors.lastname: Ferretti
authors.forename: Francesco
authors.initials: F
authors.lastname: La Torre
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fares
authors.forename: Mercedes
authors.initials: M
authors.lastname: Camalli
authors.forename: Cristina
authors.initials: C
authors.lastname: Faggi
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D011743:Pyrimidines