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.
Cirilli
Roberto
R
Dipartimento del Farmaco, Istituto Superiore di Sanità, Rome, Italy. rcirilli@iss.it
Ferretti
Rosella
R
La Torre
Francesco
F
Borioni
Anna
A
Fares
Vincenzo
V
Camalli
Mercedes
M
Faggi
Cristina
C
Rotili
Dante
D
Mai
Antonello
A
D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D011743:Pyrimidines