Ligand-exchange enantioresolution of dihydroisoxazole amino acid derivatives acting as glutamatergic modulators
Articolo
Data di Pubblicazione:
2012
Citazione:
Ligand-exchange enantioresolution of dihydroisoxazole amino acid derivatives acting as glutamatergic modulators / R. Sardella, F. Ianni, N. Giacchè, A. Lisanti, P. Conti, A. Pinto, L. Tamborini, B. Natalini. - In: TRENDS IN CHROMATOGRAPHY. - ISSN 0972-8635. - 7:(2012), pp. 43-56.
Abstract:
Four dihydroisoxazole prolines (1-4) and four
dihydroisoxazole cyclopentane (5-8) derivatives,
evaluated as glutamatergic modulators, were
submitted to chiral ligand-exchange chromatography
(CLEC) analysis. A chiral stationary phase (CSP)
obtained through the coating of C-18 chains with
S-trityl-(R)-cysteine [(R)-STC] failed the
enantioseparation of compounds 3, 4, 7 and 8. On
the other hand, a chiral mobile phase (CMP)
system from O-benzyl-(S)-serine [(S)-OBS] coupled
with Cu(II) nitrate as the metal source into the
eluent, produced an excellent enantioseparation of
all compounds. Worthy to be mentioned is the
results achieved for compound 3: α = 7.26 and
RS = 25.75. The established CMP-CLEC method
was fully validated with the enantiomeric couple 2
as model compound. In all the cases, very good
precision (RSD% values ranging from 1.77 to
4.09% in the long-period) and accuracy
(Recovery% values ranging from 97.58 to 99.92%
in the long-period) values along with appreciably
low LOD (25.61 μg mL-1, and 24.79 μg mL-1, for the
first and second eluted enantiomer, respectively)
and LOQ (77.62 μg mL-1, and 75.08 μg mL-1, for
the first and second eluted enantiomer, respectively)
values turned out. The statistical relevance of the
developed CMP-CLEC method allowed us to
successfully undertake the semi-preparative scale enantioisolation of compounds 7 and 8. As a result
of a quantitative structure-property relationship
(QSPR) study, the van der Waals energy was
found to be the most suitable descriptor for
explaining the retention behaviour with the
(S)-OBS-based system, outlining the prominent
role of hydrophobic and dispersive interactions in
this CMP-CLEC environment.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
glutamatergic modulators; chiral ligand exchange chromatography; chiral mobile phase; chiral stationary phase; semi-preparative scale-up; quantitative structure-property relationship study;
Elenco autori:
R. Sardella, F. Ianni, N. Giacchè, A. Lisanti, P. Conti, A. Pinto, L. Tamborini, B. Natalini
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