TY - JOUR
T1 - Enantiomeric HPLC resolution and absolute stereochemistry assignment of a new poligamain derivative
AU - Pistolozzi, M.
AU - Royo, V.
AU - Pereira, A. C.
AU - Silva, M. L.A.
AU - Silva, R.
AU - Cunha, W. R.
AU - Vaconcelos, K.
AU - Cass, Q. B.
AU - Martins, C. H.G.
AU - Bastos, J. K.
AU - Varchi, G.
AU - Guerrini, A.
AU - Bertucci, C.
N1 - Funding Information:
This work was supported by FAPESP (Brazil) , University of Bologna (Italy) , and MIUR (PRIN 2008 National Program) .
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/3/5
Y1 - 2013/3/5
N2 - A new aryltetralin lignan derivative, 1, was obtained by reacting dimethyl succinate and piperonal, furnishing the lactone 4-(3',4'-methylenedioxybenzyl)-4,5-dihydro-2(3H)-furanone, which was reacted once again with piperonal and LDA to give the dibenzylbutirolactone 7-hydroxyhinokinin. The cyclization of 7-hydroxyhinokinin into polygamain occurred in the presence of trifluoroacetic acid. The reduction of the furanic ring of polygamain was done by its reaction with DIBAL in THF, furnishing the diol functionalized lignin derivative 1 as single diastereomer. The enantiomeric fractions of 1 were obtained by preparative enantioselective HPLC. The absolute stereochemistry was assigned by electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) spectroscopy. An all-trans relative configuration was determined by NMR on the bases of 1H coupling constants and nuclear Overhauser effect (n.O.e.) experiments. The absolute configuration at C1 was assigned on the basis of the ECD sign at 296nm by comparison to the ECD spectra of structural analogues with defined stereochemistry. The assignment of the absolute configuration was confirmed by applying the exciton chirality method to the well-defined ECD couplets at 285 and 200nm allied to the two electronic transitions Lb and Bb of the aromatic moieties, respectively. Rac-1 and its enantiomeric isomers were evaluated against important bacteria responsible for dental caries. The best results obtained for the (1R,2S,3S) isomer were against Streptococcus mutans (250μM), Streptococcus salivarius (250μM), Streptococcus sobrinus (280μM) and Streptococcus mitis (280μM). The (1S,2R,3R) isomer was active only against Streptococcus sanguinis (280μM). The enantiomeric mixture was less active than the (1R,2S,3S) isomer.
AB - A new aryltetralin lignan derivative, 1, was obtained by reacting dimethyl succinate and piperonal, furnishing the lactone 4-(3',4'-methylenedioxybenzyl)-4,5-dihydro-2(3H)-furanone, which was reacted once again with piperonal and LDA to give the dibenzylbutirolactone 7-hydroxyhinokinin. The cyclization of 7-hydroxyhinokinin into polygamain occurred in the presence of trifluoroacetic acid. The reduction of the furanic ring of polygamain was done by its reaction with DIBAL in THF, furnishing the diol functionalized lignin derivative 1 as single diastereomer. The enantiomeric fractions of 1 were obtained by preparative enantioselective HPLC. The absolute stereochemistry was assigned by electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) spectroscopy. An all-trans relative configuration was determined by NMR on the bases of 1H coupling constants and nuclear Overhauser effect (n.O.e.) experiments. The absolute configuration at C1 was assigned on the basis of the ECD sign at 296nm by comparison to the ECD spectra of structural analogues with defined stereochemistry. The assignment of the absolute configuration was confirmed by applying the exciton chirality method to the well-defined ECD couplets at 285 and 200nm allied to the two electronic transitions Lb and Bb of the aromatic moieties, respectively. Rac-1 and its enantiomeric isomers were evaluated against important bacteria responsible for dental caries. The best results obtained for the (1R,2S,3S) isomer were against Streptococcus mutans (250μM), Streptococcus salivarius (250μM), Streptococcus sobrinus (280μM) and Streptococcus mitis (280μM). The (1S,2R,3R) isomer was active only against Streptococcus sanguinis (280μM). The enantiomeric mixture was less active than the (1R,2S,3S) isomer.
KW - Absolute configuration
KW - Antibacterial activity
KW - Electronic circular dichroism
KW - Enantioselective HPLC
KW - Lignans
KW - NMR
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U2 - 10.1016/j.jpba.2012.11.012
DO - 10.1016/j.jpba.2012.11.012
M3 - Article
C2 - 23312389
AN - SCOPUS:84871798018
VL - 75
SP - 118
EP - 122
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
ER -