Enantiomeric HPLC resolution and absolute stereochemistry assignment of a new poligamain derivative

M. Pistolozzi, V. Royo, A. C. Pereira, M. L.A. Silva, R. Silva, W. R. Cunha, K. Vaconcelos, Q. B. Cass, C. H.G. Martins, J. K. Bastos, G. Varchi, A. Guerrini, C. Bertucci

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)118-122
Number of pages5
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume75
DOIs
StatePublished - Mar 5 2013

Keywords

  • Absolute configuration
  • Antibacterial activity
  • Electronic circular dichroism
  • Enantioselective HPLC
  • Lignans
  • NMR

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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