Fagopyrin is a phenantro-perylenequinone present in the flowers of Fagopyrum aesculentum (buckwheat), endowed with photodynamic activity and responsible of a certain number of photosensitizing syndromes in grazing animals (fagopyrism)1. This molecule was firstly extracted, more than 30 years ago, by Brockmann, who ascertained its chemical constitution.2 More accurate structural investigations, performed on the related compound hypericin, showed that a high degree of structural and conformational complexity might be present,3 as the aromatic system is involved in different equilibria of tautomerism, dissociation, torsional isomerism, and homoassociation. In the case of fagopyrin, the presence of two piperidine rings at positions 2 and 5 introduces two new stereogenic centres, in addition to the axial chirality of the aromatic system. Apart from the fundamental work of Brockmann, who did not establish the absolute configuration of the isolated fagopyrin, no other study has appeared, reporting a detailed analysis of the various stereogenic centres. Here, we wish to report our results regarding the stereochemistry of fagopyrin, as well as the composition of fagopyrin extracts; which actually proved to be complex mixtures of up to twenty molecules. Some of them are constituted by the same perylene-quinone, linked not only to piperidine, but also to pirrolidine moieties. This generates three different groups of closely related molecules (see Figure), depending on the nature of the linked heterocycles, with the generation of up to 8 stereoisomers within each family. The configuration of each stereocenter has been established by NMR and CD measurements, combined with ab-initio calculations (Gaussian03). Finally, the highly acidic hydroxyl groups allow the formation of zwitterionic species constituted by ion-pairs between the protonated amino groups and the negatively charged hypericinate ion. 1. Wender S. H., Gortner R. A., Inman O. L., J. Am. Chem. Soc., 1943, 65, 1733-1735. 2. Brockmann H., Lackner H., Tetrahedron Lett., 1979, 1575-1578. 3. Falk H., Angew. Chem. Int. Ed., 1999, 38, 3116-3136.

Structural Analysis of Fagopyrin Extracts by HPLC-MS, NMR and CD / A. Tagliabue, V. Galbusera, V. Bertacche, S. Mazzini, E. M. Ragg. ((Intervento presentato al 8. convegno Nat8 : Giornate di Chimica delle Sostanze Naturali tenutosi a Forte dei Marmi nel 2009.

Structural Analysis of Fagopyrin Extracts by HPLC-MS, NMR and CD

A. Tagliabue
Primo
;
V. Galbusera
Secondo
;
V. Bertacche;S. Mazzini
Penultimo
;
E.M. Ragg
Ultimo
2009-05-22

Abstract

Fagopyrin is a phenantro-perylenequinone present in the flowers of Fagopyrum aesculentum (buckwheat), endowed with photodynamic activity and responsible of a certain number of photosensitizing syndromes in grazing animals (fagopyrism)1. This molecule was firstly extracted, more than 30 years ago, by Brockmann, who ascertained its chemical constitution.2 More accurate structural investigations, performed on the related compound hypericin, showed that a high degree of structural and conformational complexity might be present,3 as the aromatic system is involved in different equilibria of tautomerism, dissociation, torsional isomerism, and homoassociation. In the case of fagopyrin, the presence of two piperidine rings at positions 2 and 5 introduces two new stereogenic centres, in addition to the axial chirality of the aromatic system. Apart from the fundamental work of Brockmann, who did not establish the absolute configuration of the isolated fagopyrin, no other study has appeared, reporting a detailed analysis of the various stereogenic centres. Here, we wish to report our results regarding the stereochemistry of fagopyrin, as well as the composition of fagopyrin extracts; which actually proved to be complex mixtures of up to twenty molecules. Some of them are constituted by the same perylene-quinone, linked not only to piperidine, but also to pirrolidine moieties. This generates three different groups of closely related molecules (see Figure), depending on the nature of the linked heterocycles, with the generation of up to 8 stereoisomers within each family. The configuration of each stereocenter has been established by NMR and CD measurements, combined with ab-initio calculations (Gaussian03). Finally, the highly acidic hydroxyl groups allow the formation of zwitterionic species constituted by ion-pairs between the protonated amino groups and the negatively charged hypericinate ion. 1. Wender S. H., Gortner R. A., Inman O. L., J. Am. Chem. Soc., 1943, 65, 1733-1735. 2. Brockmann H., Lackner H., Tetrahedron Lett., 1979, 1575-1578. 3. Falk H., Angew. Chem. Int. Ed., 1999, 38, 3116-3136.
fagopyrin ; fagopyrum aesculentum ; phenantroperylenequinone ; NMR ; Circular Dichroism
Settore CHIM/06 - Chimica Organica
Società Chimica Italiana
Structural Analysis of Fagopyrin Extracts by HPLC-MS, NMR and CD / A. Tagliabue, V. Galbusera, V. Bertacche, S. Mazzini, E. M. Ragg. ((Intervento presentato al 8. convegno Nat8 : Giornate di Chimica delle Sostanze Naturali tenutosi a Forte dei Marmi nel 2009.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/165041
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