Additional Insights into Hypericum perforatum Content: Isolation, Total Synthesis, and Absolute Configuration of Hyperbiphenyls A and B from Immunomodulatory Root Extracts

Dimitri Bréard (1) , Guillaume Viault (1) , Marie-Charlotte Mezier (2, 3) , Sylvain Pagie (2, 3) , Antoine Bruguière (1) , Pascal Richomme (1) , Béatrice Charreau (3, 4) , Séverine Derbré (1)

1 SONAS - Substances d'Origine Naturelle et Analogues Structuraux
2 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
3 ITUN - Institut de transplantation urologie-néphrologie
4 Team 4 - U1064 Inserm - CRTI - Immunoregulation And Immunointervention in Transplantation and Autoimmunity

Phytochemical investigation of the root extracts of Hypericum perforatum led to the isolation of two biphenyl derivatives named hyperbiphenyls A and B (1 and 2) and four known xanthones (3−6). These structures were elucidated by spectroscopic and spectrometric methods including UV, NMR, and HRMS. The absolute configuration of the biphenyl derivatives was defined by two different approaches: biomimetic total synthesis of racemic hyper-biphenyl A followed [1]H and [19]F NMR Mosher's esters analysis and stereoselective total synthesis of hyperbiphenyl B, permitting assignment of the S absolute configuration for both compounds. The bioactivity of compounds 1−6 toward a set of biomolecules, including major histocompatibility complex (MHC) molecules expressed on vascular endothelial cells, was measured. The results showed that the major xanthone, i.e., 5-O-methyl-2-deprenylrheediaxanthone B (3), is a potent inhibitor of MHC that efficiently reduces HLA-E, MHC-II, and MICA biomolecules on cell surfaces.

Domaines: Médecine humaine et pathologie

Dimitri Bréard, Guillaume Viault, Marie-Charlotte Mezier, Sylvain Pagie, Antoine Bruguière, et al.. Additional Insights into Hypericum perforatum Content: Isolation, Total Synthesis, and Absolute Configuration of Hyperbiphenyls A and B from Immunomodulatory Root Extracts. Journal of Natural Products, 2018, 81 (8), pp.1850-1859. ⟨10.1021/acs.jnatprod.8b00325⟩. ⟨inserm-02157665⟩