Development of Bioactive Functions in Hydrangeae Dulcis Folium. VI.Syntheses of Thunberginols A and F and Their 3'-Deoxy-Derivatives Using Regiospecific Lactonization of Stilbene Carboxylic Acid : Structures and Inhibitory Activity on Histamine Release of Hydramacrophyllols A and B

Abstract

Lactonization reaction of 2-carboxystilbene mediated by copper(II) chloride proceeded regiospecifically to give the five-membered lactone, while the bromolactonizations using N-bromosuccinimide and anodic oxidation were found to furnish the six-membered lactone. Using these regiospecific lactonization reactions as a key step, antiallergic and antimicrobial isocoumarins and the benzylidenephthalides thunberginols A and F and their 3'-deoxyanalogs were synthesized from phyllodulcin and hydrangenol.Two phthalides called hydramacrophyllols A and B were isolated from Hydrangeae Dulcis Folium and their stereostructures were determined on the basis of physicochemical and chemical evidence, which included the syntheses of hydramacrophyllols A and B from hydrangenol by the application of the lactonization method using copper(II)chloride. In addition, hydramacrophyllols A and B were found to exhibit an inhibitory effect on the histamine release from rat peritoneal exudate cells induced by antigen-antibody reaction.