DEVELOPMENT OF BIOACTIVE FUNCTIONS IN HYDRANGEAE DULCIS FOLIUM .6. SYNTHESES OF THUNBERGINOL-A AND THUNBERGINOL-F AND THEIR 3'-DEOXY-DERIVATIVES USING REGIOSPECIFIC LACTONIZATION OF STILBENE CARBOXYLIC-ACID - STRUCTURES AND INHIBITORY ACTIVITY ON HISTAMINE-RELEASE OF HYDRAMACROPHYLLOL-A AND HYDRAMACROPHYLLOL-B

Lactonization reaction of 2-carboxystilbene mediated by copper(II) chl oride proceeded regiospecifically to give the five-membered lactone, w hile the bromolactonizations using N-bromosuccinimide and anodic oxida tion were found to furnish the six-membered lactone. Using these regio specific lactonization reactions as a key step, antiallergic and antim icrobial isocoumarins and the benzylidenephthalides thunberginols A an d F and their 3'-deoxyanalogs were synthesized from phyllodulcin and h ydrangenol. Two phthalides called hydramacrophyllols A and B were isol ated from Hydrangeae Dulcis Folium and their stereostructures were det ermined on the basis of physicochemical and chemical evidence, which i ncluded the syntheses of hydramacrophyllols A and B from hydrangenol b y the application of the lactonization method using copper(II) chlorid e. In addition, hydramacrophyllols A and B were found to exhibit an in hibitory effect on the histamine release from rat peritoneal exudate c ells induced by antigen-antibody reaction.