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.
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.
Kyoto Pharmaceutical University, Japan.
M
M
Yoshikawa
H
H
Shimada
N
N
Yagi
N
N
Murakami
H
H
Shimoda
J
J
Yamahara
H
H
Matsuda
D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D005122:Exudates and Transudates / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D049934:Isocoumarins; D007783:Lactones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D018926:Anti-Allergic Agents; D000890:Anti-Infective Agents; D001572:Benzofurans; D003374:Coumarins; D049934:Isocoumarins; D007783:Lactones; C102408:hydramacrophyllol A; C102409:hydramacrophyllol B; D062367:ortho-Aminobenzoates; C079055:thunberginol A; C079056:thunberginol B; C012293:tranilast