SCOPADULCIOL, AN INHIBITOR OF GASTRIC H+,K+-ATPASE FROM SCOPARIA-DULCIS, AND ITS STRUCTURE-ACTIVITY-RELATIONSHIPS

A new tetracyclic diterpenoid, scopadulciol {3}, together with 6-methoxybenzoxazolinone, glutinol, and acacetin, was isolated from the 70% EtOH extract of Scoparia dulcis collected in Taiwan. Its structure was elucidated to be 6-beta-benzoyl-12-methyl-13-oxo-9(12)a,9(12)b-dihomo-18-podocarpanol on the basis of spectral data. It mildly inhibited hog gastric H+,K+-ATPase. Examination of the inhibitory activities of derivatives of scopadulcic acid B {2}, including 3, revealed that methylation of the carboxyl group and introduction of an acetyl group or oxime at C-13 or C-18 markedly enhanced the inhibitory activity, while debenzoylation reduced the activity. Among the 30 compounds tested, compound 12, a methyl ester of scopadulcic acid B {2}, showed the most potent activity.