Chemistry Reference
In-Depth Information
An antiulcer agent, carbenoxolone sodium, which is derived from a terpenoid source
showed side effects including fluid retention, hypokalaemia and raised blood pressure.
The dehydroabietane nucleus was investigated to determine whether it can be used
as a substitute for the oleanane skeleton of carbenoxolone sodium. Wada and co-
workers [39] reported a series of amide derivatives with a hydrophilic moiety (such
as amino, carbamoyl, carbamoyloxy, ureido, sulfamoyl or sulfo) at positions 12 and
or 18 of the dehydroabietane nucleus (
64
) (
Scheme 6.14
). These were synthesised
from dehydroabietic acid through a chloride intermediate and their antiulcer
activities were tested by means of antisecretory and antipepsin assays in rats. Rosin
derivatives exhibited antiulcer activity. Among these compounds, the sodium salts of
12-sulfodehydroabietic acid were found to exhibit remarkably high antipepsin activity
without aldosterone-like activity. The inhibition ratio for mono- or disodium salts of
12-sulfodehydroabietic acid reached 96% and 92% respectively at 100 mg/kg dosage.
The presence of two acidic functional groups at each end of the dehydroabietane
nucleus appears to be necessary for the appearance of antipepsin activity.
Scheme 6.14
Structure of hydrophilic moiety derivatives of the dehydroabietane
nucleus (
64
)
