Four new clerodane diterpenoids, salvisplendins A-D (1-4), have been isolated from an acetone extract of the flowers
of SalVia splendens, together with an artifact (5), arising from salvisplendin D (4) by addition of diazomethane, and the
already known clerodane olearin (6). The structures of the new compounds (1-5) were established mainly by 1D and
2D NMR spectroscopic studies and, in the case of salvisplendin A (1), by chemical correlation with splenolide B (7).
Complete 1H and 13C NMR assignments for olearin (6), not published hitherto, are also reported.
The clerodane diterpenoid salvinorin A (1), the main active component of the psychotropic herb
Salvia divinorum, has been reported to be a potent agonist at the k-opioid receptor. Computer modeling
suggested that splendidin (2) from S. splendens, as well as related compounds, might possess similar
activities. In the present study, this hypothesis was tested by determination of the binding properties of a
series of structural congeners, compounds 2–8, at the m-, d-, and k-opioid receptors. However, none of
these compounds showed significant binding to any of the opioid-receptor subtypes, thus disproving the
above hypothesis.
The novel compounds 7 and 8 were obtained semi-synthetically by selective modification of
salvifarin (5), isolated from Salvia farinacea, upon epoxide-ring opening with AcOH in the presence of
indium(III) triflate. Also, the X-ray crystal structure of salvifaricin (6; Fig.), obtained from S. farinacea,
was determined for the first time and used, in combination with in-depth NMR experiments, to elucidate
the absolute configurations of the new products. Our experiments demonstrate that the relatively wellaccessible
diterpenoid 6 could be used as starting material for future studies into the structure–activity
relationship at the k-opioid receptor.
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