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.Introduction. -Salvia divinorum, also referred to as magic mint or holy mint, is a psychotropic plant first described in the 1960s [1]. A number of clerodane diterpenoids have been isolated from this species [2], of which salvinorin A (1) was identified as the major active constituent [3] [4]. This compound was subsequently shown to act as an agonist at the k-opioid receptor, the first non-nitrogenous compound to do so [5] [6]. Modeling studies with 1 led to the hypothesis that splendidin (2), another clerodane diterpenoid from Salvia splendens, might also possess k-opioid activity [5]. However, the study of structure -activity relationships (SAR) by a number of groups using modified derivatives of 1 have shown particular structural requirements lacking in 2, including an acetyl (Ac) group or another small substituent at the C(2) atom [7], as well as trans-fused B/C rings, with a b-orientated H-atom at C(8) [8].The purpose of the present study was to test whether or not splendidin (2) is, indeed, a k-opioid agonist, and to compare its biological properties with those of other diterpenoids from S. splendens, including salviarin (3) and splenolide B (4). We also isolated the clerodanes salvifarin (5) and salvifaricin (6) from S. farinacea, and tested them together with the semi-synthetic derivatives 7 and 8.