Salvifarin, x-ray structure determination of a cis neo-clerodane diterpenoid from salvia farinacea

Eguren, Liliana; Fayos, J.; Perales, Aurea; Savona, Giuseppe; Rodrı́guez, Benjamı́n

doi:10.1016/s0031-9422(00)80356-8

Cited by 19 publications

(8 citation statements)

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“…The known compounds 2 -6 were isolated from the corresponding natural sources, and identified by comparison of their spectroscopic data with those published previously. The X-ray crystal structures of 1 [3], 3 [9], and 5 [10] have been published before, and a singlecrystal X-ray diffraction analysis of salvifaricin (6) was carried out in this study (Figure), which confirmed that the configuration of 6 is the same as in salvifarin (5). 2.…”

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confidence: 72%

Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.

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Mahon

et al. 2007

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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.

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confidence: 72%

Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.

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Mahon

et al. 2007

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“…In comparison with previous studies on compounds 1-3, 7,8,10 the data in Tables 1, 2 and 3 provide the complete assignment of the 1 H NMR spectra and the amendment of some previous 13 C NMR assignments 7 for 1 and 2, as shown in Table 2.…”

Section: Resultsmentioning

confidence: 74%

“…Br., whereas chamaedroxide (6) was found 12 in the acetone extract of Teucrium chamaedrys L. The structures of 1-6 were established by chemical transformations and IR, UV and 1 H and 13 C NMR spectroscopic studies 7 -10,12 and, in the case of 2 and 6, by single-crystal x-ray diffraction analyses. 8,12 Complete 1 H NMR assignments of 1-6 have not been performed previously, 7,9,10,12 particularly those corresponding to the pro-R and pro-S hydrogens of the C-19 (in 1-6) and C-11 (in 1-3 and 6) methylene groups, and those of the C-3 0 methylene of the pyrazoline part of 3. The previous assignments 7,9 of the 13 C NMR spectra for 1, 2 and been recorded previously.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 These substances have attracted interest in recent years on account of their interesting biological activities, 1 particularly as modifying agents of the feeding behaviour of many economically important insect phytophagous pests. 3 -5 Compounds 1-6, all of them possessing a neoclerodane absolute stereochemistry, 6 are representatives of this kind of substance and they were isolated from plants some years ago, except for 3 and 5, which are semisynthetic derivatives previously obtained from 2 (by treatment with diazomethane 7,8 ) and from 4 (by dehydration 9 ), respectively. Salvifaricin (1) 7,10 and salvifarin (2) 7,8 are constituents of Salvia farinacea Bent., salviacoccin (4) was extracted 9,11 from Salvia coccinea Juss.…”

Section: Introductionmentioning

confidence: 99%

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Complete assignments of the ¹H and ¹³C NMR spectra of six highly functionalized neoclerodane diterpenoids

Rodrı́guez

2001

Magnetic Reson in Chemistry

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“…Like in 12 , the β-orientation of H-8 in 17 and 18 was strongly supported by nOe experiments and by the observed vicinal J (H,H) couplings of the H-8 methine and H-7 methylene protons (see Experimental Section). Treatment of salvisplendin C ( 7 ) with an ethereal solution of diazomethane9,17,18 gave the pyrazoline derivative 19 (scheme 2). The regio-and stereochemistry of the pyrazoline moiety of 19 are identical to those of the already described derivative 9 ,9 as it was evidenced by comparison of their 1 H and 13 C NMR spectra (see ref 9.…”

Section: Resultsmentioning

confidence: 99%

Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity

et al. 2008

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Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific κ-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens (2 -8) together with a series of semisynthetic derivatives (9 -24), some of which possess a pyrazoline structural moiety (9, 19 -22), have been tested for affinity at human μ, δ, and κ opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for κ receptors suggesting other naturally neoclerodanes from different Salvia species may possess opioid affinity.

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Salvifarin, x-ray structure determination of a cis neo-clerodane diterpenoid from salvia farinacea

Cited by 19 publications

References 2 publications

Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.

Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.

Complete assignments of the ¹H and ¹³C NMR spectra of six highly functionalized neoclerodane diterpenoids

Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity

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Salvifarin, x-ray structure determination of a cis neo-clerodane diterpenoid from salvia farinacea

Cited by 19 publications

References 2 publications

Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.

Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.

Complete assignments of the 1H and 13C NMR spectra of six highly functionalized neoclerodane diterpenoids

Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity

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Complete assignments of the ¹H and ¹³C NMR spectra of six highly functionalized neoclerodane diterpenoids