Salvinorin

Salvinorins are a group of natural chemical compounds and their structural analogs. Several salvinorins have been isolated from Salvia divinorum . They are classified as diterpenoid furanolactones. Salvinorin A is a hallucinogen with dissociative effects.

Several salvinorins have been isolated and characterized.

Natural salvinorins

Name	Structure	R1	R2	Chemical formula	Molar mass	CAS number	PubChem
Salvinorin A		–OCOCH3	−	C23H28O8	432.46 g·mol−1	83729-01-5	CID 128563 from PubChem
Salvinorin B		–OH	−	C21H26O7	390.43 g·mol−1	92545-30-7	CID 11440685 from PubChem
Salvinorin C		–OCOCH3	–OCOCH3	C25H30O9	475.29 g·mol−1	385785-99-9	–
Salvinorin D [1]		–OH	–OCOCH3	C23H28O8	432.47 g·mol−1	540770-13-6	–
Salvinorin E [1]		–OCOCH3	–OH	C23H28O8	432.47 g·mol−1	540770-14-7	–
Salvinorin F [1]		–H	–OH	C21H26O6	374.43 g·mol−1	540770-15-8	–
Salvinorin G		=O	–OCOCH3	C23H26O8	430.45 g·mol−1	866622-54-0	–
Salvinorin H		–OH	–OH	C21H26O7	390.43 g·mol−1	872004-62-1	–
Salvinorin I		–	–	C21H28O7	392.45 g·mol−1	917951-71-4	–
17α-Salvinorin J		–	–	C23H30O8	434.49 g·mol−1	1157894-83-1	–
17β-Salvinorin J		–	–	C23H30O8	434.49 g·mol−1	1157894-85-3	–

Occurrence

Originally isolated from S. divinorum, salvinorins are also detected in smaller amounts in:

• Salvia recognita (salvinorin A, 212.9 μg/g) ^[2]
• Salvia absconditiflora (salvinorin A at 51.5 μg/g, and salvinorin B at 402.2 μg/g) ^[2]
• Salvia glutinosa (salvinorin A, 38.9 μg/g) ^[2]
• Salvia potentillifolia (salvinorin B, 2352.0 μg/g) ^[2]
• Salvia adenocaulon (salvinorin B, 768.8 μg/g) ^[2]

For comparison, the amount of salvinorin A in S. divinorum ranges from 0.89 to 3.70 mg/g. All fractions reported are based on dry mass. ^[2]

Interestingly, the above reported species are not very closely related to S. divinorum. ^[2]

Associated compounds

In search for useful biological activity, several synthetic and semi-synthetic analogs have been prepared for study. Semi-synthetic analogs include salvinorin B ethoxymethyl ether and salvinorin B methoxymethyl ether. Fully synthetic analogs include herkinorin.

Several derivates can be conveniently made from salvinorin B. Most derivatives are selective kappa opioid agonists as with salvinorin A, although some are even more potent, with the most potent compound 2-ethoxymethyl salvinorin B being ten times stronger than salvinorin A. Some derivatives, such as herkinorin, reduce kappa opioid action and instead act as mu opioid agonists. ^{[3] [4] [5] [6]}

22-Thiocyanato-salvinorin A is notable because of its functional selectivity. ^[7] 2-Methoxymethyl Salvinorin B is seven times more potent than Salvinorin A at KOPr in GTP-γS assays. ^[8]

Many other terpenoids have been isolated from Salvia divinorum, including classes named divinatorins and salvinicins. None of these compounds have shown significant (sub-micromolar) affinity at the kappa-opioid receptor, and there is no evidence that they contribute to the plant's psychoactivity. ^{[9] [1]}

References

1. Munro TA; Rizzacasa MA (2003). "Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A". Journal of Natural Products. 66 (5): 703–5. doi:10.1021/np0205699. PMID   12762813.
2. Hatipoglu, SD; Yalcinkaya, B; Akgoz, M; Ozturk, T; Goren, AC; Topcu, G (November 2017). "Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species". Phytochemical Analysis. 28 (6): 541–549. doi:10.1002/pca.2703. PMID   28722248.
3. Munro TA; Duncan KK; Xu W; Wang Y; Liu-Chen LY; Carlezon WA; Cohen BM; Béguin C (2008). "Standard protecting groups create potent and selective κ opioids: salvinorin B alkoxymethyl ethers". Bioorganic & Medicinal Chemistry. 16 (3): 1279–86. doi:10.1016/j.bmc.2007.10.067. PMC   2568987 . PMID   17981041.
4. Holden KG; Tidgewell K; Marquam A; Rothman RB; Navarro H; Prisinzano TE (2007). "Synthetic studies of neoclerodane diterpenes from Salvia divinorum: exploration of the 1-position". Bioorganic & Medicinal Chemistry Letters. 17 (22): 6111–5. doi:10.1016/j.bmcl.2007.09.050. PMC   2111044 . PMID   17904842.
5. Lee DY; He M; Liu-Chen LY; Wang Y; Li JG; Xu W; Ma Z; Carlezon WA; Cohen B (2006). "Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A analogues". Bioorganic & Medicinal Chemistry Letters. 16 (21): 5498–502. doi:10.1016/j.bmcl.2006.08.051. PMID   16945525.
6. Béguin C; Richards MR; Li JG; Wang Y; Xu W; Liu-Chen LY; Carlezon WA; Cohen BM (2006). "Synthesis and in vitro evaluation of salvinorin A analogues: effect of configuration at C(2) and substitution at C(18)". Bioorganic & Medicinal Chemistry Letters. 16 (17): 4679–85. doi:10.1016/j.bmcl.2006.05.093. PMID   16777411.
7. White K, Robinson JE, Zhu H, et al. (2014). "The G-protein biased k-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo". J. Pharmacol. Exp. Ther. 352 (1): 98–109. doi:10.1124/jpet.114.216820. PMC   4279099 . PMID   25320048.
8. Wang, Y.; Chen, Y.; Xu, W.; Lee, D.; Ma, Z; Rawls, S.; Cowan, A.; Liu-Chen, L. (2008). "2-methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A." Journal of Pharmacology and Experimental Therapeutics. 324 (3): 1073–1083. doi:10.1124/jpet.107.132142. PMC   2519046 . PMID   18089845.
9. Bigham AK; Munro TA; Rizzacasa MA; Robins-Browne RM (2003). "Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage Salvia divinorum". Journal of Natural Products. 66 (9): 1242–4. CiteSeerX   10.1.1.693.6690 . doi:10.1021/np030313i. PMID   14510607.