6465-30-1

Upstream product

• 500-66-3 Olivetol 
• 5392-40-5 (E/Z)-3,7-dimethyl-2,6-octadienal 
• 141-27-5 3,7-dimethyl-2,6-octadienal 
• 16850-65-0 Methyl tetrahydrocannabinolate 
• 3411-09-4 (E)-4-(2,6-dimethoxy-4-pentylphenyl)but-3-en-2-one 
• 7663-54-9 2',6'-dimethoxy-1'-((E)-3-methylbuta-1,3-dienyl)-4'-pentylbenzene 
• 3410-84-2 2,6-dimethoxy-4-pentylbenzaldehyde 

Relevant academic research and scientific papers

Δ9-cis-Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology

Thecis-stereoisomers of Δ9-THC [(?)- 3 and (+)- 3 ] were identified and quantified in a series of low-THC-containing varieties ofCannabis sativaregistered in Europe as fiber hemp and in research accessions of cannabis. While Δ9-cis-THC ( 3 ) occurs in cannabis fiber hemp in the concentration range of (?)-Δ9-trans-THC [(?)- 1 ], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ9-cis-THC ( 3 ) is scalemic (ca. 80-90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6aS,10aR[(?)- 3 ] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (?)-Δ9-cis-THC [(?)- 3 ], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of “Δ9-THC and isomers” and needs therefore revision, or at least a more specific wording, to account for the presence of Δ9-cis-THCs [(+)- 3 and (?)- 3 ] in cannabis fiber hemp varieties.

High-pressure access to the Δ9-cis - And Δ9-trans-tetrahydrocannabinols family

Diels-Alder reactions of a range of 1-(alkoxy/alkyl-substituted phenyl)buta-1,3-dienes with methyl vinyl ketone and methyl acrylate carried out in ethanol as the reaction medium under 9 kbar pressure were investigated. The use of high pressure as the activating method of the Diels-Alder reactions allows the efficient and endodiastereoselective generation of a series of cis-cyclohexenyl-benzene cycloadducts, which are selectively converted into their trans-epimers. The cis-cyclohexenyl-benzenes and trans-cyclohexenyl- benzenes produced are useful precursors for accessing substituted privileged cis-6a,7,8,10a-tetrahydro-6H-benzo[c]chromene and trans-6a,7,8,10a-tetrahydro- 6H-benzo[c]chromene skeletons. The total syntheses of Δ9-cis- tetrahydrocannabinol (THC) and Δ9-trans-THC, through the use of selected Diels-Alder adducts, are described. Finally, a route for obtaining Δ9-trans-THC in both enantiomeric pure forms based on the (S)-(-)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP)-hydrazone method is also reported.

Tetrahydrocannabinol revisited: Synthetic approaches utilizing molybdenum catalysts

Δ9-Tetrahydrocannabinol 1 and its isomers were synthesized via domino-type methodology. The first approach, leading to (±)-1, relies on the Mo(IV)-catalyzed, one-pot cascade reaction of citral (4) with olivetol (15), affording (±)-Δ9-tetrahydrocannabinol as a 69 : 31 mixture of the trans-(natural) and cis-isomers in 20% yield. The alternative approach, leading to natural (-)-1, commenced with epoxidation of (+)-limonene (R)-(+)-16; opening of the resulting cis-epoxide 17 with PhSeNa, followed by elimination, afforded tertiary alcohol 21, whose acetate 22 was treated with olivetol 15 in the presence of Mo(II) catalyst IV to afford (-)-1 in 52% yield.

A BIOMIMETIC SYNTHESIS OF 1Δ-TETRAHYDROCANNABIOL

Condensation of 1,3-bis(trimethylsiloxy)-1-methoxybutadiene with the acid chloride 12 gave methyl olivetolate (13).Condensation of 13 with (+)-p-mentha-2,8-dien-1-ol gave methyl 1Δ-tetrahydrocannabiolate (14) in 55percent isolated yield.Alkaline hydrolysis of 14 gave 1Δ-tetrahydrocannabinol (1, 1Δ-THC).The synthesis is patterned after the biogenesis of 1.