title: High-pressure access to the Δ9-cis- and Δ9-trans-tetrahydrocannabinols family.
abstract: 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 Δ(9)-cis-tetrahydrocannabinol (THC) and Δ(9)-trans-THC, through the use of selected Diels-Alder adducts, are described. Finally, a route for obtaining Δ(9)-trans-THC in both enantiomeric pure forms based on the (S)-(-)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP)-hydrazone method is also reported.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, via Elce di Sotto 8, 06123 Perugia, Italy. lucio@unipg.it
authors.forename: Lucio
authors.initials: L
authors.lastname: Minuti
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ballerini
mesh_terms: D013759:Dronabinol / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011312:Pressure; D013237:Stereoisomerism
chemical_list: D013759:Dronabinol