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. 2020 Oct 23;83(10):2894-2901.
doi: 10.1021/acs.jnatprod.0c00436. Epub 2020 Sep 29.

Cannabidiol as the Substrate in Acid-Catalyzed Intramolecular Cyclization

Paola Marzullo  1 , Francesca Foschi  1 , Davide Andrea Coppini  1 , Fabiola Fanchini  1 , Lucia Magnani  1 , Selina Rusconi  1 , Marcello Luzzani  1 , Daniele Passarella  1
Affiliations

Cannabidiol as the Substrate in Acid-Catalyzed Intramolecular Cyclization

Paola Marzullo et al. J Nat Prod. .

Abstract

The chemical reactivity of cannabidiol is based on its ability to undergo intramolecular cyclization driven by the addition of a phenolic group to one of its two double bonds. The main products of this cyclization are Δ9-THC (trans-Δ-9-tetrahydrocannabinol) and Δ8-THC (trans-Δ-8-tetrahydrocannabinol). These two cannabinoids are isomers, and the first one is a frequently investigated psychoactive compound and pharmaceutical agent. The isomers Δ8-iso-THC (trans-Δ-8-iso-tetrahydrocannabinol) and Δ4(8)-iso-THC (trans-Δ-4,8-iso-tetrahydrocannabinol) have been identified as additional products of intramolecular cyclization. The use of Lewis and protic acids in different solvents has been studied to investigate the possible modulation of the reactivity of CBD (cannabidiol). The complete NMR spectroscopic characterizations of the four isomers are reported. High-performance liquid chromatography analysis and 1H NMR spectra of the reaction mixture were used to assess the percentage ratio of the compounds formed.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Structures of cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (Δ9-THC).
Scheme 1
Scheme 1. CBD Acid-Promoted Cyclization
Scheme 2
Scheme 2. CBD Conversions with Acids and the Structures of the Products
Figure 2
Figure 2
1H NMR spectrum in CDCl3 of a mixture of CBD, Δ9-THC, Δ8-THC, and Δ8-iso-THC.
Figure 3
Figure 3
Representative chromatogram of the standard cannabinoid mixture.
See this image and copyright information in PMC

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