Minor Cannabinoids of Cannabis sativa L.

Keywords: Cannabis sativa, Cannabinoids, Tetrahydrocannabinol, Cannabidiol, Cannabichromene, Minor cannabinoids, cannabinomics, cannabielsoin, cannabitriol

Abstract

Cannabinoids from Cannabis sativa L. play an important role as natural products in clinics. The major cannabinoids compromise tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) and its decarboxylated analogs. In this review, we focus on often neglected minor cannabinoids and discuss biosynthetic and chemical degradation routes to other neglected cannabinoids in Cannabis sativa starting from THCA, CBDA and cannabichromenic acid (CBCA). Based on the literature, patents and scientific reports, essential routes for the chemical modification of cannabinoids are discussed to explain chemical diversity chemical conversion and degradation by UV light, as well as temperature and pH leading to the formation of structurally unusual cannabinoids in planta called as minor cannabinoids. Based on known bioorganic reaction schemes and organic chemistry, principles for minor cannabinoid formation like [2+2] cycloaddition, Markonov condensation, radical introduction, or aromatization are discussed. Finally, the non-aqueous environment in Cannabis sativa trichomes is analyzed to clarify their role of a miniaturized bioreactors the light-induced conversion in  a non-aqueous enviroment. The overall objective is to bridge from metabolic profiling via cannabinomics to structural and chemical diversity that allows the definition of patterns with consequences also to pharmacology and plant breeding.

References

Pollastro F, De Petrocellis L, Schiano‑Moriello A, Chianese G, Heyman H, Appendino G, et al. Amorfrutin‑type phytocannabinoids from Helichrysum umbraculigerum. Fitoterapia. 2017.

Nagashima F, Asakawa Y. Terpenoids and bibenzyls from three argentine liverworts. Molecules. 2011.

Asakawa Y, Hashimoto T, Takikawa K, Tori M, Ogawa S. Prenyl bibenzyls from the liverworts Radula perrottetii and Radula complanata. Phytochemistry. 1991;30(1):235–51.

Degenhardt F, Stehle F, Kayser O. The Biosynthesis of Cannabinoids. In: Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis, and Treatment. 2017. p. 13–23.

Hanuš LO, Meyer SM, Muñoz E, Taglialatela‑Scafati O, Appendino G. Phytocannabinoids: a unified critical inventory. Nat Prod Rep [Internet]. 2016;33(12):1357–92.

ElSohly MA, Radwan MMM, Gul W, Chandra S, Galal A. Phytochemistry of Cannabis sativa L. In: Progress in the chemistry of organic natural products [Internet]. 2017. p. 1–36.

Muntendam R, Flemming T, Steup C, Kayser O. Chemistry and biological activity of Tetrahydrocannabinol and its derivatives. In: Topics in Heterocyclic Chemistry Bioactive Heterocycles IV. 2007. p. 1–42.

Citti C, Pacchetti B, Vandelli MA, Forni F, Cannazza G. Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA). J Pharm Biomed Anal. 2018;149:532–40.

Muhammad T. Akhtar, Shaari K, Verpoorte R. Biotransformation of Cannabinoids.

Flores‑Sanchez IJ. Polyketide synthases in Cannabis sativa L. Phytochemistry Reviews. 2008.

Onofri C, De Meijer EPM, Mandolino G. Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid‑synthase in Cannabis sativa L. and its relationship with chemical phenotype. Phytochemistry. 2015.

Tuner S, Williams C, Iversen L, Whalley B. Molecular Pharmacology of Phytocannabinoids. Prog Chem Org Nat Prod. 2017;103:81–101.

Wood TB, Spiye WTN, Easterfi TH. Cannabinol. Part1. J Chem Soc Trans. 1898;75(20):20–36.

Uliss DB, Razdan RK, Dalzell HC, Handrick GR. Synthesis of racemic and optically active Δ1- and Δ6–3,4-cis‑tetrahydrocannabinols. Tetrahedron. 1977.

Radwan MM, ElSohly MA, El‑Alfy AT, Ahmed SA, Slade D, Husni AS, et al. Isolation and Pharmacological Evaluation of Minor Cannabinoids from High‑Potency Cannabis sativa. J Nat Prod. 2015.

Carbone M, Castelluccio F, Daniele A, Sutton A, Ligresti A, Di Marzo V, et al. Chemical characterisation of oxidative degradation products of Δ9-THC. Tetrahedron. 2010.

Smith RN. High‑pressure liquid chromatography of cannabis. Identification of separated constituents. J Chromatogr A. 1975;115(1):101–6.

Sirikantaramas S, Taura F, Morimoto S, Shoyama Y. Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology. Curr Pharm Biotechnol [Internet]. 2007;8(4):237–43.

Turner CE, Elsohly MA, Boeren EG. Constituents of cannabis sativa l. XVII. a review of the natural constituents. J Nat Prod. 1980.

Kane V V. Structure of cannabicyclol, a detailed NMR study of a synthetic analog. Tetrahedron Lett. 1971.

de Zeeuw RA, Vree TB, Breimer DD, van Ginneken CAM. Cannabivarichromene, a new cannabinoid with a propyl side chain in cannabis. Experientia. 1973.

Braemer R, Paris M. Biotransformation of cannabinoids by a cell suspension culture of Cannabis sativa L. Plant Cell Rep. 1987;6(2):150–2.

Ikuo Yamamoto, Hiroshi Gohda, Shizuo Narimatsu, Kazuhito Watanabe, Hidetoshi Yoshimura. Cannabielsoin as a new metabolite of cannabidiol in mammals. Pharmacol Biochem Behav. 1991.

Yamamoto I, Gohda H, Narimatsu S, Yoshimura H. Identification of cannabielsoin, a new metabolite of cannabidiol formed by guinea‑pig hepatic microsomal enzymes, and its pharmacological activity in mice. J Pharmacobiodyn. 2011.

Mahlberg PG, Kim E. Secretory Vesicle Formation in Glandular Trichomes of Cannabis sativa (Cannabaceae). Am J Bot. 1992;79(2):166–73.

Rodziewicz P, Loroch S, Marczak Ł, Sickmann A, Kayser O. Cannabinoid synthases and osmoprotective metabolites accumulate in the exudates of Cannabis sativa L. glandular trichomes. Plant Sci. 2019.

Published
2019-10-01
How to Cite
Thomas, F., & Kayser, O. (2019). Minor Cannabinoids of Cannabis sativa L. Journal of Medical Science, 88(3), 141-149. https://doi.org/10.20883/jms.367
Section
Original Papers