Biosynthesis and Chemical Modifications of Minor Cannabinoids

Abstract

Minor cannabinoids are cannabinoids at very low abundances in Cannabis sativa L. essential oils (<0.5% of dried weight). The pharmacological properties of minor cannabinoids have never been determined or validated in clinical assays or in rational in vitro and in vivo assays. Due to this lack of biological and pharmacological information, minor cannabinoids have great potential as future drug candidates. The biosynthesis of minor cannabinoids is not clear in C. sativa L., but, likely, chemical conversion in the trichomes influenced by light, temperature and ultraviolet (UV) radiation is the main catalytic mode. This chemical conversion may explain the high chemodiversity and low structural stability.

Key Concepts

  • Minor cannabinoids are at very low abundance in Cannabis sativa L.
  • Chemical diversity of essential oil is a consequence of chemical transformation.
  • The role of minor cannabinoids in planta is unknown and needs further investigations.
  • Minor cannabinoids can be considered as future candidates in drug discovery.
  • Minor cannabinoids are found in other species (plant, moss, fungus) and chemical diversity is not limited to Cannabaceae only.

Keywords: Cannabis sativa; cannabinoids; tetrahydrocannabinol; cannabidiol; cannabichromene; 2 + 2 cycloaddition; photochemistry

Figure 1. The basic concept of the tetrahydrocannabinolic acid biosynthesis in C. sativa L.
Figure 10. Price categories for selected rare cannabinoids.
Figure 2. Important minor phytocannabinoids in various organisms. (a) THC‐C7. (b) Cannabinol (CBN‐C5). (c) Cannabinodiol (CBDN‐C5). (d) Cannabioxepane (CBX). (e) Cannabicyclol (CBL). (f) Cannabichromene (CBC).
Figure 3. Biosynthetic units of the cannabinoid skeleton.
Figure 4. Compartmentalised enzymatic (right) and nonenzymatic (left) conversion and synthesis of cannabinoids in Cannabis sativa L. stalked trichomes.
Figure 5. Metabolisation of THC by plants (green), humans (yellow) and microorganisms (grey).
Figure 6. Basic routes in the formation of minor cannabinoids starting from CBG‐C5.
Figure 7. A theoretical model to explain the aromatisation of THC to CBN.
Figure 8. Chemical conversion of CBD‐C5 to Δ810‐THC at pH 1.
Figure 9. Proposed [2 + 2] cycloaddition from CBC‐C5 (left) to CBL‐C5 (right).
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Nguyen, Gia‐Nam, and Kayser, Oliver(May 2020) Biosynthesis and Chemical Modifications of Minor Cannabinoids. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028875]