Natural Cannabichromene (CBC) Shows Distinct Scalemicity Grades and Enantiomeric Dominance in Cannabis sativa Strains

Abstract

Cannabichromene (CBC, 1a) occurs in Cannabis (Cannabis sativa) as a scalemate having a composition that is strain-dependent in terms of both enantiomeric excess and enantiomeric dominance. In the present work, the chirality of CBC (1a), a noncrystalline compound, was shown not to be significantly affected by standard conditions of isolation and purification, and enantiomeric self-disproportionation effects were minimized by carrying out the chiral analysis on crude fractions rather than on purified products. A genetic basis for the different enantiomeric state of CBC in Cannabis therefore seems to exist, implying that the chirality status of natural CBC (1a) in the plant is associated with the differential expression of CBCA-synthase isoforms and/or of associated directing proteins with antipodal enantiospecificity. The biological profile of both enantiomers of CBC should therefore be investigated independently to assess the contribution of this compound to the activity of Cannabis preparations.

Figure 1

Structures of CBC (1a), CBCA (1b), CBD (2), Δ⁹-THC (3), CBG (4), and CBN (5).

Figure 2

Crude plant ethanol extracts of CBG-rich and CBD-rich Cannabis strains (the red-line chromatogram refers to Finola, and the black-line chromatogram to the C37 cultivar).

Figure 3

Bar-chart graph showing the CBC (1a) content (% w/w) for cultivars reported in Table 1.

Figure 4

Relative percentage areas (%) of the CBC (1a) enantiomer peaks in the cultivars reported in Table 2 as resolved on an (S,S)-Whelk-O1 column (first eluted in blue, second eluted in orange). The enantiomeric excesses (ee %) are reported as gray bars.

Scheme 1. Formation of CBCA (1b) and cis-Δ⁹-THCA (8a) from the Electrocyclization of the Diastereomeric Forms of the Quinone Methide Intermediates 7a and 7b