Cannabichromene Racemization and Absolute Stereochemistry Based on a Cannabicyclol Analog

Cannabichromene (CBC) is unusual among cannabinoids in having been described as both a racemic and a scalemic compound from natural Cannabis sources. Several explanations are available for this circumstance, including facile racemization. Cannabichromene was resolved chromatographically, and the enantiomer matching CBC from local Cannabis was identified. To preclude racemization, CBC was converted to cannabicyclol for further stereochemical analysis. This permitted the (R) absolute stereochemistry to be assigned to natural CBC based on chiroptical data for related natural products and the absolute configuration of a cannabicyclol analog determined by X-ray crystallography. The racemization of CBC was found to be rather slow in the laboratory, but handling practices for natural cannabis products can be inferred to promote the process.