The present disclosure relates to new cannabinoid derivatives and precursors and catalytic asymmetric processes for their preparation. The disclosure also relates to pharmaceutical compositions and pharmaceutical and analytical uses of the new cannabinoid derivatives. For instance, the disclosure relates to the preparation of new precursors, and the use of such precursor compounds for the preparation of isotope labelled cannabinoid products using chiral and achiral catalysts and catalytic processes. The deuterium, carbon-13 and carbon-14 containing compounds can be prepared and purified prior to transformation to the desired individual deuterated cannabinoid products.

This disclosure relates generally to cannabinoid derivatives having the formula (I), wherein R.sup.4 is hydrogen, —C(Q.sup.1)N(R.sup.4a)(R.sup.4b) or —C(R.sup.4J)(R.sup.4k)N(R.sup.4e)C(0)R.sup.4f, R.sup.6 is hydrogen, —C(Q.sup.2)N(R.sup.6a)(R.sup.6b) or —C(R.sup.6J)(R.sup.6k)N(R.sup.6e)C(0)R.sup.6f, provided that R.sup.6 is not hydrogen when R.sup.4 is hydrogen. Pharmaceutical compositions for the prevention or treatment of a disease associated with a cannabinoid receptor (such as CB1 or CB2) in a subject in need thereof, and methods of using the cannabinoid derivatives are also described.

This disclosure relates generally to cannabinoid derivatives having the formula (I), wherein R.sup.4 is hydrogen, —C(Q.sup.1)N(R.sup.4a)(R.sup.4b) or —C(R.sup.4J)(R.sup.4k)N(R.sup.4e)C(0)R.sup.4f, R.sup.6 is hydrogen, —C(Q.sup.2)N(R.sup.6a)(R.sup.6b) or —C(R.sup.6J)(R.sup.6k)N(R.sup.6e)C(0)R.sup.6f, provided that R.sup.6 is not hydrogen when R.sup.4 is hydrogen. Pharmaceutical compositions for the prevention or treatment of a disease associated with a cannabinoid receptor (such as CB1 or CB2) in a subject in need thereof, and methods of using the cannabinoid derivatives are also described.

The present invention provides a dynamic interface system between an extraction device and a chromatographic purification device for separating and purifying substance(s) from a mixture or matrix. One embodiment is the Supercritical Fluid Interface (“SFI”) between Supercritical Fluid Extraction (“SFE”), and Supercritical Fluid Chromatography (“SFC”). The SFI is capable of interfacing; gas, subcritical and supercritical fluid extraction methods and pair with gas, subcritical and supercritical fluid chromatography technologies that operate within the pressure and temperature parameters of the SFI. The SFI can operate up to 200 degrees celsius and 5000 psi. This interface technology allows for an inline oil extraction and chromatographic separation, the SFI can pair extraction and chromatography with the same solvent in different mobile phases, whereas the extraction can be performed using CO.sub.2 as a solvent in sub-critical phase and the SFI can receive the subcritical solution and then increase pressure and/or temperature to achieve supercritical state as required for injection into supercritical fluid chromatography technologies. The SFI coupling between SFE and SFC can to extract and refine cannabinoids from the cannabis industrious, hemp, plant and can also be applied to improve efficiency in an industry that extracts and refines oils, through chromatography, from organic materials using a gas, or sub/supercritical fluid as a solvent and mobile phase.

The present invention provides a dynamic interface system between an extraction device and a chromatographic purification device for separating and purifying substance(s) from a mixture or matrix. One embodiment is the Supercritical Fluid Interface (“SFI”) between Supercritical Fluid Extraction (“SFE”), and Supercritical Fluid Chromatography (“SFC”). The SFI is capable of interfacing; gas, subcritical and supercritical fluid extraction methods and pair with gas, subcritical and supercritical fluid chromatography technologies that operate within the pressure and temperature parameters of the SFI. The SFI can operate up to 200 degrees celsius and 5000 psi. This interface technology allows for an inline oil extraction and chromatographic separation, the SFI can pair extraction and chromatography with the same solvent in different mobile phases, whereas the extraction can be performed using CO.sub.2 as a solvent in sub-critical phase and the SFI can receive the subcritical solution and then increase pressure and/or temperature to achieve supercritical state as required for injection into supercritical fluid chromatography technologies. The SFI coupling between SFE and SFC can to extract and refine cannabinoids from the cannabis industrious, hemp, plant and can also be applied to improve efficiency in an industry that extracts and refines oils, through chromatography, from organic materials using a gas, or sub/supercritical fluid as a solvent and mobile phase.

This invention is for improving the manufacturing pharmaceutical grade CBD and other cannabinoids following current Good Manufacturing Practices (cGMP) of the US FDA for use in clinical trials for CNS and other indications by the NIH and other researchers. The major cannabinoids in marijuana (Cannabis) and hemp originate from Cannabigerolic Acid (CBGA) present in the biomass of the plant. Plant enzymes that are specific to different strains of biomass converts CBGA to different carboxylic acids of cannabinoids including Cannabidiolic Acid (CBDA) and Δ9-Tetrahydrocannabinolic Acid (Δ9-THCA). These are relatively stable in the growing and fresh-cut plants. These are converted by thermal decarboxylation to Cannabidiol (CBD) and Δ9-Tetrahydrocannabinol (Δ9-THC), carbon dioxide and water. Cannabinoids can be manufactured by first heating the Cannabis biomass to convert carboxylic acids prior to extraction and purification. Alternatively, and preferably because of manufacturing cost and product stability, the carboxylic acids can be first extracted and purified. They can be utilized in the carboxylic acid form or stored in a stable manner until converted to cannabinoids for use in medicine. This invention provides an efficient method for their conversion utilizing a high-pressure reactor under inert conditions.

This invention is for improving the manufacturing pharmaceutical grade CBD and other cannabinoids following current Good Manufacturing Practices (cGMP) of the US FDA for use in clinical trials for CNS and other indications by the NIH and other researchers. The major cannabinoids in marijuana (Cannabis) and hemp originate from Cannabigerolic Acid (CBGA) present in the biomass of the plant. Plant enzymes that are specific to different strains of biomass converts CBGA to different carboxylic acids of cannabinoids including Cannabidiolic Acid (CBDA) and Δ9-Tetrahydrocannabinolic Acid (Δ9-THCA). These are relatively stable in the growing and fresh-cut plants. These are converted by thermal decarboxylation to Cannabidiol (CBD) and Δ9-Tetrahydrocannabinol (Δ9-THC), carbon dioxide and water. Cannabinoids can be manufactured by first heating the Cannabis biomass to convert carboxylic acids prior to extraction and purification. Alternatively, and preferably because of manufacturing cost and product stability, the carboxylic acids can be first extracted and purified. They can be utilized in the carboxylic acid form or stored in a stable manner until converted to cannabinoids for use in medicine. This invention provides an efficient method for their conversion utilizing a high-pressure reactor under inert conditions.

Described is an extraction device for extracting compounds from plant material and a method for using such an extraction device. The extraction device comprises an extraction tank receiving plant material and dissolving soluble compounds inside the plant material into a solvent to form a micelle. A series of fluidly connected separation chambers separate purified compounds from the micelle, resulting in purified compounds in each of the separation chambers and solvent. A heat exchanger and a chilled reservoir are used for cooling and storing the solvent. A pump is used for pumping and circulating the solvent into the extraction device. Finally, a control system automatically controls temperature and flow in the extraction device.

Described is an extraction device for extracting compounds from plant material and a method for using such an extraction device. The extraction device comprises an extraction tank receiving plant material and dissolving soluble compounds inside the plant material into a solvent to form a micelle. A series of fluidly connected separation chambers separate purified compounds from the micelle, resulting in purified compounds in each of the separation chambers and solvent. A heat exchanger and a chilled reservoir are used for cooling and storing the solvent. A pump is used for pumping and circulating the solvent into the extraction device. Finally, a control system automatically controls temperature and flow in the extraction device.

The novel water-soluble salts of cannabinoids with increased bioavailability, their preparation and uses.