- Efficient synthesis of cannabigerol, grifolin, and piperogalin via alumina-promoted allylation
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The synthesis of three phenolic natural products has been accomplished with unprecedented efficiency using a new alumina-promoted regioselective aromatic allylation reaction. Cannabigerol and grifolin were prepared in one step from the inexpensive 5-alkyl-resorcinols olivetol and orcinol. Piperogalin was synthesized, for the first time, via two sequential allylations of orcinol with geraniol and prenol.
- Jentsch, Nicholas G.,Zhang, Xiong,Magolan, Jakob
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- Uncovering the Hidden Antibiotic Potential of Cannabis
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The spread of antimicrobial resistance continues to be a priority health concern worldwide, necessitating the exploration of alternative therapies. Cannabis sativa has long been known to contain antibacterial cannabinoids, but their potential to address antibiotic resistance has only been superficially investigated. Here, we show that cannabinoids exhibit antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), inhibit its ability to form biofilms, and eradicate preformed biofilms and stationary phase cells persistent to antibiotics. We show that the mechanism of action of cannabigerol is through targeting the cytoplasmic membrane of Gram-positive bacteria and demonstrate in vivo efficacy of cannabigerol in a murine systemic infection model caused by MRSA. We also show that cannabinoids are effective against Gram-negative organisms whose outer membrane is permeabilized, where cannabigerol acts on the inner membrane. Finally, we demonstrate that cannabinoids work in combination with polymyxin B against multidrug resistant Gram-negative pathogens, revealing the broad-spectrum therapeutic potential for cannabinoids.
- Brown, Eric D.,Carfrae, Lindsey A.,El-Halfawy, Omar M.,Farha, Maya A.,Gale, Robert T.,Jentsch, Nicholas G.,Macnair, Craig R.,Magolan, Jakob,Zhang, Xiong
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Read Online
- CATALYTIC CANNABIGEROL PROCESSES AND PRECURSORS
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The present disclosure relates to cannabigerol sulfonate esters and processes for their use to prepare cannabigerol (CBG) and related compounds, including cannabigerobutol (CBGB), cannabigerovarin (CBGV), and cannabigerophorbol (CBGP). In a preferred embodiment, the cannabigerol sulfonate ester is (E)-4-(3, 7-5 dimethylocta-2,6-dienyl)-3,5-bis(trimetbylsilyloxy)phenyl trifluoromethanesulfonate. In a preferred process, the trifluoromethansulfonate leaving group is replaced by an alkyl group. The disclosure also relates to the use of catalysts and catalytic processes for the preparation of cannabigerol and related compounds from the cannabigerol sulfonate esters.
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- PROCESS FOR THE PRODUCTION OF CANNABINOIDS AND CANNABINOID ACIDS
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The present invention relates to a process for the preparation of diverse known and novel cannabinoids 5, which include cannabigerol (CBG, 1), cannabigerolic acid (CBGA, 2), cannabigerovarin (CBGV, 3), cannabigerovarinic acid (CBGVA, 4) and other naturally occurring monocyclic cannabinoids and other analogues from simple inexpensive starting materials using a cascade sequence of allylic rearrangement and aromatization. Novel cannabinoids of series 5 are also claimed as part of the invention. These synthesized cannabinoids, unlike the minor cannabinoids isolated from Cannabis saliva or synthesized from the condensation reactions such as the reactions of substituted resorcinols with monoterpenes, are much easier to obtain at high purity levels. In particular, these cannabinoids, including but not limited to cannabigerol (CBG, 1), cannabigerolic acid (CBGA, 2), cannabigerovarin (CBGV, 3) and cannabigerovarinic acid (CBGVA, 4) are obtained without contamination with impurities with variation in RA and RB (e.g. contamination of CBG with CBGV).
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Page/Page column 25
(2021/04/17)
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- PROCESSES FOR THE PREPARATION OF ORTHO-ALLYLATED HYDROXY ARYL COMPOUNDS
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The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).
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Paragraph 00261; 00268
(2021/12/08)
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- METHODS OF SYNTHESIZING CANNABIGERGOL, CANNABIGEROLIC ACID, AND ANALOGS THEREOF
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Disclosed are methods for preparing carmabigerol (CBG) or a CBG analog, embodiments of the method comprising providing a compound (I); combining the compound (I) with geraniol and a solvent to form a reaction mixture; and combining the reaction mixture with an acid catalyst to form a product mixture comprising CBG or the CBG analog. The method may further comprise separating the CBG or the CBG analog for the product mixture and may further comprise purifying the CBG or CBG analog. Methods for preparing cannabigerolic acid (CBGA) or a CBGA analog are also disclosed. The present disclosure also provides high purity CBG, CBGA and analogs thereof. CBG can be useful as a neuroprotectant, an antibacterial agent, etc.
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Paragraph 00102-00110
(2021/11/20)
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- PREPARING AND MODIFYING MEROTERPENE POLYKETIDES, KETONES, AND LACTONES FOR CANNABINOID SEMISYNTHESIS
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Provided herein are processes, including semi-synthetic, and synthetic processes for preparing cannabinoids, and cannabinoid compositions provided thereby.
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Page/Page column 29
(2021/08/20)
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- CRYSTALLINE CANNABIGEROL
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The application relates to crystalline cannabigerol comprising at least one X-ray powder diffraction peak selected from the group consisting of 4.73°, 9.52°, 14.30°, and 23.93° 2Θ (each ± 0.20° 2Θ), to methods of making the crystalline cannabigerol and its medical uses.
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Paragraph 00106; 00107
(2020/12/30)
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- ONE-STEP FLOW-MEDIATED SYNTHESIS OF CANNABIDIOL (CBD) AND DERIVATIVES
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Herein are described apparatus and processes for the preparation of cannabinoids, such as cannabidiol (CBD) and derivatives thereof. The apparatus and processes described can be used for the one-step, flow-mediated synthesis of cannabidiol and derivatives with improved overall yield, material throughput, and product purity relative to batch processes.
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Paragraph 0244
(2020/10/23)
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- SYNTHESIS OF CANNABIGEROL
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Multiple methods of synthesizing cannabigerol are presented. Combining olivetol with geraniol derivatives are provided. Cross-coupling methods of combing functionalized resorcinols are provided. Useful intermediates are formed during such cross-coupling steps.
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- METHODS FOR SYNTHESIS OF CANNABINOID COMPOUNDS
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The present invention provides simple synthetic routes for the preparation of cannabinoid compounds such as CBD, CBDV, THC, THCV, CBN, HU-308, CBG, CBC, and derivatives thereof, which are stereoselective and provide the desired cannabinoid compound in high yield.
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- HEMP POWDER
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A mixture of cannabinoids, drying agents, flowing agents, and/or stabilization agents are provided. The mixture may be a dry powder formulation similar to the consistency of flour or sand. The mixture may comprise a cannabinoid raffinate, an isolated cannabinoid, maltodextrin, and or silica. The ratio of raffinate to solids may be less than 0.625.
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- BIOENZYMATIC SYNTHESIS OF THC-v, CBV AND CBN AND THEIR USE AS THERAPEUTIC AGENTS
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The present invention provides methods for producing cannabinoids. More specifically, the invention is directed to the bio-enzymatic synthesis of THC-v, CBV and CBN by contacting a compound according to Formula I with a cannabinoid synthase enzyme. Also described is a system for producing these pharmaceutically important cannabinoids and the use of such cannabinoids as therapeutic agents.
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Paragraph 0130; 0131; 0132; 0133
(2017/10/18)
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- BIOSYNTHESIS OF CANNABINOID PRODRUGS AND THEIR USE AS THERAPEUTIC AGENTS
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The present invention provides methods for producing cannabinoid prodrugs. Also described are pharmaceuticals acceptable compositions of the prodrugs and a system for the large-scale production of the prodrugs.
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Paragraph 0193-0197
(2017/11/07)
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- METHODS FOR THE MANUFACTURE OF CANNABINOID PRODRUGS, PHARMACEUTICAL FORMULATIONS AND THEIR USE
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Described are methods for producing cannabinoid prodrugs as well as methods for formulating such prodrugs in a pharmaceutically acceptable form and their use as therapeutic agents for treating diseases.
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Paragraph 0138; 0139
(2018/01/18)
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- APPARATUS AND METHODS FOR THE SIMULTANEOUS PRODUCTION OF CANNABINOID COMPOUNDS
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The present invention provides an apparatus and methods for simultaneously producing different compounds in various ratios under set conditions.
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Page/Page column 67; 68
(2016/03/22)
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- BIOSYNTHESIS OF CANNABINOIDS
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The present invention provides methods for producing cannabinoids and cannabinoid analogs as well as a system for producing these compounds. The inventive method is directed to contacting a compound according to Formula I or Formula II with a cannabinoid synthase. Also described is a system for producing cannabinoids and cannabinoid analogs by contacting a THCA synthase with a cannabinoid precursor and modifying at least one property of the reaction mixture to influence the quantity formed of a first cannabinoid relative to the quantity formed of a second cannabinoid.
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Paragraph 0124-0126
(2014/09/16)
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- Chemoenzymatic syntheses of prenylated aromatic small molecules using Streptomyces prenyltransferases with relaxed substrate specificities
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NphB is a soluble prenyltransferase from Streptomyces sp. strain CL190 that attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide during the biosynthesis of anti-oxidant naphterpin. Here we report multiple chemoenzymatic syntheses of various prenylated compounds from aromatic substrates including flavonoids using two prenyltransferases NphB and SCO7190, a NphB homolog from Streptomyces coelicolor A3(2), as biocatalysts. NphB catalyzes carbon-carbon-based and carbon-oxygen-based geranylation of a diverse collection of hydroxyl-containing aromatic acceptors. Thus, this simple method using the prenyltransferases can be used to explore novel prenylated aromatic compounds with biological activities. Kinetic studies with NphB reveal that the prenylation reaction follows a sequential ordered mechanism.
- Kumano, Takuto,Richard, Stephane B.,Noel, Joseph P.,Nishiyama, Makoto,Kuzuyama, Tomohisa
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p. 8117 - 8126
(2008/12/23)
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- BORON TRIFLUORIDE ETHERATE ON ALUMINA - A MODIFIED LEWIS ACID REAGENT. AN IMPROVED SYNTHESIS OF CANNABIDIOL.
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Boron trifluoride etherate on alumina catalyses the condensation of resorcinols and monomethyl resorcinols with several monoterpenoid allylic alcohols: in contrast to paralell reactions with boron trifluoride etherate in solution the products obtained do not undergo further cyclisations.
- Baek, Seung-Hwa,Srebnik, Morris,Mechoulam, Raphael
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p. 1083 - 1086
(2007/10/02)
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