- Using (+)-carvone to access novel derivatives of (+)-ent-cannabidiol: The first asymmetric syntheses of (+)-ent-CBDP and (+)-ent-CBDV
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(?)-Cannabidiol [(?)-CBD] has recently gained prominence as a treatment for neuro-inflammation and other neurodegenerative disorders; interest is also developing in its synthetic enantiomer, (+)-CBD, which has a higher affinity to CB1/CB2 receptors than the natural stereoisomer. We have developed an inexpensive, stereoselective route to access ent-CBD derivatives using (+)-carvone as a starting material. In addition to (+)-CBD, we report the first syntheses of (+)-cannabidivarin, (+)-cannabidiphorol as well as C-6/C-8 homologues.
- Golliher, Alexandra E.,Tenorio, Antonio J.,Dimauro, Nina O.,Mairata, Nicolas R.,Holguin, F. Omar,Maio, William
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supporting information
(2021/02/20)
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- A Novel and Practical Continuous Flow Chemical Synthesis of Cannabidiol (CBD) and its CBDV and CBDB Analogues
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Cannabidiol is one of the main non-psychoactive cannabinoids present in Cannabis sativa and, in the last decade, it is gaining great interest among the scientific community for its pharmaceutical, nutraceutical, and cosmetic applications. Herein, we report the first continuous flow chemical synthesis of cannabidiol (CBD) and its analogues cannabidivarin (CBDV) and cannabidibutol (CBDB). This approach permits to synthesize products in very good yields (55–59 %), limiting the formation of psychoactive and illegal cannabinoids such as tetrahydrocannabinol (THC).
- Chiurchiù, Elena,Sampaolesi, Susanna,Allegrini, Pietro,Ciceri, Daniele,Ballini, Roberto,Palmieri, Alessandro
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supporting information
p. 1286 - 1289
(2021/02/05)
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- Cannabidiol derivative as well as preparation method and medical application thereof
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The invention relates to a cannabidiol derivative and application thereof in medicine, in particular to a pyrimidine derivative as shown in a general formula (I), or a stereoisomer, a solvate, a metabolite, a prodrug, a pharmaceutically acceptable salt or a co-crystal thereof, and definition of each substituent in the general formula (I) is the same as that in the specification.
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Paragraph 0153; 0156; 0163-0168
(2021/07/10)
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- A Revised Modular Approach to (–)-trans-Δ8-THC and Derivatives Through Late-Stage Suzuki–Miyaura Cross-Coupling Reactions
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A revised modular approach to various synthetic (–)-trans-Δ8-THC derivatives through late-stage Suzuki–Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp2- and sp3-hybridized cross-coupling partners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki–Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature.
- Bloemendal, Victor R. L. J.,Sondag, Daan,Elferink, Hidde,Boltje, Thomas J.,van Hest, Jan. C. M.,Rutjes, Floris P. J. T.
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p. 2289 - 2296
(2019/04/03)
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- PROCESS FOR THE PRODUCTION OF CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL
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The present disclosure relates to the preparation of a cannabidiol compound or a derivative thereof. The cannabidiol compound or derivatives thereof can be prepared by an acid-catalyzed reaction of a suitably selected and substituted di-halo-olivetol or derivative thereof with a suitably selected and substituted cyclic alkene to produce a dihalo-cannabidiol compound or derivative thereof. The dihalo-cannabidiol compound or derivative thereof can be produced in high yield, high stereospecificity, or both. It can then be converted under reducing conditions to a cannabidiol compound or derivatives thereof.
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Paragraph 0232; 0233
(2017/01/31)
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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 0145; 0146
(2017/10/18)
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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 71
(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 0120-0122; 0138
(2014/09/16)
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- Simple synthesis of 5-substituted resorcinols: A revisited family of interesting bioactive molecules
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The reaction of 3,5-dimethoxybenzyl trimethylsilyl ether (3) with different aldehydes (n-PrCHO, n-C11H23CHO, MeCHO, PhCHO) in the presence of lithium powder and a catalytic amount of naphthalene (4 mol %) gave, after hydrolysis, the expected alcohols 4 in moderate yields. The dehydroxylation of these compounds through the corresponding mesylates 5 or directly from benzylic derivatives by catalytic hydrogenation, afforded compounds 6, which are finally demethylated to yield 5-alkyl-3,5-dihydroxyresorcinols, such as olivetol (7a), grevillol (7b), 1,3-dihydroxy-5-propylbenzene (7c), or dihydropinosilvine (7d). Dehydration of alcohol derivatives 4 followed by demethylation led to hydroxylated stilbene-type structures, such as pinosilvine (9d), resveratrol (9e), or piceatannol (9f), which in some cases can be hydrogenated to give saturated molecules such as combretastanin B-4 tetramethyl ether (6f) or chrysotobibenzyl (6g). Finally, when the naphthalene-catalyzed lithiation of compound 3 was performed in the presence of other electrophiles [Me3SiCl, t-BuCHO, CH3(CH2)4CHO, 4-Me3SiOC6H4CHO, (CH2)5CO, PhN = C = O, PhN = CHPh], the expected reaction products 12 were isolated, after hydrolysis.
- Alonso, Emma,Ramon, Diego J.,Yus, Miguel
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p. 417 - 421
(2007/10/03)
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- Substrate selective catalysis by rhodium metallohosts
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A novel supramolecular catalyst functioning according to the principles of enzymatic catalysis is described. It consists of a basket-shaped molecule to which a catalytically active Rh(I) complex is attached. The catalyst selectively hydrogenates and isomerizes allyl-substituted dihydroxyarene substrates that are bound in its cavity. The reactivity of this supramolecular catalyst and its affinity for several substrates is compared with that of the corresponding catalyst without a binding site. Features known from enzymatic catalysis, e.g. Michaelis-Menten kinetics and rate enhancement by cooperative binding, are described and discussed.
- Coolen, Hein K. A. C.,Meeuwis, Johannes A. M.,Van Leeuwen, Piet W. N. M.,Nolte, Roeland J. M.
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p. 11906 - 11913
(2007/10/03)
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- Synthesis and pharmacological evaluation of ether and related analogues of Δ8-, Δ9-, and Δ9,11-tetrahydrocannabinol
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The primary goal of this research was to synthesize a series of ether analogues of the cannabinoid drug class and to evaluate their agonist and antagonist pharmacological properties in either the mouse or the rat. Agonist and antagonist activity was evaluated in mice using a multiple-evaluation procedure (locomotor activity, tail-flick latency, hypothermia, ring immobility) and activity in rats determined in a discriminative stimulus paradigm. Additionally, novel analogues were evaluated for their ability to bind to the THC receptor site labeled by 3H-CP-55,940. None of the cannabinoid analogues were capable of attenuating the effects of Δ9-THC (3 mg/kg) in either the rat (doses up to 10 mg/kg) or in the mouse (doses up to 30 mg/kg). It also appears that the compounds with minimal in vivo activity are not mixed agonist/antagonists. These data would suggest that the phenolic hydroxyl is important for receptor recognition (binding) and in vivo potency. Additionally, cannabinoid methyl ethers previously considered inactive have been found to produce limited activity. Lastly, data suggest that Δ9,11- THC is more potent than previous reports indicated, and does possess pharmacological activity.
- Compton,Prescott Jr.,Martin,Siegel,Gordon,Razdan
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p. 3310 - 3316
(2007/10/02)
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- BIOLOGICALLY ACTIVE PHENOLIC METABOLITES OF A VERTICICLADIELLA SPECIES
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The metabolites produced when a Verticicladiella species (Canadian Forestry Service strain C728), the causative agent of the black stain root disease of many conifers, is grown in liquid culture have been investigated.Orcinol, orcinol monomethyl ether, 1,3,6,8-tetrahydroxyanthraquinone, and the α-L-rhamnopyranosides of orcinol and orcinol methyl ether have been isolated and indentified.Orcinol methyl ether and its rhamnoside both show antibacterial activity and orcinol methyl ether also inhibits the growth of pine germlings.The general antibacterial activity of 5-alkylresorcinols and their monomethyl ethers is reported.-Key Word Index-Verticicladiella sp.; Deuteromycontina; blue-stain fungus; phytotoxin; phenols; methylorcinol rhamnoside; phenol monomethyl ethers; antiseptics.
- Ayer, William A.,Browne, Lois M.,Lovell, Sarah H.
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p. 2267 - 2272
(2007/10/02)
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- Long-chain Phenols. Part 16. A Novel Synthesis of Homologous Orsellinic Acids and their Methyl Ethers
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By the novel reaction of 3,5-dimethoxyfluorobenzene with n-alkyl-lithium compounds, followed by carbonation, homologous orsellinic acid dimethyl ethers (6-alkyl-2,4-dimethoxybenzoic acids) have been obtained.The reactions proceeded best with the homologues of methyl-lithium.These reactions are considered to occur by way of 3,5-dimethoxybenzyne. 2,4-Dimethoxyfluorobenzene did not form an aryne but gave 3-fluoro-2,6-dimethoxybenzoic acid instead.Decomposition with water of alkyl-lithium reaction mixtures from 3,5-dimethoxyfluorobenzene yielded 5-n-alkylresorcinol dimethyl ethers.Demethylaton of 6-alkyl-2,4-dimethoxybenzoic acids with boron trichloride proceeded partially and selectively to give the 6-alkyl-2-hydroxy-4-methoxybenzoic acids, and completely with aluminium chloride to give the homologous orsellinic acids.Boron tribromide was less effective, but readily gave the 5-alkyl resorcinols from the corresponding dimethyl ethers.
- Durrani, Aziz A.,Tyman, John H. P.
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p. 1658 - 1666
(2007/10/02)
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