Y. Gaoni's research while affiliated with Weizmann Institute of Science and other places

Publications (28)

Article
Addition von Citral (I) an das Li-Derivat des Olivetoldiäthers (II) und nachfolgende Reaktion mit p-Tosylchlorid liefert den (i)-Diäther (IIIa), der durch Demethylierung (Erhitzen mit Methyl-MgJ bei 155-160°C) (i)-Cannabidiol (IIIb) liefert.
Article
Addition of citral to the lithium derivative of olivetol dimethyl ether, followed by reaction with p-toluenesulfonyl chloride, gave (±)-cannabidiol dimethyl ether (1b). Demethylation afforded (±)-cannabidiol (1a), which was converted into (±)-Δ1-tetrahydrocannabinol (Δ1-THC) (2) in a low overall yield. An improved synthesis of (±)-Δ1-THC was achiev...
Article
The isolation and elucidation of the structures of Δ1-tetrahydrocannabinol (Δ1-THC), cannabigerol, cannabichromene, and cannabicyclol are described. A facile conversion of cannabidiol into Δ1-THC takes place on treatment with boron trifluoride etherate. The absolute configuration of the chiral centers at C-3 and C-4 of Δ1-THC is established as R.
Article
The purple colour produced by treatment of cannabidiol (I) with 5% ethanolic potassium hydroxide (Beam test) is due to the anions of the hydroxy-quinone II and its dimer III. Compounds II and III are formed from I by air oxidation during the reaction. The quinone III is reduced in the mass spectrometer to a M+ + 4 species (probably the dihydroquino...
Article
Synthetic routes are described which lead to iso-tetrahydrocannabinols, a new series of structural isomers of the natural Δ1-tetrahydrocannabinol. In this group of compounds a dihydrobenzopyran ring system is formed by cyclization of one of the phenolic groups of a cannabinoid with the C1 carbon in the terpene moiety of the molecule.
Article
Reaction of a series of γδ-unsaturated ketones with m-chloroperbenzoic acid did not yield the expected epoxides. Depending on the nature of the unsaturated ketone, the reaction products are two (occasionally one) 2,7-dioxabicyclo[2,2,1]heptanes or a mixture of these with two epimeric 6-hydroxy-2,7-dioxabicyclo[2,2,1]heptanes and a 5-hydroxymethyldi...
Article
The n.m.r. spectra of nine substituted 2,7-dioxabicyclo[2,2,1]heptanes are discussed in terms of chemical shifts and coupling constants. The relative chemical shifts of endo- and exo-protons are the reverse of those in the analogous carbocyclic systems. The spectra are also characterised by a relatively large 4J(exo,exo)(3·0 c./sec.). There is stro...
Article
Oxidation of several 1,4-dimethyl-6-phenyl-2,7-dioxabicyclo[2,2,1]heptanes with m-chloroperbenzoic acid yielded the title bicyclic orthoesters, with conservation of configuration of the 6-substituents. With 6-endo-alkyl-6-exo-phenyl substituents, the oxidation was directed towards the 1-methyl, yielding the 1-hydroxymethyl analogue of the starting...
Article
Cannabis saliva L. (family Moraceae) is a dioecious plant of which two varieties exist, var. indica and var. non indica or typica. The flowering top of the female plant is covered with glandular hairs which secrete a resin. The resin formation ceases when the seeds mature and its function is to protect them during the ripening period. The cannabis...
Article
Base treatment of the tosylhydrazone of dimethyldimedone leads to unsaturated ketones. Similar reactions on the monotosylates of its hydride reduction products result in ring scission. Selenium dioxide oxidation of dimethyldimedone yields a trione or tetrone, end products also of successive treatments of the diketone with lead tetraacetate, aqueous...
Article
Depending on the reaction conditions used, the physiologically active products obtained by Adams on isomerization of the inactive cannabidiol (Ia) with acids are shown to be either Δ1(6) tetrahydrocannabinol (II) or a mixture of II, Δ1 tetrahydrocannabinol (IIIa) and the two isomers of 1-ethoxy hexahydrocannabinol (VIIIa, VIIIb).
Article
The mass spectra of several constituents of hashish and compounds derived from them are discussed. Fragmentation occurs preferentially in the alicyclic portion of the molecules, while the benzene ring functions as a charge stabilizing element. Numerous rearrangement reactions are observed which are typical for monoterpenes.
Article
The methyl esters of cannabinolic, cannabidiolic and cannabigerolic acids are shown to possess structures, VIb, IVb and Ib respectively.

Citations

... Contribution to cannabinoid profile and biological activity (structures in Fig. 4, properties in Table 4). CBL (33) and other metabolites of the CBL-type generally occur at very low concentrations (up to 0.32 mg/g) and are rarely assessed quantitatively Gaoni and Mechoulam (1966), Claussen et al. (1966) 28 From hashish Korte and Sieper (1964), Gaoni and Mechoulam (1967), Claussen et al. (1968) 34 Adams et al. (1940a; and Jacob and Todd (1940) reported incorrect structures Mechoulam and Shvo (1963) 40 Gaoni and Mechoulam (1964), Mechoulam and Gaoni (1965b) 64 D 9 -trans-Tetrahydrocannabinolic acid A Fig. 4, properties in Table 4). CBL can be obtained from CBC by irradiation-mediated intramolecular [2 ? ...
... Cannabigerol (CBG) was first isolated in 1964 [76], and its structure was proposed in 1971 by Gaoni and Mechoulam [77]. Little is known about this cannabinoid, but similar to CBD, CBG lacks the ability to induce psychotropic effects. ...
... The acid-catalyzed reaction was reported as the cyclization reaction of CBD, leading to D 9 -THC and iso-THC (Scheme 1). 3,27,28 The D 9 -THC may further isomerize to D 8 -THC (Scheme 1). 29 The HPLC chromatogram initially detected a signal of D 8 -THC within 5 days in CS, and a trace amount of D 8 -THC showed at t R 9.2 min (Supplementary Figs. ...
... their chromatographic characteristics, the latter could be CBNRA, in agreement with abundances reported in the hemp leaves [35]. Further cannabinoids, such as CBD [40], cannabidiolic acid [41], cannabitriol [42], together with 3 isomers of dihydrocannabinol [27,43] and hexahydrocannabinol [44,45], were identified through the comparison of their mass spectra with those previously published in the literature. They were detected in low amounts. ...
... Compared to Δ 9 -THC, the Δ 8 -THC isomer is far less abundant, representing less than 1% of total THC, and like cannabinol (CBN) it occurs as a degradation product of Δ 9 -THC (Hazekamp et al. 2010;Hazekamp et al. 2016), with no evidence to support natural synthesis of Δ 8 -THC by the plant. Given its low natural abundance in plant material, large quantities of ∆ 8 -THC are being chemically synthesized from hemp-derived cannabidiol (CBD), a process for which was originally described by colleagues in 1966 (Gaoni andMechoulam 1966) and later improved and patented (Webster et al. n.d.). ∆ 8 -THC has been reported to be less psychoactive compared to ∆ 9 -THC (Razdan 1986;Hollister and Gillespie 1973); however, Huffman et al. found these two molecules to be nearly equipotent at the CB 1 and CB 2 cannabinoid receptors (Huffman et al. 1999;Bow and Rimoldi 2016), while Radwan et al. reported ∆ 9 -THC to have a CB 1 receptor affinity four times that of ∆ 8 -THC, which had an affinity for the CB 2 receptor 3.5 times that of ∆ 9 -THC (Radwan et al. 2015). ...
... Contribution to cannabinoid profile and biological activity (structures in Fig. 4, properties in Table 4). The content of CBC (27) (first described by Claussen et al. 1966, andMechoulam 1966) in cannabis tends to be extremely low but, in hashish samples, high concentrations of up to 5.4 mg/g have been reported to occur in certain chemovars (Fischedick et al. 2010;Jin et al. 2017;Richins et al. 2018;Wang et al. 2018;Zager et al. 2019) (Table 1). Quantitative data for other CBC-type metabolites have not been reported. ...
... The reaction was first reported by Adams using sulfur as the oxidant under relatively harsh conditions (heating neat at ca. 250°C). 10 More recently, chloranyl (tetrachloro-1,4-benzoquinone) was found to selectively oxidize Δ 9 -THC to CBN while leaving other isomeric tetrahydrocannabinols unaffected, 11 and a dehydrogenation protocol based on refluxing a chloroform solution of Δ 9 -THC with selenium dioxide and trimethylsilyl polyphosphate (prepared from P 4 O 10 and hexamethyldisiloxane) was also described. 12 We have developed a mild protocol to convert p-menthane phytocannabinoids, including cannabidiol (CBD, 3a), to CBN, extending its availability to nonnarcotic cannabis biomasses, as well as to crude extracts, sidecuts, and mother liquors from the purification of the major medicinal phytocannabinoids (Δ 9 -THC and CBD). ...
... The Baeyer-Villiger reaction [1][2][3][4][5][6], known already tbr more than a century, has tbund wide application in synthesis of lactones and cc-hydroxycarboxylic acids. The oxidation of acetals (obtained from cyclic ketones) under action of peracids was investigated in a small number of works [7][8][9][10][11]. Practically all of these works describe the reaction with participation of MCPBA as oxidative agent. ...
... 2,2,5,5-Tetramethylcyclohexane-1,3-dione and 3,3,6,6-tetramethylcyclohexane-1,2,4,5-tetraone were synthesized by conventional procedures. 18 The condensation reaction of the latter tetraone and two molecules of 1H-benzotriazole-5,6diamine [19][20][21] leads to the organic bistriazolate ligand H 2 -tqpt, which was previously used for the synthesis of the CFA-7 metal-organic framework (Scheme 1). 22 Metal-organic framework CFA-8 can be synthesized from H 2 -tqpt and anhydrous CuCl 2 in a good yield by using N,N-dimethylacetamide (DMA) as a solvent at 140°C (Scheme 2). ...
... CBD wurde zunächst vernachlässigt, vermutlich aufgrund ihre fehlende Psychoaktivität, man könnte sagen, dass CBD von THC in den Schatten gestellt wurde (Mechoulam & Gaoni, 2002;Pertwee, 2006). Die Bestimmung der Strukturen des wichtigsten psychoaktiven Phytocannabinoids, THC erfolgte in 1964 in Israel von Mechoulam und Gaoni (Mechoulam & Gaoni, 2002;Pertwee, 2006). ...