51768-56-0Relevant academic research and scientific papers
Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB2Receptor Derived from the Natural Product Cannabidiol
Navarro, Gemma,Gonzalez, Angel,Sánchez-Morales, Adrià,Casajuana-Martin, Nil,Gómez-Ventura, Marc,Cordomí, Arnau,Busqué, Félix,Alibés, Ramon,Pardo, Leonardo,Franco, Rafael
, p. 9354 - 9364 (2021/07/19)
Cannabidiol (CBD), the second most abundant of the active compounds found in the Cannabis sativa plant, is of increasing interest because it is approved for human use and is neither euphorizing nor addictive. Here, we design and synthesize novel compounds taking into account that CBD is both a partial agonist, when it binds to the orthosteric site, and a negative allosteric modulator, when it binds to the allosteric site of the cannabinoid CB2 receptor. Molecular dynamic simulations and site-directed mutagenesis studies have identified the allosteric site near the receptor entrance. This knowledge has permitted to perform structure-guided design of negative and positive allosteric modulators of the CB2 receptor with potential therapeutic utility.
Synthesis of chiloglottones - Semiochemicals from sexually deceptive orchids and their pollinators
Poldy, Jacqueline,Peakall, Rod,Barrow, Russell Allan
supporting information; experimental part, p. 4296 - 4300 (2009/12/06)
A five-step synthesis of monoalkyl- and 2,5-dialkyl-1,3-cyclohexanediones (1) is described via a sequence involving sequential Birch reductions and alkylations from the readily accessible and inexpensive starting material, 3,5-dimethoxybenzoic acid. Two approaches were considered in which alkylation at C-2 occurs either prior or subsequent to the proposed reduction. The successful route, in which Birch reduction of a 3-alkyl resorcinol derivative (3) precedes alkylation was applied in the synthesis of chiloglottone 1 (1dc), in 58% overall yield. Chiloglottone 1 is a member of a new class of natural products, representing a known sex pheromone of the thynnine wasp Neozeleboria cryptoides and pollinator attractant in the Australian sexually deceptive orchid genus Chiloglottis. The synthetic homologues were assessed for their biological activity via electroantennographic detection.
Amidino derivatives and their use as thrombin inhibitors
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, (2008/06/13)
There is provided compounds of formula I, wherein R1, R2, R3, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.
Propiophenone derivatives and process for preparing the same
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, (2008/06/13)
A propiophenone derivative of the formula (I): wherein OX is a hydroxy group which may optionally be protected, Y is a lower alkyl group, and Z is a beta -D-glucopyranosyl group wherein one or more hydroxy groups may optionally be protected, or a pharmace
1,3-Dimethoxy-5-methylene-1,3-cyclohexadiene Compounds with Leaving Groups at C6: Generation, Solvolytic Reactivity, and Their Importance in the Photochemistry of 3,5-Dimethoxybenzyl Derivatives
DeCosta,Howell,Pincock,Pincock,Rifai
, p. 4698 - 4705 (2007/10/03)
The photochemistry of 3,5-dimethoxybenzyl compounds with the leaving groups acetate (1a), chloride (1b), bromide (1c), iodide (1d), diethyl phosphate (1e), and trimethylamine (1f), as the chloride, was examined by both product studies and flash photolysis. The isomeric triene, 5-methylene-1,3-cyclohexadiene derivative was observed for the acetate (2a), diethyl phosphate (2e) and trimethylammonium chloride (2f). The solvolysis of these derivatives, 2, was examined in alcohol solvents and the rate correlation with YOTS values gave m = 0.47 (2a) and 0.63 (2e), suggesting SN1 reactivity but with an early transition state. Quantum yields for formation of 2a and 2e indicated that these trienes play only a minor role (～16%) in the overall photochemistry of the corresponding arylmethyl substrates.
On-line monitoring of the photolysis of benzyl acetate and 3,5-dimethoxybenzyl acetate by membrane introduction mass spectrometry
Wong, Philip S. H.,Srinivasan,Kasthurikrishnan,Cooks,Pincock,Grossert
, p. 6627 - 6632 (2007/10/03)
Membrane introduction mass spectrometry (MIMS) allows on-line monitoring of the products of photolysis (254 nm) of benzyl acetate in aqueous methanol and 3,5-dimethoxybenzyl acetate in water. The reaction mixture is continuously exposed to a silicone membrane through which analyte molecules permeate into a triple quadrupole mass spectrometer for qualitative and quantitative analysis. Ionization is achieved by either isobutane or ammonia chemical ionization, and ions characteristic of the reactant ester and its products are monitored simultaneously and continuously. Three products, benzyl methyl ether, ethylbenzene, and bibenzyl are observed in the benzyl acetate photolysis. Two products, 3,5-dimethoxybenzyl alcohol and 3,5-dimethoxyethylbenzene, are formed in the photolysis of 3,5-dimethoxybenzyl acetate. Quantitation is achieved through calibration using external standard solutions and, in the case of benzyl methyl ether, tandem mass spectrometry is used to verify product identification. During the photolysis of benzyl acetate, benzyl methyl ether and ethylbenzene are produced at onset with similar efficiencies. For the 3,5-dimethoxy ester photolysis, performed in aqueous solution, the efficiency of formation of the polar product 3,5-dimethoxybenzyl alcohol is about 300 times greater than that of the nonpolar product 3,5-dimethoxyethylbenzene. The results show that the relative reaction rates are dependent on the solvent and on the photon intensity and are consistent with earlier off-line experiments by Pincock et al. which showed that the photolysis proceeds through both ion and radical pair intermediates. To the best of our knowledge, the work reported here describes the first analysis of the photochemistry of an aralkyl ester in water and the first use of on-line mass spectrometry in a mechanistic study.
The Photochemistry of Methoxy-Substituted Benzyl Acetates and Benzyl Pivalates: Homolytic vs Heterolytic Cleavage
Pincock, J. A.,Wedge, P. J.
, p. 5587 - 5595 (2007/10/02)
The multiple methoxy-substituted benzyl acetates (3g-i) and benzyl pivalates (4g-i) have been photolyzed in methanol solution.The products of these reactions are derived from two critical intermediates; the benzyl radical/acyloxy radical pair and the benzyl cation/carboxylate anion pair.As predicted by the meta effect, the yield of ion-derived product, the methyl ether in this case, was enhanced by the presence of the m-methoxy groups.The yield of ether, for the acetate esters, varied from 2percent for the 4-methoxy-substituted ester to 66percent for the 3,4,5-trimethoxy-substituted ester.In contrast, the yield of ether, for the pivalate esters, varied from 1percent for the 4-methoxy-substituted ester to 20percent for the 3,4,5-trimethoxy-substituted one.The meta effect does not explain these differences; electron transfer converting the radical pair to the ion pair is still an important pathway in the mechanism for ion formation.A quantitative analysis of the yield of the ethers was done in order to obtain the electron-transfer rate constants.This analysis revealed that the yield of the ethers was higher than expected based on previous results for other substituted benzyl acetates.A possible explanation for this discrepancy is that internal return of the radical pair to starting material for the acetate esters is more efficient than for the pivalate esters.Also, the esters 3k and 3l, were prepared to study the effect of electron-withdrawing groups in the meta position.For these esters, the benzylic cleavage reactions were inefficient and an isomerization reaction, the benzvalene rearrangement, was competitive.
BIOLOGICALLY ACTIVE PHENOLIC METABOLITES OF A VERTICICLADIELLA SPECIES
Ayer, William A.,Browne, Lois M.,Lovell, Sarah H.
, p. 2267 - 2272 (2007/10/02)
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.
