1808-26-0Relevant articles and documents
A methodology for radiolabeling of the endocannabinoid 2- arachidonoylglycerol (2-AG)
Duclos, Richard I.,Johnston, Meghan,Vadivel, Subramanian K.,Makriyannis, Alexandros,Glaser, Sherrye T.,Gatley, S. John
, p. 2049 - 2055 (2011)
The metabolic intermediate and endocannabinoid signaling lipid 2-arachidonoylglycerol (2-AG) has not been readily labeled, primarily because of its instability toward rearrangement. We now detail a synthetic method that easily gives tritiated 2-AG from [5,6,8,9,11,12,14,15-3H(N)] arachidonic acid in two steps. We utilized a short chain 1,3-diacylglycerol and proceeded through the "structured lipid" [5′′, 6′′,8′′,9′′,11′′, 12′′,14′′,15′′-3H(N)]2- arachidonoyl-1,3-dibutyrylglycerol, a triacylglycerol that was conveniently deprotected in ethanol with acrylic beads containing Candida antarctica lipase B to give [5′′,6′′,8′′,9′′, 11′′,12′′,14′′,15′′- 3H(N)]2-arachidonoylglycerol ([3H]2-AG). The flash chromatographic separation necessary to isolate the labeled 2-acylglycerol [3H]2-AG resulted in only 4% of the rearrangement byproducts that have been a particular problem with previous methodologies. This reliable "kit" method to prepare the radiolabeled endocannabinoid as needed gave tritiated 2-arachidonoylglycerol [3H]2-AG with a specific activity of 200 Ci/mmol for enzyme assays, metabolic studies, and tissue imaging. It has been run on unlabeled materials on over 10 mg scales and should be generally applicable to other 2-acylglycerols.
Improved enzymatic procedure for the synthesis of anandamide and N-fatty acylalkanolamine analogues: A combination strategy to antitumor activity
Quintana, Paula G.,Garca Liares, Guadalupe,Chanquia, Santiago N.,Gorojod, Roxana M.,Kotler, Mnica L.,Baldessari, Alicia
, p. 518 - 528 (2016/02/18)
Twenty N-fatty acylamines from linolenic and arachidonic acids, fifteen of them new compounds, were obtained through Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields and with high chemoselectivity. The optimal reaction conditions were achieved by studying the reaction parameters (temperature, E/S ratio, alcohol and alkanolamine/fatty acid ratio, time, solvent, free-solvent system, etc.). To identify ideal enzymatic methods for generating the alkanolamides we evaluated enzyme performance in three procedures: i) aminolysis of ethyl ester, ii) direct condensation between the fatty acid and the alkanolamine, and iii) a one-pot/two-step conversion of fatty acids into alkanolamides via in situ formation of the ethyl ester and subsequent aminolysis by the alkanolamine. The advantages noted with the enzymatic methodology, such as mild reaction conditions and low environmental impact, underscore biocatalysis as a convenient way to prepare the reported compounds. The cytotoxic activities of all compounds and mixtures of anandamide and its analogues were evaluated in rat glioma C6 cells. These studies reveal that some anandamide analogues enhance the antitumor effects of anandamide, suggesting their possible application as therapeutic tools in cancer treatment. Twenty N-fatty acylamines from linolenic and arachidonic acids were obtained by one-pot/two-step Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields with high chemoselectivity. Cytotoxicity assays using rat glioma C6 cells revealed that some analogues enhanced the antitumor effects of anandamide (AEA), suggesting possible anticancer applications.
