Diacylglycerol metabolism and arachidonic acid release in human fetal membranes and decidua vera.

Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines

“…1-Chloro-6-iodohexane (1.0 mL, 6.6 mmol) was dropwise added over 5 min, and the resulting mixture was stirred for 18 h and then refluxed for 1 h. The solvent was removed by distillation under reduced pressure, and the crude was purified by FC (SiO 2 , AcOEt/hexane 50:50) to give 66.7 mg of the expected product 10a as a colorless oil (37%). 1 In an amber glass vial with a seal, piperidine (58 μL, 0.6 mmol) was added to a stirred suspension of K 2 CO 3 (169.0 mg, 1.22 mmol), KI (8.0 mg, 0.05 mmol), and 10a (66.4 mg, 0.25 mmol) in anhydrous DMF (1.0 mL). Upon the completion of addition, the reaction mixture was heated to 110 °C and stirred under a nitrogen atmosphere for 6 h. The volatiles were removed under reduced pressure, and the crude reaction mixture was diluted with AcOEt, the salts were removed by filtration, and the solvent was evaporated under reduced pressure.…”

“…FC (SiO 2 , DCM/MeOH 95:5) furnished 33.0 mg (41%) of 11 as a colorless oil. 1 2-(Chlorocarbonyl)phenyl Hypochlorothioite 12. To a suspension of 2,2′-dithiosalicyclic acid (2.02 g, 6.58 mmol) in toluene (10 mL) at 0 °C, thionyl chloride (1.65 g, 13.83 mmol) and a catalytic amount of DMF (few drops) were added.…”

“…According to method A, after purification by FC (SiO 2 hexane/ AcOEt 70:30) and crystallization from n-hexane, 14 (25 mg, 14%) was obtained as pale yellow crystals. 1 2-Phenethylisothiazol-3(2H)-one 18. A solution of SO 2 Cl 2 in anhydrous 1,2-dichloroethane (0.75 M, 4.8 mL, 3.6 mmol) was added dropwise to a 0 °C stirring suspension of 3,3′-disulfanediylbis(Nphenethylpropanamide) 17 (500.2 mg, 1.20 mmol) in anhydrous 1,2dichloroethane (7.0 mL) over 2 h. The solvent was evaporated under reduced pressure, and the yellow oily residue was taken up with DCM.…”

“…Monoacylglycerol lipase (MGL) is a serine hydrolase that cleaves medium-and long-chain monoacylglycerols into fatty acid and glycerol, with the highest rate for arachidonic acid derivatives. 1 MGL expression is widespread in the body and particularly high in the central nervous system (CNS) where it is exclusively localized to presynaptic nerve terminals. 2 In peripheral tissues, MGL serves two main functions: it mediates the last step in hormone-dependent lipolysis and contributes to the release of energy-rich fatty acids from triacylglycerol stores, 3 and, second, it controls platelet aggregation by regulating the availability of nonesterified arachidonate for thromboxane A 2 biosynthesis.…”

Diacylglycerol Lipase-Alpha Regulates Hippocampal-Dependent Learning and Memory Processes in Mice

“…A growing body of evidence implicates the importance of 2-arachidonoyl glycerol (2-AG), the most highly expressed en-dogenous cannabinoid in brain, in regulating learning and memory. Diacylglycerol lipase (DAGL) forms 2-AG through the hydrolysis of diacylglycerols (Chau and Tai, 1981;Okazaki et al, 1981) and exists as two distinct biosynthetic enzymes, DAGL-␣ and DAGL-␤ (Bisogno et al, 2003), which are expressed on distinct cell types, as well as in brain areas important for learning and memory (Katona et al, 2006;Lafourcade et al, 2007). Within the CNS, DAGL-␤ is highly expressed on microglia, whereas DAGL-␣, expressed on synapse-rich plasma membranes of dendritic spines (Yoshida et al, 2006), serves as the principal synthetic enzyme of 2-AG on neurons (Viader et al, 2015).…”