Arachidonic acid derivatives and

Laffi G (1997) Arachidonic acid derivatives and renal function in liver cirrhosis. Semin Nephrol 17 530-548. 

Figures 21.1 to 21.3 show several arachidonic acid-derived and other bioactive natural products synthesized using chiral propargyl alcohol (CPA) in the authors own group (Fig. 21.1) and other groups (Figs. 21.2 and 21.3).

A different type of endocannabinoid that is also an arachidonic acid derivative was first isolated from canine gut and identified as 2-arachidonyl glycerol (2-AG) (Fig. 3) (Mechoulam, 1995a). 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

The asymmetric Horner-Wadsworth-Emmons (HWE) reaction of l,3-dioxan-5-ones with phosphonate 184 and a chiral diamine was reported. With the /i r/-butyl-substituted l,3-dioxan-5-one, the product possesses a chiral axis. It was obtained in good yield and with 80% ee (Scheme 53) <2002TL281>. The HWE reaction with similar heterocyclic substrates was used to provide conformationally restricted arachidonic acid derivatives <1999TA139>. 

Jasmonic acid is an 18-carbon pentacyclic polyunsaturated fatty acid derived from lino-lenic acid, plays a role in plants similar to arachidonic acid,58 and has a structure similar to... 

The basis for the analgesic action of NSAIDs is their ability to prevent the production of prostaglandins. Prostaglandins are derived from the arachidonic acid cascade and are implicated in the production of inflammatory pain and in sensitizing nociceptors to the actions of other mediators. 

Cyclooxygenase (COX), one of the two activities of prostaglandin endoperoxide synthase (PGHS), is the key enzyme in the conversion of arachidonic acid derived from lipids of the cell membrane to prostaglandins and other eicosanoids (Fig. 3). 

Croxtall, J.D., Choudhury, Q., and RJ. Flower, 1998, Inhibitory effect of peptides derived from the N-terminus of lipocortin 1 on arachidonic acid release and proliferation in die A549 cell line identification of E-Q-E-Y-V as a crucial component Br J Pharmacol. 123(5) 975—83. 

The precise mechanism of post-traumatic vasogenic edema is unknown, but Chan and colleagues [51] have provided data suggesting an important role for an arachidonic-acid-derived oxygen-radical-mediated process. In initial in vitro experiments, it has been discovered that when rat-brain cortical slices are... 

Prostaglandins, thromboxanes and leucotrienes are eicosanoids deriving from oxidation of arachidonic acid. Arachidonic acid (deriving from PLA2 action on phospholipids) is cyclized by constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2) to yield... 

Diacerein (diacetylrhein), an anthraquinone derivative, is said to be effective in the treatment of osteoarthritis. Its active metabolite is rhein, about which there are very few clinical data. Diacerein does not affect arachidonic acid metabolism and might be better tolerated than other NSAIDs with regards to renal and gastric toxicity. Epigastric or abdominal pain and diarrhea are the most frequent adverse effects. Diarrhea occurred in 37% of patients with osteoarthritis taking diacerein (1). Acute hepatitis has been described (SEDA-22, 119), as have skin reactions. 

Pho.sphoinosiiides serve as storage forms for secondary messengers. Phosphoinositidc.s compose only a minor fraction (2-8 f) of the lipids in cell membranes, yet they can be converted to at least three intracellular messenger molecules arachidonic acid, inositol 1.4,5-ua.sphosphale (IP i). and 1.2-diacylglyeerol (DAG). The functions of arachidonic acid derivatives are discus.sed in Chapter 24. IP releases intracellular calcium, and DAG is an essential cofuctor in the activation of protein kina.se C." ... 

Endogenous ligands for the cannabinoid receptor have not yet been identified. Arachidonylethanolamide, a new arachidonic acid derivative named anandamide, was isolated from porcine brain. Its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. It inhibits the specific binding of a labelled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands, and produces a concentration-dependent inhibition of the electrically-evoked twitch response of the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. Similar compounds were synthesized and their pharmacological properties were investigated. 

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