Synthesis of 15N-, 13C-, and 2H-labeled methanandamide analogs

Four isotopically labeled, metabolically stable analogs of arachidonylethanolamide (anandamide), an endogenous cannabinoid ligand, were synthesized via a five-step reaction sequence starting from arachidonic acid. These stable methanandamide derivatives will serve as probes for studying the conformational properties of anandamide in model membrane systems using solid-state NMR spectroscopy. The synthetic methods described can be applied to the preparations of other anandamide analogs with isotopic labeling in different positions of the molecule, which could be utilized in biochemical and pharmacological experiments. Copyright (C) 2002 John Wiley Sons, Ltd.