Synthesis and biological activities of 2- arachidonoylglycerol, an endogenous cannabinoid receptor ligand, and its metabolically stable ether-linked analogues

Yoshitomo Suhara, Hiroaki Takayama, Shinji Nakane, Tomoyuki Miyashita, Keizo Waku, Takayuki Sugiura

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We synthesized 2-arachidonoylglycerol (1), an endogenous cannabinoid receptor ligand, and its metabolically stable ether- linked analogues. Compound 1 was synthesized from 1,3- benzylideneglycerol (6) and arachidonic acid in the presence of N,N'-dicyclohexylcarbodiimide and 4-dimethylaminopyridine followed by treatment with boric acid and trimethyl borate. An ether-linked analogue of 2-arachidonoylglycerol (2) was synthesized from 6 and 5,8,11,14-eicosatetraenyl iodide (9). The ether-linked analogues of 2-palmitoylglycerol (4) and 2- oleoyglycerol (5) were synthesized from 6 and hexadecyl iodide (12) and 9-octadecenyl iodide (14), respectively. We confirmed that 1 stimulates NG108-15 cells to induce rapid transient elevation of the intracellular free Ca2+ concentrations through a CB1 receptor-dependent mechanism. Noticeably, 2 exhibited appreciable agonistic activity, although its activity was significantly lower than that of 1. Compound 2 would be a useful tool in exploring the physiological significance of 1, because this compound is resistant to hydrolyzing enzymes in contrast to 1. On the other hand, the ether-linked analogues of either 4 or 5 failed to act as a CB1 receptor agonist. Compounds 4 and 5 would also be valuable as control molecules in experiments where 2 is employed.

Original languageEnglish
Pages (from-to)903-907
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume48
Issue number7
Publication statusPublished - 2000 Jul
Externally publishedYes

Fingerprint

Cannabinoid Receptors
Bioactivity
Ether
Iodides
Ligands
Cannabinoid Receptor CB1
Dicyclohexylcarbodiimide
Arachidonic Acid
Molecules
2-arachidonylglycerol
Enzymes
Experiments

Keywords

  • Δ- tetrahydrocannabinol
  • 2-arachidonoylglycerol
  • Anandamide
  • Cannabinoid
  • Ether-linked analogue
  • Monoacylglycerol

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Pharmacology

Cite this

Synthesis and biological activities of 2- arachidonoylglycerol, an endogenous cannabinoid receptor ligand, and its metabolically stable ether-linked analogues. / Suhara, Yoshitomo; Takayama, Hiroaki; Nakane, Shinji; Miyashita, Tomoyuki; Waku, Keizo; Sugiura, Takayuki.

In: Chemical and Pharmaceutical Bulletin, Vol. 48, No. 7, 07.2000, p. 903-907.

Research output: Contribution to journalArticle

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