(2R-trans)-2-Butyl-5-heptylpyrrolidine as a Potent Sigma Receptor Ligand Produced by Streptomyces longispororuber

• Published in: Journal of antibiotics Vol. 53; no. 5; pp. 467 - 473
• Main Authors: KUMAGAI, KAZUO, SHONO, KAZUSHIGE, NAKAYAMA, HIROSHI, OHNO, YUKIHIRO, SAJI, IKUTARO
• Format: Journal Article
• Language: English
• Published: TOKYO JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 2000; Japan Antibiotics Research Assoc; Japan Antibiotics Research Association
• Subjects: 2-Butyl-5-heptylpyrrolidine; Animals; Biological and medical sciences; Biotechnology & Applied Microbiology; Fermentation; Immunology; In Vitro Techniques; Life Sciences & Biomedicine; Ligands; Medical sciences; Microbiology; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyrrolidines - metabolism; Rats; Receptors, sigma - metabolism; Science & Technology; Spectrum Analysis; Streptomyces - metabolism; VENOM; ANT; ANTIPSYCHOTIC-DRUGS; MEMBRANES; SITES; OPIATES; GUINEA-PIG BRAIN; BINDING; Streptomycetaceae; Ligand; Opioid receptor; Sigma receptor; Fermentation; In vitro; Pyrrolidine derivatives; Actinomycetales; Biological fixation; D2 Dopamine receptor; Enantiomer; Microorganism culture; Bacteria; Actinomycetes; Structural analysis
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.53.467

A potent sigma (σ) receptor ligand was isolated from the culture broth of Streptomyces longispororuber #525. The active compound was identified to be (2R-trans)-2-butyl-5-heptylpyrrolidine by spectroscopic and chemical studies. The compound exhibited high affinity and selectivity for σ receptors. The IC50 values toward σ1, σ2 and dopamine D2 receptors were 2.0, 22.7 and more than 40, 000 nM, respectively. Its (2S-trans)- and (±)-cis-isomers, both synthesized, were also found to be high affinity σ ligands.