Synthesis of (−)-Homogalanthamine from Naltrexone

• Published in: Journal of organic chemistry Vol. 76; no. 7; pp. 2257 - 2260
• Main Authors: Yamamoto, Naoshi, Fujii, Hideaki, Imaide, Satomi, Hirayama, Shigeto, Nemoto, Toru, Inokoshi, Junji, Tomoda, Hiroshi, Nagase, Hiroshi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.04.2011; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Crown Ethers - chemistry; Exact sciences and technology; Galantamine - chemical synthesis; Galantamine - chemistry; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Magnetic Resonance Spectroscopy; Molecular Structure; Naltrexone - chemical synthesis; Naltrexone - chemistry; Narcotic Antagonists - chemical synthesis; Narcotic Antagonists - chemistry; Organic chemistry; Physical Sciences; Preparations and properties; Receptors, Opioid, mu - antagonists & inhibitors; Receptors, Opioid, mu - chemistry; Science & Technology; GALANTHAMINE; ETHERS; (-)-GALANTHAMINE; ALZHEIMERS-DISEASE; TRI-TERT-BUTOXYALUMINOHYDRIDE; GALANTAMINE; (+/-)-GALANTHAMINE; DERIVATIVES; FRAGMENTATION REACTION; ALKALOIDS; Crown compound; Antagonist; Oxygen heterocycle; Naltrexone; Chemical synthesis; Grob fragmentation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo1022487

Acetylcholinesterase inhibitor (−)-homogalanthamine 3 was synthesized from μ opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5.