Extension of the Nenitzescu reaction to simple ketones provides an efficient route to 1'-alkyl-5'-hydroxynaltrindole analogues, potent and selective delta-opioid receptor antagonists.
The well-established Nenitzescu reaction of imines of beta-dicarbonyl systems, as their enamine tautomers, with benzoquinone has been applied to a wide range of such imines to give 5-hydroxyindoles, some of which are of significant biological importance. This reaction has now been extended to the benzylimines of simple ketones, including those of the potent mu-opioid receptor antagonists naltrexone and naloxone. The products of the latter reactions, 1'-benzyl-5'-hydroxyindolomorphinans (7), are potent delta-opioid receptor (DOR) antagonists, confirming the enhancement of DOR antagonist potency and selectivity resulting from the introduction of the 1'-benzyl group.
Shefali
Shefali
S
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.
Srivastava
Sanjay K
SK
Husbands
Stephen M
SM
Lewis
John W
JW
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007536:Isomerism; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*
D007659:Ketones; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole