Synthesis and pharmacology of 5-noralkyl-9beta-methyl-6,7-benzomorphans and stereochemistry of some intermediates.
2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereochemical assignments of 9, 10 (and thus 7 and 8), and 18 follow from analogy and from NMR data of 9, 10, 17, and 18. Compound 18 and the deoxy analog 16 are as potent as morphine and codeine, respectively, as analgetics (mice) and are without physical dependence capacity (monkeys).
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000882:Haplorhini; D006358:Hot Temperature; D006801:Humans; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D009019:Morphinans / Q000138:chemical synthesis*; D009021:Morphine Dependence / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism; D019966:Substance-Related Disorders / Q000503:physiopathology
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans