18,19-Dehydrobuprenorphine (2) was prepared in five steps starting from thevinone (3) which is readily available from thebaine by Diels-Alder reaction. Grignard reaction with tert-BuMgBr afforded tert-butylthevinol (4) which was N-demethylated via N-cyano-tert-butylthevinol (5) using BrCN. Alkali treatment gave N-nor-tert-butylthevinol (6) which was alkylated with cyclopropylmethyl bromide to give N-cyclopropylmethyl-tert-butylthevinol (7), followed by ether cleavage with thiolate to yield 2. 18,19-Dehydrobuprenorphine displayed in opioid receptor binding studies very high affinity for mu receptors, while the affinity for kappa and delta receptors was lower. In the tail-flick test in mice, compound (2) was 25 times more potent than morphine and ca. 2.5 times as potent as buprenorphine.

SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF 18,19-DEHYDROBUPRENORPHINE / Schutz, J.; Krassing, R.; Schmidhammer, H.; Wurst, K.; Lattanzi, Roberta; Negri, Lucia. - In: HETEROCYCLES. - ISSN 0385-5414. - STAMPA. - 54:(2001), pp. 989-998. [10.3987/COM-00-S(I)46]

SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF 18,19-DEHYDROBUPRENORPHINE

LATTANZI, Roberta;NEGRI, Lucia
2001

Abstract

18,19-Dehydrobuprenorphine (2) was prepared in five steps starting from thevinone (3) which is readily available from thebaine by Diels-Alder reaction. Grignard reaction with tert-BuMgBr afforded tert-butylthevinol (4) which was N-demethylated via N-cyano-tert-butylthevinol (5) using BrCN. Alkali treatment gave N-nor-tert-butylthevinol (6) which was alkylated with cyclopropylmethyl bromide to give N-cyclopropylmethyl-tert-butylthevinol (7), followed by ether cleavage with thiolate to yield 2. 18,19-Dehydrobuprenorphine displayed in opioid receptor binding studies very high affinity for mu receptors, while the affinity for kappa and delta receptors was lower. In the tail-flick test in mice, compound (2) was 25 times more potent than morphine and ca. 2.5 times as potent as buprenorphine.
2001
morphinan; buprenorphine analogue; dehydrobuprenorphine; analgesic; opioid
01 Pubblicazione su rivista::01a Articolo in rivista
SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF 18,19-DEHYDROBUPRENORPHINE / Schutz, J.; Krassing, R.; Schmidhammer, H.; Wurst, K.; Lattanzi, Roberta; Negri, Lucia. - In: HETEROCYCLES. - ISSN 0385-5414. - STAMPA. - 54:(2001), pp. 989-998. [10.3987/COM-00-S(I)46]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/252622
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