Preparation and Cleavage of Some Codeine Glycols¹

Synthesis of 7β-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors

“…The epoxidation of morphine proved unsuccessful and a 7β,8β-epoxide could only be obtained from 3-methoxymethylmorphinone, using hydrogen peroxide in aqueous methanol containing sodium hydroxide, revealing the relevance of the C6 substituent on the outcome of this oxidation [23,24]. Oxidations with osmium tetroxide succeeded to give the respective diols [25][26][27][28]. However, they were also highly dependent on the substituent present at C6, with more electron withdrawing substituents giving lower product yields.…”

6,7-Benzomorphans. Stereospecific synthesis of 2,9.alpha.- and 2,9.beta.-dimethyl-2'-methoxy-6,7-benzomorphans

“…2,9a-Dimethyl-8-methylene-2'-methoxy-6,7-benzomorphan (70) . Methylenebenzomorphan 70 was prepared as described for the ß isomer with reaction times of 20 and 24 h. Distillation gave methylenebenzomorphan 70, bp 120-150 °C/0.1 mm, in 59% yield.…”

“…Nitrile 67 was converted to ketone 69 in the normal manner and cyclized with BF3-Et20 to give methylenebenzomorphan 70 Since the isomeric purity of the 9a-methylbenzomorphan was now dependent on the cis/trans ratio obtained in the hydrogenation of methylene lactam 2, optimization of the 90:10 ratio of cis-/trans-amides 42 and 43 became desirable. The isomer distribution was examined as a function of both catalyst (Pd/C, Pd/BaCOa, Rh/Al203, Rh/C, Pt02) and solvent.…”

“…Alternatives to osione included direct oxidative cleavage with chromic acid or formation of glycol followed by oxidative cleavage. Oxidation of methylenebenzomorphan 70 with Cr03 in dilute H2S0468 afforded only a 30% yield of ketone 72 in a multicomponent mixture. Oxidation with NaI04 in the presence of 10 mol % Os04 in aqueous HOAc,69 stoichiometric osmolation either in HOAc or in ether/pyridine,70 and Pb(OAc)4/HOAc also afforded mixtures of products.…”