Naltrexone 10-keto

Reduction of the 6-keto functionality in the narcotic antagonist naltrexone can lead to either the epimeric 6a- nr 6)8-h toxy metabolites, depending on the animal pecies. In humans and rabbits, bioreduction of naltrexone Ls highly stereoselective and generates only... 

O-Benzylation can also be achieved using oxymorphone and derivatives thereof (e.g. naltrexone). Since 14-0-alkvlation of morphinan-6-ones without 7,8 double bond does not proceed as smoothly when other alkylating reagents than dimethyl or diethyl sulfate (see above) are used, the 6-keto function was protected by ketaliza-tion [47, 48]. For instance, 3-O-benzyl-protected ketals 32 and 33 were 14-0-alkylated with different benzyl bromides in DMF in the presence of NaH to afford compounds 34 and 35, respectively. Removal of the protecting groups... 

The 6-keto group of naltrexone (1) is accessible to nucleophilic attack from the [5-side to provide 6ot-alcohol derivatives. Therefore, we attempted to synthesize a 6a-epoxide derivative 24 of naltrexone with a stable sulfur ylide derived from trimethylsulfoxonium iodide [24]. The 6ot-epoxide 24 was expected to convert to the objective oxabicyclo[2.2.2]octane derivative 20. Instead, the 6 3-epoxide 23 was obtained in 67% yield, but not the objective 6ot-epoxide 24 (Scheme 6). The structure of 23 was determined by X-ray crystallographic analysis (Fig. 8). 

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