First Synthesis and Utilization of Oripavidine – A Concise and Efficient Route to Important Morphinans and Apomorphines

Abstract

The synthesis and transformation of oripavidine (8) offer an efficient and simple route to highly active dopamine agonist apomorphines and a variety of important 14b-hydroxy-morphinan derivatives. Natural origin thebaine (6), the starting compound of the procedure, was converted into its N-{[1,2-bis(ethoxycarbonyl)hydrazinyl]methyl} counterpart. l-Selectride was found to be an efficient agent to perform a one-pot O-and N-deprotection at positions 3 and 17, respectively.

Synthesis of Nororipavine and Noroxymorphone via N- and O-Demethylation of Iron Tricarbonyl Complex of Thebaine

“…This protocol gave nororipavine in an overall yield of 64%. 32 Recently, we reported on a high yielding O-demethylation of thebaine derivatives in which the diene moiety was 'protected' either as its iron tricarbonyl complex or as a bicyclic dihydrothiopyran Diels-Alder adduct. For successful O-demethylation, such protective operations of the methoxydiene moiety in thebaine proved to be an absolute necessity.…”

Recent Advances in the Chemistry of Oripavine and Its Derivatives

“…Sipos and coworkers [49] reported the synthesis of nororipavine (28) Scammells et al [50] employed a modified nonclassical Polonovski reaction for the N-demethylation of morphine alkaloids and this method was suitable for the preparation of northebaine (29) and nororipavine (28). This approach involved the conversion of the tertiary N-methyl amine to the corresponding N-oxide (by treatment with hydrogen peroxide or m-chloroperbenzoic acid) followed by treatment with iron sulfate.…”

Conversion of Thebaine to Oripavine and Other Useful Intermediates for the Semisynthesis of Opiate‐Derived Agents: Synthesis of Hydromorphone

“…In addition to the reactivity with thiolate, the diene of thebaine and oripavine are acid‐sensitive (Lewis and Brønsted) and undergo a variety of rearrangements. The acid‐catalyzed apomorphine rearrangement or vinyl ether hydrolysis during 3‐ O ‐demethylation was prevented by unusual protecting group chemistry 12,25. Our method employs protection of the cyclohexadiene moiety in thebaine 1 with either iron(0) pentacarbonyl developed by Birch19,20 or as a bicyclic dihydrothiopyran‐Diels–Alder adduct 21–24…”