Studies on the synthesis of β-thevinone derivatives

N-Demethylation of Alkaloids

“…The scope and limitations of the von Braun reaction have been previously reported in the literature [15]. The von Braun reaction has been applied to N-demethylate opiate alkaloids, although poor to moderate yields are often obtained [16][17][18][19]. Examples of opiate derivatives obtained in reasonable yields include N-norcodeinone dimethyl ketal (16b) from codeinone dimethyl ketal (16a, Figure 5).…”

“…This synthetic intermediate was subsequently alkylated to afford the pharmaceutical opiate, naloxone (12). The β-thevinone derivative 18a was converted to the corresponding N-cyanamide in 90% yield which was subsequently hydrolysed to the secondary amine 18b in 77% yield [19]. The benzomorphan 19a was treated with CNBr to afford the N-cyanamide intermediate in 94% yield, which was hydrolysed to give the N-nor analog 19b in 72% yield [21].…”

A Facile Synthesis and Structural Verification of Etorphine and Dihydroetorphine from Codeine

“…9,26-31 Compound 6 reacted with Grignard reagent (PrMgBr) to give alcohol 7. 10,14,26,28,32 An efficient protocol reported in the literature for demethylation of 7 to etorphine 9 in good purity using KOPh 33 was therefore attempted. Dihydroetorphine 13 was prepared through the reduction of 6, 10,26,31,[34][35] and then follow the same proce-dures as the preparation of 9.…”

“…1). 32 The intermediate 14 has a four member ring transition state that is a disfavor pathway to give a minor product. In the intermediate 15, the b-hydrogen was added to carbonyl group through a six member ring transition state to give a reduction product 8.…”

Synthesis of deuterium‐labelled etorphine and dihydroetorphine

“…Although etorphine and DHE have been readily prepared via several synthetic routes, 5,[12][13][14][15][16] Deuterium-labelled codeine methyl ether (2) was prepared by treating codeine with sodium hydride in tetrahydrofuran, in which the codeine sodium salt was methylated with [ 2 H 3 ]-methyl iodide to give 4,5aepoxy-3,6a-[ 2 H 3 ]-dimethoxy-17-methylmorphin-7-ene (2) in a 98% yield. 4,5a-Epoxy-3,6-dimethoxy-17-methylmorphina-6,8(14)-diene (3) was successfully prepared by oxidizing compound 2 with 2,3-dichloro-5,6dicyano-1,4-benzoquinone (DDQ).…”