NMR Analysis of a Series of 6,14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances**

Abstract

The new semisynthetic oripavine derivative 3-O-trityl-6-Odesmethyl-dihydroetorphine was synthesized from the poppy alkaloid thebaine in a six-step procedure. This compound can be applied as precursor for the radiosynthesis of [6-O-methyl-11 C]-dihydroetorphine ([ 11 C]DHE). We present a detailed description of 1 H and 13 C NMR data of reference standards and precursors for [6-O-methyl-11 C]-and [6-O-(2-[ 18 F]fluoroethyl] orvinols. This includes the complete assignment for 19 oripavine derivatives examined in 1D and 2D NMR experiments. We also investigated the molecular basis for regioselectivity of fluoroalkylation of 3-O-trityl-6-O-desmethyl-phenethyl-orvinol (TDPEO) using computational methods.

Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations

“…As a second example of Grignard difficulties, we mention the reaction of 7α-dihydro thevinone (104, Figure 31) with six equivalents of n-propylmagnesium bromide [100] under identical conditions as described above for the reaction of thevinone (16a) and 2-phenethylmagnesium bromide [98]. Four compounds were isolated from the complex product mixture: 20R-dihydroethorphine methyl ether (20R-90, 51%) as the main product, 20S-dihydrothevinol (91, 20%) as the main by-product, a small amount of 20Sdihydroetorphine methyl ether (20S-90, 4.2%), and finally the product of the base-catalyzed rearrangement (92, 7.6%).…”

“…The synthesis of orvinol derivatives (95)(96)(97)(98)(99)(100)(101)(102)(103) starting from thebaine (4) involves, in most cases, the following transformations: Diels-Alder reaction, Grignard addition, N-demethylation, N-alkylation of the secondary amine, and finally 3-O-demethylation. DPN (95), BPN (96), DHE (98), and PEO (99) can be prepared by the original method by Bentley [74,97,111] or one of the more recently developed multistep procedures [102,103] starting from the poppy alkaloid thebaine (4).…”