Synthesis of novel morphinan peptides based on ethenoisomorphinans and enkephalin residues containing L- and D-phenylalanine; conformational analysis and preliminary pharmacology (Chemistry of opium alkaloids, Part XXXIII)
✍ Scribed by J. J. Cappon; T. S. Lie; L. Maat
- Book ID
- 104589210
- Publisher
- Elsevier Science
- Year
- 2010
- Tongue
- English
- Weight
- 550 KB
- Volume
- 109
- Category
- Article
- ISSN
- 0165-0513
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✦ Synopsis
Abstract
The morphinan peptides N‐(4,5α‐epoxy‐3,6‐dihydroxy‐17‐methyl‐6α,14α‐ethenoisomorphinan‐7α‐carbonyl)‐L‐phenylalanine ethyl ester (4), N‐(4,5α‐epoxy‐3,6‐dihydroxy‐17‐methyl‐6α,14α‐ethenoisomorphinan‐7α‐carbonyl)‐D‐phenylalanine ethyl ester (5) and N‐[N‐(4.5α‐epoxy‐3.6‐dihydroxy‐17‐methyl‐6α,14α‐ethenoisomorphinan‐7α‐carbonyl)glycinyl]‐L‐phenylalanine ethyl ester (6) have been prepared from 4,5α‐epoxy‐3,6‐dimethoxy‐17‐methyl‐6α,14α‐ethenoisomorphinan‐7α‐carboxylic acid (7) and the protected amino acids. The morphinan moiety was coupled to the peptide residue via the acid chloride of 7, after which the morphinan peptides were O‐demethylated with the aid of hydrogen bromide in glacial acetic acid. The dipeptide N‐glycinyl‐L‐phenylalanine ethyl ester was synthesized via the Excess Mixed Anhydride method (EMA). The new morphinan peptides have been characterized by ^1^H and ^13^C NMR spectroscopy. For conformational analysis, the relative stabilities of two possible hydrogen bonds around the C7‐C20 bond have been calculated on a model compound 11, using molecular mechanics.