The design and synthesis of nonpeptide compounds as mimics of a conformation of methionine-enkephaline
- 15 April 1982
- journal article
- research article
- Published by Canadian Science Publishing in Canadian Journal of Chemistry
- Vol. 60 (8), 1019-1029
- https://doi.org/10.1139/v82-151
Abstract
A model for the active conformation of methionine-enkephalin containing a β-turn was derived from computer modeling. Using a trans-perhydronaphthalene as a structural template and a mimic of the β-turn, target compounds were designed and synthesized. Thus, a key intermediate, trans-3-oxo-5β-formamidomethyl-8a-phenylmethylperhydronaphthalene, was prepared by two different routes from cyclohexanone.The addition of a methionine-like side-chain to this key intermediate was best achieved by a reaction with the anion of methyl 2-trimethylsilyl-4-methylthiobutanoate. This led to the preparation of an exo-tetrasubstituted double bond in high yield. Subsequent addition of tyrosine through coupling with the 5β-aminomethyl group provided the desired perhydronaphthalene mimics of met-enkaphalin.This publication has 3 references indexed in Scilit:
- Molecular conformations of met-enkephalin: Comparison of the zwitterionic and cationic formsBiochemical and Biophysical Research Communications, 1977
- Evidence for topographical analogy between methionine-enkephalin and morphine derivativesBiochemistry, 1977
- Conformational states of enkephalins in solutionBiochemical and Biophysical Research Communications, 1977