An Efficient Synthesis of Simple β,β -Cyclobisalkylated Melatoninergic Phenylalkylamides

Title: An Efficient Synthesis of Simple β,β -Cyclobisalkylated Melatoninergic Phenylalkylamides

Volume: 4 Issue: 2

Author(s): Andrew Tsotinis, Margarita Vlachou, Demetris P. Papahatjis, Spyros P. Nikas and David Sugden

Affiliation:

Keywords: N-acyl 1-(3-methoxyphenyl)cycloalkanomethanamines, design, synthesis, melatoninergic activity

Abstract: Treatment of the commercially available 3-methoxyphenylacetonitrile (6) with sodium bis (trimethylsilyl)amide and subsequent cyclobisalkylation with α,ω-dibromo or dichloroalkanes in THF at 0 °C produces adducts 7a-d, which serve as precursors to the new conformationally constrained phenylalkylamides 5a-h. Compounds 5a-f are melatonin receptor agonists in the Xenopus laevis melanophore assay and their potency depends on both the size of the R group and the size and shape of the β-substituent. The fact that the cyclohexano-substituted analogs 5g and 5h are, regardless of the size of the R group, melatonin receptor antagonists, implies that the nature of the β-substituent constitutes a functional probe in the receptors dynamic agonist-antagonist conformational equilibrium.

Cite this article as:

Tsotinis Andrew, Vlachou Margarita, Papahatjis P. Demetris, Nikas P. Spyros and Sugden David, An Efficient Synthesis of Simple β,β -Cyclobisalkylated Melatoninergic Phenylalkylamides, Letters in Organic Chemistry 2007; 4 (2) . https://dx.doi.org/10.2174/157017807780414154