Ivan Collado

4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists

Twenty-four 4-alkylidene glutamic acids were synthesised and tested as potential subtype selective GluR5 and 6 ligands. It was found that a critical size of alkylidene group gave potent and selective GluR5 receptor agonists. LY339624 had Kis of 0.0326 and >100 microM on GluR5 and 6 receptors, respectively.

Stereoselective cyclopropanation of enones with ethyl dimethylsulfonium acetate bromide in the presence of DBU

Abstract The cyclopropanation reaction of α, β-unsaturated ketones 1a-c with ethyl (dimethyl sulfuranylidene) acetate (EDSA), generated in situ from the corresponding sulfonium bromide salt and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) in toluene, leads exclusively to the exo adduct 2a-c (d.e.=100%). Acyclic enones 1d-g , give mainly the “trans” cyclopropanes 4d-g with a high degree of stereocontrol (d.e. 3 80%). Changing the solvent to CHCl 3 affords a 2:1 mixture of “trans” and “cis” cyclopropanes 4d-g and 5d-g respectively. The “cis” isomers 5d-g can be epimerizated to the alternative “trans” isomers 6d-g under basic conditions.

First Trapping Reaction of N-Boc Ethyl 3,4-Dehydropyroglutamate with Cyclopentadiene

Abstract (2S)-N-Boc ethyl 3,4-dehydropyroglutamate 3, generated in situ by sulfoxide elimination was trapped with cyclopentadiene in a Diels-Alder reaction giving rise the endo adduct 12 with 50% e.e. When the protecting group was removed, V isomerises into ethyl 2,3-dehydropyroglutamale VI which undergoes Diels-Alder reaction delivering the exo adduct 15.