Nalin L. Subasinghe

An efficient and high yield method for the N-tert-butoxycarbonyl protection of sterically hindered amino acids

Abstract An improved method for the N - tert -butoxycarbonyl protection of the amino functionality of α-alkylated prolines and other sterically hindered α,α-disubstituted amino acids has been developed in which the lipophilic base tetramethylammonium hydroxide is used to solubilize the otherwise insoluble zwitterionic amino acid in acetonitrile, thereby obviating the need for an aqueous medium.

Discovery and optimization of a novel series of pyrazolyltetrahydropyran N-type calcium channel (Cav 2.2) blockers for the treatment of pain

A novel series of pyrazolyltetrahydropyran N-type calcium channel blockers are described. Structural modifications of the series led to potent compounds in both a cell-based fluorescent calcium influx assay and a patch clamp electrophysiology assay. Representative compounds from the series were bioavailable and showed efficacy in the rat CFA and CCI models of inflammatory and neuropathic pain.

Reactivity of dehydroaspartic acid derivatives under peptide coupling conditions

Abstract The reactivity of α-carboxy-activated dehydroaspartic acid derivativs with various N- and O-nucleophiles is described for the first time. Reaction of amino acid derivatives with Ac-Δ Z Asp(OBu t )-OH ( 4a ) under a variety of coupling conditions gave very poor yields of the resulting dehydroasparyl dipeptides, while the coupling of 4a with oxygen nucleophiles gave very good yields of the dehydroaspartyl esters. In contrast, the coupling of amino acids with Cbz-Δ Z Asp(OBu t )-OH ( 4b ) gave good yields of dehydroaspartyl dipeptides. The formaton of a highly reactive oxazolone intermediate is proposed to explain the low yields of peptide coupling between 4a and amino acids.