RESUMO
Carbon-14 (14 C)-labelled active pharmaceutical ingredients (APIs) and investigational medicinal products (IMPs) are required for phase 0/I to phase III mass balance and micro-dosing clinical trials. In some cases, this may involve the synthesis of 14 C-labelled peptides, and the analysis can be performed by accelerated mass spectrometry (AMS). The 14 C-peptide is typically prepared by the solid-phase peptide synthesis (SPPS) approach using custom-made glassware for the key coupling steps. Further modification of the purified 14 C-peptide can then be performed.
Assuntos
Radioisótopos de Carbono/química , Peptídeos/química , Peptídeos/síntese química , Biotinilação , Técnicas de Química Sintética , Dissulfetos/química , Marcação por Isótopo , Modelos Moleculares , Conformação ProteicaRESUMO
An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of ß-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3-dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.