Synthetic studies of salinosporamide A through the intramolecular hydroamidation of alkynes

Rhodium-catalyzed intramolecular hydroamidation of alkynes was carried out to construct the synthetic intermediates of a proteasome inhibitor, salinosporamide A. Several alkynyl formamides were synthesized and subjected to the hydroamidation reaction. Some derivatives with a methoxymethyl (MOM) or 2-methoxy-2-propyl (MOP) group near the reaction site were converted to the corresponding lactams in excellent yields.

With aiming at the total synthesis of a proteasome inhibitor, salinosporamide A, we investigated rhodium-catalyzed intramolecular hydroamidation of several alkynyl formamides. As a result, the MOM or MOP group is revealed to be a suitable protecting group of the hydroxy group, and the corresponding lactams were obtained in excellent yields.Figure optionsDownload as PowerPoint slide