Synthesis of Potent Calcimimetics (+)-NPS R-568 by Palladium-Catalyzed Oxidative Kinetic Resolution

Abstract

A practical and efficient procedure for the synthesis of potent calcimimetics (+)-NPS R-568 was developed. This procedure includes palladium-catalyzed oxidative kinetic resolution of benzylic alcohol with molecular oxygen and (-)-sparteine, as a source of chirality. The synthesis was achieved in six steps from commercially available 3-methoxyacetophenone at 18.58% overall yield and the final compound, calcimimetics (+)-NPS R-568 1 had 87% enantioselectivity.

Mitsunobu Reaction: A Powerful Tool for the Synthesis of Natural Products: A Review

“…Similarly, the synthesis of anti-proliferative menaquinone 4 , which is a homologue of vitamin K, and synthesis of cannabidiol derivatives 3 , which is used for the treatment of arthritis, immune system disorders, and diabetes, include the Mitsunobu reaction as a key step [ 8 , 9 ]. It has played a great role in the synthesis of drugs and their derivatives, such as the synthesis of NPS R-568 2 , which is a calcimimetic drug used for the treatment of primary and secondary hyperparathyroidism [ 10 ]. This paper reviews the importance of the Mitsunobu reaction in the synthesis of some of the natural products reported in recent years.…”