An effective method for the synthesis of a promising neurokinin receptor antagonist has been developed at the ZIOC

Neurokinin receptor antagonists are an important component of the complex of chemotherapeutic agents used to treat cancer. Most often, preparations of this type are polyfunctional structures with several asymmetric centers. One such promising compound is the polysubstituted pyrrolizidinone proposed by MSD Pharmaceuticals. However, the developed synthetic route includes 14 stages with a total product yield of only <2% due to the low regio- and diastereoselectivity of the reactions.

Over the past 10 years, scientists from the Laboratory of Organic and Organometallic Nitrogen-Oxygen Systems of the Zelinsky Institute have been actively researching stereoselective approaches to bioactive pyrrolidine derivatives. In one of their latest works, they developed a route for the production of polysubstituted pyrrolizidinone, a promising neurokinin receptor antagonist, the structure of which was previously proposed by MSD Pharmaceuticals. The synthesis includes 7 stages with a total product yield of 15%. The key steps are the stereoselective assembly of the functionalized six-membered cyclic nitronate and its reductive recycling under catalytic hydrogenation conditions. The stereoconfiguration of the resulting compound was unambiguously determined by X-ray diffraction analysis.

The research results were published in the international journal European Journal of Organic Chemistry, where the paper was awarded the status of "Very Important Article".

Source:

Ilya V. Okladnikov, Yaroslav D. Boyko, Yulia V. Nelyubina, Sema L. Ioffe, Alexey Yu. Sukhorukov Asymmetric Synthesis of a Pyrrolizidinone-Based hNK1 Antagonist through Reductive Ring Contraction of a Six-Membered Cyclic Nitronate // Eur. J. Org. Chem., 2022, accepted manuscript. DOI: 10.1002/ejoc.202200796.