Methods for stereodivergent synthesis of polyheterocyclic spiro[oxindolepyrrolidine] derivatives were developed in ZIOC RAS

Condensed and spirofused nitrogen- and sulfur-containing heterocycles attract considerable attention of researchers around the world due to a wide range of useful properties, especially their biological activity. This structural fragment is a part of a large family of natural alkaloids and a variety of anti-cancer drugs. The reaction of 1,3-dipolar cycloaddition of azomethine ylides to electron-deficient alkenes is one of the key approaches to the synthesis of various condensed and spiroheterocyclic compounds. High regio- and stereoselectivity of these processes is also worth noting. It is ensured by the proximity of the reagents and conformational constraints. Nevertheless, the synthesis of different diastereomers from the same starting compounds is rather problematic.

Researchers from laboratory № 19 of ZIOC RAS succeeded in developing an effective and highly regio- and diastereoselective methods for the synthesis of two different diastereomers of polynuclear dispiroheterocyclic structures with five chiral centers. The reactions proceed as a sequence of 1,3-dipolar cycloaddition and intramolecular rearrangement of the thiazolotriazine fragment under the action of alkali. Interestingly, the different order of the cycloaddition and rearrangement steps allows the synthesis of two different diastereomerically pure products from the same starting compounds.

A. N. Izmest’ev, G. A. Gazieva, V. A. Karnoukhova, and A. N. Kravchenko Diastereodivergent synthesis of dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties Org. Biomol. Chem., 2020, 18, 6905-6911. DOI: 10.1039/d0ob01628d.