RUDN University chemists have found a new method that makes it possible to obtain key fragments of alkaloids under mild conditions. These substances are in demand in the pharmaceutical industry. The new approach works on the principle of dominoes – reactions automatically occur one after another. The results are published in Tetrahedron letters.
Alkaloids are a group of nitrogen-containing organic compounds that are usually obtained from plants, such as tobacco, cocoa, tea. Many alkaloids are used in medicine – for example, atropine, codeine, quinine. Chemists have learned to reproduce the structure of natural alkaloids and create their synthetic counterparts. However, this is a complex and multi-step process. Key fragments of a number of natural and synthetic alkaloids are isoquinolines with a condensed pyrrole ring, which must first be obtained from simpler compounds. RUDN University chemists presented a new protocol for the preparation of various new pyrroloisoquinolines during the reaction under mild conditions. Moreover, the synthesis proceeds according to the type of a multicomponent reaction, when several substances are combined into one at once according to the principle of a domino effect, without additional intervention.
“One of the main directions in the synthesis of alkaloid analogues is the modification of known molecular frameworks. For this, multicomponent reactions are increasingly being used. This approach makes it possible to expand the functional characteristics of molecules. In addition, this opens up interesting opportunities for creating biologically significant structures,” Leonid Voskressensky, Doctor of Science in Chemistry, Dean of the Science Faculty, RUDN University.
Three types of substances are involved in the synthesis of new compounds – dihydroisoquinolines, alkynes and NH-acids. The latter are needed so that the future product receives the necessary nitrogen-containing fragments. The reaction goes by domino principle – one stage automatically starts another until the target substance is obtained. This does not require harsh conditions – the synthesis takes place at a temperature of 130 ℃ in acetonitrile under the influence of microwave radiation.
Using the new method, RUDN University chemists have obtained more than 30 pyrroloisoquinolines with various structures. Previously, such compounds were unknown. Depending on the reaction conditions and reagents, the production efficiency ranged from 6% to 85%. In the future, chemists will have to study the properties of new compounds and determine the range of possible applications.
“The three-component domino reaction allows the synthesis of previously undescribed pyrroloisoquinoline derivatives in one step . They contain cyclic nitrogen-containing fragments. A convenient method for the introduction of various types of nitrogen-containing groups proved to be the use of NH-acids. This will help create analogues of biologically active compounds,” Almira Miftyakhova, RUDN laboratory research assistant.
