Modular Synthesis of Four-membered Carbo- and Heterocycles

One of the main aspects of the modern pharmaceutical industry is the development of new medicines for the treatment of disease and improvement of overall quality of life. Herein organic chemistry is of profound importance, as it provides the necessary means to make new drugs. The development of new chemical reactions enables more and more complex molecules to be made, allowing for the incorporation of structural features into these compounds which were previously difficult to introduce. The method which will be investigated in this project aims to build molecules that contain a so-called cyclobutane. These structures consist of four carbon atoms where each carbon forms a chemical bond to two other carbons respectively, resulting in a molecule that is shaped like a square, in which each corner represents one carbon atom. As carbon can make chemical bonds to four other atoms, each carbon at the corner of this square is connected to two other atoms, usually hydrogen or other carbons that can be a part of a larger organic molecule, which can be used as a drug for example. The presence of a cyclobutane structure in drug molecules can be beneficial as the unusual structure makes them less recognizable to our metabolic enzymes, which break down drugs. As a result the drug can last longer in the body without being degraded, giving it more time to do its job. Unfortunately, the introduction of cyclobutanes to organic molecules is often difficult and there is only a limited set of methods to accomplish this. Our aim is to develop a new method to generate cyclobutanes from compounds that are called bicyclobutanes. These bicyclobutanes can be readily made from simple and cheap substances. It is planned to find the best way to add additional molecules to the bicyclobutane, turning it into a cyclobutane. Once this method is established it will grant efficient access to a broad variety of complex molecules containing cyclobutanes. As it is known that the incorporation of cyclobutanes into drug molecules can lead to improved properties, this project holds considerable promise for the development of drugs that could greatly benefit mankind.

One of the main aspects of the modern pharmaceutical industry is the development of new medicines for the treatment of disease and improvement of overall quality of life. Herein organic chemistry is of profound importance, as it provides the necessary means to make new drugs. The development of new chemical reactions enables more and more complex molecules to be made, allowing for the incorporation of structural features into these compounds which were previously difficult to introduce. The method which will be investigated in this project aims to build molecules that contain a so-called cyclobutane. These structures consist of four carbon atoms where each carbon forms a chemical bond to two other carbons respectively, resulting in a molecule that is shaped like a square, in which each corner represents one carbon atom. As carbon can make chemical bonds to four other atoms, each carbon at the corner of this square is connected to two other atoms, usually hydrogen or other carbons that can be a part of a larger organic molecule, which can be used as a drug for example. The presence of a cyclobutane structure in drug molecules can be beneficial as the unusual structure makes them less recognizable to our metabolic enzymes, which break down drugs. As a result, the drug can last longer in the body without being degraded, giving it more time to do its job. Unfortunately, the introduction of cyclobutanes to organic molecules is often difficult and there is only a limited set of methods to accomplish this. Consequently, we investigated reactions that would enable us to generate new types of cyclobutanes. In one of these reactions spirocyclic cyclobutanes were generated. These were molecules in which a carbon atom of the cyclobutane ring is linked to yet another carbon atom and an oxygen atom or nitrogen atom, these two additional atoms also being chemically bonded to one another. During this project, the synthesis of these compounds was optimized and a wide variety of simple and complex spirocyclic cyclobutanes were generated. These cyclobutanes can be efficiently integrated into complex molecules by other known simple methods. So-called bicyclobutane, which can be produced from simple and cheap chemicals in an uncomplicated manner, served as the starting material. As it is known that the incorporation of cyclobutanes into drug molecules can lead to improved properties, an innovative method was developed for the development of novel drugs that could greatly benefit mankind.