Self-organizing peptidic systems-catalyzed reactions in continuous flow reactor and structure characterization thereof

Summary of the research and its aims for experts

Describe the major aims of the research for experts.

The most important benefits of the application of CF reactions are as follows: (i) short reaction time, (ii) high conversions (iii) easy product isolation and (iv) eco-friendly protocols. The major goal of the proposed project is the application of peptidic catalysts in CF reactor for organocatalytic transformations leading valuable substances under cheap and green conditions.

I aim to perform a highly robust asymmetric carbon-carbon bond forming reaction in a CF reactor catalyzed by immobilized peptidic catalysts. The effect of the solid support used for immobilization will be investigated. Asymmetric carbon-heteroatom bond forming reactions are of considerable current interest as well. The synthesis of chiral epoxides and amino acids or amino alcohols in a CF reactor would further broaden the scope of applicability of peptidic catalysts. Cascade reaction in CF will be performed as well.

As a further step, I aim to develop novel foldamer based catalysts as well. These systems will be synthetized and applied in various, novel organocatalytic reactions. I target to create a foldamer with dynamically variable secondary structure that can differently catalyze asymmetric transformations. Parallel to this, I aim to investigate the mechanism of peptidic organocatalysis and to examine the effect of solvent on foldameric structure and on stereoselectivity.

To improve the efficiency of the proposed methods, I will apply a highly functionalized amino acid as skeleton for peptide synthesis. This will lead to higher catalyst density and to a molecular basket of which can further complex molecules potentially resulting in higher stereoselectivity.

What is the major research question?

Describe here briefly the problem to be solved by the research, the starting hypothesis, and the questions addressed by the experiments.

The starting point of the proposed research is the application of peptidic catalysts in a CF reactor for organocatalytic transformations.

A mainstream question in fundamental research and applied science as well, is that, how can we reduce the environmental impact of chemical transformations. I would like to investigate whether the peptidic catalyst synthesis and immobilization can be performed generally in one single step.

A more exact question to be answered is whether the reaction profile of peptide catalyzed asymmetric reactions can be broadened or not. An additional controversy is that, what is the effect of solid support on the result of the reaction. We wish to investigate the issue whether the polarity, porosity and loading of the resin has a special influence on an organocatalytic transformation. Another important point is catalyst reusability. I would like to investigate, that how many times a catalyst can be reused without a significant loss in its activity.

A significant subject is that whether foldameric structures can be used in organocatalytic transformations? If yes, is it possible to perform yet unprecedented or known but problematic reactions with such catalyst systems? In addition, is it possible that foldamers with variable secondary structure can catalyze reactions differently? The effect of solvent polarity on secondary structure and on catalyst activity is of interest, as well.

In terms of a fundamental research question, I will investigate the mechanism of peptidic organocatalysis.

I will answer the question, that how can we increase the loading of the resin with the ultimate goal of gaining more active heterogenized catalysts.

What is the significance of the research?

Describe the new perspectives opened by the results achieved, including the scientific basics of potential societal applications. Please describe the unique strengths of your proposal in comparison to your domestic and international competitors in the given field.

The principles and methodology of a novel platform will be established, which is based on CF, organocatalysis and peptidic foldamer chemistry. The basic research proposed herein might not lead directly to an industrially reliable synthetic method; however the expected outcomes could be utilized to create novel synthetic technologies.

A dominant significance of the proposed methodology is that the peptide synthesis and immobilization is performed in one single step. Consequently, wide range of resins can be applied and the peptide cleavage and purification step can be avoided which results in an overall lower impact on the environment.

I aim to develop a continuous process that will lead to carbon-carbon bond forming chemical transformations. Significant advantages of the method are as follows: (i) reaction times measured in minutes, (ii) easy product isolation (iii) high conversion and enantioselectivity and (iv) a robust technique with high catalyst reusability. These benefits make the utilization of this technique easier for the society. A further significant result would be the asymmetric synthesis of epoxides and amines. With N-terminal proline containing peptides, such reactions have never been described. To perform cascade organocatalytic reaction is a real significance of the proposed technique.

The application of foldames in organocatalysis can open a completely new era in this field. Because of the advantageous properties of foldamers (stable and predictable secondary structures, resistance against proteolytic degradation) we might be able to create a new class of organocatalysts. The excellent helix forming property of these polymers provides an outstanding chiral environment for organocatalytic transformations. Consequently, novel reactions will be carried out with unprecedented selectivity. This method can be combined with (i) a foldamer with variable secondary structure and (ii) multifunctional amino acid based molecular basket leading to enhanced catalyst loading and activity. Structure characterization of foldameric catalysts will help to understand the mechanism of peptidic organocatalytic reactions.

Summary and aims of the research for the public

Describe here the major aims of the research for an audience with average background information. This summary is especially important for NKFI in order to inform decision-makers, media, and the taxpayers.

Nowadays, the challenges associated with the treatment of different diseases are growing. Consequently, a lot of potentially pharmaceutically active and chemically complex molecules should be synthetized. On the other hand, the resources of the Earth are decreasing and we need to find efficient and sustainable techniques to produce such chemical entities.

I aim to perform efficient, sustainable and environmentally sound chemical transformations for the synthesis of chemically complex molecules. This method implies the utilization of lesser amount of chemicals, while includes the fine tuning of potentially important reaction parameters. The products gained by these reactions are of considerable current interest because of their pharmaceutical and industrial applications.

The method to be used is organocatalysis, that itself is biomimetic. Furthermore, we make an attempt to incorporate protein and peptide mimics to this reaction and utilize them. These biomimetic molecules can be specifically modified to obtain the best result. Moreover, with this methodology the catalyst can be reused many times leading to a more eco-friendly solution.

The principles and methodology of a novel platform will be established. The fundamental research proposed herein might not necessarily lead directly to any industrially reliable synthetic method; however the expected findings could be utilized to create synthetic technologies by means of entirely new reactions can be performed in a dramatically faster manner with lesser amount of the usage of the resources of the world.