טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentGal Suez
SubjectDevelopment of New Organocatalysts Based on the Molecular
Recognition of DNA Bases
DepartmentDepartment of Chemistry
Supervisor Professor Gandelman Mark
Full Thesis textFull thesis text - English Version


Abstract

Over the past four decades, the dominant strategy for enantioselective catalysis has involved the utilization of metal-based catalysts. This has led to the development of numerous groundbreaking synthetic applications. Within the last few years, utilization of relatively small metal-free chiral molecules (“enzyme-like” species) which can mediate enantioselective transformations has emerged as an attractive and powerful tool in organic synthesis. Although the practical application and mechanistic understanding of these types of catalysts are in their infancy, a number of important features are already evident: (1) reactions can be performed under aerobic conditions; (2) the catalysts are inexpensive and are often more stable than enzymes or other bioorganic catalysts; (3) environmentally benign chemical processes could be expected. Catalysis by chiral molecules involves hydrogen bonding as a mechanism for substrate (usually, electrophile) activation in a way similar to that of biological catalytic machines such as enzymes and RNAs. In those cases, binding and activation of a substrate takes place via donor-acceptor hydrogen bonds.

In this research we present our work towards rational design and development of a new type of organocatalysts and investigation of their reactivity in asymmetric synthesis. 

The proposed organocatalysts contain hydrogen-bonding recognition point for binding certain organic molecules with a complementarily pattern similar to Lewis acid-base interactions between two natural DNA bases.

Numerous potential organocatalysts based on the structure of guanine were synthesized and fully characterized by multinuclear NMR techniques and X-ray analysis. In addition, we present a good crystallographic evidence for the suggested substrates binding by the designed catalysts.

As a proof of concept, few reactions were tested using the proposed catalysts. For example; [4+2] cycloadditions and 1,4- conjugate additions were primarily studied. These reactions are known to be catalyzed by Lewis acids.

Utilization of these catalysts in the aza-Baylis-Hillman reaction was demonstrated. When alkyl or aryl imines are used as the substrates, defined catalytic activity was observed with the prepared catalysts.

In addition, an initial work towards bifunctional organocatalyst based on guanine analog is presented.

The development of chiral catalysts capable of simultaneous activation of nucleophiles and electrophiles is an active and promising area of investigation. Although some fruitful achievements have been accomplished in this facet, only few molecularly well-defined bifunctional catalysts are known. The synthesis of the bifunctional organocatalyst is reported here.

Further investigation including the optimization and understanding of studied processes as well as application of the prepared catalysts to other interesting asymmetric reactions are required.