Design Of Novel Chiral Melamine Derivatives, Synthesis And Chiral Recognition Electrospray Ionization Mass Spectrometry Study

Chirality is of increasing importance in many fields such as pharmaceutics, chemical industry, and agriculture, etc. More and more single-enantiomers have been researched and developed. As a result, demand for chiral recognition and separation of chiral compounds has increased in the past few decades. At the same time, the development of the combinational chemistry and asymmetric synthesis require chiral analysis method to be more rapid and accurate. Thus, mass spectrometry has become an attractive alternative method in chiral analysis due to its many advantages such as the speed of analysis, high sensitivity, molecular specificity, and small amount of sample. However, limited selectivity a nd limited application range of recognition of the chiral selectors in chiral mass spectrometry is still the main problem that should be solved. The search for novel either broadly or dedicatedly applicable chiral selectors is always an open field attracting the creativity and efforts of the researchers. The goal of this study is to try to explore the potentiality of chiral melamine derivatives as a new class of selectors using chiral mass spectrometry, and develop a simple, fast and sensitive chiral analysis method. The dissertation is divided into following sections:In the introductory chapter, the application of the electrospray ionization mass spectrometry in chiral analysis and the main chiral selectors in chiral mass spectrometry are reviewed. The research proposal of this dissertation was presented.In chapter two, a series of new chiral melamine derivatives with various N-substituents were synthesized in order to better understand the role played by the structural features of the melamine derivatives on the enantioselective properties and to identify more effective chiral selectors.In c hapter t hree, the aggregation of the chiral melamine d erivatives and amino acids (or some chiral drugs) in electrospray ionization mass spectra was observed and investigated to elucidate the roles played by various noncovalent interactions in the process of the association. The results show that melamine derivatives have unique structure and properties that make them easy to possess various groups that canprovide multiple interactions for chiral recognition, and they can produce polymer clusters with amino acids in electrospray ionization mass spectrometry easily. So they are very suitable to be employed as chiral selectors for MS analysis. Moreover, some obvious isomeric differences in combination can be observed directly from the peak abundances in the single-stage mass spectra, which can be further proved by measuring the associate constant.Chapter four describes the use of electrospray ionization tandem mass spectrometry to probe the chiral recognition ability of chiral melamine derivatives. Some mechanism and regularity in the chiral recognition process using chiral melamine derivatives as chiral selectors were elucidated. The effect of different noncovalent interactions caused by various chiral or achiral moieties in melamine derivatives on the chiral recognition has been studied. The results show that the chiral melamine derivatives synthesized could provide excellent chiral discriminations for amino acids, and enantiodiscrimination for analytes with different structure and properties c ould b e i mproved b y m odifying s ubstituents i n m elamine d erivatives o n purpose. The fundamental process and mechanism of the chiral recognition is that the chiral selector and the analyte are pulled together to form polymer clusters by hydrogen bond, electrostatic interaction and n-n interaction, which are the main driving forces for association. Then, some other interactions, especially the interactions on chiral moieties will assist to achieve chiral recognition. Multiple interactions such as electrostatic interaction, hydrogen bond, 71-71 stacking and steric interaction between selector and analyte may play important roles in the association and enantioselective recognition of amino acids, and these multiple interactions should interact in balance and coordination to obtain better chiral selectivities.In chapter five, electrospray ionization tandem mass spectrometry coupled with nuclear magnetic resonance are used to investigate the recognition ability and mechanism of chiral melamine derivatives toward Nateglinide. The results show that most chiral melamine derivatives can well recognize three isomers of Nateglinide. The results of nuclear magnetic resonance experiments show that hydrogen bonds and 7t-7t...