Proline-Based Diboronic Acid For Chiral Recognition Of Glucose

Saccharides,which are the main source of energy for living cells,play an important role in metabolic processes.It is known that glucose is a general chiral hexose,and its metabolic level affects human health significantly,such as diabetes mellitus,which suffers from inadequate control of blood glucose.Therefore,it is demanding to develop convenient and efficient methods of measurement for glucose.There is an extremely difficult challenge of discrimination for monosaccharides because of their structural similarity and complexity of multiple chiral centers and enantiomers.It is a major breakthrough that there boronic acid can form a five-or six-memberedcyclic boronate by reversible and covalent interaction with cis-1,2-or 1,3-diol and the interaction is governed by the orientation and spatial position of the hydroxyl groups of saccharides towards boronic acid.Effort to have been made to develop boronic acid-based chemosensors for chiral recognition of saccharides with high sensitivity and selectivity.According to the research progress in our laboratory,we proposed to employ the specific chirality and folding structure of proline residue by incorporation two boronic acid groups modified at its N-and C-terminals,to design and synthesize a series of boronate-based chemosensor with a chiral framework of proline,for application in chiral recognition of glucose.This dissertation consists of four chapters.In chapter 1,research progress in recognition of saccharides is introduced at first,followed by the description of the importance of chirality and chiral recognition is A brief review is presented on the boronic acid-based chiral chemosensors for the recognition of hydroxyl compounds.Chapter 2 present the synthesis and characterizations of the fluorine-containing boronate-based and benzyl boronate-based chemosensors.In chapter 3,19F NMR,UV and CD spectral research of the interactions between L-proline-based fluorinated diboronic acid based chemosensors with glucose was described.Fluorine substition adds a simple research method of 19F NMR spectra,and leads to the longer spectral wavelength because of its strong electron-withdrawn effect,which is beneficial to the study of the interaction between host and guest.The mass spectra of the conjugates and Job-plot experiments indicate that F,F-L-1 and L-glucose covalently interact forming a 1:1 cyclic boronate.However,this 1:1 cyclic binding mode is not applicable to the interaction between F,F-L-1 and D-glucose.The results demonstrate that the L-proline-based fluorinated diboronic acid can selectively discriminate L-/D-glucose.In chapter 4,benzyl boronate-based chemosensors are designed in an attempt to weaken the rigidity of the L-proline residues by inserting a methylene group between proline residues and phenylboronic acid.The research reveal that only L-1 among the derivatives exhibits the best chiral selectivity for D-glucose,which is in accordance with the favored chirality of L-amino acid and D-glucose in nature.The binding ability of L-1 to L-glucose and other monosaccharides is weak,leading to significant differences from D-glucose in the spectral profiles.In addition,boronic acid groups substituted at para-/para-positions of the benzene rings,the obtained L-4 designed is similar to L-1,bearing meta-/meta-boronic acid group,in the chiral recognition of L-/D-glucose,demonstrating that the substitution position of boronic acid has little influence on the chiral selectivity of L-/D-glucose.