Studies On The Synthesis Of 5-Bromo-1,2,3-Triazole And Its Application On The Synthesis Of CADPR Analogues Moiety

Recently, click chemistry has provided a simple method to join together organic molecules in high yields under mild conditions in the presence of diverse functional groups. The Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC) is considered as a typical''click''reaction, in which a 1,2,3-triazole is formed with very high yields and good regioselectivity in the presence of Cu(I). As the product of click reaction, 1,2,3-triazoles can well mimic natural peptide and heterocycle in the geometrical shape and interaction function as the bioisostere. 1,2,3-triazole derivatives have shown a broad spectrum of biological activities such as antibacterial, antiallergic, and anti-HIV. A new type of cyclic ADP-ribose (cADPR) analogue containing 4-amide-1,2,3-triazole nucleobase instead of adenine nucleobase has shown good membrane permeable property and calcium releasing activity as a biological tool. Thus design and synthesis of cADPR analogues containing 4-amide-5-bromine-1,2,3-triazole nucleobase is promising to get a new cADPR analogues with good biological functions.The diverse modifications on the 1,2,3-triazole moiety are essential for the investigation of structure-activity relationship on the 1,2,3-triazole derivatives and obtaining the drug candidate with better biological activities. But it is still a challenge in organic sysnthic chemisty to efficient and convient preparation of 5-substituted-1,2,3-triazoles, especially to concise and effieient preparation of 5-bromo-1,2,3-triazole derivatives. Therefore, in this dissertation, we investigated the methodology of sysnthesis of 5-bromo-1,4-disubstituted-1,2,3-triazoles for the first part. And then, we applied the methodology that we built to design and sysnthesis of new cADPR anaologe containing a 5-bromo-4-amide-1,2,3-triazole nucleobase. The detailed content of the dissertation are shown as follows: 1. Based on the previous study in our lab, we applied CuX-oxidant reaction system into the preparation of 5-bromo-1,4-dissubstituted-1,2,3-triazoles. And CuBr-NCS reaction system was found to be a mild and efficient reaction system for the preparation of 5-bromo-1,4-dissubstituted-1,2,3-triazoles. With this novel reaction system, terminal alkynes and azides can react smoothly to give 5-bromo-1,4-disubstituted-1,2,3-triazoles in moderate to good yields with a wide tolerance of sensitive groups. Furthermore, this CuBr-NCS reaction system has been applied successfully in sugar buiding blocks and cADPR analogues.2. During our investigation about the preparation of 5-chloro-1,2,3-triazoles, we found CuCl-NBS as a non-oxidative reaction system could also promote the synthesis of 5-bromo-1,4-dissubstituted-1,2,3-triazoles for terminal alkynes and azides under mild conditions.3. Base on our methods to synthesize 5-bromo-1,4-disubstituted-1,2,3-triazoles, we designed and synthesized the structure moiety of a new cADPR analogue. We have got the precursor of the cADPR analogue now. The following phosphorylation of the precursor is still ongoing.