Exploration Synthesis Of 6-Chlorine 9-Substituted Guanine Derivative

Guanine derivatives are an important class of pharmaceutical intermediates. At the 2-,6-,8-or 9-site of guanine ring, the corresponding derivatives display antiviral, anticancer and antihypertensive activity for biomedical application. In DNA, the formation of G-C base pair in duplex and G-quadruplex at the terminal of telomere by hydrogen bonding interaction is very important to genetic replication. From chemical engineering, it's rarely reported that the molecule carrying multi-base groups was synthesized chemically. In this thesis, the compounds of carrying multi-base groups are synthesized through N9-site of guanine. Generally, the content in this thesis is listed below:1. In this study, starting from 6-chlorine guanine,6-chlorine-9H-diguanine derivatives, which were attached by alkyl or ether link, were successfully synthesized in DMF solvent and characterized by IR, MS and 1H NMR spectra. The reaction conditions including solvent, alkali, and reaction temperature have been optimized.2. 2-Amino-6-chlorine-9-bromopropyl guanine and 6-chlorine- 9H-diguanine derivatives had been prepared by the reaction between 6-chlorine guanine and 1,3-dibromo-propane. Two derivatives of aza-heterocyclic ring,9,9'-(piperazine-1,4-diylbis(propane-3,1-diyl)) bis(6-chloro-9H-purin-2-amine) and 9,9'-((1,4-diazepane-1,4-diyl)bis (propane-3,1-diyl))bis(6-chloro-9H-purin-2-amine), had been synthesized by reaction between 2-Amino-6-chlorine-9-bromopropyl guanine and piperazine or 1,4-diazepane. Both derivatives were characterized by the FT-IR,1H NMR,13C NMR, MS methods.3. The structural minimum energy of the synthesized guanine derivatives had been optimized with UFF force field in Gaussian-03 software package. Based on the optimization, Mulliken charge distribution of guanine derivatives were calculated by RB3LYP method in 6-31G(d) basis set.