Abstract
There are many forms of DNA damage which may arise from the modifications DNA bases. Deazaguanine is a modified DNA base which is recognised by DNA repair enzyme, Methylguanine DNA-methyltranferase (MGMT). The synthesis of <i>Bis</i>chlorinated deazaguanine was successfully carried out via two different routes. The first route was achieved through the reaction of pyrrolopyrimidine with benzyl(triethyl)ammonium chloride, dry dimethylaniline and freshly distilled phosphoryl chloride in acetonitrile under argon atmosphere. An alternative method was employed toward achieving the <i>Bis</i>cholorinated through the debenzoylation of the protected pyrrolopyrimidine with 1 M NaOH at 50°C for 1h followed by double chlorination reaction using phosphoryl chloride alone at 80°C for 1h. Both routes were found to be successful with lower impurities recorded from the second route though it gives a low yield but it was shorter.
Highlights
There are many ways of modifying DNA in which alkylation is one of the most common arising from the addition of an alkyl group [1]
Methylation at the O6-position of guanine changes the Watson-Crick hydrogen bonding with the opposite cytosine [5], which leads to the loss of a proton at the N1-position of G, the N1-atom is changed from being a donor to an acceptor and this results in distortion of the double helix which subsequently slows down the DNA polymerase during replication [6]
This intermediate is reactive toward cytosine which subsequently leads to an interstrand cross-links between the bases [7]
Summary
There are many ways of modifying DNA in which alkylation is one of the most common arising from the addition of an alkyl group [1]. Chlorination was undertaken by treating 1 with benzyl(triethyl)ammonium chloride (2 equivalents), dry dimethylaniline (1.4 equivalents) and freshly distilled phosphoryl chloride (6 equivalents) were dissolved in acetonitrile under argon and refluxed for 30 min [10 & 11]. After cooling to room temperature the reaction mixture was poured onto a crushed ice and neutralised using conc.
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