Microwave-assisted N-allylation of uracil and thymine pyrimidine bases

Abstract

This work presents a new synthetic approach to N(1)-allylation of pyrimidine nucleobases with allyl bromide. The increased efficiency of the proposed method is based on two specific elements: (a) the nucleoside N-deprotonation is carried out in a homogeneous system by using sodium methylsulfinylmethylide in DMSO; (b) the allylation reaction is microwave-assisted. This method ensures high yields (87-88%) of the monoallylated products and short reaction time (1.5 h as compared to tens of hours for classical methods), and provides protection against side reactions. NMR analysis of the crude reaction mixture indicated a ratio of 6-8 : 1 between N(1)-allyl derivatives and N(1),N(3)-diallyl derivatives.

Customizable and Regioselective One‐Pot N−H Functionalization of DNA Nucleobases to Create a Library of Nucleobase Derivatives for Biomedical Applications

“…The N-allylation of T was also described involving two reaction steps, first heating at 65°C for 30 min followed by MW irradiation for 2 min. [29] In this work, the treatment of A, T, C and G with allyl bromide 22, in basic conditions under MW, led to the desired N-allylic pyrimidine and purine derivatives 18-21 in low to moderate yields (16-43 %, Table 3) in a shorter reaction time.…”

“…Recently, it has been shown that primary alcohols are appropriate candidates to react with nucleobases, leading to N-alkyl derivatives in good yield and with low toxicity. [21] The chemical modification of nucleobases with either terminal alkyne, [22][23][24] acrylate, [25][26][27] allyl, [28,29] acrylonitrile [26,[30][31][32] or thiol [33] functional groups at the secondary amine has been explored in the last decades and, in most of the cases, A and T have been at the limelight. From the chemical functionalization standpoint, the major bottlenecks associated to these functionalization strategies include the development of efficient synthetic methodologies for the successful introduction of reactive terminals at C and G, as well as simple and direct methods for the regioselective functionalization of the DNA nucleobases, aiming to preserve their hydrogen bonding capabilities.…”