Purines, which are regarded as relatively stable heterocyclic systems, can be opened at both pyrimidine and imidazole rings. Purine ring opening also serves as a tool for the preparation of ring-modified purines through rearrangement/recyclization mechanisms. The obtained imidazole, pyrimidine, and purine derivatives are privileged molecular scaffolds in medicinal and agricultural chemistry. Purine ring-opening approach is a useful alternative for their synthesis, which competes well with de novo approach or modification of a conserved heterocyclic core. The substitution patterns and groups that activate purines towards ring opening are reviewed. Moreover, mechanistic studies using labelled substrates, which are leading to rearranged purine derivatives are covered. Furthermore, an insight into imidazole ring opening upon exposure of purine system to DNA damaging agents is provided.
Copper (II) and indium (III) triflate catalyzes the Rupe rearrangement of propargylic alcohols in liquid sulfur dioxide as the reaction medium. 1-Ethynylcyclohexanol and 1-(phenylethynyl) cyclohexan-1-ol were used as the model substrates and the expected 1-(cyclohex-1-en-1-yl) ethanone and 1-(cyclohex-1-en-1-yl)-2-phenylethanone were obtained in average yields.
A straightforward method for the synthesis of 5-substituted tetrazolo[1,5-a]pyrido[2,3-e]pyrimidines from 2,4-diazidopyrido[3,2-d]pyrimidine in SNAr reactions with N-, O-, and S- nucleophiles has been developed. The various N- and S-substituted products were obtained with yields from 47% to 98%, but the substitution with O-nucleophiles gave lower yields (20–32%). Furthermore, the fused tetrazolo[1,5-a]pyrimidine derivatives can be regarded as 2-azidopyrimidines and functionalized in copper(I)-catalyzed azide-alkyne dipolar cycloaddition (CuAAC) and Staudinger reactions due to the presence of a sufficient concentration of the reactive azide tautomer in solution. In total, seven products were fully characterized by their single crystal X-ray studies, while five of them were representatives of the tetrazolo[1,5-a]pyrido[2,3-e]pyrimidine heterocyclic system. Equilibrium constants and thermodynamic values were determined using variable temperature 1H NMR and are in agreement of favoring the tetrazole tautomeric form (ΔG298 = −3.33 to −7.52 (kJ/mol), ΔH = −19.92 to −48.02 (kJ/mol) and ΔS = −43.74 to −143.27 (J/mol·K)). The key starting material 2,4-diazidopyrido[3,2-d]pyrimidine presents a high degree of tautomerization in different solvents.
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