Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

Abstract

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.

Synthesis of 6,8-diaminopurines via acid-induced cascade cyclization of 5-aminoimidazole precursors and preliminary anticancer evaluation

“…However, the reaction was so fast that the first new signals observed in the spectrum already corresponded to the final products 3 . Thus, based on these results and comparing them with similar mechanisms previously reported, 26–28 the mechanism here presented for this reaction involves a cascade of ring-opening/ring-closing reactions (Scheme 3). Under acidic conditions, the amidine group becomes protonated and the 5-aminoimidazole moiety can tautomerize to the reactive 5-iminoimidazol-4-ylidene form, which is very susceptible to nucleophilic addition at C-2.…”

Reactivity and Stability of Natural Clay Minerals with Various Phyllosilicate Structures as Catalysts for Hydrothermal Liquefaction of Wet Biomass Waste

“…Amides may get the −NH 2 group directly cleaved to yield an amine and a carboxylic acid. Pyrimidines, such as 3-amino-5 H ,6 H ,8 H -[1,2,4]­triazolo­[4,3- a ]­pyrimidin-7-one, underwent ring opening by cleavage of (1) N-1 and N-2 and (2) N-8 and C-9, yielding 3-( N -carbamimidoylformimidamido)­propanamide . The subsequent C–N cleavage produced propionic acid and N -carbamimidoylformimidamide, which may be deaminated into 3 mol NH 3 and 1 mol dimethylamine ( R 36).…”

“…Pyrimidines, such as 3-amino-5H,6H,8H- [1,2,4]triazolo [4,3-a]pyrimidin-7one, underwent ring opening by cleavage of (1) N-1 and N-2 a n d ( 2 ) N -8 a n d C -9 , y i e l d i n g 3 -( Ncarbamimidoylformimidamido)propanamide. 73 The subsequent C−N cleavage produced propionic acid and Ncarbamimidoylformimidamide, which may be deaminated into 3 mol NH 3 and 1 mol dimethylamine (R36). The enhanced amines production in HTL-AP increased the Org-N yield-AP , confirming the positive linear correlation between Org-N yield-AP and SLA composition.…”

O6-[(2″,3″-O-Isopropylidene-5″-O-tbutyldimethylsilyl)pentyl]-5′-O-tbutyldiphenylsilyl-2′,3′-O-isopropylideneinosine

“…The reaction between the protected inosine 10 with the electrophile 11 has been studied in detail. In principle, as hypoxanthine is an ambident nucleophile [28] at the N1 and O6 purine positions [29,30], the two regioisomers 12 and 9 could be expected. In our studies focused on the inosine N1 functionalization, we discovered that the Mitsunobu reaction was not a good method to regioselectivity obtain the N1-alkylated isomer.…”