“…Fused 1,2,4‐triazolopurines can be opened either in basic or acidic media to give imidazolyltriazoles 92 a – d . Similarly to the previous example, excessively acidic (concentrated HCl) or basic (2 N NaOH) reaction media led to ring opening with further formyl group cleavage to 92 a and 92 c , while under mild conditions (in this case, HCOOH or 1 N NaOH) formamido (R 4 =CHO) products 92 b and 92 d were obtained [92] …”
Section: Ring Opening Of the Pyrimidine Moiety In Purinesmentioning
confidence: 56%
“…Similarly to the previous example, excessively acidic (concentrated HCl) or basic (2 N NaOH) reaction media led to ring opening with further formyl group cleavage to 92 a and 92 c, while under mild conditions (in this case, HCOOH or 1 N NaOH) formamido (R 4 = CHO) products 92 b and 92 d were obtained. [92] Imidazo [1,6]purines 93 readily underwent pyrimidine ring cleavage in alkaline media at room temperature, giving diimidazoles 94 [93,94] in 66-95 % yields. The ring opening products could be further transformed into imidazotriazines 95, [95,96] 2-thioimidazopurines 96 [97,98] or 2-deuteroimidazopurines 97 [99,100] (Scheme 16).…”
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.
“…Fused 1,2,4‐triazolopurines can be opened either in basic or acidic media to give imidazolyltriazoles 92 a – d . Similarly to the previous example, excessively acidic (concentrated HCl) or basic (2 N NaOH) reaction media led to ring opening with further formyl group cleavage to 92 a and 92 c , while under mild conditions (in this case, HCOOH or 1 N NaOH) formamido (R 4 =CHO) products 92 b and 92 d were obtained [92] …”
Section: Ring Opening Of the Pyrimidine Moiety In Purinesmentioning
confidence: 56%
“…Similarly to the previous example, excessively acidic (concentrated HCl) or basic (2 N NaOH) reaction media led to ring opening with further formyl group cleavage to 92 a and 92 c, while under mild conditions (in this case, HCOOH or 1 N NaOH) formamido (R 4 = CHO) products 92 b and 92 d were obtained. [92] Imidazo [1,6]purines 93 readily underwent pyrimidine ring cleavage in alkaline media at room temperature, giving diimidazoles 94 [93,94] in 66-95 % yields. The ring opening products could be further transformed into imidazotriazines 95, [95,96] 2-thioimidazopurines 96 [97,98] or 2-deuteroimidazopurines 97 [99,100] (Scheme 16).…”
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.
“…The only hitherto known [ f ]-fused purines include pyrrolo[2,1- f ]-, oxazolo[2,3- f ]-, , imidazo[2,1- f ]-, − pyrido[2,1- f ]-, pyrimido[2,1- f ]-, , oxazino[2,3- f ]-, pyrazino[2,1- f ]-, [1,2,4]triazino[3,2- f ]-, and [1,2,4]triazepino [3,2- f ]- 11 purines. Also, [1,2,4]triazolo[3,4- i ]- and [1,2,4]triazolo[5,1- i ]purines were also reported. , The interest in synthesis of derivatives of the title ring system results from the fact that certain fused xanthines, with theophylline as the prototype, were reported to inhibit many of the pharmacological and physiological effects of adenosine, by acting as competitive antagonists at A 1 - and A 2 -adenosine receptor subtypes . For this reason, considerable efforts have been devoted in recent years to synthesize functionalized xanthine congeners, as selective antagonists for one or the other type of adenosine receptors. ,, …”
“…Since the first report 13 on the synthesis of compounds having a 7H- [1,2,4]triazolo [3,4-i]purine ring system in 1965, which is of interest in view of the chemical and biological properties, only two reports 14,15 have hitherto appeared in the literature. Halogenated purine nucleosides are good synthetic intermediates for the synthesis of a number of the purine nucleoside derivatives.…”
Novel, general, and facile syntheses of 3-and/or 5-substituted 7-b-D-ribofuranosyl-7H- [1,2,4]triazolo [3,4-i]purines (5-8) via compounds 4 as a new class of potential xanthine oxidase inhibitors are described. The key intermediates 4b-j were prepared by oxidative cyclization of the aldehyde hydrazones 3a-i, derived from 6-hydrazino-2-iodo-9-(2¢,3¢,5¢-tri-O-acetyl-b-D-ribofuranosyl)-9H-purines (2) and an appropriate aldehyde, with diethyl azodicarboxylate (DEAD) (Method A) or lead tetraacetate (Method B) in good yields. The intermediates 4a-j were also synthesized from heating of 2 with triethyl orthoesters (Method C) or with aldehydes and DEAD in one-pot reactions (Method D).In connection with ongoing work aimed at the synthesis and biological evaluation of novel fused purine systems, 1,2 we tried to prepare the angular type purine analogues, 7H-[1,2,4]triazolo[3,4-i]purine nucleosides, which have very recently been investigated as a new class of potential xanthine oxidase (XO) / xanthine dehydrogenase (XDH) inhibitors in our laboratory. 3 Some of them showed more potent bovine milk XO inhibitory activity than that of allopurinol. Allopurinol and oxypurinol are known to inhibit xanthine oxidase, 4 and allopurinol is now widely employed in treatment of gout and hyperuricemia resulting from uric acid. 5-7 Although XO / XDH inhibitory activities have recently been discovered in some synthetic compounds, 8-12 no clinically effective XO inhibitors for the treatment of hyperuricemia have been developed since allopurinol was introduced for clinical use in 1963. 4 Here we report a new, convenient, and general synthesis of the tricyclic purine compounds, 3-and/or 5-substituted 7-b-D-ribofuranosyl-7H-[1,2,4]triazolo[3,4-i]purines (5-8) as a new class of the xanthine oxidase inhibitors.Since the first report 13 on the synthesis of compounds having a 7H-[1,2,4]triazolo[3,4-i]purine ring system in 1965, which is of interest in view of the chemical and biological properties, only two reports 14, 15 have hitherto appeared in the literature. Halogenated purine nucleosides are good synthetic intermediates for the synthesis of a number of the purine nucleoside derivatives. Thus the availability of 6-chloro-2-iodo-9-(2¢,3¢,5¢-tri-O-acetyl-b-D-ribofuranosyl)-9H-purine (1) 16 for the starting material enabled us to synthesize the tricyclic purine derivatives 4a-j as shown in Scheme 1.Treatment of compound 1 with excess anhydrous hydrazine (2.3 mol equiv) in acetonitrile at room temperature afforded 6-hydrazino-2-iodo-9-(2¢,3¢,5¢-tri-O-acetyl-b-Dribofuranosyl)-9H-purine (2) in 94% yield. The structure was verified by satisfactory spectral and analytical data. In particular, the IR spectrum showed the characteristic N-H bands at n as = 3410, n s = 3360, n = 3260, and d = 1610 cm -1 for the NHNH 2 group, and the structure was substantiated by the appearance of the molecular ion peak (MH + : m/z = 535), which was attributable to the 6-hydrazino derivative 2 rather than 2-hydrazino derivative (MH + : m/z = Method A: DEAD, MeCN, reflux, 5...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
