A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• reports found in the literature suffer from the requirement of hazardous intermediates and harsh reaction conditions. Here, we report a new six-step synthesis for c1G base, starting from 6-iodo-1-deazapurine. The key transformations are copper catalyzed C–O-bond formation followed by site-specific

• nitration. A further strength of our route is divergency, additionally enabling the synthesis of 1-deazahypoxanthine (c1I base). Keywords: deazapurine; heterocycles; imidazopyridines; nucleoside; nucleotides; pyrrolopyrimidines; RNA atomic mutagenesis; Introduction Deazapurines (imidazopyridines and

• , glycogen synthase kinase 3 (GSK-3), leucine-rich repeat kinase 2 (LRRK2), tyrosine phosphorylation-regulated kinase-1A (DYRK1A) and CDC2-like kinase 1 (CLK1), and fatty acid amide hydrolase (FAAH) [4]). Similar properties were ascertained for 1-deazapurine derivatives (imidazo[4,5-b]pyridines) and

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• natural sources. Earlier syntheses of preQ1, preQ0 and m6preQ0 The synthesis of preQ1 has been first described by Goto starting from 2-methylthio-6-methoxy-7-methyl-7-deazapurine and requiring more than ten steps [21]. More efficient was a procedure reported by Nishimura applying a Mannich reaction with

• % (Scheme 2) which is significantly lower compared to the cyclocondensations with 2,6-diamino-4-pyrimidin-4-one mentioned above [23][24][25][26][27]. We therefore envisaged a path involving 6-chloro-7-deazapurine derivative 3 (Scheme 3) as this compound is readily available from cheap starting materials

• ] and gave nearly quantitative yields of N2-pivaloyl preQ0 in our hands. Finally, transformation of the 6-carbonyl group by using phosphorus oxychloride gave 6-chloro-7-deazapurine derivative 3 [33]. Notably, attempts to directly transform preQ0 (without N2 protection) into 6-chloro-7-cyano-7

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• purine scaffolds, 5-aza-9-deazapurine and 5-azapurine have been identified as a favorable skeleton for the construction of new compounds such as 108 and 109 (Figure 8) [95][96]. Considering this fact, Dolzhenko and co-workers [97] reported the first microwave-assisted multicomponent strategy for the

• reaction time of 24 h. A scale protocol adapted with same reaction conditions afforded the product with a better yield of 92% supporting the scale-up strategy with microwaves. The protocol provided an easy admittance to 5-aza-7-deazapurine molecules used as antiviral and cytotoxic agents [101]. The

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• -triazolylpurine and 7-deazapurine derivatives is described. A new C(2)-regioselectivity in the nucleophilic aromatic substitution reactions of 9-alkylated-2,6-diazidopurines and 7-deazapurines with secondary amines has been disclosed. The obtained intermediates, 9-alkylated-2-amino-6-azido-(7-deaza)purines, were

• transformed into the title compounds by CuAAC reaction. The designed compounds belong to the push–pull systems and possess promising fluorescence properties with quantum yields in the range from 28% to 60% in acetonitrile solution. Due to electron-withdrawing properties of purine and 7-deazapurine

• heterocycles, which were additionally extended by triazole moieties, the compounds with electron-donating groups showed intramolecular charge transfer character (ICT/TICT) of the excited states which was proved by solvatochromic dynamics and supported by DFT calculations. In the 7-deazapurine series this led

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• towards different heterocyclic bases was carried out and temperature-dependence and magnesium chloride concentration-dependence of enzymes activity were determined. TthHPRT can be used for the synthesis of nucleotides containing different purine derivatives including 8-aza- and 8-aza-7-deazapurine. The

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• , however, it lacked a full experimental procedure (Scheme 7). The synthesis started from 6-chloro-7-iodo-7-deazapurine functionalized at the N-9 position with Hoffer’s α-chloro sugar (31, Scheme 7). This material was functionalized further using a Stille coupling to afford a mono-Boc-protected o

• screen a larger set of new compounds for fluorescent properties we envisioned that it was unnecessary to carry the entire sugar moiety through the synthesis. Thus, by alkylation of 6-chloro-7-iodo-7-deazapurine (41, Scheme 9) followed by a Miyaura-style borylation of compound 42, inspired by Thompson et

• first construct a common intermediate that could be used for various Suzuki-coupling partners similar to what we previously reported [55], by first protecting 6-chloro-7-iodo-7-deazapurine with tert-butyldimethylsilyloxymethyl (TBDMSOM) in 86% yield over two steps (44, Scheme 10). A Miyaura-type

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• metals found in Langlois’ reagent could be responsible for reaction initiation. The scope was evaluated on pyridines, pyrroles, indoles, pyrimidines, pyrazines, phthalazines, quinoxalines, deazapurine, thiadiazoles, uracils, xanthenes and pyrazolino-pyrimidines (Scheme 35). The combination of previous

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• -amino-3-deazapurine and benzoyl-protected 1-O-acetylribose. The novel path is superior to previously described syntheses in terms of efficacy and ease of laboratory handling. Keywords: deazapurine nucleoside; nucleosidation; protection groups; ribozymes; Introduction The synthesis of 3-deazaadenosine

• nucleosidation of 4-chloroimidazo[4,5-c]pyridine and 1,2,3,5-tetraacetyl-ß-D-ribofuranose in the presence of chloro acetic acid to yield the corresponding 6-chloro-3-deazapurine nucleoside (Scheme 1) [22]. Subsequent attempts to convert the chlorine atom directly by amination under various conditions failed

• handling excluded this route for our purposes. In 1977, Montgomery, Shortnacy, and Clayton, reported the preparation of 6-chloro-3-deazapurine ribonucleoside via nucleosidation of 4,6-dichloroimidazo[4,5-c]pyridine with 1,2,3,5-tetraacetyl-ß-D-ribofuranose in the presence of p-toluenesulfonic acid (Scheme

The role of alkyl substituents in deazaadenine-based diarylethene photoswitches

• Christopher Sarter,
• Michael Heimes and
• Andres Jäschke

Beilstein J. Org. Chem. 2016, 12, 1103–1110, doi:10.3762/bjoc.12.106

• -2’-deoxyadenosine (9), required for the photoswitches with two methyl groups (2a–d), was synthesized using an optimized route based on our original work (Scheme 2) [43]. This route started from commercial 6-chloro-7-deazapurine and involved a transient protection of ring nitrogen N9 with

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• derivatives with complementary 15N-labeling patterns (Scheme 1). The synthesis of preQ1 base has been described first in 1979 by Goto and coworkers from 2-methylthio-6-methoxy-7-methyl-7-deazapurine in 13 steps [9]. Another early, but more efficient procedure was reported by Nishimura in 1988 based on the

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• acid as a co-solvent. However, in the case of 7-deaza-2'-deoxyguanosine (8) the regioselectivity of the reaction changed from the C-7 to the C-8 position of the 7-deazapurine system (Scheme 4). The formation of product 9 could be explained by the influence of the electron-donating properties of the C-2

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• ; stereoselective amine synthesis; triol synthesis; Introduction 7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are commonly found in nature playing a variety of roles such as building blocks of nucleic acids and tRNA, metabolites or antimetabolites [1]. Deazapurine ribonucleosides also show interesting

• medicinal chemistry literature reveals >200 publications in the field. Additionally, PreQ0 meets all the criteria dictated by the “2-0” rule of kinase-likeness proposed by Aronov et al. [8]. It is likely that compounds derived from PreQ0 display kinase activity. 7-Deazapurine nucleoside chemistry has been