On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• ; purine nucleoside phosphorylases; recombinant E. coli uridine; thymidine; Introduction Diverse variants of enzymatic syntheses of nucleosides using nucleoside phosphorylases as biocatalysts have been repeatedly described in original studies and discussed in a number of recent reviews (see, e.g., [1][2

• more complicated in comparison with the enzymatic reaction of a heterocyclic base with an individual PF-1Pi [17][18][27]. However, it is known that most of purine heterocycles are poorly soluble in aqueous phosphate buffers, and the use of a cross-glycosylation scheme, i.e., a purine nucleoside as a

• Serianni et al. [39] a multienzyme one-pot methodology was investigated in detail and applied for the synthesis of Rib-1Pi and dRib-1Pi. This methodology consisted in the phosphorolysis of inosine (Ino) or 2′-deoxyinosine (dIno) by purine nucleoside phosphorylase (PNP) accompanied by the xanthine oxidase

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• conditions. There are a few thorough studies on this reaction with pyrimidine and purine nucleoside bases and their derivatives which are most closely related to fluorine-containing substrates 1 [40][41][42]. However, considering the high sensitivity and capricious nature of CEL reaction, we wish to report

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

• for this type of molecules. Traditionally, fluorescent purine nucleoside analogs were recognized as valuable fluorescent probes for DNA and RNA research [17]. This paved a way for development of various adenosine and guanosine analogs which in many cases contained an additional substituent at C(8

• →4) followed by a SNAr process (4→5) which showcases the use of 1,2,3-triazoles as leaving groups. It is well established during our previous research in the purine nucleoside series that such an approach provides 6-amino-2-(1,2,3-triazol-1-yl) derivatives [25]. On the other hand, it was also

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• enzymatic synthesis of NR+ from α-D-ribose-1-phosphate and Nam by catalysis with purine nucleoside phosphorylase and sucrose phosphorylase is described in a US patent application by Velasquez et al. [46]. In the NMR experiments, the authors demonstrated the preparation of NR+ but did not isolate pure NR+. 3

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• absence of any observable intramolecular cyclisation of the unprotected purine nucleoside derivatives typical of solution-phase reactions using such substrates. More variable yields were obtained using potassium selenocyanate which required grinding in the presence of DMF to promote the reaction with

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• , synthetic C-nucleosides, such as immucillin-H and GS-5734, have shown potent activity against purine nucleoside phosphorylases (PNP) and broad spectrum antiviral activities. Synthetic approaches to C-nucleosides. A. Two common strategies for C-nucleoside synthesis involve functionalization at C1' and

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• , 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases

• ; recombinant E. coli uridine, thymidine and purine nucleoside phosphorylases; substrate properties; 4(2)-thioxo- and 6(5)-aza-uacil and -thymine; Introduction Nucleosides of 4- and 2-thioxopyrimidines and 6-azapyrimidines attract much attention from the time of pioneering works in the early 1950s on the

• reaction [37][38] using 2'-deoxyguanosine (dG) as a donor of the pentofuranose moiety in a combination with the recombinant E. coli purine nucleoside phosphorylase (PNP; product of deoD gene; EC 2.4.2.1) [36] were tested under standard reaction conditions and then individual nucleosides 1b, 3b–5b were

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• University of Chicago Medical Center, Chicago, Illinois 60637, USA 10.3762/bjoc.11.272 Abstract A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3’-fluorinated analogues were constructed from a common 3’-deoxy-3

• analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon cancer) and 143B (osteosarcoma cancer) tumor cell lines. We have demonstrated 3’-fluorine purine nucleoside analogues display

• potent tumor cell growth inhibition activity at sub- or low micromolar concentration. Keywords: anticancer; 3’-fluororibonucleoside; purine nucleoside; 6-substituted purine; synthesis; Introduction Antimetabolites are extremely useful for the treatment of cancers and viral infections and are one of the

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• ) – inhibitors of thymidine phosphorylase isolated from spontaneous lymphoma of SD rats (IC50 = 15 and 11 nM, respectively) [4], guanine derivative 5 – a potent inhibitor of human purine nucleoside phosphorylase PNP (Ki = 10 nM) [5], and finally guanine derivative 6 – exhibiting inhibitory activity against 6

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

• 19b (DADMe-Immucilin-G) were reported to be potent transition state analog inhibitors of human purine nucleoside phosphorylase (PNP). Ulodesine 19a has completed two phase II clinical trials in 2013 [68][69]. Using the fluorinated pyrrolidine (3S,4S)-22 (Scheme 9), Mason et al. obtained azanucleoside

• presence sodium acetate in dioxane at 100 °C. The compound was prepared on the 10 mg scale in 67% yield. In contrast to its (3R,4R)-enantiomer (not shown), compound (3S,4S)-23 showed inhibitory activity toward human purine nucleoside phosphorylase (PNP) with a slow-onset binding constant Ki* = 0.032 nM. In

• purine nucleoside (i.e., adenosine) was modified (Scheme 25). Tungstophosphoric acid (H3PW12O40) was employed as a catalyst (2 mol %). Hybrids 71 originated from the pseudo-four component cascade employing two equivalents of barbituric acid. The authors demonstrated that the method was applicable with

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• -arabinofuranose (9) into the phosphate 12a without isolation of intermediary products. Condensation of 12a with 2-chloroadenine catalyzed by the recombinant E. coli purine nucleoside phosphorylase (PNP) resulted in the formation of clofarabine in 67% yield. The reaction was also studied with a number of purine

• residue of FMAU was realized by the concerted action of E. coli thymidine phosphorylase (TP) absorbed on DEAE cellulose for the intermediary generation of the phosphate 12a and E. coli purine nucleoside phosphorylase (PNP) for the condensation of the latter with bases. The two most challenging features of

• recombinant E. coli enzymes used in the present work is described in [23][24][27]. For the preparation of purine nucleoside phosphorylase (PNP; the product of the deoD gene; EC 2.4.2.1; 52 units/mg; 15 mg/mL) see [23]. HPLC was performed on Waters systems (Waters 1525, Waters 2487, Breeze 2; USA) with column

A novel and efficient method to prepare 2-aryltetrahydrofuran-2-ylphosphonic acids

• Vsevolod V. Komissarov,
• Anatoly M. Kritzyn and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2010, 6, No. 63, doi:10.3762/bjoc.6.63

• [1][2][3][4]. As a part of our ongoing project, it seemed important to synthesize compounds with phosphonate and phenyl groups at one end of the hydrocarbon chain and a nucleic base residue at the other end. Previously, it was shown that compounds with similar structures inhibit purine nucleoside