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Search for "uracil" in Full Text gives 53 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis and properties of 6-alkynyl-5-aryluracils
- Ruben Manuel Figueira de Abreu,
- Till Brockmann,
- Alexander Villinger,
- Peter Ehlers and
- Peter Langer
Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80
- Abstract The development of a new and straightforward chemoselective method for the synthesis of uracil-based structures by combining Suzuki–Miyaura and Sonogashira–Hagihara cross-coupling is reported. The methodology was applied to synthesize a series of novel compounds. The tolerance of the combination
- of different functional groups was tested. The influence of different functional groups on the physical properties was studied by ultraviolet–visible (UV–vis) and fluorescence spectroscopy, providing new insights into the potential applications of uracil-based structures. Keywords: catalysis; cross
- -coupling; fluorescence; heterocycles; regioselectivity; Introduction Organic life is a complex interplay of many different building blocks. One of these building blocks is uracil. Discovered for the first time in 1901 by Alberto Ascoli, it is now known to be one of the four nucleobases of RNA [1]. It
Graphical Abstract
Figure 1: Uracil derivatives in drugs.
Figure 2: Present work as compared to previous studies [25,57-59].
Scheme 1: Synthesis of 1,3-dimethly-5-[2-(aryl)ethynyl]-6-[2-(aryl)ethynyl]uracils 4 and 1,3-dimethyl-5-aryl-...
Scheme 2: Synthesis of 5-bromo-1,3-dimethyl-6-[2-(aryl)ethynyl]uracils 3a–j. Reaction conditions: 2 (1.0 equi...
Scheme 3: Structure of the starting material 2 with its possible mesomeric structures.
Scheme 4: Synthesis of 1,3-dimethyl-5-[2-(aryl)ethynyl]-6-[2-(aryl)ethynyl]uracils 4a–h. Reaction conditions: ...
Scheme 5: Synthesis of 1,3-dimethyl-5-aryl-6-[2-(aryl)ethynyl]uracils 5a–t. Reaction conditions: 3 (1 equiv),...
Figure 3: ORTEP diagram of 5a front view (a) and side view (b). a) Interactions of the molecules within and b...
Figure 4: UV–vis absorption (left) and emission (right, λex = 400 nm) spectra of 1,3-dimethyl-5-phenyl-6-[2-(...
Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process
- Kazuhiro Okamoto,
- Naoki Shida and
- Mahito Atobe
Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27
- this case, intramolecular radical trapping by the uracil nucleobase was preferred, leading to the formation of the cyclized alkyl radical D. Continuous radical recombination furnished dimer 4. Conclusion We observed additive-controlled inter- and intramolecular chemoselectivity in the hydroamination of
Graphical Abstract
Figure 1: Application of amidyl radical species generated by PCET.
Figure 2: (A) Effect of phosphate base on the cyclic voltammogram of 1. (B) Cyclic voltammograms of 1 in the ...
Figure 3: Plausible models illustrating the size effect of the hydrogen bond complex on the interaction effic...
Figure 4: Plausible mechanism for the inter-/intramolecular hydroamination of 1.
Ferrocenoyl-adenines: substituent effects on regioselective acylation
- Mateja Toma,
- Gabrijel Zubčić,
- Jasmina Lapić,
- Senka Djaković,
- Davor Šakić and
- Valerije Vrček
Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133
- kinetic and thermodynamic control of the acylation reaction. Results and Discussion It was shown that the reaction between the pyrimidine anion (uracil, thymine, or 5-fluorouracil) and FcCOCl in N,N-dimethylformamide (DMF) proceeded in a full regiospecific mode [19]. In the purine series, however, the
Graphical Abstract
Scheme 1: Regioselective ferrocenoylation of the adenine anion 1 and its derivatives 2–6 substituted at the N6...
Figure 1: 1H NMR spectrum (downfield region) of the reaction mixture (adenine anion 1 and FcCOCl) in DMF, tak...
Figure 2: HOMO map of space distribution (left) of adenine anion (1) at the B3LYP/6-31+G(d) level of theory (...
Figure 3: Dependence of N9-isomer product ratio (%), in the reaction between FcCOCl and adenine anions 1–6, o...
Figure 4: B3LYP/6-31+G(d)/SDD optimized transition state structures for N7- (6-TSN7) and N9-ferrocenoylation (...
Figure 5: Relation between the Gibbs free energy barrier (ΔG‡) for the N7-ferrocenoylation of C6-substituted ...
Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues
- Sandeep Kumar,
- Jyotirmoy Maity,
- Banty Kumar,
- Sumit Kumar and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10
- , University of Delhi, Delhi- 110 015, India 10.3762/bjoc.18.10 Abstract Conformationally restricted diastereomeric homoarabinofuranosylpyrimidines (AZT analogue), i.e., (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosylthymine and -uracil had been synthesized starting from diacetone ᴅ
- ]. Azidofuranoside 11 on acetolysis with acetic acid/acetic anhydride/sulfuric acid (100:10:0.1) at room temperature afforded an anomeric mixture of 1,2,5,6-tetra-O-acetyl-3-azido-3-deoxy-α,β-ᴅ-allofuranose (12a,b), which on Vorbrüggen base coupling [29] with thymine and uracil in the presence of N,O-bis
- anomeric triacetylated sugars 19a,b with thymine and uracil in the presence of BSA and TMSOTf in acetonitrile afforded nucleosides 20a,b, respectively in high yields. The deacetylation of these nucleosides was carried out using K2CO3 in a solvent mixture of methanol and water (9:1) to afford nucleoside 21a
Graphical Abstract
Figure 1: Structure of AZT and representative related bicyclic nucleosides.
Scheme 1: Retrosynthetic routes for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabin...
Scheme 2: Synthesis of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylthymine (14a) and -uracil (14b).
Scheme 3: Biocatalytic acetylation of the primary hydroxy group of nucleosides 14a,b.
Scheme 4: Synthesis of (5'R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosyl nucleosides 9a,b.
Scheme 5: Chemical synthesis of nucleosides 9a,b starting from diacetone ᴅ-glucofuranose.
Figure 2: Structure elucidation of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosylthymine (...
Scheme 6: a) Plausible mechanism for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabi...
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
- Nikita Brodyagin,
- Martins Katkevics,
- Venubabu Kotikam,
- Christopher A. Ryan and
- Eriks Rozners
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
- uracil with fluorine or trifluoromethyl improved PNA binding affinity for complementary DNA and RNA [127]. Moreover, fluorination increased the cellular uptake of PNAs [127]. Fluorinated uracil derivatives are also useful probes for studying different binding modes of PNA using 19F NMR [128]. PNA
- any Watson–Crick base pairing scheme, AOVP lowered the stability of PNA duplexes with complementary DNA and RNA [132]. Similarly, vinyl-modified purine (AVP) effectively crosslinked with thymine in DNA and with uracil in RNA. The crosslinking resulted in inhibition of Dicer processing of microRNA
Graphical Abstract
Figure 1: Structure of DNA and PNA.
Figure 2: PNA binding modes: (A) PNA–dsDNA 1:1 triplex; (B) PNA–DNA–PNA strand-invasion triplex; (C) the Hoog...
Figure 3: Structure of P-form PNA–DNA–PNA triplex from reference [41]. (A) view in the major groove and (B) view ...
Figure 4: Structures of backbone-modified PNA.
Figure 5: Structures of PNA having α- and γ-substituted backbones.
Figure 6: Structures of modified nucleobases in PNA to improve Hoogsteen hydrogen bonding to guanine and aden...
Figure 7: Proposed hydrogen bonding schemes for modified PNA nucleobases designed to recognize pyrimidines or...
Figure 8: Modified nucleobases to modulate Watson–Crick base pairing and chemically reactive crosslinking PNA...
Figure 9: Examples of triplets formed by Janus-wedge PNA nucleobases (blue). R1 denotes DNA, RNA, or PNA back...
Figure 10: Examples of fluorescent PNA nucleobases. R1 denotes DNA, RNA, or PNA backbones.
Figure 11: Endosomal entrapment and escape pathways of PNA and PNA conjugates.
Figure 12: (A) representative cell-penetrating peptides (CPPs), (B) conjugation designs and linker chemistries....
Figure 13: Proposed delivery mode by pHLIP-PNA conjugates (A) the transmembrane section of pHLIP interacting w...
Figure 14: Structures of modified penetratin CPP conjugates with PNA linked through either disulfide (for stud...
Figure 15: Chemical structure of C9–PNA, a stable amphipathic (cyclic-peptide)–PNA conjugate.
Figure 16: Structures of PNA conjugates with a lipophilic triphenylphosphonium cation (TPP–PNA) through (A) th...
Figure 17: Structures of (A) chloesteryl–PNA, (B) cholate–PNA and (C) cholate–PNA(cholate)3.
Figure 18: Structures of PNA–GalNAc conjugates (A) (GalNAc)2K, (B) triantennary (GalNAc)3, and (C) trivalent (...
Figure 19: Vitamin B12–PNA conjugates with different linkages.
Figure 20: Structures of (A) neomycin B, (B) PNA–neamine conjugate, and (C) PNA–neosamine conjugate.
Figure 21: PNA clamp (red) binding to target DNA containing a mixture of sequences (A) PNA binds with higher a...
Figure 22: Rolling circle amplification using PNA openers (red) to invade a dsDNA target forming a P-loop. A p...
Figure 23: Molecular beacons containing generic fluorophores (Fl) and quenchers (Q) recognizing a complementar...
Figure 24: (A) Light-up fluorophores such as thiazole orange display fluorescence enhancement upon binding to ...
Figure 25: Templated fluorogenic detection of oligonucleotides using two PNAs. (A) Templated FRET depends on h...
Figure 26: Lateral flow devices use a streptavidin labeled strip on nitrocellulose paper to anchor a capture P...
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
- literature search regarding double-headed nucleosides disclosed that these modified nucleosides were constituted with any two naturally occurring nucleobases, i.e., adenine, guanine, thymine, uracil, and cytosine [9][10] or one naturally occurring nucleobase and one heterocyclic/carbocyclic moiety either
- ]. Nielsen and co-workers [42] additionally synthesized 2′-(N-benzoylcytosin-1-yl)methylarabinofuranosyl-N-benzoylcytosine (7) from uridine using a similar methodology. Thus, the nucleophilic epoxide ring opening in spironucleoside 2 with uracil in DMF in a N1-regioselective manner afforded the TIPDS
- -protected double-headed nucleoside 5 having two uracil bases (the additional uracil being attached through a methylene linker to the 2′-position of arabinouracil). Subsequently, the two uracil bases of the TIPDS-protected double-headed nucleoside 5 were converted to N-benzoylated cytosines in a three-step
Graphical Abstract
Figure 1: Double-headed nucleosides. B1 and B2 = nucleobases or heterocyclic/carbocyclic moieties; L = linker....
Scheme 1: Synthesis of 2′-(pyrimidin-1-yl)methyl- or 2′-(purin-9-yl)methyl-substituted double-headed nucleosi...
Scheme 2: Synthesis of double-headed nucleoside 7 having two cytosine moieties.
Scheme 3: Synthesis of double-headed nucleoside 2′-deoxy-2′-C-(2-(thymine-1-yl)ethyl)-uridine (11).
Scheme 4: Double-headed nucleosides 14 and 15 obtained by click reaction.
Scheme 5: Synthesis of the double-headed nucleoside 19.
Scheme 6: Synthesis of the double-headed nucleosides 24 and 25.
Scheme 7: Synthesis of double-headed nucleosides 28 and 29.
Scheme 8: Synthesis of double-headed nucleoside 33.
Scheme 9: Synthesis of double-headed nucleoside 37.
Scheme 10: Synthesis of the double-headed nucleoside 1-(5′-O-(4,4′-dimethoxytrityl)-2′-C-((4-(pyren-1-yl)-1,2,...
Scheme 11: Synthesis of triazole-containing double-headed ribonucleosides 46a–c and 50a–e.
Scheme 12: Synthesis of double-headed nucleosides 54a–g.
Scheme 13: Synthesis of double-headed nucleosides 59 and 60.
Scheme 14: Synthesis of the double-headed nucleosides 63 and 64.
Scheme 15: Synthesis of double-headed nucleosides 66a–c.
Scheme 16: Synthesis of benzoxazole-containing double-headed nucleosides 69 and 71 from 5′-amino-5′-deoxynucle...
Scheme 17: Synthesis of 4′-C-((N6-benzoyladenin-9-yl)methyl)thymidine (75) and 4′-C-((thymin-1-yl)methyl)thymi...
Scheme 18: Synthesis of double-headed nucleosides 5′-(adenine-9-yl)-5′-deoxythymidine (79) and 5′-(adenine-9-y...
Scheme 19: Synthesis of double-headed nucleosides 85–87 via reversed nucleosides methodology.
Scheme 20: Double-headed nucleosides 91 and 92 derived from ω-terminal-acetylenic sugar derivatives 90a,b.
Scheme 21: Synthesis of double-headed nucleosides 96a–g.
Scheme 22: Synthesis of double-headed nucleosides 100 and 103.
Scheme 23: Double-headed nucleosides 104 and 105 with a triazole motif.
Scheme 24: Synthesis of the double-headed nucleosides 107 and 108.
Scheme 25: Synthesis of double-headed nucleoside 110 with additional nucleobase in 5′-(S)-C-position joined th...
Scheme 26: Synthesis of double-headed nucleosides 111–113 with additional nucleobases in the 5′-(S)-C-position...
Scheme 27: Synthesis of double-headed nucleoside 114 by click reaction.
Scheme 28: Synthesis of double-headed nucleosides 118 with an additional nucleobase at the 5′-(S)-C-position.
Scheme 29: Synthesis of bicyclic double-headed nucleoside 122.
Scheme 30: Synthesis of double-headed nucleosides 125a–c derived from 2′-amino-LNA.
Scheme 31: Double-headed nucleoside 127 obtained by click reaction.
Scheme 32: Synthesis of double-headed nucleoside 130.
Scheme 33: Double-headed nucleosides 132a–d and 134a–d synthesized by Sonogashira cross coupling reaction.
Scheme 34: Synthesis of double-headed nucleosides 137 and 138 via Suzuki coupling.
Scheme 35: Synthesis of double-headed nucleosides 140 and 141 via Sonogashira cross coupling reaction.
Scheme 36: Synthesis of double-headed nucleoside 143.
Scheme 37: Synthesis of the double-headed nucleoside 146.
Scheme 38: Synthesis of 5-C-alkynyl-functionalized double-headed nucleosides 151a–d.
Scheme 39: Synthesis of 5-C-triazolyl-functionalized double-headed nucleosides 154a, b.
Scheme 40: Synthesis of double-headed nucleosides 157a–c.
Scheme 41: Synthesis of double-headed nucleoside 159, phosphoramidite 160 and the corresponding nucleotide mon...
Scheme 42: Synthesis of double-headed nucleoside 163, phosphoramidite 164 and the corresponding nucleotide mon...
Scheme 43: Synthesis of double-headed nucleoside 167, phosphoramidite 168, and the corresponding nucleotide mo...
Scheme 44: Synthesis of double-headed nucleoside 171, phosphoramidite 172, and the corresponding nucleotide mo...
Scheme 45: Synthesis of double-headed nucleoside 175, phosphoramidite 176, and the corresponding nucleotide mo...
Scheme 46: Synthesis of double-headed nucleoside 178.
Scheme 47: Synthesis of the double-headed nucleosides 181 and 183.
Scheme 48: Alternative synthesis of the double-headed nucleoside 183.
Scheme 49: Synthesis of double-headed nucleoside 188 through thermal [2 + 3] sydnone–alkyne cycloaddition reac...
Scheme 50: Synthesis of the double-headed nucleosides 190 and 191.
Scheme 51: Synthesis of 1-((5S)-2,3,4-tri-O-acetyl-5-(2,6-dichloropurin-9-yl)-β-ᴅ-xylopyranosyl)uracil (195).
Scheme 52: Synthesis of hexopyranosyl double-headed pyrimidine homonucleosides 200a–c.
Figure 2: 3′-C-Ethynyl-β-ᴅ-allopyranonucleoside derivatives 201a–f.
Scheme 53: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 203–207.
Scheme 54: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 208 and 209.
Scheme 55: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleoside 210.
Scheme 56: Synthesis of double-headed acyclic nucleosides (2S,3R)-1,4-bis(thymine-1-yl)butane-2,3-diol (213a) ...
Scheme 57: Synthesis of double-headed acyclic nucleosides (2R,3S)-1,4-bis(thymine-1-yl)butane-2,3-diol (213c) ...
Scheme 58: Synthesis of double-headed acetylated 1,3,4-oxadiazino[6,5-b]indolium-substituted C-nucleosides 218b...
Scheme 59: Synthesis of double-headed acyclic nucleoside 222.
Scheme 60: Synthesis of functionalized 1,2-bis(1,2,4-triazol-3-yl)ethane-1,2-diols 223a–f.
Scheme 61: Synthesis of acyclic double-headed 1,2,4-triazino[5,6-b]indole C-nucleosides 226–231.
Scheme 62: Synthesis of double-headed 1,3,4-thiadiazoline, 1,3,4-oxadiazoline, and 1,2,4-triazoline acyclo C-n...
Scheme 63: Synthesis of double-headed acyclo C-nucleosides 240–242.
Scheme 64: Synthesis of double-headed acyclo C-nucleoside 246.
Scheme 65: Synthesis of acyclo double-headed nucleoside 250.
Scheme 66: Synthesis of acyclo double-headed nucleoside 253.
Scheme 67: Synthesis of acyclo double-headed nucleosides 259a–d.
Scheme 68: Synthesis of acyclo double-headed nucleoside 261.
Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV
- Santiago Ramos-Carreño,
- Ivone Giffard-Mena,
- Jose N. Zamudio-Ocadiz,
- Alfredo Nuñez-Rivera,
- Ricardo Valencia-Yañez,
- Jaime Ruiz-Garcia,
- Maria Teresa Viana and
- Ruben D. Cadena-Nava
Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95
- ® Fast Advanced Master Mix kit (Applied Biosystems, USA). Amplification reactions of 20 μL were prepared by mixing 23.33 ng of DNA, 0.3 μM of each primer, and 0.15 μM of TaqMan probe, and the qPCR was performed following Durand and Lightner [51] methodology. In summary, 2.0 min at 50 °C for uracil-N
Graphical Abstract
Figure 1: Analysis of the VLP-dsRNAvp28 assembly by electrophoresis mobility shift assay (EMSA) in a 1% nativ...
Figure 2: TEM micrographs of different stages of the assemblies of CCMV CP with dsRNAvp28. In section A, the ...
Figure 3: P. vannamei survival when exposed to WSSV and treatments. (A) IM inoculum activation in two consecu...
Figure 4: Cumulative survival curves of P. vannamei infected with WSSV and provided with VLPs antiviral treat...
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications
- Christopher Liczner,
- Kieran Duke,
- Gabrielle Juneau,
- Martin Egli and
- Christopher J. Wilds
Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76
- simplicity combined with the five natural bases, adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U, in RNA) belies the fact that both DNA and RNA are decorated with chemical modifications. For a catalogue of natural modifications in DNA, see https://dnamod.hoffmanlab.org/ [1], and in RNA, see
- modification is accommodated in an A'-form duplex [75]. Interestingly, an unconventional C–H···O hydrogen bond was observed between the amide’s carbonyl oxygen and the nearby uracil C6–H6. The thermal stability of this modified duplex was, however, quite similar to native RNA. Typically, there is a decrease of
- (R) or (S) starting material, respectively. These simple nucleic acid building blocks were first synthesized in 1971 by Ueda et al. [96]. The group was able to synthesize adenine, cytosine, and uracil GNA analogues by reacting these bases with glycerol α-chlorohydrin or glycidol. The following year
Graphical Abstract
Figure 1: Structures of the chemically modified oligonucleotides (A) N3' → P5' phosphoramidate linkage, (B) a...
Scheme 1: Synthesis of a N3' → P5' phosphoramidate linkage by solid-phase synthesis. (a) dichloroacetic acid;...
Figure 2: Crystal structures of (A) N3' → P5' phosphoramidate DNA (PDB ID 363D) [71] and (B) amide (AM1) RNA in c...
Scheme 2: Synthesis of a phosphorodithioate linkage by solid-phase synthesis. (a) detritylation; (b) tetrazol...
Figure 3: Close-up view of a key interaction between the PS2-modified antithrombin RNA aptamer and thrombin i...
Scheme 3: Synthesis of the (S)-GNA thymine phosphoramidite from (S)-glycidyl 4,4'-dimethoxytrityl ether. (a) ...
Figure 4: Surface models of the crystal structures of RNA dodecamers with single (A) (S)-GNA-T (PDB ID 5V1L) [54]...
Figure 5: Structures of 2'-O-alkyl modifications. (A) 2'-O-methoxy RNA (2'-OMe RNA), (B) 2'-O-(2-methoxyethyl...
Scheme 4: Synthesis of the 2'-OMe uridine from 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine. (a) Benzoy...
Scheme 5: Synthesis of the 2'-O-MOE uridine from uridine. (a) (PhO)2CO, NaHCO3, DMA, 100 °C; (b) Al(OCH2CH2OCH...
Figure 6: Structure of 2'-O-(2-methoxyethyl)-RNA (MOE-RNA). (A) View into the minor groove of an A-form DNA d...
Figure 7: Structures of locked nucleic acids (LNA)/bridged nucleic acids (BNA) modifications. (A) LNA/BNA, (B...
Scheme 6: Synthesis of the uridine LNA phosphoramidite. (a) i) NaH, BnBr, DMF, ii) acetic anhydride, pyridine...
Scheme 7: Synthesis of the 2'-fluoroarabinothymidine. (a) 30% HBr in acetic acid; (b) 2,4-bis-O-(trimethylsil...
Figure 8: Sugar puckers of arabinose (ANA) and arabinofluoro (FANA) nucleic acids compared with the puckers o...
Figure 9: Structures of C4'-modified nucleic acids. (A) 4'-methoxy, (B) 4'-(2-methoxyethoxy), (C) 2',4'-diflu...
Scheme 8: Synthesis of the 4'-F-rU phosphoramidite. (a) AgF, I2, dichloromethane, tetrahydrofuran; (b) NH3, m...
Scheme 9: Synthesis of the thymine FHNA phosphoramidite. (a) thymine, 1,8-diazabicyclo[5.4.0]undec-7-ene, ace...
Scheme 10: Synthesis of the thymine Ara-FHNA phosphoramidite. (a) i) trifluoromethanesulfonic anhydride, pyrid...
Figure 10: Crystal structures of (A) FHNA and (B) Ara-FHNA in modified A-form DNA decamers (PDB IDs 3Q61 and 3...
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
- intermediate D which on the loss of a water molecule yields the products 87 (Scheme 31). Choudhury and co-workers [83] disclosed a three-component reaction of substituted arylglyoxal monohydrate 33, 6-amino-1,3-disubstituted uracil 86 and substituted thiols 88 under microwave conditions using acetic acid as a
- under microwave conditions delivered the desired product in better yields than the reflux strategy. Scheme 33 depicts the most probable pathway for the desired products 89 and 90. Initially, an acid-catalyzed reaction between arylglyoxal and amino uracil yields intermediate A. Nucleophilic addition of
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
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
- substrates of the phosphorolysis of uridine, thymidine, and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) catalyzed by recombinant E. coli uridine (UP) and thymidine (TP) phosphorylases. α-ᴅ-Pentofuranose-1-phosphates (PF-1Pis) obtained by phosphorolysis were used in the enzymatic synthesis of nucleosides. It was
- attracted the attention of researchers. Recently, the phosphorolysis of commercially available uridine (Urd), thymidine (Thd), and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) under the action of recombinant (i) uridine phosphorylase (UP) and thymidine phosphorylase (TP) from E. coli [28], and (ii) thermostable
- enzymatic syntheses of biologically important purine nucleosides, on the other hand (Scheme 1). As might be expected, the replacement of phosphate buffer with Dowex-nPi in the phosphorolysis of uridine (Urd), thymidine (Thd), and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) slowed down the reaction rate and
Graphical Abstract
Scheme 1: General scheme of the suggested synthesis of nucleosides employing the enzymatic phosphorolysis of ...
Figure 1: Phosphorolysis (5.0 mM K-phosphate buffer, pH 7.0; 23 °C) of Ara-U and thymidine (Thd) catalyzed by...
Scheme 2: Transarabinosylation of O6-methylguanine (OMG) employing Ara-U as a donor of the Ara-1Pi (1:1.5 mol...
Figure 2: Optimized conditions of phosphorolysis of Ara-U: 0.20 mmol of Ara-U in distilled water (30 mL) cont...
Scheme 3: Synthesis of nelarabine with intermediate preparation of crude Ara-1Pi.
Scheme 4: Synthesis of kinetin riboside with intermediate preparation of crude Rib-1Pi.
Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines
- Ksenia I. Kaskevich,
- Anastasia A. Babushkina,
- Vladislav V. Gurzhiy,
- Dmitrij M. Egorov,
- Nataly I. Svintsitskaya and
- Albina V. Dogadina
Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161
- establish from the 1H and 13C NMR spectral data. The signals of the vinyl proton of the uracil moiety are represented by quartets (4JHH = 1.4 Hz) in the δH 8.1 ppm region (quartet at δH 6 ppm for 6-methyl-5-oxo isomer). In the 13C NMR spectra, the signals of ethylene carbons of the uracil ring are presented
- the N3 nitrogen atom of the uracil fragment followed by cyclization. The mixture of phosphonylated 5-oxothiazolopyrimidines 8c and 9c was separated by column chromatography and the 1Н, 13С, and 31Р NMR spectral data of the individual thiazolopyrimidine isomers did not allow convincing assignment. In
- the 1H NMR spectra, the proton of the thiazole ring of both isomers is represented by a doublet signal in the low field region at δH 7.91 (3JHP = 3.2 Hz) and 8.41 ppm (3JHP = 7.5 Hz), whereas the corresponding proton of the uracil ring resonated as a singlet at δH 6.61 and 6.71 ppm, respectively. Note
Graphical Abstract
Figure 1: Structure of ritanserin and setoperone drugs.
Scheme 1: One-pot synthesis of 5(7)-oxothiazolopyrimidine-6-carbonitriles.
Scheme 2: Synthesis of thiazolopyrimidine-5-ones through the reaction of 2-aminothiazoles with ethyl acetoace...
Scheme 3: Synthesis of 2-(benzo[d]thiazol-2-yl)-2-(7-R-5-oxo-5H-thiazolo[3,2-a]pyrimidin-3-yl)acetonitriles.
Scheme 4: Synthesis of 3-acyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-ones.
Scheme 5: Sonogashira coupling reaction of 6-amino-2-thiouracil with propargyl bromide.
Scheme 6: Reactions of 6-substituted 2-thiouracils 1a,b with chloroethynylphosphonates 2a–c.
Scheme 7: Reaction of 5-methyl-2-thiouracil (1c) with chloroethynylphosphonates 2a–c.
Scheme 8: Reaction of 2-thiouracil (1d) with chloroethynylphosphonates 2a–c.
Scheme 9: Reaction of 6-trifluoromethyl-2-thiouracil (1e) with chloroethynylphosphonates 2a–c.
Scheme 10: A plausible mechanism of the reaction between 6-trifluoromethyl-2-thiouracil (1e) and chloroethynyl...
Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction
- Renata Kaczmarek,
- Dariusz Korczyński,
- James R. Green and
- Roman Dembinski
Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1
- hexacarbonyl complexes; Nicholas reaction; nucleosides; propargyl cation; Introduction Nucleoside analogs are molecules of high pharmacological interest for the treatment of various conditions, especially cancer and viral diseases [1][2][3][4][5]. The substitution at C-5 of the uracil nucleobase provides a
Graphical Abstract
Scheme 1: Preparation of (2'-deoxy)-5-alkynyluridines 2 and 3, their dicobalt hexacarbonyl derivatives 4 and 5...
Figure 1: Structures of nucleosides 6 and 7, products of the Nicholas reaction.
Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates
- Yuichi Yoshimura,
- Hideaki Wakamatsu,
- Yoshihiro Natori,
- Yukako Saito and
- Noriaki Minakawa
Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137
- 28, by treating with 2,4-bis(trimethylsilyl)uracil (29) and excess diisopropylethylamine (DIPEA) in the presence of TMSOTf, gave 4’-thiouridine derivative 30 in a good yield. The reaction stereoselectively proceeded and resulted the predominant formation of the β-anomer due to steric hindrance of the
- subjected to the Pummerer-type glycosylation mediated by hypervalent iodine. Treatment of 36 with bis(trifluoroacetoxy)iodobenzene (PIFA) and uracil in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine gave a 5:1 mixture of 4’-thiouridine derivative 37 in 55% yield. The
- consecutive inter-/intramolecular SN2 reactions of 66 by selenide anion gave a 4-seleno sugar 67 in an excellent yield. After converting 67 to the corresponding selenoxide, the resulting 68 was immediately treated with uracil or N4-benzoylcytosine under the same conditions for Pummerer-type glycosylation to
Graphical Abstract
Figure 1: Design of potential antineoplastic nucleosides.
Scheme 1: Synthesis of 4’-thioDMDC.
Scheme 2: Synthesis of 4’-thioribonucleosides by Minakawa and Matsuda.
Scheme 3: Synthesis of 4’-thioribonucleosides by Yoshimura.
Figure 2: Concept of the Pummerer-type glycosylation and hypervalent iodine-mediated glycosylation.
Scheme 4: Oxidative glycosylation of 4-thioribose mediated by hypervalent iodine.
Figure 3: Speculated mechanism of oxidative glycosylation mediated by hypervalent iodine.
Scheme 5: Synthesis of purine 4’-thioribonucleosides using hypervalent iodine-mediated glycosylation.
Scheme 6: Unexpected glycosylation of a thietanose derivative.
Scheme 7: Speculated mechanism of the ring expansion of a thietanose derivative.
Scheme 8: Synthesis of thietanonucleosides using the Pummerer-type glycosylation.
Scheme 9: First synthesis of 4’-selenonucleosides.
Scheme 10: The Pummerer-type glycosylation of 4-selenoxide 74.
Scheme 11: Synthesis of purine 4’-selenonucleosides using hypervalent iodine-mediated glycosylation.
Figure 4: Concept of the oxidative coupling reaction applicable to the synthesis of carbocyclic nucleosides.
Scheme 12: Oxidative coupling reaction mediated by hypervalent iodine.
Scheme 13: Synthesis of cyclohexenyl nucleosides using an oxidative coupling reaction.
Figure 5: Concept of the oxidative coupling reaction of glycal derivatives.
Scheme 14: Oxidative coupling reaction of silylated uracil and DHP using hypervalent iodine.
Scheme 15: Proposed mechanism of the oxidative coupling reaction mediated by hypervalent iodine.
Figure 6: Synthesis of 2’,3’-unsaturated nucleosides using hypervalent iodine and a co-catalyst.
Scheme 16: Synthesis of dihydropyranonucleoside.
Scheme 17: Synthesis of acetoxyacetals using hypervalent iodine and addition of silylated base.
Scheme 18: One-pot fragmentation-nucleophilic additions mediated by hypervalent iodine.
Figure 7: The reaction of thioglycoside with hypervalent iodine in the presence of Lewis acids.
Scheme 19: Synthesis of disaccharides employing thioglycosides under an oxidative coupling reaction mediated b...
Scheme 20: Synthesis of disaccharides using disarmed thioglycosides by hypervalent iodine-mediated glycosylati...
Scheme 21: Glycosylation using aryl(trifluoroethyl)iodium triflimide.
Figure 8: Expected mechanism of hypervalent iodine-mediated glycosylation with glycals.
Scheme 22: Synthesis of oligosaccharides by hypervalent iodine-mediated glycosylation with glycals.
Scheme 23: Synthesis of 2-deoxy amino acid glycosides.
Figure 9: Rationale for the intramolecular migration of the amino acid unit.
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
- latter reaction rapidly decomposed during work-up in solution. Regioselective and stereoselective glycosidation of adenine, N6-benzoyladenine, N4-benzoylcytosine, thymine and uracil to the corresponding β-N9-purine or β-N1-pyrimidine ribosides was achieved on gram scales under Vorbrüggen-type conditions
Graphical Abstract
Figure 1: Examples of equipment used to perform mechanochemistry on nucleoside and nucleotide substrates (not...
Figure 2: Ganciclovir.
Scheme 1: Nucleoside tritylation effected by hand grinding in a heated mortar and pestle.
Scheme 2: Persilylation of ribonucleoside hydroxy groups (and in situ acylation of cytidine) in a MBM.
Scheme 3: Nucleoside amine and carboxylic acid Boc protection using an improvised attritor-type mill.
Scheme 4: Nucleobase Boc protection via transient silylation using an improvised attritor-type mill.
Scheme 5: Chemoselective N-acylation of an aminonucleoside using LAG in a MBM.
Scheme 6: Azide–alkyne cycloaddition reactions performed in a copper vessel in a MBM.
Figure 3: a) Custom-machined copper vessel and zirconia balls used to perform CuAAC reactions (showing: upper...
Scheme 7: Thiolate displacement reactions of nucleoside derivatives in a MBM.
Scheme 8: Selenocyanate displacement reactions of nucleoside derivatives in a MBM.
Scheme 9: Nucleobase glycosidation reactions and subsequent deacetylation performed in a MBM.
Scheme 10: Regioselective phosphorylation of nicotinamide riboside in a MBM.
Scheme 11: Preparation of nucleoside phosphoramidites in a MBM using ionic liquid-stabilised chlorophosphorami...
Scheme 12: Preparation of a nucleoside phosphite triester using LAG in a MBM.
Scheme 13: Internucleoside phosphate coupling linkages in a MBM.
Scheme 14: Preparation of ADPR analogues using in a MBM.
Scheme 15: Synthesis of pyrophosphorothiolate-linked dinucleoside cap analogues in a MBM to effect hydrolytic ...
Figure 4: Early low temperature mechanised ball mill as described by Mudd et al. – adapted from reference [78].
Scheme 16: Co-crystal grinding of alkylated nucleobases in an amalgam mill (N.B. no frequency was recorded in ...
Figure 5: Materials used to prepare a smectic phase.
Figure 6: Structures of 5-fluorouracil (5FU) and nucleoside analogue prodrugs subject to mechanochemical co-c...
Scheme 17: Preparation of DNA-SWNT complex in a MBM.
Phosphodiester models for cleavage of nucleic acids
- Satu Mikkola,
- Tuomas Lönnberg and
- Harri Lönnberg
Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68
- guanidinium compound. This low basicity was suggested to be a central factor behind the catalytic activity. A clarification of the mechanism of guanidine-based catalysis has more recently been attempted by anchoring a 2,4-diamino-1,3,5-triazine core to the N3 of uracil bases of UpU by two side arms, each
- containing uracil or guanine base were cleaved exceptionally fast [82]. No mechanistic explanation was given. Interestingly, these two bases may undergo deprotonation under mildly basic conditions (pKa ≈ 9) in contrast to adenine and cytosine. Aliphatic amines are poor catalysts for the cleavage of RNA. The
- hydrogen bonding to the carbonyl groups of uracil base and the other cyclen serves as an electrophilic catalyst by interacting with the phosphodiester linkage. The tetra- and penta-cations of 2,6-bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)pyridine (11b) have given similar results. The possible role of
Graphical Abstract
Figure 1: Enzymatic cleavage of phosphodiester linkages of DNA and RNA.
Figure 2: Energy profiles for a concerted ANDN (A) and stepwise mechanisms (AN + DN) with rate-limiting break...
Figure 3: Pseudorotation of a trigonal bipyramidal phosphorane intermediate by Berry pseudorotation [20].
Figure 4: Protolytic equilibria of phosphorane intermediate of RNA transesterification.
Figure 5: Structures of acyclic analogs of ribonucleosides.
Figure 6: First-order rate constants for buffer-independent partial reactions of uridyl-3´,5´-uridine at pH 5...
Scheme 1: pH- and buffer-independent cleavage and isomerization of RNA phosphodiester linkages. Observed firs...
Scheme 2: Mechanism for the pH- and buffer-independent cleavage of RNA phosphodiester linkages.
Scheme 3: Hydroxide-ion-catalyzed cleavage of RNA phosphodiester linkages.
Scheme 4: Anslyn's and Breslow's mechanism for the buffer-catalyzed cleavage and isomerization of RNA phospho...
Scheme 5: General base-catalyzed cleavage of RNA phosphodiester bonds.
Scheme 6: Kirby´s mechanism for the buffer-catalyzed cleavage of RNA phosphodiester bonds [65].
Figure 7: Guanidinium-group-based cleaving agents of RNA.
Scheme 7: Tautomers of triazine-based cleaving agents and cleavage of RNA phosphodiester bonds by these agent...
Figure 8: Bifunctional guanidine/guanidinium group-based cleaving agents of RNA.
Scheme 8: Cleavage of HPNP by 1,3-distal calix[4]arene bearing two guanidine groups [80].
Figure 9: Cyclic amine-based cleaving agents of RNA.
Scheme 9: Mechanism for the pH-independent cleavage and isomerization of model compound 12a in the pH-range 7...
Scheme 10: Mechanism for the pH-independent cleavage of guanylyl-3´,3´-(2´-amino-2´-deoxyuridine) at pH 6-8 [89].
Scheme 11: Cleavage of uridine 3´-dimethyl phosphate by A) intermolecular attack of methoxide ion and B) intra...
Scheme 12: Transesterification of group I introns and hydrolysis of phosphotriester models proceed through a s...
Scheme 13: Cleavage of trinucleoside 3´,3´,5´-monophosphates by A) P–O3´ and B) P–O5´ bond fission.
Figure 10: Model compounds (23–25) and metal ion binding ligands used in kinetic studies of metal-ion-promoted...
Figure 11: Zn2+-ion-based mono- and di-nuclear cleaving agents of nucleic acids.
Figure 12: Miscellaneous complexes and ligands used in kinetic studies of metal-ion-promoted cleavage of nucle...
Figure 13: Azacrown ligands 34 and 35 and dinuclear Zn2+ complex 36 used in kinetic studies of metal-ion-promo...
Figure 14: Metal ion complexes used for determination of βlg values of metal-ion-promoted cleavage of RNA mode...
Figure 15: Metal ion complexes used in kinetic studies of medium effects on the cleavage of RNA model compound...
Scheme 14: Alternative mechanisms for metal-ion-promoted cleavage of phosphodiesters.
Figure 16: Nucleic acid cleaving agents where the attacking oxyanion is not coordinated to metal ion.
An uracil-linked hydroxyflavone probe for the recognition of ATP
- Márton Bojtár,
- Péter Zoltán Janzsó-Berend,
- Dávid Mester,
- Dóra Hessz,
- Mihály Kállay,
- Miklós Kubinyi and
- István Bitter
Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63
- a uracil nucleobase to the known 4’-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of
- . Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum. Keywords: ATP sensing; base-pairing; fluorescent probes; 3-hydroxyflavone
- way to enhance the selectivity. Since ATP has one adenine nucleobase, a simple uracil/thymine unit appended to a neutral chemosensor operating mainly through π-interaction could be a good model for investigation. We selected DMHF as the fluorophore and core scaffold because of its easy synthesis and
Graphical Abstract
Figure 1: Structures of the studied hydroxyflavone derivatives.
Figure 2: Optimized geometries for (a) DEHF∙ATP, (b) UHF∙ATP with the adenine of ATP “sandwiched” between the...
Scheme 1: Synthesis of UHF. (i) 4-Dimethylaminobenzaldehyde, DMF, NaOMe, rt, 17 h, (ii) hydrogen peroxide, Na...
Figure 3: Variation of fluorescence spectra of UHF (1.0 μM) upon addition of increasing amounts of ATP in 0.0...
Figure 4: Excitation spectra of UHF (dark green line, 1 μM) and UHF + 300 equiv ATP (red line), measured at d...
Figure 5: Fluorescence enhancement (F/F0) values of UHF (1.0 μM) upon addition of different nucleotides at 54...
Figure 6: Ratio of the fluorescence intensities at 540 nm, the samples were excited at 470 and 400 nm. The re...
Fluorogenic PNA probes
- Tirayut Vilaivan
Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17
- uracils have also been extensively studied as fluorescent nucleobases in the context of aegPNA. Modifications have invariably been made at the 5-position of uracil, which could be functionalized by various aromatics or alkynes via palladium-catalyzed cross couplings of the corresponding iodouridine
- derivative. 5-Benzothiophene- and 5-benzofuran-modified uracil in aegPNA exhibited a fluorescence that was marginally sensitive to the environment [195]. When incorporated into PNA, benzothiophene-uracil exhibited an increased fluorescence compared to the free nucleoside. The opposite effect was observed
- with benzofuran-uracil, and the fluorescence was almost completely quenched when G was the flanking nucleobase. Significant fluorescence enhancement with a small blue-shift of the emission maxima was observed upon duplex formation with DNA for both modified uracil derivatives. Unfortunately, the
Graphical Abstract
Figure 1: The design of classical DNA molecular beacons.
Figure 2: Structures of DNA and selected PNA systems.
Figure 3: Various binding modes of PNA to double stranded DNA including triplex formation, triplex invasion, ...
Figure 4: The design and working principle of the PNA beacons according to (A) Ortiz et al. [41] and (B) Armitage...
Figure 5: The design of "stemless" PNA beacons.
Figure 6: The applications of PNA openers to facilitate the binding of PNA beacons to double stranded DNA [40,47].
Figure 7: The working principle of snap-to-it probes that employed metal chelation to bring the dyes in close...
Figure 8: Examples of pre-formed dye-labeled PNA monomers and functionalizable PNA monomers.
Figure 9: Dual-labeled PNA beacons with end-stacking or intercalating quencher.
Figure 10: The working principle of hybrid PNA-peptide beacons for detection of (A) proteins [80] and (B) protease...
Figure 11: The working principle of binary probes.
Figure 12: The working principle of nucleic acid templated fluorogenic reactions leading to a (A) ligated prod...
Figure 13: Catalytic cycles in fluorogenic nucleic acid templated reactions [90].
Figure 14: The working principle of strand displacement probes.
Figure 15: (A) Examples of CPP successfully used with labeled PNA probes. (B) The use of single-labeled PNA pr...
Figure 16: The concept of PNA–GO platform for DNA/RNA sensing.
Figure 17: Single-labeled fluorogenic PNA probes.
Figure 18: Examples of environment sensitive fluorescent labels that have been incorporated into PNA probes as...
Figure 19: The mechanism of fluorescence change in TO dye.
Figure 20: Fluorescent nucleobases capable of hydrogen bonding that have been incorporated into PNA probes.
Figure 21: Comparison of the designs of the (A) light-up PNA probe and (B) FIT PNA probe.
Figure 22: The structures of TO and its analogues that have successfully been used in FIT PNA probes.
Figure 23: The working principle of dual-labeled FIT PNA probes [222,223].
Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial
- Tamara Šmidlehner,
- Ivo Piantanida and
- Gennaro Pescitelli
Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5
Graphical Abstract
Figure 1: Plane polarized light (PP, cyan) as the sum of the left and right circularly polarized light (L-CP,...
Figure 2: Schematic representation of ligand binding modes to DNA or RNA (left to right: DNA minor groove bin...
Scheme 1: Principal electronic transitions of nucleobases (uracil is similar to thymine, Thy). The arrows dep...
Figure 3: Exciton coupling mechanism in its degenerate (top) and non-degenerate version (bottom). a) Chiralit...
Figure 4: ECD and UV (inset) spectra of poly(dG-dC)–poly(dG-dC) in the B and Z-form, obtained in 59% and 67% ...
Figure 5: Schematic illustration of an ECD instrument. Legend: S, source; M, monochromator (wavelength select...
Figure 6: Exciton coupling in the G-quadruplex [d(TG4T)]4. For this sequence, the quadruplex is formed by fou...
Figure 7: Empirical analysis of ECD and flow LD spectra to establish the preferred orientation of a ligand bo...
Figure 8: CD titration of poly rA-poly rU (left) and poly rU (right) (c(polynucleotide) = 2.0 × 10−5 mol dm−3...
Figure 9: a) Schematic diagram of a flow LD instrument. b) Definition of the optical factor relating the dire...
Figure 10: LD spectrum of calf thymus (ct) DNA (c = 2 × 10−4 M), pH 7, sodium cacodylate buffer, I = 0.05 M.
Figure 11: Schematic illustration of an FDCD a) and a CPL b) instrument. Legend: S, source; M, monochromator (...
Figure 12: Minimal model to be considered to simulate the ICD spectrum of an intercalated ligand. ICD will be ...
Figure 13: Schematic representation of the main steps for calculating the ICD spectrum of a ligand bound to a ...
Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides
- Neha Rana,
- Manish Kumar,
- Vinod Khatri,
- Jyotirmoy Maity and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205
- ) in 98% yield. The glycosyl donor 7a,b was prepared from acetolysis of compound 6 with acetic acid/acetic anhydride/sulfuric acid (100:10:0.1) in 93% yield. The Vorbrüggen coupling [17] of 7a,b with uracil in the presence of N,O-bis(trimethylsilyl)acetamide (BSA) and trimethylsilyltrifluoromethane
- 95% yield, which on Vorbrüggen coupling with uracil under earlier used base-coupling conditions afforded the corresponding acetylated nucleoside 13 in 92% yield. Subsequent deacetylation of nucleosides 13 followed by concomitant cyclization with 2 M NaOH solution in water/dioxane (1:1) afforded 2′-O
- Vorbrüggen coupling of tetraacetylated sugar derivatives 7a,b and 12a,b: synthesis of acetylated nucleosides 8 and 13. Similar as described in [18] to a stirred solution of compound 7a,b (3.0 g, 5.97 mmol) and nucleobase uracil (1.0 g, 8.9 mmol) in anhydrous acetonitrile (25 mL), N,O-bis(trimethylsilyl
Graphical Abstract
Scheme 1: Formation of a 1:1 epimeric mixture of 3a and 3b.
Scheme 2: Lipase-catalysed separation of a mixture of ribo- and xylotrihydroxyfuranosides.
Figure 1: Screening of Novozyme®-435 and Lipozyme TL IM in different organic solvents at 35 °C for regioselec...
Figure 2: ORTEP diagram of tosylated sugar derivatives 5 and 10.
Scheme 3: Convergent synthesis of 3′-O,4′-C-methyleneuridine.
Scheme 4: Convergent synthesis of 2′-O,4′-C-methylene-xylouridine.
Figure 3: ORTEP diagram and preferential N-type sugar ring puckering of 2′-O,4′-C-methylene-xylouridine (14).
Mechanochemical N-alkylation of imides
- Anamarija Briš,
- Mateja Đud and
- Davor Margetić
Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169
- considered for LAG in mechanosynthesis. A comparison of results with literature values demonstrates the benefits of mechanosynthesis. For instance, alkylation of theobromine (14) [34] in a microwave reactor in solution gives two side-products, an O-alkylated and a uracil ring-opened product (induced by base
- . For instance in the reaction of uracil (17) or 7,8-dimethylalloxazine (36). The required substrate 36 was prepared by mechanochemical condensation [35] of alloxane (34) and 4,5-dimethyl-1,2-phenylenediamine (35) in the presence of p-toluenesulfonic acid [36][37] (Scheme 3). The α-dione/α-diamine
- . Computational section To elucidate reasons for the observed regioselectivities, the reactions of uracil and 7,8-dimethylalloxazine with benzylamine and ethyl bromide were studied by DFT calculations using the B3LYP/6-311+G**//B3LYP/6-31G*+ZPVE method. The transition-state calculations of the SN2 reaction of
Graphical Abstract
Scheme 1: N-Alkylation of imide 1 with 1,3-dibromopropane (2) in a ball mill.
Scheme 2: Mechanochemical N-alkylation of imide 1.
Figure 1: Products of alkylation of imides 11–17.
Figure 2: Ex situ IR spectroscopy of the reaction of 12 and benzyl bromide in the ball mill: a) phthalimide 12...
Scheme 3: Mechanosynthesis of 7,8-dimethylalloxazine (36) and its N-alkylation.
Scheme 4: Gabriel synthesis of amines in ball mill.
Scheme 5: Three-step, two-pot Gabriel synthesis of amines in ball mill.
Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation
- Raja Ben Othman,
- Mickaël J. Fer,
- Laurent Le Corre,
- Sandrine Calvet-Vitale and
- Christine Gravier-Pelletier
Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153
- temperature [52] but, even at 0 °C, the components in the reaction mixture were largely degraded. The protection of uracil nitrogen at N-3 position by an allyl group did not significantly modify the 5’R/5’S ratio (Table 2, entry 3). Increasing the bulkiness of the ketal protecting group by introducing an
- uracil (Table 2, entry 8) did not significantly change the 5’R/5’S ratio. In both cases, using 3.5 equivalents of Grignard reagent was required to complete the reaction. In order to improve this reverse diastereoselectivity, we envisaged the use of a more bulky protecting group, such as the
Graphical Abstract
Figure 1: C-5’ configuration of nucleoside derivatives and related biological activity.
Scheme 1: Synthesis of alcohols 1–5.
Scheme 2: Synthesis of propargylic alcohols 11–15 and their partial or complete deprotection.
Scheme 3: Synthesis of reference compounds and strategy for assignment of C-5’ configuration.
Figure 2: 1H NMR of (5’R)-16 and (5’S)-16 and of a (5’R)/(5’S)-16 mixture.
Figure 3: 1H NMR of (5’R)-17 and (5’S)-17 and example of configuration determination for a pure isolated comp...
Figure 4: Hypothetical Cram chelated models.
Figure 5: Proposed stereochemical models.
Strategies toward protecting group-free glycosylation through selective activation of the anomeric center
- A. Michael Downey and
- Michal Hocek
Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123
Graphical Abstract
Scheme 1: Solution-state conformations of D-glucose.
Scheme 2: Enzymatic synthesis of oligosaccharides.
Scheme 3: Enzymatic synthesis of a phosphorylated glycoprotein containing a mannose-6-phosphate (M6P)-termina...
Scheme 4: A) Selected GTs-mediated syntheses of oligosaccharides and other biologically active glycosides. B)...
Scheme 5: Enzymatic synthesis of nucleosides.
Scheme 6: Fischer glycosylation strategies.
Scheme 7: The basis of remote activation (adapted from [37]).
Scheme 8: Classic remote activation employing a MOP donor to access α-anomeric alcohols, carboxylates, and ph...
Figure 1: Synthesis of monoprotected glycosides from a (3-bromo-2-pyridyloxy) β-D-glycopyranosyl donor under ...
Scheme 9: Plausible mechanism for the synthesis of α-galactosides. TBDPS = tert-butyldiphenylsilyl.
Scheme 10: Synthesis of the 6-O-monoprotected galactopyranoside donor for remote activation.
Scheme 11: UDP-galactopyranose mutase-catalyzed isomerization of UDP-Galp to UDP-Galf.
Scheme 12: Synthesis of the 1-thioimidoyl galactofuranosyl donor.
Scheme 13: Glycosylation of MeOH using a self-activating donor in the absence of an external activator. a) Syn...
Scheme 14: The classical Lewis acid-catalyzed glycosylation.
Figure 2: Unprotected glycosyl donors used for the Lewis acid-catalyzed protecting group-free glycosylation r...
Scheme 15: Four-step synthesis of the phenyl β-galactothiopyranosyl donor.
Scheme 16: Protecting-group-free C3′-regioselective glycosylation of sucrose with α–F Glc.
Scheme 17: Synthesis of the α-fluoroglucosyl donor.
Figure 3: Protecting-group-free glycosyl donors and acceptors used in the Au(III)-catalyzed glycosylation.
Scheme 18: Synthesis of the mannosyl donor used in the study [62].
Scheme 19: The Pd-catalyzed stereoretentive glycosylation of arenes using anomeric stannane donors.
Scheme 20: Preparation of the protecting-group-free α and β-stannanes from advanced intermediates for stereoch...
Figure 4: Selective anomeric activating agents providing donors for direct activation of the anomeric carbon.
Scheme 21: One-step access to sugar oxazolines or 1,6-anhydrosugars.
Scheme 22: Enzymatic synthesis of a chitoheptaose using a mutant chitinase.
Scheme 23: One-pot access to glycosyl azides [73], dithiocarbamates [74], and aryl thiols using DMC activation and sub...
Scheme 24: Plausible reaction mechanism.
Scheme 25: Protecting-group-free synthesis of anomeric thiols from unprotected 2-deoxy-2-N-acetyl sugars.
Scheme 26: Protein conjugation of TTL221-PentK with a hyaluronan hexasaccharide thiol.
Scheme 27: Proposed mechanism.
Scheme 28: Direct two-step one-pot access to glycoconjugates through the in situ formation of the glycosyl azi...
Scheme 29: DMC as a phosphate-activating moiety for the synthesis of diphosphates. aβ-1,4-galactose transferas...
Figure 5: Triazinylmorpholinium salts as selective anomeric activating agents.
Scheme 30: One-step synthesis of DBT glycosides from unprotected sugars in aqueous medium.
Scheme 31: Postulated mechanism for the stereoselective formation of α-glycosides.
Scheme 32: DMT-donor synthesis used for metal-catalyzed glycosylation of simple alcohols.
Figure 6: Protecting group-free synthesis of glycosyl sulfonohydrazides (GSH).
Figure 7: The use of GSHs to access 1-O-phosphoryl and alkyl glycosides. A) Glycosylation of aliphatic alcoho...
Scheme 33: A) Proposed mechanism of glycosylation. B) Proposed mechanism for stereoselective azidation of the ...
Scheme 34: Mounting GlcNAc onto a sepharose solid support through a GSH donor.
Scheme 35: Lawesson’s reagent for the formation of 1,2-trans glycosides.
Scheme 36: Protecting-group-free protein conjugation via an in situ-formed thiol glycoside [98].
Scheme 37: pH-Specific glycosylation to functionalize SAMs on gold.
Figure 8: Protecting-group-free availability of phenolic glycosides under Mitsunobu conditions. DEAD = diethy...
Scheme 38: Accessing hydroxyazobenzenes under Mitsunobu conditions for the study of photoswitchable labels. DE...
Scheme 39: Stereoselective protecting-group-free glycosylation of D-glucose to provide the β-glucosyl benzoic ...
Figure 9: Direct synthesis of pyranosyl nucleosides from unactivated and unprotected ribose using optimized M...
Figure 10: Direct synthesis of furanosyl nucleosides from 5-O-monoprotected ribose in a one-pot glycosylation–...
Figure 11: Synthesis of ribofuranosides using a monoprotected ribosyl donor via an anhydrose intermediate.
Figure 12: C5′-modified nucleosides available under our conditions.
Scheme 40: Plausible reaction mechanism for the formation of the anhydrose.
Figure 13: Direct glycosylation of several aliphatic alcohols using catalytic Ti(Ot-Bu)4 in the presence of D-...
Figure 14: Access to glycosides using catalytic PPh3 and CBr4.
Figure 15: Access to ribofuranosyl glycosides as the major product under catalytic conditions. aLiOCl4 (2.0 eq...
Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience
- Serge Pérez and
- Daniele de Sanctis
Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114
- that had been synthesized. They all included a substrate donor, either UDP-Gal or UDP-GalNAc with an additional group on the sugar or on the uracil. Photolysis at 100 K was monitored by UV–vis absorption, both in solution and in crystals in order to assess the efficiency of the laser ablation in the
Graphical Abstract
Figure 1: Complementarity of synchrotron radiation and neutron sources to investigate the structure of matter....
Figure 2: A representation of a synchrotron storage ring, including linear accelerator, booster and two beaml...
Figure 3: Schematic representation of a sector of a storage ring. Bending magnets and insertion devices are a...
Figure 4: Structural features of the resin glycoside tricolorin A. (a) Extracted from the Mexican variety of ...
Figure 5: Powder diffractogram measured on a synthetic pentasaccharide from heparin, at ESRF beamline ID31, λ...
Figure 6: Three dimensional ribbon representation of a heavily N-glycosylated Aspergilllus sp. Family GH3 β-D...
Figure 7: Histogram of the number of deposited crystal structures of glycan-binding proteins deposited over t...
Figure 8: Ribbon diagram representations of prototypical members of the GT-A and GT-B super-family fold, resp...
Figure 9: Representation of the FUT1 structure determined in complex with the acceptor (carbon atoms in green...
Figure 10: Representation of the seven folds most commonly found in glycoside hydrolases. From the classificat...
Figure 11: The multivalent carbohydrate binding features of lectins from X-ray structures. (a) Monovalent. E-s...
Figure 12: Three-dimensional depiction of the ternary complex formed by a heparin mimetic in interaction with ...
Figure 13: 3D representation of different sugar transporter structures: (left to right, top to down) lactose p...
Figure 14: Kinetic crystallography. Protein crystals are soaked with the cage compound (Step 1) followed by fl...
Figure 15: Reconstruction of the full three-dimensional structure of the soluble lectin (BC2L-C) from the oppo...
Figure 16: Characterization by synchrotron X-ray reflectometry of the transverse structures of a model membran...
Figure 17: Complementary use of X-ray synchrotron and neutron fiber diffraction to unravel the three-dimension...
Figure 18: Scanning electron micrograph of high-quality micrometer-sized A-amylose microcrystals grown from sh...
Figure 19: Cartography of distribution and orientation of cellulose in wood using a 3 µm X-ray beam. The scann...
Figure 20: Structural micro-diffraction scanning of a starch granule from Phajus grandifolius with dimensions ...
From chemical metabolism to life: the origin of the genetic coding process
- Antoine Danchin
Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111
- living cells these pathways associate interconversions between purines and pyrimidines [34][35]. Furthermore, the nitrogen-rich intermediate 5-amino-6-(D-ribitylamino)uracil comprises building blocks that are commonly found under prebiotic conditions. Once phosphorylated (as discussed previously, via
Graphical Abstract
Figure 1: Selective surface metabolism. Prebiotic carbon-based molecules accumulated in a neutral or slightly...
Figure 2: Building up membranes, peptides and co-enzymes. Thioester-based metabolism resulted in the synthesi...
Figure 3: The RNA metabolism world. Among molecules built up by a swinging-arm thioester are pyrimidines coup...
