- Design and synthesis of 2,6-disubstituted-4′-selenoadenosine- 5′-N,N-dimethyluronamide derivatives as human A3 adenosine receptor antagonists
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A new series of 4′-selenoadenosine-5′-N,N-dimethyluronamide derivatives as highly potent and selective human A3 adenosine receptor (hA3AR) antagonists, is described. The highly selective A3AR agonists, 4′-selenoadenosine-5′-N-methyluronamides were successfully converted into selective antagonists by adding a second N-methyl group to the 5′-uronamide position. All the syn-thesized compounds showed medium to high binding affinity at the hA3AR. Among the synthe-sized compounds, 2-H-N6-3-iodobenzylamine derivative 9f exhibited the highest binding affinity at hA3AR. (Ki = 22.7 nM). The 2-H analogues generally showed better binding affinity than the 2-Cl analogues. The cAMP functional assay with 2-Cl-N6-3-iodobenzylamine derivative 9l demonstrated hA3AR antagonist activity. A molecular modelling study suggests an important role of the hydrogen of 5′-uronamide as an essential hydrogen bonding donor for hA3AR activation.
- Choi, Hongseok,Jacobson, Kenneth A.,Yu, Jinha,Jeong, Lak Shin
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- Novel synthesis method for synthesizing remdesivir
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The invention discloses a novel synthesis method for synthesizing remdesivir. According to the synthesis method disclosed by the invention, D-ribose is taken as a raw material and is subjected to a series of reactions such as oxidation, cyclohexanone protection, silanization protection, substitution, substitution, deprotection, coupling, deprotection and the like to synthesize the remdesivir. The post-treatment operation is optimized, and the method has the advantages of being short in reaction time, high in yield, low in cost, suitable for industrial production and the like. The structure of the remdesivir provided by the invention is shown in the specification.
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Paragraph 0073-0076
(2021/08/14)
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- Stereoselective Palladium-Catalyzed Arylation of Exo-Glycals with Aryl Iodides
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A novel methodology for the arylation of exo-glycals has been developed. A range of exo-glycals underwent reactions with aryl iodides in the presence of a palladium catalyst. The transformation proceeded in a stereoselective manner to afford Z-isomers. Th
- Bolshan, Yuri,Ghanty, Supriya,Regier, Jeffery
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supporting information
(2022/01/12)
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- High-Yielding Diastereoselective syn-Dihydroxylation of Protected HBO: An Access to D-(+)-Ribono-1,4-lactone and 5-O-Protected Analogues
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A diastereoselective chemoenzymatic synthetic pathway to D-(+)-ribono-1,4-lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose-based levoglucosenone (LGO). This route involves a sustainable Baeyer-Villiger oxidation of LGO to produce enantiopure (S)-γ-hydroxymethyl-α,β-butenolide (HBO) that is further functionalized with various protecting groups to provide 5-O-protected γ-hydroxymethyl-α,β-butenolides. The latter then undergo a diastereoselective and high-yielding syn-dihydroxylation of the α,β-unsaturated lactone moiety followed by a deprotection step to give D-(+)-ribono-1,4-lactone. Through this 4-step synthetic route from LGO, D-(+)-ribono-1,4-lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5-O-tert-butyldimethylsilyl-, 5-O-tert-butyldiphenylsilyl- as well as 5-O-benzyl-ribono-1,4-lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively.
- Moreaux, Maxime,Bonneau, Guillaume,Peru, Aurélien,Brunissen, Fanny,Janvier, Marine,Haudrechy, Arnaud,Allais, Florent
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supporting information
p. 1600 - 1604
(2019/01/14)
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- Antioxidant composition comprising marliolide derivatives
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The present invention relates to a marliolide derivative and an antioxidant composition containing the same as an active component, wherein the marliolide derivative increases the expression of a transcription factor Nrf2 that regulates the expression of an antioxidant-related protein without cytotoxicity, thereby increasing the expression of HO-1 and NQO1, which are antioxidant-related proteins. In addition, since the marliolide derivative is confirmed to inhibit the oxidation of DNA and lipids induced by TPA that induces oxidative stress, a composition containing the marliolide derivative can be provided as the antioxidant composition.(AA) Compound 1 (10 andmu;M)COPYRIGHT KIPO 2019
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Paragraph 0039-0045
(2019/11/23)
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- Highly (Z)-Diastereoselective Synthesis of Trifluoromethylated exo-Glycals via Photoredox and Copper Catalysis
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Highly (Z)-diastereoselective approaches for the synthesis of trifluoromethylated exo-glycals by copper and photoredox catalysis are described. These complementary reactions are applicable to a wide range of methylene exo-glycals generated from the corresponding pyranoses and furanoses and give trifluoromethylated compounds under mild conditions in moderate to good yields. DFT calculations have allowed a rationalization of the observed (Z)-stereoselectivity.
- Frédéric, Christophe J.-M.,Cornil, Jér?me,Vandamme, Mathilde,Dumitrescu, Lidia,Tikad, Abdellatif,Robiette, Rapha?l,Vincent, Stéphane P.
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supporting information
p. 6769 - 6773
(2018/10/24)
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- Practical synthesis of 4′-selenopurine nucleosides by combining chlorinated purines and ‘armed’ 4-selenosugar
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The synthesis of a variety of chemically modified oligonucleotides requires the development of a practical synthetic method for its building block, i.e., nucleoside analogs. The one-pot Pummerer-like reaction using hypervalent iodine in combination with 6-chloropurine and an ‘armed’ 4-selenosugar bearing an electron-donating group at the 2-position gave the desired 4′-seleno-6-chloropurine derivative in higher yield as compared to the previous method using a ‘disarmed’ 4-selenosugar bearing an electron-withdrawing group at the 2-position. In addition, the use of 2,6-dichloropurine as a nucleobase transformable into guanine skeleton enabled an effective Pummerer-like reaction followed by isomerization to the desired N9 isomer under the acidic conditions. This Pummerer-like reaction between chlorinated purine bases and an ‘armed’ 4-selenosugar is advantageous because it affords 4′-selenopurine nucleosides in one-pot without the need for isolation of the unstable selenoxide derivative.
- Ishii, Kazuki,Saito-Tarashima, Noriko,Ota, Masashi,Yamamoto, Seigi,Okamoto, Yasuko,Tanaka, Yoshiyuki,Minakawa, Noriaki
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supporting information
p. 6589 - 6594
(2016/09/23)
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- Convenient syntheses of orthogonally protected aminocyclopentitols from aldopentoses
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Orthogonally protected aminocyclopentitols were synthesized from commercially available aldopentoses using a convenient three-step procedure that does not require protection of the free anomeric hydroxyl group of the starting carbohydrate. The synthesized compounds are important building blocks with potential use in medicinal chemistry and drug discovery.
- Ko?ak, Urban,Hrast, Martina,Knez, Damijan,Mara?, Nenad,?rnugelj, Martin,Gobec, Stanislav
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supporting information
p. 529 - 531
(2015/03/03)
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- Molecular sieves mediated green per-O-acetylation of carbohydrate templates and lipase catalyzed regioselective alcoholysis of 2,3,5-Tri-O-acetyl-D-ribonolactone
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The per-O-acetylation of D-ribono-1,4-lactone and representative carbohydrates through the combination of acetic anhydride and molecular sieves under solvent-free conditions is demonstrated. The use of 13X/KCl molecular sieves as the heterogeneous catalyst was found to be more efficient than the excess of pyridine normally employed in the conventional method, giving high yields of the expected peracetylated product after 3 h at 25 °C or 1 h at 50 °C. The transformation can be carried out in gram scale and in an open flask. Additionally, the catalyst is readily separated from the reaction medium and can be reutilized without significant loss of activity. This green procedure for acetylation was extended to D-ribonolactone derivatives and natural carbohydrates. To demonstrate the synthetic utility of the method, 2,3,5-tri-O-acetyl-D-ribonolactone was selected as the substrate for the regioselective alcoholysis of acetyl group catalyzed by Candida antarctica lipase B in EtOH to selectively produce 2,3-di-O-acetyl-D-ribonolactone in gram scale.
- Cardozo, Herbert M.,Ribeiro, Thaís F.,Sá, Marcus M.,Sebr?o, Damianni,Nascimento, Maria G.,Silveira, Gustavo P.
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p. 755 - 764
(2015/04/14)
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- A general and enantioselective approach to pentoses: A rapid synthesis of PSI-6130, the nucleoside core of sofosbuvir
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An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.
- Peifer, Manuel,Berger, Rapha?lle,Shurtleff, Valerie W.,Conrad, Jay C.,Macmillan, David W. C.
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supporting information
p. 5900 - 5903
(2014/05/20)
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- ANTIVIRAL AZASUGAR-CONTAINING NUCLEOSIDES
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Disclosed are compounds comprising an azasugar attached to a heterocyclic base, including pharmaceutically acceptable salts thereof, suitable for use in inhibiting viral RNA polymerase activity or viral replication, and treating viral infections. The compounds are characterized, in part, by favorable pharmacokinetics for the active pharmaceutical ingredient, particularly in conjunction with enteral administration, including, in particular, oral administration. Also disclosed are pharmaceutical compositions comprising one or more compounds mentioned above, or pharmaceutically acceptable salts thereof, as well as methods for preparing same. Also provided are methods for inhibiting viral RNA polymerase activity, viral replication, and treating viral infections.
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Page/Page column 93
(2014/06/11)
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- Synthetic studies towards an advanced precursor of the jatrophane diterpene Pl-4
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Jatrophane diterpenes, isolated from members of the Euphorbiaceae plant family, constitute a class of biologically and structurally intriguing natural products. Herein, different strategies for the preparation of an advanced intermediate towards the total synthesis of the jatrophane diterpene Pl-4 are described. Key strategies for the elaboration of the jatrophane precursors include hydrometalation and radical reactions. Georg Thieme Verlag KG Stuttgart · New York.
- Fürst, Rita,Lentsch, Christoph,Rinner, Uwe
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supporting information
p. 357 - 367
(2014/02/14)
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- COMPOSITIONS AND METHODS FOR INHIBITING VIRAL POLYMERASE
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Provided are compounds of Formula (I) as described herein. Compounds of Formula (I) are useful in methods of inhibiting viral RNA polymerase activity and viral replication. Also provided are pharmaceutical compositions comprising compounds of Formula (I), as well as methods of treating viral infections using compounds of Formula (I).
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Page/Page column 74
(2013/11/05)
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- MW-assisted Er(OTf)3-catalyzed mild cleavage of isopropylidene acetals in Tricky substrates
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Erbium(III) trifluoromethane sulfonate is proposed as a very gentle Lewis acid catalyst in a MW-assisted chemoselective method for the cleavage of isopropylidene acetals in awkward substrates by using pure water as the solvent.
- Procopio, Antonio,Gaspari, Marco,Nardi, Monica,Oliverio, Manuela,Romeo, Roberto
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p. 1961 - 1964
(2008/09/19)
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- Simple and efficient MW-assisted cleavage of acetals and ketals in pure water
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Simple and efficient MW-assisted cleavage of acetal and ketal is proposed in deionized water and in a very short time.
- Procopio, Antonio,Gaspari, Marco,Nardi, Monica,Oliverio, Manuela,Tagarelli, Antonio,Sindona, Giovanni
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p. 8623 - 8627
(2008/03/30)
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- A concise, efficient and production-scale synthesis of a protected L-lyxonolactone derivative: An important aldonolactone core
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A multikilogram-scale synthesis of L-lyxonolactone-2,3-O-isopropylidene is reported. It proceeds efficiently from an optimized, large-scale, aqueous bromine oxidation of D-ribose to D-ribonolactone including a one-pot isopropylidene formation, and subsequent conversion of the D-ribonolactone-2,3- 0-isopropylidene to L-lyxonolactone-2,3-O-isopropylidene via the derived C 5-mesylate and intramolecular relactonization of the product of aqueous potassium hydroxide cleavage of the D-ribonolactone ring. The inversion of configuration at the C4-chiral center is understood in terms of an intermediating C4-C5-epoxide. The overall process is noteworthy for its operational simplicity, stereochemical integrity, and use of inexpensive chemicals.
- Batra, Hitesh,Moriarty, Robert M.,Penmasta, Raju,Sharma, Vijay,Stanciuc, Gabriela,Staszewski, James P.,Tuladhar, Sudersan M.,Walsh, David A.,Datla, Satyanarayana,Krishnaswamy, Sunderraj
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p. 484 - 486
(2012/12/22)
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- A new efficient access to glycono-1,4-lactones by oxidation of unprotected itols by catalytic hydrogen transfer with RhH(PPh3)4-benzalacetone system
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Treatment of unprotected pentitols and hexitols with RhH(PPh3)4-benzalacetone system leads exclusively to glycono-1,4-lactones in 60-96% yield.
- Isaac,Aizel,Stasik,Wadouachi,Beaupère
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p. 475 - 476
(2007/10/03)
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- Stereocontrol in organic synthesis using silicon-containing compounds. Syntheses of (±)-2-deoxyribonolactone and (±)-arabonolactone
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Samarium iodide reacts with methyl (Z)-3-dimethyl(4-methylphenyl)silylprop-2-enoate 5b to give dimethyl (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]hexane-1,6-dioate 8b with high stereoselectivity. This meso diester can be converted into (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]pentan-5-olide 16 by Dieckmann cyclisation, demethoxycarbonylation and Baeyer-Villiger reaction. Silyl-to-hydroxy conversion and relactonisation gave (±)-deoxyribonolactone, and anti-selective enolate hydroxylation followed by silyl-to-hydroxy conversion gave (±)-arabonolactone. An attempt to synthesise sugars with the relative configuration (3RS,4RS) was thwarted by an unprecedented retention of configuration at the migration origin in the cationic rearrangement of (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]-5-hydroxypentanoic acid 28 to (3RS,4SR)-3,5-bis[dimethyl(4-methylphenyl)silyl]pentan-1,4-olide 30.
- Fleming, Ian,Ghosh, Sunil K.
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p. 2711 - 2720
(2007/10/03)
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- Kinetics and mechanism of the oxidation of sugars and nucleotides by oxoruthenium(IV): Model studies for predicting cleavage patterns in polymeric DNA and RNA
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Kinetic parameters for the oxidation of D-ribose, 2-deoxy-D-ribose, adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), 2'-deoxyadenosine 5'-monophosphate (dAMP), cytidine 5'-monophosphate (CMP), 2'-deoxycytidine 5'-monophosphate (dCMP), and thymidine 5'-monophosphate (TMP) by Ru(tpy)(bpy)O2+ were determined in pH 7 phosphate buffer (tpy = 2,2',2''-terpyridine, bpy = 2,2'-bipyridine). Plots of k(obs) vs [substrate] were linear for the oxidation of ribose, 2-deoxyribose, TMP, and dCMP, yielding second-order rate constants of 0.029, 0.082, 0.38, and 0.46 M-1 s-1, respectively. From the temperature dependence of the rate constant, activation parameters consistent with the oxidation of other organic molecules by hydride transfer were found. For GMP, AMP, and dAMP, k(obs) vs [substrate] plots were curved due to electrostatic binding of Ru(tpy)(bpy)O2+ to the dianionic nucleotides, and the data were treated using double-reciprocal plots, yielding effective second-order rate constants of 0.10, 0.39, and 2.5 M-1 s-1, respectively. Product analysis by HPLC shows that a quantitative yield of free cytosine is obtained upon oxidation of dCMP based on nucleotide consumed. In TMP oxidations, an 80% yield of free thymine is observed based on Ru(tpy)(bpy)O2+ consumed. The kinetics and product analyses are consistent with sugar oxidation at the 1' position, and the increased reactivity of DNA compared to RNA can be understood on the basis of deactivation of the sugar oxidation product by the polar effect of the 2'-hydroxyl. The oxidation of the guanine base in GMP by Ru(tpy)(bpy)O2+ proceeds via an oxo transfer mechanism where the initial step is formation of a bound Ru(III)OR2+ intermediate. The ratio of the rate-determining rate constant for oxidation of guanine nucleotides to the average rate constant of sugar oxidation predicts the relative yields of base and sugar oxidation on sequencing gels.
- Neyhart,Cheng,Thorp
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p. 1463 - 1471
(2007/10/02)
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- A NEW AND DIRECT ACCESS TO GLYCONO-1,4-LACTONES FROM GLYCOPYRANOSES BY REGIOSELECTIVE OXIDATION AND SUBSEQUENT RING RESTRICTION
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Treatment of partially protected or unprotected carbohydrates with the RhH(PPh3)4-benzalacetone system leads exclusively to glycono-1,4-lactones by regioselective oxidation and subsequent ring restriction.
- Isaac, Isabelle,Stasik, Imane,Beaupere, Daniel,Uzan, Raoul
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p. 383 - 386
(2007/10/02)
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- Stereoselective Samarium(II)-induced Coupling of β-Silylacrylic Esters: a Synthesis of (+/-)-2-Deoxyribonolactone
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Samarium iodide converts the β-silylacrylate 1c with high stereoselectivity into the racemic diester 2c, from which (+/-)deoxyribonolactone 11 can be prepared.
- Fleming, Ian,Ghosh, Sunil K.
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p. 1775 - 1777
(2007/10/02)
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- Synthesis of D-erythroascorbic acid from D-glucose
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Reaction of a 4:1 mixture of D-ribono- and D-arabinono-1,4-lactones with benzaldehyde and hydrochloric acid gave 59percent crystalline 3,4-O-benzylidene-D-ribono-1,5-lactone.This acetal was oxidized with manganese dioxide in acetone to its 2-keto-derivative (6) in 76percent yield.Acid-catalyzed methanolysis of 6 gave a syrupy mixture of products, which upon tautomerization in hot methanolic sodium acetate followed by removal of sodium ions gave 78percent D-erythroascorbic acid (7).The overall yield of 7 starting from D-glucose was 20percent.
- Gan, Li-Xian,Seib, Paul A.
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p. 117 - 126
(2007/10/02)
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