10457-14-4Relevant articles and documents
Total synthesis of uradl polyoxin c
Kato, Keisuke,Chen, Cheng Yu,Akita, Hiroyuki
, p. 1527 - 1533 (1998)
An improved synthesis of methyl (methyl 5-azido-5deoxy-2,3-O-isopropylidene-β-D-allofuranosid)uronate (7) from methyl 2,3-0-isopropylidene-β-D-rifro-pentodialdo-l,4-furanoside (6), using vinylmagnesium bromide in the key step, and its application to the total synthesis of uracil polyoxin C (1) are described.
Bicyclic nucleoside analogues from D-glucose: Synthesis of chiral as well as racemic 1,4-dioxepane ring-fused derivatives
Tripathi, Subhankar,Maity, Joy Krishna,Achari, Basudeb,Mandal, Sukhendu B.
, p. 1081 - 1087 (2005)
The dioxepanofuranose derivatives 4 and 12, obtained through the cyclization of the 3-(2-hydroxyethyl) ether of a d-xylo-pentodialdose derivative, were appropriately functionalized and elaborated to the first examples of the new class of 3′-O and 5′-O-bicyclic nucleoside analogues 9, 10, and 14 with a fused seven-membered ring. Reactions carried out through the intermediacy of the d-xylo-pentodialdose derivative 5 yielded racemic products, while prior protection of the 4-formyl group (as in 7) before deprotection of the 1,2-hydroxyl groups led to optically active analogues.
Stereoselective synthesis of novel C-azanucleoside analogues by microwave-assisted nucleophilic addition of sugar-derived cyclic nitrones
Li, Xiaoliu,Qin, Zhanbin,Wang, Rui,Chen, Hua,Zhang, Pingzhu
, p. 1792 - 1798 (2011)
A series of C-azanucleoside analogues were synthesized by microwave-assisted nucleophilic addition of electron-rich hetero-aromatics to sugar-derived cyclic nitrones, and followed by reduction and deprotection. The nucleophilic addition afforded the 2′,3′-trans isomer as the dominant by the favorite exo attack and showed high stereoselectivity in polar solvent.
Synthesis of 3',4'-C-bishydroxymethyl-2',3',4'-trideoxy-β-L-threo- pentopyranosyl nucleosides as potential inhibitors of HIV
Lundquist,Kvarnstrom,Svensson,Classon,Samuelsson
, p. 1493 - 1502 (1995)
The synthesis of 3',4'-bishydroxymethyl-2',3',4'-trideoxy pentopyranosyl derivatives of thymine, uracil, cytosine, and adenine is described. trans- (3S,4S)-Bis(methoxycarbonyl)cyclopentanone (3) was converted to 1-O-acetyl- 3,4-C-bis[(tert-butyldiphenylsiloxy)methyl]-2,3,4-trideoxy-α,β-L-threo- pentopyranose (6), which was subsequently condensed with the silylated purine and pyrimidine bases.
Experimental evidence for intramolecular attractive nonbonded C-F ··· H-C interactions in 2',3'-dideoxy-4'-(fluoromethyl)nucleosides - Through- space J(CF) and J(HF) NMR coupling constants, correlation with empirical parameters of solvent polarity and single-crystal X-ray structures
Mele, Andrea,Vergani, Barbara,Viani, Fiorenza,Meille, Stefano Valdo,Farina, Alessandra,Bravo, Pierfrancesco
, p. 187 - 196 (1999)
A collection of 5'-O-benzyl-2',3'-dideoxy-4'-(fluoromethyl)nucleosides carrying both purinic and pyrimidinic nucleobases (uracil, 5-Br-uracil, 5- O2N-uracil, 6-Cl-purine and inosine) were synthesized in both the α and the β form. Through-space-transmitted 6J(CF) NMR coupling constants between F and C-6 (pyrimidinic base) or C-8 (purinic base) were observed for all of the α anomers of the compounds examined, whilst the corresponding 7J(HF) coupling constants were resolved only for the 5-substituted uracil derivatives. The absolute values of all the through-space couplings were found to decrease monotonically with increasing solvent polarity (CDCl3, MeOD, [D6]acetone, [D6]DMSO). This trend suggests that the through-space interaction is mediated by an intramolecular (sp3)C-F ··· H-C(sp2) hydrogen bond. The possibility of any relevant solvent-induced conformational change influencing the F/base mutual spatial relationship in the molecules investigated was ruled out by heteronuclear steady-state 1H{19F}-NOE experiments. A linear correlation was observed between 6J(CF) and 7J(HF) coupling constants and the Kamlet-Taft's hydrogen bond basicity parameter β. The crystal structures of the α and β anomers of the 5-nitrouracil nucleoside show evidence that the H-6 of the nucleobase forms hydrogen-bond- like interactions involving the O-benzyl oxygen atom in the β anomer, and that in the case of the α anomer this is replaced by the F atom of the fluoromethyl group.
Effective synthesis of nucleosides utilizing O-acetyl-glycosyl chlorides as glycosyl donors in the absence of catalyst: Mechanism revision and application to silyl-hilbert-johnson reaction
Liang, Chengyuan,Ju, Weihui,Ding, Shunjun,Sun, Han,Mao, Gennian
, (2017)
An effective synthesis of nucleosides using glycosyl chlorides as glycosyl donors in the absence of Lewis acid has been developed. Glycosyl chlorides have been shown to be pivotal intermediates in the classical silyl-Hilbert-Johnson reaction. A possible mechanism that differs from the currently accepted mechanism advanced by Vorbrueggen has been proposed and verified by experiments. In practice, this catalyst-free method provides easy access to Capecitabine in high yield.
SYNTHESIS OF 1-(3-HALOTETRAHYDRO-2-FURYL) DERIVATIVES OF URACIL, 5-SUBSTITUTED URACILS, AND CYTOSINE
Kaulinya, L. T.,Lidak, M. Yu.
, p. 77 - 81 (1987)
The cis and trans isomers of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils, and cytosine were obtained by alkylation of 2,4-bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine with 2,3-dihalotetrahydrofurans . 2,3'-Anhydro compounds are also formed in the alkylation of 5-halouracil derivatives.The physicochemical properties of the compounds obtained and the antineoplastic activities of the 5-fluorouracil derivatives were studied.
HMDS/KI a simple, a cheap and efficient catalyst for the one-pot synthesis of N-functionalized pyrimidines
Mansouri, Az-Eddine El,Zahouily, Mohamed,Lazrek, Hassan B.
, p. 1802 - 1812 (2019)
The syntheses of N-Alkylpyrimidine derivatives by reacting pyrimidin-2,4-diones with appropriate alkyl halide under microwave irradiation at 400 W were compared to the conventional synthesis route. These methodologies are regioselective and compatible with numerous substrates and furnish the corresponding N-alkylpyrimidines in good yields using a cheap catalyst HMDS/KI in MeCN. A comparison study between these two different modes of heating was investigated.
SYNTHESIS AND ANTIVIRAL ACTIVITY OF 1-- AND 1-PYRIMIDINES
Novikov, M. S.,Ozerov, A. A.,Brel', A. K.,Boreko, E. I.,Korobchenko, L. V.,Vladyko, G. V.
, p. 110 - 113 (1994)
-
The synthesis of new acyclic analogs of 3-phenacyluridine and comparative evaluation of their in vivo biological activity
Novakov, Ivan А.,Brunilina, Leila L.,Kirillov, Ivan А.,Nawrozkij, Maxim B.,Robinovich, Mariya D.,Titova, Evgeniya S.,Sheikin, Dmitry S.,Ruchko, Evsey А.,Pavlova, Alla V.,Kotlyarova, Anastasiya А.,Tolstikova, Tatyana G.
, p. 769 - 775 (2020)
[Figure not available: see fulltext.] New structural analogs of 3-phenacyluridine were obtained as a result of N(3)-alkylation of 1-(2-acetoxyethyl)- and 1-(2-acetoxyethoxymethyl) uracil. Biological studies of the title compounds in an acute in vivo experiment did not reveal their hypnotic properties and ability to enhance the effects of diazepam and chloral hydrate.
5-Methylcytosine is Oxidized to the Natural Metabolites of TET Enzymes by a Biomimetic Iron(IV)-Oxo Complex
Jonasson, Niko S. W.,Daumann, Lena J.
, p. 12091 - 12097 (2019)
Ten-eleven-translocation (TET) methyl cytosine dioxygenases play a key role in epigenetics by oxidizing the epigenetic marker 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxy cytosine (5cC). Although much of the metabolism of 5mC has been studied closely, certain aspects—such as discrepancies among the observed catalytic activity of TET enzymes and calculated bond dissociation energies of the different cytosine substrates—remain elusive. Here, it is reported that the DNA base 5mC is oxidized to 5hmC, 5fC, and 5cC by a biomimetic iron(IV)-oxo complex, reminiscent of the activity of TET enzymes. Studies show that 5hmC is preferentially turned over compared with 5mC and 5fC and that this is in line with the calculated bond dissociation energies. The optimized syntheses of d3-5mC and d2-5hmC are also reported and in the reaction with the biomimetic iron(IV)-oxo complex these deuterated substrates showed large kinetic isotope effects, confirming the hydrogen abstraction as the rate-limiting step. Taken together, these results shed light on the intrinsic reactivity of the C?H bonds of epigenetic markers and the contribution of the second coordination sphere in TET enzymes.
A complex of 5-hydroxypyrrolidin-2-one and pyrimidine-2,4-dione isolated from Jatropha curcas
Staubmann, Ruth,Schubert-Zsilavecz, Manfred,Hiermann, Alois,Kartnig, Theodor
, p. 337 - 338 (1999)
A complex of 5-hydroxypyrrolidin-2-one and pyrimidine-2,4-dione was isolated from the leaves of Jatropha curcas L. by extraction with ethyl acetate and subsequent fractionation of the extract by column chromatography on Sephadex LH20, silica gel and fractogel TSK HW 40. Final purification was carried out by HPLC on a preparative RP-18 column and the structure was proposed mainly by mass spectrometry, 1H- and 13C-NMR.
Practical and reliable synthesis of 2′,3′,5′,5″-tetradeuterated uridine derivatives
Miyamoto, Noriko,Ohno, Hiroki,Kitamura, Yoshiaki,Park, Kwihwan,Sawama, Yoshinari,Sajiki, Hironao,Kitade, Yukio
, p. 236 - 244 (2020)
Deuterated drugs are valuable in the fields of drug discovery and medicinal chemistry. 2′,3′,5′,5″-tetradeuterated uridine derivatives were synthesised from 2,3,5,5′-selectively tetradeuterated ribose using Sajiki’s H–D exchanged Ru/C–H2–D2O–NaOH system and silyl–Hilbert–Johnson methods. The total deuterium content of the tetradeuterated uridines was over 92% using either basic or acidic reaction conditions. These derivatives would be expected as building blocks for the synthesis of deuterium-substituted nucleic acid probes for tracking the pharmacokinetics of nucleic acid drugs.
1-cyclopentyluracils: Synthesis and conformational analysis by X-ray crystallography and AM1 theoretical calculations
Teran,Teijeira,Santana,Uriarte,Castineiras
, p. 69 - 75 (1998)
A series of 1-cyclopentyl 5-substituted pyrimidines was synthesized and their energy-minimized structures were determined by AM1 and compared with the crystal structure of the parent compound, 1-cyclopentyluracil (2). As has been reported for other nucleoside analogues, the energy-minimized conformations were similar for all the compounds, but were not fully in agreement with the X-ray crystal structure obtained for 2.
Synthesis and biological evaluation of novel thioapio dideoxynucleosides.
Moon, Hyung Ryong,Kim, Hea Ok,Lee, Sang Kook,Choi, Won Jun,Chun, Moon Woo,Jeong, Lak Shin
, p. 1499 - 1507 (2002)
On the basis of the bioisosteric rationale to apio dideoxynucleosides, novel thioapio dideoxynucleosides have been synthesized, starting from 1,3-dihydroxyacetone via thioapio sugar acetate as a key intermediate. The intermediate was condensed with silylated pyrimidine bases such as N(4)-benzoylcytosine, uracil or thymine in the presence of TMSOTf to give the beta-anomers and alpha-anomers, respectively. The intermediate was also condensed with silylated 6-chloropurine to give the 6-chloropurine derivatives and which were converted to adenine derivatives and, N(6)-methyladenine derivatives and, and hypoxanthine derivatives and, respectively. The guanine analogues and were also synthesized from the condensation of sugar acetate with 2-acetamido-6-chloropurine. All synthesized final compounds were tested against HIV-1. Most of the synthesized compounds exhibited toxicity-dependent anti-HIV-1 activity, among which 6-chloropurine derivative was found to be the most cytotoxic and showed good cytotoxicity against colon cancer cell lines. Although we could not find good anti-HIV agents in this study, findings of some anticancer activity in this series will allow this class of nucleosides to be the new template for the development of new anticancer agents (Fig. 1).
Synthesis and RT inhibitory activity evaluation of new pyrimidine-based Seco-nucleosides
Vargas, Genaro,Escalona, Iker,Salas, Magali,Gordillo, Barbara,Sierra, Adolfo
, p. 243 - 257 (2006)
Eleven new 3 ′,4 ′- seco acyclic nucleosides (4-14) were prepared by nucleophilic substitution of protected pyrimidine bases on ethyl 3,3-diethoxypropanoate (3). Structures were characterized spectroscopically and a brief analysis of their conformation in solution was performed by the vicinal coupling constants 3 J H 2′ aH 3′ and 3 J H 2′ bH 3′. In solid state, compound 6 forms a homodimer linked by hydrogen bonding. In preliminary tests all compounds show low toxicity and gentle activity against HIV-1 RT in vitro. Copyright Taylor & Francis Group, LLC.
Total synthesis of carbocyclic nikkomycin C
Ward, Simon E.,Holmes, Andrew B.,McCague, Ray
, p. 2085 - 2086 (1997)
The carbocyclic analogue 11 of nikkomycin C1 is prepared by a sequence involving allylic rearrangement of the imino ester adduct 3, palladium-mediated substitution of the allylic lactone 4c with uracil bis(trimethylsilyl)ether 6, and osmylation of the double bond.
Nucleoside synthesis from 3-alkylated sugars: Role of 3β-oxy substituents in directing nucleoside formation
Sahabuddin, Sk.,Ghosh, Ramprasad,Achari, Basudeb,Mandal, Sukhendu B.
, p. 551 - 557 (2006)
Using Vorbrueggen's protocol, reaction of persilylated uracil with xylofuranose derivatives having 3β-oxy-3α-alkyl substitution produced both α- and β-nucleosides. Only the β-nucleosides were formed from substrates having the reverse stereochemistry at C-3 or lacking the 3-alkyl substituent. Participation of the 3β-oxy substituent in stabilizing the incipient C-1 carbonium ion (or oxonium ion) intermediate has been suggested from analysis of energy-minimized conformations. The Royal Society of Chemistry 2006.
ANN-QSAR model for selection of anticancer leads from structurally heterogeneous series of compounds
Gonzalez-Diaz, Humberto,Bonet, Isis,Teran, Carmen,De Clercq, Erik,Bello, Rafael,Garcia, Maria M.,Santana, Lourdes,Uriarte, Eugenio
, p. 580 - 585 (2007)
Developing a model for predicting anticancer activity of any classes of organic compounds based on molecular structure is very important goal for medicinal chemist. Different molecular descriptors can be used to solve this problem. Stochastic molecular descriptors so-called the MARCH-INSIDE approach, shown to be very successful in drug design. Nevertheless, the structural diversity of compounds is so vast that we may need non-linear models such as artificial neural networks (ANN) instead of linear ones. SmartMLP-ANN analysis used to model the anticancer activity of organic compounds has shown high average accuracy of 93.79% (train performance) and predictability of 90.88% (validation performance) for the 8:3-MLP topology with different training and predicting series. This ANN model favourably compares with respect to a previous linear discriminant analysis (LDA) model [H. Gonzalez-Diaz et al., J. Mol. Model 9 (2003) 395] that showed only 80.49% of accuracy and 79.34% of predictability. The present SmartMLP approach employed shorter training times of only 10 h while previous models give accuracies of 70-89% only after 25-46 h of training. In order to illustrate the practical use of the model in bioorganic medicinal chemistry, we report the in silico prediction, and in vitro evaluation of six new synthetic tegafur analogues having IC50 values in a broad range between 37.1 and 138 μg mL-1 for leukemia (L1210/0) and human T-lymphocyte (Molt4/C8, CEM/0) cells. Theoretical predictions coincide very well with experimental results.
Stereoselective cyclopropanation in the synthesis of 3'-deoxy-3'-C-hydroxymethyl-2',3'-methylene-uridine
Komsta, Zofia,Mayes, Benjamin A.,Moussa, Adel,Shelbourne, Montserrat,Stewart, Alistair,Tyrrell, Andrew J.,Wallis, Laura L.,Weymouth-Wilson, Alexander C.,Yurek-George, Alexander
, p. 4878 - 4880 (2014)
The synthesis of the novel 2',3'-cyclopropane nucleoside 3'-deoxy-3'-C-hydroxymethyl-2',3'-methylene-uridine is described. Stereoselective construction of the cyclopropane ring was achieved via Simmons-Smith cyclopropanation of a benzyl protected silyl enol ether, which was itself derived from 1,2-O-isopropylidene-α-D-xylofuranose.
The silyl method for the synthesis of 1[-2(phenoxy)ethyl]uracils
Novikov,Ozerov
, p. 905 - 908 (2005)
A modification of the method for the synthesis of N(1)- substituted derivatives of uracil is proposed using the Gilbert-Johnson reaction, which consists of the alkylation of 5-substituted 2,4- bis(trimethylsiloxy)pyrimidines with 1-bromo-2-(phenoxy)ethanes of low reactivity at 180-185° without solvent. The corresponding 1-[2-(phenoxy)ethyl]uracils, which were obtained in 55-74% yield, contained no impurities of the N(1), N(3)-disubstituted compounds. 2005 Springer Science+Business Media, Inc.
SYNTHESIS, ANTITUMORIGENIC ACTIVITY, AND ELECTROCHEMICAL PROPERTIES OF URACIL DERIVATIVES OF THE FURAN SERIES
Trushule, M.,Kupche, E.,Augustane, I.,Verovskii, N. V.,Lukevits, E.,et al.
, p. 1358 - 1364 (1991)
1-(Tetrahydrofuryl) derivatives of 5-trimethylgermyl(silyl)uracil and uracil derivatives of 3-(5-nitro-2-furyl)acrylic acid, as well as 1-(γ-triethylgermyl)- and 1-(γ-triethoxysilyl)propylcarbamoyl-5-fluorouracils, were synthesized.Six of the 14 new investigated compounds have high cytotoxic activity in a culture of melanoma B16 cells. 5-Fluorouracil derivatives of 3-(5-nitro-2-furyl)acrylic acid display antitumorigenic activity with respect to lympholeucosis P388 that is comparable to the activity of ftorafur.It was demonstrated by electrochemical studies that the antitumorigenic activity is not determined by the redox properties of the investigated compounds.
Natural phosphate as Lewis acid catalyst: A simple and convenient method for acyclonucleoside synthesis
Alahiane,Rochdi,Taourirte,Redwane,Sebti,Lazrek
, p. 3579 - 3581 (2001)
A new and efficient method for the synthesis of N-1/N-9-[(2-acetoxyethoxy)methyl]pyrimidine/purine using natural phosphate as Lewis acid catalyst was developed.
