共查询到20条相似文献,搜索用时 15 毫秒
1.
Velcicky J Lanver A Lex J Prokop A Wieder T Schmalz HG 《Chemistry (Weinheim an der Bergstrasse, Germany)》2004,10(20):5087-5110
A diversity-oriented, enantioselective synthesis of new (monoprotected) carbocyclic nucleoside analogues (CNAs) with the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethylcyclopent-2-en-1-yl scaffold was developed. As a key intermediate, racemic (5SR,8RS)-8-allyloxy-2-trimethylsilyl-7-oxa-bicyclo[3.3.0]-oct-1-en-3-one was prepared from 1,1-diallyloxy-3-trimethylsilyl-2-propyne in a cobalt-mediated Pauson-Khand reaction. The enantiomerically pure material was obtained through efficient kinetic resolution (selectivity factor s >/= 40 at -78 degrees C) by means of an oxazaborolidine-catalyzed borane reduction (CBS reduction) with catecholborane. The absolute configuration of the resolved products was determined by CD spectroscopy, Mosher ester analysis, and chemical correlation. Subsequent steps involve diastereoselective ketone reduction and fully regio- and diastereoselective introduction of the nucleobase through Pd(0)-catalyzed allylic substitution. The generality of the method was demonstrated by preparation of CNAs in both enantiomeric series with all five natural nucleobases, as well as 5-bromouracil, 5-fluorouracil, and 6-chloropurine. Screening of the various compounds in a cytotoxicity assay with BJAB and ALL tumor cell lines revealed that some of the compounds possess pronounced antitumoral properties (LD50 values down to 9 microM, as determined by lactate dehydrogenase release after 48 h). By measuring DNA fragmentation, it could be shown that the activity results from induction of apoptosis. 相似文献
2.
[reaction: see text] A fast and efficient synthetic route to novel Northern locked carbocyclic nucleosides (as precursors of carbocyclic locked nucleic acids or cLNAs) is described. The target nucleoside with a oxabicyclo[2.2.1]heptane ring system was prepared from a simple starting material, diethyl malonate. Ring closure by intramolecular O-alkylation provided the target ring system as the major isomer over the [3.2.0] oxetane system. The adenine moiety was introduced through a reactive triflate after inversion of the stereochemistry of the corresponding alcohol by oxidation and reduction. 相似文献
3.
Proton NMR spectra of some carbocyclic nucleoside analogs of tuberculin have been analyzed at 100 MHz in DMSO-d6. The spectral characteristics and nuclear Overhauser effects indicate a preferential syn conformation about the glycosidic bond when a hydroxyl group, oriented toward the base, is available for intramolecular hydrogen bond formation. 相似文献
4.
Lorenzo De Napoli Luciano Mayol Gennaro Piccialli Mos Rossi Ciro Santacroce 《Journal of heterocyclic chemistry》1986,23(5):1401-1403
Two new tetrazolopyrimidinedeoxynucleosides were synthesized and their physico-chemical data are described. Results of preliminary analyses of their biological properties are also reported. 相似文献
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An expedient synthesis of 2-deoxy (10) and 3-deoxy (11) cyclohexenyl analogues of 2-deoxy and 3-deoxy-d-ribose sugar from commercially available starting materials is reported. Highly efficient enzymatic resolution of the key compound 10 is described using lipase under hydrolytic conditions. The robust methodology applied here will be useful to synthesize cyclohexenyl nucleosides, which possess potent antiviral activity and are capable of gene silencing via RNAi or antisense applications. 相似文献
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Hergueta AR Fernandez F López C Balzarini J De Clercq E 《Chemical & pharmaceutical bulletin》2001,49(9):1174-1177
(1S,1'R)-cis-1-(3'-aminomethyl-2',2'-dimethylcyclobutyl)ethanol (1) and (1S,1'R)-cis-1-[3'-(2-aminoethyl)-2',2'-dimethylcyclobutyl]ethanol (2) were used as precursors in the synthesis of cyclobutyl nucleoside analogues containing adenine and 8-azaadenine moieties, which were tested as antiviral and antitumoral agents in a variety of assay systems. Compounds 8 and 9 displayed significant activity against respiratory syncytial virus, and compounds 14 and 15 were moderately active against vaccinia virus. 相似文献
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Yuri Moggio Laura Legnani Bruna Bovio Misal Giuseppe Memeo Paolo Quadrelli 《Tetrahedron》2012,68(5):1384-1392
The synthesis of isoxazolino-carbocyclic nor-nucleosides incorporating an anthracene moiety was properly tuned through nitrosocarbonyl intermediates chemistry, and a variety of analogues were attained starting from stereodefined heterocyclic aminols through the linear construction of purine heterocyclic rings. The synthesis hinges on the exo selective 1,3-dipolar cycloaddition of the stable anthracenenitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene and simple elaborations of the cycloadducts. A selection of nucleoside derivatives were initially tested for their inhibitory activity against a variety of viruses, including Hepatitis B and C, Human Papilloma virus as well as Influenza viruses of type A and B. Modest anti-viral activities were observed in Hepatitis assays while the activities in the cases of Influenza viruses were almost negligible. Good anti-viral activity was found for compound 11bC with no cellular toxicity at the dose tested in the case of Human Papilloma virus. 相似文献
12.
Using 3-O-methyl-D-chiro-inositol as starting material, the title compound 5 was synthesized by condensation of adenine and methanesulfonate 3. Additionally, compounds 8 and 9 were prepared through the opening of the epoxide ring in 7 by adenine. The key intermediate 7 was obtained in good yield via an epoxidation from mono-mesylate 6. The process of opening of epoxide ring appeared to be regioselective in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU).
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Translated from Chemistry, 2008, 71(2): 150–153 相似文献
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Handler N Jaeger W Puschacher H Leisser K Erker T 《Chemical & pharmaceutical bulletin》2007,55(1):64-71
Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that cyclooxygenase-1 (COX-1) plays an important role in inflammation and carcinogenesis. In order to find more selective COX-1 inhibitors a series of novel curcumin derivatives was synthesized and evaluated for their ability to inhibit this enzyme using in vitro inhibition assays for COX-1 and COX-2 by measuring PGE(2) production. All curcumin analogues showed a higher rate of COX-1 inhibition. The most potent curcumin compounds were (1E,6E)-1,7-di-(2,3,4-trimethoxyphenyl)-1,6-heptadien-3,5-dione (4) (COX-1: IC(50) = 0.06 microM, COX-2: IC(50) > 100 microM, selectivity index>1666) and (1E,6E)-methyl 4-[7-(4-methoxycarbonyl)phenyl]-3,5-dioxo-1,6-heptadienyl]benzoate (6) (COX-1: IC(50) = 0.05 microM, COX-2: IC(50) > 100 microM, selectivity index > 2000). Curcumin analogues therefore represent a novel class of highly selective COX-1 inhibitors and promising candidates for in vivo studies. 相似文献
15.
A new synthetic route to (North)-methanocarba nucleosides designed as A3 adenosine receptor agonists
Joshi BV Moon HR Fettinger JC Marquez VE Jacobson KA 《The Journal of organic chemistry》2005,70(2):439-447
Activation of the A3 adenosine receptor (AR) is associated with cerebroprotective, cardioprotective, and anticancer effects. Among potent and selective A3 AR agonists are novel methanocarba adenosine analogues in which the conformation of a pseudo-ribose moiety is locked in the North (N) hemisphere of the pseudorotational cycle. 5'-Uronamide (N)-methanocarba nucleosides, such as MRS1898 and MRS2346, are examples of full agonists of the human A3 AR. An improved convergent approach from easily accessible 2,3-O-isopropylidene-d-erythrose (2b), and the combination of a strategic intramolecular cyclopropanation step plus the acid-catalyzed isomerization of an isopropylidene group, provided a suitable pseudosugar precursor (23) for the synthesis of MRS1898, MRS2346, and related analogues. This new synthetic route uses readily available building blocks and opens the way for the preparation of a variety of targets on a reasonable scale. 相似文献
16.
H. Kapeller H. Baumgartner C. Marschner R. Pucher H. Griengl 《Monatshefte für Chemie / Chemical Monthly》1997,128(8-9):953-960
Summary Various carbocyclic nucleosides withxylo-configuration have been synthesized using ring opening of 5-O-acetyl-1,2-anhydro-3-O-benzylcarba--DL-xylo-pentofuranose (6) by thymine, uracil, 4-N-benzoylcytosine, adenine, 6-N-benzoyladenine, and 2-amino-6-chloropurine in alkaline medium. For this purpose, the use of triethylaluminum is introduced into carbanucleoside chemistry. The new method proved to be superior over the application of sodium hydride and potassium or caesium carbonate.
Ringöffnung von Cyclopentenoxiden mit Pyrimidinen und Purinen als Syntheseweg zu carbocyclischen Nucleosidanalogen
Zusammenfassung Ringöffnung von 5-O-Acetyl-1,2-anhydro-3-O-benzylcarba--DL-xylo-pentofuranose (6) mit Thymin, Uracil, 4-N-Benzoylcytosin, Adenin, 6-N-Benzoyladenin und 2-Amino-6-chlorpurin in alkalischem Medium ergab die entsprechendenxylo-konfigurierten carbocyclischen Nucleoside. Als Hilfsbase wurde Triethylaluminium verwendet, was deutliche Vorteile gegenüber der Verwendung von Natriumhydrid und Kalium- oder Cäsiumcarbonat bezüglich Produktreinheit und Ausbeute bietet.相似文献
17.
Suzuki M Ohuchi Y Asanuma H Kaneko T Yokomori S Ito C Isobe Y Muramatsu M 《Chemical & pharmaceutical bulletin》2001,49(1):29-39
A series of 8'-substituted N-(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized. The 5-HT4 receptor agonistic activity was evaluated using the isolated guinea pig ileum preparation. Of the compounds synthesized, N-(endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (15a, TS-951) exhibited the most potent serotonin 5-HT4 receptor agonistic activity. This compound had a high affinity for the serotonin 5-HT4 receptor although it had no affinities for other broad spectrum receptors. Furthermore, it remarkably enhanced gastrointestinal motility in conscious fed dogs without unfavorable effects that non-selective serotonin 5-HT4 receptor agonist has. TS-951 may be useful in improving gastrointestinal dysfunction. 相似文献
18.
《Tetrahedron letters》1986,27(36):4291-4292
(±)-1-[(1α,3α,4α)-3-Hydroxy-4-hydroxymethlcyclopentyl]- (1H,3H-pyrimidin-2,4-dione (6) was synthesized starting from endo-5-norbornen-2-yl acetate via the urea derivative 5 in 32% overall yield. 相似文献
19.
Verónica Valdivia Aida Rivera Ali Loukaci Leticia Quintero 《Tetrahedron letters》2005,46(38):6511-6514
Based on an unusual furanose ring opening of 1,2-O-isopropylidene pentofuranoside derivatives, a preparation scheme of a new series of furanopyrimidine nucleoside analogues has been devised. 相似文献
20.
Boyle GA Edlin CD Li Y Liotta DC Morgans GL Musonda CC 《Organic & biomolecular chemistry》2012,10(9):1870-1876
An enantiopure β-lactam with a suitably disposed electron withdrawing group on nitrogen, participated in a π-allylpalladium mediated reaction with 2,6-dichloropurine tetrabutylammonium salt to afford an advanced cis-1,4-substituted cyclopentenoid with both high regio- and stereoselectivity. This advanced intermediate was successfully manipulated to the total synthesis of (-)-Abacavir. 相似文献