- Oxidative and hydrolytic cleavage of cyclopropane and spirocyclobutane derivatives of 6,8-dioxabicyclo[3.2.1]octane, the products of transformation of levoglucosenone
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A new method for the synthesis of (1R,4S,5S)-4-hydroxymethyl-3- oxabicyclo[3.1.0]hexan-2-one, the cyclopropane analog of (S)-5-hydroxypent-2-en- 4-olide, has been suggested based on oxidation of (1S,2S,4R,6R)-7,9- dioxatricyclo[4.2.1.02,4]nonan-5-one. Oxidation of cyclobutanones, spirojoined with the fragments of 6,8-dioxabicyclo[3.2.1]oct-2-ene, 6,8-dioxabicyclo[3.2.1]octane (at position 4), or 7,9-dioxatricyclo[4.2.1.0 2,4]nonane (at position 5), upon the action of m-chloroperoxybenzoic acid or the KMnO4-H2SO4-H2O system leads to the corresponding spirojoined butanolides in 73-85% yields. The same cyclobutanones easily undergo the four-membered ring opening upon the action of dilute H2SO4 at 50-90 °C to form 6,8-dioxabicyclo[3.2. 1]octane-4-or 7,9-dioxatricyclo[4.2.1.02,4]nonane-5-propionic acid.
- Novikov,Rafikov,Shulishov,Tomilov
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- Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation of O-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR
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Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been dee
- Annunziato, Giannamaria,Pieroni, Marco,Benoni, Roberto,Campanini, Barbara,Pertinhez, Thelma A.,Pecchini, Chiara,Bruno, Agostino,Magalh?es, Joana,Bettati, Stefano,Franko, Nina,Mozzarelli, Andrea,Costantino, Gabriele
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- Cyclopropane derivatives as potential human serine racemase inhibitors: Unveiling novel insights into a difficult target
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d-Serine is the co-agonist of NMDA receptors and binds to the so-called glycine site. d-Serine is synthesized by human serine racemase (SR). Over activation of NMDA receptors is involved in many neurodegenerative diseases and, therefore, the inhibition of SR might represent a novel strategy for the treatment of these pathologies. SR is a very difficult target, with only few compounds so far identified exhibiting weak inhibitory activity. This study was aimed at the identification of novel SR inhibitor by mimicking malonic acid, the best-known SR inhibitor, with a cyclopropane scaffold. We developed, synthesized, and tested a series of cyclopropane dicarboxylic acid derivatives, complementing the synthetic effort with molecular docking. We identified few compounds that bind SR in high micromolar range with a lack of significant correlation between experimental and predicted binding affinities. The thorough analysis of the results can be exploited for the development of more potent SR inhibitors.
- Beato, Claudia,Pecchini, Chiara,Cocconcelli, Chiara,Campanini, Barbara,Marchetti, Marialaura,Pieroni, Marco,Mozzarelli, Andrea,Costantino, Gabriele
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p. 645 - 652
(2016/05/09)
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- An efficient and improved process for the scale-up preparation of cis-cyclopropanediamine dihydrochloride
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An effective and improved process for the preparation of cis-cyclopro panediamine dihydrochloride was developed in a 100 g scale. The key step in the process is the preparation of ciscyclopropane-1, 2-dicarboxylic acid from a mixture of cis- and transisomers by the formation of cyclic acidic anhydride. The whole process and all of the procedures are economical, industrially reliable and easily scaled up.
- Wang, Fan,Xu, Xiao-Ying,Wang, Fei-Ying,Peng, Lin,Zhang, Yong,Wang, Liang-Liang,Wang, Li-Xin
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p. 741 - 744
(2016/03/25)
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- Design, synthesis and activity of novel derivatives of Oxybutynin and Tolterodine
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Novel derivatives of Tolterodine (1) and Oxybutynin (2) have been designed using conformationally restricted azabicyclics as replacement for open-chain amines. The synthesis and structure-activity relationships are presented.
- Kaur, Kirandeep,Aeron, Shelly,Bruhaspathy, Miriyala,Shetty, Shankar J.,Gupta, Suman,Hegde, Laxminarayan H.,Silamkoti, Arun D. V.,Mehta, Anita,Chugh, Anita,Gupta, Jang B.,Sarma,Kumar, Naresh
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p. 2093 - 2096
(2007/10/03)
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- Design and Synthesis of Novel Dimeric Morphinan Ligands for κ and μ Opioid Receptors
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A novel series of morphinans were synthesized, and their binding affinity at and functional selectivity for μ, δ, and κ opioid receptors were evaluated. These dimeric ligands can be viewed as dimeric morphinans, which were formed by coupling two identical
- Neumeyer, John L.,Zhang, Ao,Xiong, Wennan,Gu, Xiao-Hui,Hilbert, James E.,Knapp, Brian I.,Negus, S. Stevens,Mello, Nancy K.,Bidlack, Jean M.
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p. 5162 - 5170
(2007/10/03)
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- Benzamides derived from 1,2-diaminocyclopropane as novel ligands for human D2 and D3 dopamine receptors
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Benzamides (3a-f) derived from 4-amino-5-chloro-2-methoxybenzoic acid and either cis or trans 1,2-diaminocyclopropane were synthesised and were evaluated in binding assays employing, bovine striatal D2 receptors, recombinant human hD2/sub
- Yang, Donglai,Kefi, Slaheddine,Audinot, Valerie,Millan, Mark-J.,Langlois, Michel
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p. 321 - 327
(2007/10/03)
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- Synthesis of racemic carbocyclic cyclopropanoid nucleoside analogues
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As further representatives of a novel class of carbocyclic nucleoside analogues (±)-cis- and (±)-trans-(2-hydroxymethylcyclopropyl)-uracil, -thymine, and -inosine were synthesized from the corresponding dialkyl 1,2-cyclopropane dicarboxylates.
- Csuk, Rene,Von Scholz, Yvonne
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p. 7193 - 7206
(2007/10/02)
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- Synthesis of Cyclopropyl Carbocyclic Nucleosides
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As representatives of a novel class of carboxylic nucleoside analogues (+/-)-cis-, (-)-cis and (+/-)-trans 9-(2-hydroxymethylcyclopropyl)-adenine (= -methanol) were synthesized from the corresponding dialkyl 1,2-cyclopropane dicarboxylates.
- Csuk, Rene,Scholz, Yvonne von
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p. 10431 - 10442
(2007/10/02)
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- Aragusterol A: A Potent Antitumor Marine Steroid from the Okinawan Spronge of the Genus, Xestospongia
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Aragusterol A, a new marine steroid possesing antitumor activity , was isolated from Okinawan sponge of the genus Xestospongia and its structure was determined by spectroscopic analysis and chemical evidence.The compoumd strongly inhibited the cell proliferation of KB, HeLaS3, P388 and LoVo cells in vitro, and also showed potent in vivo antitumor activity toward P388 in mice and L1210 in mice.
- Iguchi, Kazuo,Fujita, Michinari,Nagakoa, Hiroto,Mitome, Hidemichi,Yamada, Yasuhi
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p. 6277 - 6280
(2007/10/02)
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- Cyclopropanediamines, 3. - Pure Diastereomers of 1,2-Cyclopropanedicarboxylic Acids and Derivatives
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Efficient preparations of pure diastereomers of dimethyl 1,2-cyclopropanedicarboxylates 2, dicarboxylic acids 3, dicarbonyl dichlorides 4, and dihydrazides 5 are reported.Mixtures of diastereomers of dimethyl dicarboxylates 2a, b, d, e are obtained from α,β-unsaturated methyl carboxylates 7 and methyl α-chlorocarboxylates 8 as well as from 7c, d and the sulfur ylide 10 (2c, d).The diastereomers are separated by fractionating distillations (2a, b, c, e) or crystallization (2d) on a 100-g to 1-kg scale (d.e. >99percent).Only low yields of 2c are obtained in the reaction of methyl crotonate (7c) with methyl α-chloroacetate (8a), since 7c predominantly dimerizes to afford 12.The diesters 2 are converted into the pure diastereomeric diacids 3, dicarbonyl dichlorides 4, and dihydrazides 5. 3,3-Dimethyl-cis-1,2-cyclopropanedicarboxylic acid (cis-3f) is obtained by trans-->cis isomerization of trans-3f with the help of acetic anhydride and sodium acetate as catalyst.The configurations of 2-6 and 12 are confirmed by 1H NMR spectroscopy.Derivatives of cis-1,2-dimethyl-1,2-cyclopropanedicarboxylic acid tend to form bicyclic products.Thus, the reaction of cis-3e with phosphorus pentachloride yields mainly the cyclic anhydride 6e and only small amounts of the dicarbonyl dichloride cis-4e.Furthermore, the dihydrazide cis-5e slowly cyclizes in the solid state to give the N-aminoimide 13 and hydrazine, a reaction which is fast in solution.Pure 13 is obtained by thermolysis of cis-5e at 60-65 deg C under high vacuum.
- Saal, Wolfgang von der,Reinhardt, Robert,Seidenspinner, Hubert-Matthias,Stawitz, Josef,Quast, Helmut
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p. 703 - 712
(2007/10/02)
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- Synthesis and antiherpetic activity of (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine and related compounds
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A series of analogues of acyclovir and ganciclovir were prepared in which conformational constrainst were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related base-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a. Another group, typified by (±)-9-[[(E)-2-(hydroxymethyl)cyclopropyl]methyl]adenine (17b), possessed modest antiviral activity despite an apparent inability to be enzymatically phosphorylated. The relationship of side-chain conformation and flexibility to biological activity in this series is discussed.
- Ashton,Canning Meurer,Cantone,Field,Hannah,Karkas,Liou,Patel,Perry,Wagner,Walton,Tolman
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p. 2304 - 2315
(2007/10/02)
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- Thermolysis of 7-Phenyl-2,3,7-triazabicyclooct-2-ene-6,8-dione
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Thermolysis of the title compound in boiling xylene (138 deg) produces a 7.7/10.1/1.0 mixture of the N-phenylimides of cis-1,2-cyclopropanedicarboxylic acid, citraconic acid, and itaconic acid.The imides of citraconic and itaconic acids are produced by hydrogen shifts.A completely concerted mechanism involving simultaneous hydrogen shift and cleavage of both C-N bonds is unlikely in the present case because both hydride-shift products are formed and because the optimal arrangement for the hydrogen shift requires deformation of the imide ring and loss of imide resonance.The C-N bond strengths in the title compound should be quite different.The products can arise either from two parallel pathways involving nitrogen-containing dipoles or from a single nitrogen-free trimethylene fragment.
- Majchrzak, Michael W.,Kotelko, Antoni
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p. 1475 - 1477
(2007/10/02)
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