- Synthesis and evaluation of novel ellipticines as potential anti-cancer agents
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Drugs that inhibit DNA topoisomerase I and DNA topoisomerase II have been widely used in cancer chemotherapy. We report herein the results of a focused medicinal chemistry effort around novel ellipticinium salts which target topoisomerase I and II enzymes with improved solubility. The salts were prepared by reaction of ellipticine with the required alkyl halide and evaluated for DNA intercalation, topoisomerase inhibition and growth inhibition against 12 cancer cell lines. Results from the topoisomerase I relaxation assay indicated that all novel ellipticine derivatives behaved as intercalating agents. At a concentration of 100 μM, specific topoisomerase I inhibition was not observed. Two of the derivatives under investigation were found to fully inhibit the DNA decatenation reaction at a concentration of 100 μM, indicative of topoisomerase II inhibition. N-Alkylation of ellipticine was found to enhance the observed growth inhibition across all cell lines and induce growth inhibition comparable to that of Irinotecan (CPT-11; GI50 1-18 μM) and in some cell lines better than Etoposide (VP-16; GI50 = 0.04-5.2 μM). 6-Methylellipticine was the most potent growth inhibitory compound assessed (GI50 = 0.47-0.9 μM). N-Alkylation of 6-methylellipticine was found to reduce this response with GI50 values in the range of 1.3-28 μM.
- Deane, Fiona M.,O'Sullivan, Elaine C.,Maguire, Anita R.,Gilbert, Jayne,Sakoff, Jennette A.,McCluskey, Adam,McCarthy, Florence O.
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p. 1334 - 1344
(2013/05/21)
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- Efficient synthesis of primary amides from carboxylic acids using n,n'-carbonyldiimidazole and ammonium acetate in ionic liquid
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A novel and efficient method for the conversion of carboxylic acids to primary amides using N,N'-carbonyldiimidazole in combination with ammonium acetate/triethyl amine system in [BMIM]BF4 is developed.
- Lee, Kwan Soo,Kim, Kee D.
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p. 3497 - 3500
(2011/09/30)
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- Hydrosilanes are not always reducing agents for carbonyl compounds but can also induce dehydration: A ruthenium-catalyzed conversion of primary amides to nitriles
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A practical procedure for production of nitriles is offered by the triruthenium carbonyl cluster catalyzed dehydration of primary carboxamides with hydrosilanes under neutral conditions. This is the first example that a transition-metal-catalyzed activation of Si-H bonds does not lead to the reduction of carbonyl compounds but to dehydration. Possible mechanisms for the dehydration is discussed on the basis of NMR spectroscopic detection of intermediary species. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Hanada, Shiori,Motoyama, Yukihiro,Nagashima, Hideo
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supporting information; experimental part
p. 4097 - 4100
(2009/04/10)
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- Ammonium salts from polymer-bound N-hydroxysuccinimide as solid-supported reagents for EDC-mediated amidations
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New ammonium and alkylammonium salts derived from a polymeric N-hydroxysuccinimide (P-HOSu) have been prepared and used for the amidation of carboxylic acids and amino acids mediated by 1-ethyl-3-(3′-dimethylamino-propyl)carbodiimide hydrochloride (EDC). These polymer-supported ammonium salts afforded the corresponding amides in good yield, without detectable α-racemization and with easy recovery of the P-HOSu after the amidation reaction, being especially suitable for the amidation of Fmoc-protected amino acids.
- Chinchilla, Rafael,Dodsworth, David J.,Nájera, Carmen,Soriano, José M.
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p. 463 - 466
(2007/10/03)
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- Efficient synthesis of primary amides using 2-mercaptopyridone-1-oxide-based uronium salts
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S-(1-Oxido-2-pyridinyl)-1,1,3,3-tetramethylthiouronium tetrafluoroborate (TOTT) and hexafluorophosphate (HOTT) are cheap and convenient reagents for the rapid and high-yielding preparation of primary amides when reacted with carboxylic acids and ammonium chloride in the presence of diisopropylethylamine. The reaction is chemoselective and undesired ammonolysis of other sensitive functional groups is not observed. (C) 2000 Elsevier Science Ltd.
- Bailen,Chinchilla,Dodsworth,Najera
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p. 9809 - 9813
(2007/10/03)
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- Electrochemical studies on haloamides. Part II. Electrochemical reduction of N-(1-acetoxy-2,2,2-trichloroethyl)-ω-bromoalkanamides
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The electrochemical reduction of haloamides Br(CH2)nCONHCH(OCOCH3)CCl3 2 - 5 in N,N-dimethylformamide solutions containing tetraethylammonium perchlorate as supporting electrolyte has been investigated at a mercury cathode.Acrylamide 2a, acetoxy- and chloro-amides 3a,b - 5a,b and lactames 3d - 5d were isolated after macroscale electrolysis carried out at a potential corresponding to the first voltammetric peak.The electron exchange between electrode and substrate produces a two-electron cleavage of a C-Cl bond in the CCl3 group, followed by β-elimination of acetate ion.The formation of substituted amides 3a,b - 5a,b was related to the reactivity of acetate and chloride ions as nucleophiles, that of acrylamide 2a and lactams 3d - 5d to the reactivity of acetate ion as a base.
- Casadei, M. A.,Inesi, A.
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- Orthocarbonsaeure-ester mit 2,4,10-Trioxaadamantanstruktur als Carboxylschutzgruppe; Verwendung zur Synthese von substituierten Carbonsaeuren mit Hilfe von Grignard-Reagenzien
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The surprising stability of 2,4,10-trioxa-3-adamantyl derivatives 1 against nucleophilic substitution by organomagnesium compounds is discussed and shown to be caused by unfavourable stereoelectronic and steric factors governing the substitution of these cage compounds (Scheme 2).As a consequence, a number of Grignard reagents 2 containing the carboxyl group masked as 2,4,10-trioxa-3-adamantyl group could be prepared and have been reacted in a second step with various electrophiles (cf.Scheme 4).In the products 7-13 and 15b the carboxyl masking group is removed by mild ac id hydrolysis and saponification (cf.Scheme 3) to yield the corresponding acids 16a-21a, 22, and 23a.Acids 21a and 23a have been further transformed to give the macrocyclic lactones 24 and 26, isolated from Galbanum oleo-gum-resin, and acid 22 to give 12-methyl-13-tridecanolide (25), isolated from Angelica root oil.In addition 1-bromo-ω-(2,4,10-trioxa-3-adamantyl)alkanes 1c and 1b have been used to synthesize (+/-)-methyl recifeiolate (29b) and pure cis-ambrettolic acid ((Z)-32a).
- Voss, Gundula,Gerlach, Hans
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p. 2294 - 2307
(2007/10/02)
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