- N-Methylation and N-oxidation of the less reactive nitrogen atom of a 2,3'-bipyridine. Two general methods for polyazines
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5-Carbamoyl-2,3'-bipyridine model compound was N-methylated or N-oxidized at the less reactive 2-pyridyl ring for the first time. Two different schemes were developed.
- Zoltewicz,Cruskie Jr.
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Read Online
- One-Pot Deoxygenation and Substitution of Alcohols Mediated by Sulfuryl Fluoride
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Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO2F2-mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO2F2-mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52-95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO2F2-mediated alcohol activation and enables substitution of primary and secondary alcohols in 54-95% yield. Chiral secondary alcohols undergo a highly stereospecific (90-98% ee) double nucleophilic displacement with an overall retention of configuration.
- Epifanov, Maxim,Mo, Jia Yi,Dubois, Rudy,Yu, Hao,Sammis, Glenn M.
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p. 3768 - 3777
(2021/03/01)
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- Indium(III)-catalyzed reductive bromination and iodination of carboxylic acids to alkyl bromides and iodides: Scope, mechanism, and one-pot transformation to alkyl halides and amine derivatives
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Highly effective indium(III)-catalyzed reductive bromination or iodination of a variety of carboxylic acids with 1,1,3,3-tetramethyldisiloxane (TMDS) and a source of bromine or iodine is described. This functional group interconversion has high tolerance for several functional groups, such as halogens, a hydroxy group, a nitro group, an olefin part, and a sulfide moiety. This indium catalytic system is also applicable to the reductive iodination of aldehyded, acyl chlorides, and esters. Furthermore, this reducing system can be applied to the one-pot synthesis of alkyl halides and amine derivatives via the addition of nucleophiles. Insight into the reaction mechanism was gained via the time course of 1H and 13C NMR monitoring experiments and the corresponding stepwise reactions.
- Moriya, Toshimitsu,Yoneda, Shinichiro,Kawana, Keita,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
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p. 10642 - 10650
(2013/11/19)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir 1.1) channel. The compounds act as diuretics and natriuretics and are valuable pharmaceutically active compounds for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension and conditions resulting from excessive salt and water retention.
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Page/Page column 50
(2013/05/21)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds act as diuretics and natriuretics and are valuable pharmaceutically active compounds for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension and conditions resulting from excessive salt and water retention.
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Page/Page column 33
(2013/05/21)
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- Non-standard nucleoside analogs with reduced epimerization
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This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with compositions of matter that present the donor-donor-acceptor, donor-acceptor-donor, and acceptor-donor-donor non-standard hydrogen bonding patterns on pyrimidine analogs, where nucleoside analogs bearing these pyrimidine analogs do not epimerize as easily as those known in the art. The heterocycles on these nucleoside analogs are diaminopyridines and aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.
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- Synthesis of tetrahydronaphthalene lignan esters by intramolecular cyclization of ethyl p-azidophenyl-2-phenylalkanoates and evaluation of the growth inhibition of human tumor cell lines
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Figure Presented. Intramolecular cyclization via nitrenium ion of 2-phenylpentanoic/2-phenylbutanoic acid esters with a terminal p-azidophenyl group gives direct access to tetrahydronaphthalene lignan esters. The p-azidophenyl-substituted butanoate led to
- Pinto, Orlando,Sardinha, Jo?o,Vaz, Pedro D.,Piedade, Fátima,Calhorda, Maria J.,Abramovitch, Rudolph,Nazareth, Nair,Pinto, Madalena,Nascimento, Maria S. J.,Rauter, Amélia P.
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experimental part
p. 3175 - 3187
(2011/07/30)
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- Selective conversion of alcohols into alkyl iodides using a thioiminium salt
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(Chemical Equation Presented) Treatment of a range of primary and secondary alcohols with MeSCH=NMe2+ I- affords the corresponding alkyl iodides in excellent yield with straightforward purification. Selective formation of a primary iodide in the presence of a secondary alcohol can be achieved.
- Ellwood, Adam R.,Porter, Michael J.
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supporting information; experimental part
p. 7982 - 7985
(2010/02/28)
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- Thiazolidinones, their production and use as pharmaceutical agents
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Thiazolidinones of general formula I in which Q, A, B, X, R1 and R2 have the meanings that are indicated in the description, as well as those of general formula IA in which Q, A, B, X, R1 and R2a have the meanings that are indicated in the description, their production and use as inhibitors of the polo-like kinase (PLK) for treating various diseases as well as intermediate products for the production of thiazolidinones are described.
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- N-Methylated 2,3'-Bipyridinium Ion. First Synthesis of the More Sterically Hindered Isomer
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1-Methyl-2,3'-bipyridinium salts can be prepared by deprotection of diquaternized precursors.Protecting groups are eliminated from the 1'-position under basic conditions; they include either p-nitrostyrene or 1-methyl-2-vinylpyridinium ion.In DMSO-d6-CD3O
- Zoltewicz, John A.,Bloom, Linda B.,Kem, William R.
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p. 2392 - 2395
(2007/10/02)
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- DNA-directed alkylating agents. 2. Synthesis and biological activity of platinum complexes linked to 9-anilinoacridine
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Two different classes of cis-diaminedichloroplatinum(II) complexes linked to the DNA-intercalating chromophore 9-anilinoacridine have been synthesized and evaluated as DNA-targeted antitumor agents. Two different Pt chelating ligands were investigated (based on 1,2-ethanediamine and 1,3-propanediamine), designed to deliver the Pt in an orientation likely to respectively enhance either intrastrand or interstrand cross-linking. Although both sets of ligands were somewhat unstable under neutral or basic conditions with respect to disproportionation, the corresponding Pt complexes, once prepared, appeared to be quite stable. All the Pt complexes were monitored for purity by TLC, HPLC, and FAB mass spectra, and the mode of Pt coordination was established by 195Pt NMR spectroscopy. The complexes appeared to cause simultaneous platination and intercalative unwinding of plasmid DNA. In vitro studies were carried out with both wild-type and cisplatin-resistant P388 cell lines. Whereas cisplatin itself and the ethylenediamine and 1,3-propanediamine complexes used as standards were about 10-fold less active against the resistant line, the ethylenediamine-linked Pt complexes showed no differential toxicity between the two lines and the propanediamine-linked complexes showed significant differentials (up to 8-fold) in favor of the cisplatin-resistant line. However, these were no greater than those shown by the unplatinated ligands themselves. The majority of the acridine complexes were inactive in vivo against the wild-type P388 leukemia. They were very insoluble, and although a suitable formulation was found, this may have been a factor. It is also possible that these compounds bind in such a way as to direct the Pt away from the major groove.
- Palmer,Lee,Johnson,Baguley,Wickham,Wakelin,McFadyen,Denny
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p. 3008 - 3014
(2007/10/02)
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- THE p-NITROPHENYLETHYL (NPE) GROUP. A VERSATILE NEW BLOCKING GROUP FOR PHOSPHATE AND AGLYCONE PROTECTION IN NUCLEOSIDES AND NUCLEOTIDES
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The syntheses of new monomeric building blocks for oligonucleotide synthesis via the phosphotriester approach containing the p-nitrophenylethyl group for phosphate and aglycone protection are described.Blocking of the amide function in guanosines at O6 can be achieved by the Mitsunobu reaction forming the corresponding O6-p-nitrophenylethyl derivatives (4,5,10).Sugar-protected thymidine (16) and uridine (17) have been alkylated at O4 in an SN1-type reaction by p-nitrophenylethyl iodide-silver carbonate in benzene to form the O4-p-nitrophenylethyl derivatives (18,19).Protection of the amino group in 2'-deoxycytidine (25) and cytidine (26) can be performed directly by 1-(p-nitrophenylethoxycarbonyl)-benzotriazole in DMF to obtain the corresponding carbamates (27,28) as a new type of N4-acylated cytidine derivative. p-Nitrophenylethoxycarbonylation of the amino group in 2'-deoxyadenosine (33) and adenosine (34) requires previous sugar protection by acyl or silyl groups and can then be achieved by p-nitrophenylethyl chloroformate or better by 1-methyl-3-p-nitrophenylethoxycarbonylimidazolium chloride to form N6-p-nitrophenylethoxycarbonyladenosines (38,39,40,42).The various p-nitrophenylethyl blocking groups are stable under mild hydrolytic conditions (e.g. ammonia and triethylamine) but can be cleaved selectively by DBU or DBN in aprotic solvents. 5'-O-Monomethoxytritylation (12,29,43) as well as phosphorylations at the 3'-OH group can be effected to give the corresponding 3'-(2,5-dichlorophenyl,p-nitrophenylethyl)-phosphotriesters (13,22,30,44) also in high yields.Oximate cleavage of the latter compounds to the phosphodiesters (14,24,32,46) and detritylation to the 5'-unblocked phosphotriesters (15,23,31,45) do not affect the aglycone protecting groups, thereby demonstrating their general versatility.The newly synthesized compounds have been characterized on the basis of their elementary analyses (C,N,H), and UV- and 1H-HMR-spectra.
- Himmelsbach, Frank,Schulz, Bernd S.,Trichtinger, Thomas,Charubala, Ramamurthy,Pfleiderer, Wolfgang
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- Elimination Reactions of N-(2-(p-Nitrophenyl)ethyl)alkylammonium Ions by an E1cB Mechanism
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Elimination reactions of N-(2-(p-nitrophenyl)ethyl)quinuclidinium and 2-(p-nitrophenyl)ethyl)trimethylammonium ions catalyzed by hydroxide ion and buffer bases undergo a change in rate-determining step from an (E1cB)1 to an (E1cB)R mechanism with increasing buffer concentration in aqueous solution.Exchange of labeled 2H or 3H with solvent was shown for the quinuclidine and trimethylamine derivatives in the presence of buffers.Large inverse solvent deuterium isotope effects on the initial rate confirm the E1cB mechanism with leaving group expulsion partly or entirely rate determining under the same conditions.The dependence of log k on the pK of the leaving quinuclidine gives β1lg = -0.17 for k1 (proton abstraction), βp = 0.47 for k-1/k2 (partitioning of the intermediate zwitterion), and βlg = -0.64 for k1k2/k-1 (rate-determining expulsion of the leaving group).The ratio k2/k-1 increases from 10 to 59 with increasing ethanol concentration up to 40percent as the result of an increase in the rate of amine expulsion from the zwitterionic intermediate in the presence of organic cosolvents; k2/k-1 also increases with increasing temperature.Rate constants for elimination of 2-(p-nitrophenyl)ethyl halides increase with increasing leaving ability of the halide, consistent with a concerted E2 mechanism for all but the fluoride derivative.
- Keeffe, James R.,Jencks, William P.
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p. 265 - 279
(2007/10/02)
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- SYNTHESIS OF O4-p-NITROPHENYLETHYL THYMIDINE AND URIDINE DERIVATIVES
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O4-Protection in thymidine and uridine derivatives has been achieved by the p-nitro-phenylethyl group in a silver-ion catalysed alkylation reaction to form valuable building blocks for oligonucleotides syntheses.
- Schulz, Bernd S.,Pfleiderer, Wolfgang
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p. 3587 - 3590
(2007/10/02)
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