- (Tert-butoxycarbonylamino)acetonitrile
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The title compound, C7H12N2O2, is a useful intermediate for the synthesis of peptidic nucleic acids containing a backbone composed of repeating (2-amino-ethyl)glycine units. Conjugation within the urethane system is facilitated by near planarity about both C - O and C - N bonds. There is a synperiplanar relationship between the O11 atom of the carbonyl group and the tertiary C7 atom, along with an antiperiplanar relationship between the C5 atom and the C10 methyl group.
- Sood, Geeta,Schwalbe, Carl H.,Fraser, William
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Read Online
- Design, synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids
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The development of hybrid compounds led to the discovery of new pharmacologically active agents for some of the most critical diseases, including cancer. Herein, we describe a new series of oxadiazole-containing structures designed by a molecular hybridiz
- Camacho, Cristián M.,Pizzio, Marianela G.,Roces, David L.,Boggián, Dora B.,Mata, Ernesto G.,Bellizzi, Yanina,Barrionuevo, Elizabeth,Blank, Viviana C.,Roguin, Leonor P.
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p. 29741 - 29751
(2021/10/07)
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- Preparation method and intermediate of benzodiazepine compound
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The invention discloses a preparation method of a benzodiazepine compound and an intermediate compound K. The compound K disclosed by the invention can be used for preparing the compound shown as theformula I in one step at high yield. The preparation met
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Paragraph 0052-0056
(2020/09/16)
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- Decarboxylative Cyanation of Aliphatic Carboxylic Acids via Visible-Light Flavin Photocatalysis
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An operationally simple method is disclosed for the decarboxylative cyanation of aliphatic carboxylic acids at room temperature. Riboflavin tetraacetate, which is an inexpensive organic photocatalyst, promotes the oxidation of carboxylic acids upon visible-light activation. After decarboxylation, the generated radicals are trapped by TsCN, yielding the desired nitriles without any further additive, in a redox-neutral process. Importantly, this protocol can be adapted to flow conditions.
- Ramirez, Nieves P.,K?nig, Burkhard,Gonzalez-Gomez, Jose C.
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supporting information
(2019/03/08)
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- Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl-Functionalized Tetrazines
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The inverse-electron-demand Diels–Alder/pyridazine elimination tandem reaction, in which the allylic substituent on trans-cyclooctene is eliminated following reaction with tetrazines, is gaining interest as a versatile bioorthogonal process. One potential shortcoming of such currently used reactions is their propensity to proceed faster and more efficiently at lower pH, a feature caused by the nature of the tetrazines used. Here, we present aminoethyl-substituted tetrazines as the first pH-independent reagents showing invariably fast elimination kinetics at all biologically relevant pH values.
- Sarris, Alexi J. C.,Hansen, Thomas,de Geus, Mark A. R.,Maurits, Elmer,Doelman, Ward,Overkleeft, Herman S.,Codée, Jeroen D. C.,Filippov, Dmitri V.,van Kasteren, Sander I.
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supporting information
p. 18075 - 18081
(2018/11/23)
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- 7-OXO -6-(SULFOOXY)- 1,6-DIAZABICYCLO [3.2.1] OCTANE CONTAINING COMPOUNDS AND THEIR USE IN TREATMENT OF BACTERIAL INFECTIONS
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Compounds of Formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof, their preparation, and use in treating a bacterial infection are disclosed.
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Page/Page column 33
(2017/06/19)
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- Room temperature decarboxylative cyanation of carboxylic acids using photoredox catalysis and cyanobenziodoxolones: a divergent mechanism compared to alkynylation
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The one-step conversion of aliphatic carboxylic acids to the corresponding nitriles has been accomplished via the merger of visible light mediated photoredox and cyanobenziodoxolones (CBX) reagents. The reaction proceeded in high yields with natural and non-natural α-amino and α-oxy acids, affording a broad scope of nitriles with excellent tolerance of the substituents in the α position. The direct cyanation of dipeptides and drug precursors was also achieved. The mechanism of the decarboxylative cyanation was investigated both computationally and experimentally and compared with the previously developed alkynylation reaction. Alkynylation was found to favor direct radical addition, whereas further oxidation by CBX to a carbocation and cyanide addition appeared more favorable for cyanation. A concerted mechanism is proposed for the reaction of radicals with EBX reagents, in contrast to the usually assumed addition elimination process.
- Le Vaillant, Franck,Wodrich, Matthew D.,Waser, Jér?me
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p. 1790 - 1800
(2017/03/09)
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- Decarboxylative alkynylation and cyanation of carboxylic acids using photoredox catalysis and hypervalent iodine reagents
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Alkynes and nitriles are important functional groups that serve as versatile building blocks in organic synthesis and find applications in material and medicinal sciences. A convenient and straightforward access to both classes of compounds under mild conditions is, therefore, highly desirable. Herein, we disclose the decarb-oxylative alkynylation and cyanation of broadly available carboxylic acids using photoredox catalysis and hyper-valent iodine reagents. Choices of both catalysts and reagents were crucial. Computational and experimental studies revealed two different possible mechanisms that are dictated by the oxidation potential of the reagents: radical for alkynylation, ionic for cyanation.
- Le Vaillant, Franck,Waser, Jér?me
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p. 226 - 230
(2017/06/27)
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- Substituted Cyclic Carboxamide and Urea Derivatives as Ligands of the Vanilloid Receptor
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Substituted cyclic carboxamide and urea compounds, a process for their preparation, pharmaceutical compositions containing these compounds, and the use of these compounds for the treatment and/or inhibition of pain and other conditions mediated by the vanilloid receptor 1.
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Page/Page column 37
(2012/03/10)
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- 2-Substituted 4,5-dihydrothiazole-4-carboxylic acids are novel inhibitors of metallo-β-lactamases
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Bacterial resistance to β-lactam antibiotics caused by class B metallo-β-lactamases (MBL), especially for certain hospital-acquired, Gram-negative pathogens, poses a significant threat to public health. We report several 2-substituted 4,5-dihydrothiazole-4-carboxylic acids to be novel MBL inhibitors. Structure activity relationship (SAR) and molecular modeling studies were performed and implications for further inhibitor design are discussed.
- Chen, Pinhong,Horton, Lori B.,Mikulski, Rose L.,Deng, Lisheng,Sundriyal, Sandeep,Palzkill, Timothy,Song, Yongcheng
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supporting information
p. 6229 - 6232
(2012/10/29)
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- Synthesis of Boc-amino tetrazoles derived from α-amino acids
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A simple route for the synthesis of Boc-protected tetrazole analogs of amino acids starting from Nα-Boc amino acids has been described. The [2 + 3] cycloaddition of Boc-α-amino nitrile and sodium azide in the presence of a catalytic amount of zinc bromide yielded the desired tetrazoles in good yields and purity. All the compounds obtained have been characterized by 1H and 13C-NMR and mass spectral studies. Copyright Taylor & Francis Group, LLC.
- Sureshbabu, Vommina V.,Naik, Shankar A.,Nagendra
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experimental part
p. 395 - 406
(2009/06/06)
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- N-urethane-protected amino alkyl isothiocyanates: Synthesis, isolation, characterization, and application to the synthesis of thioureidopeptides
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(Chemical Equation Presented) Synthetically useful N-Fmoc amino-alkyl isothiocyanates have been described, starting from protected amino acids. These compounds have been synthesized in excellent yields by thiocarbonylation of the monoprotected 1,2-diamines with CS2/TEA/p-TsCl, isolated as stable solids, and completely characterized. The procedure has been extended to the synthesis of amino alkyl isothiocyanates from Boc- and Z-protected amino acids as well. The utility of these isothiocyanates for peptidomimetics synthesis has been demonstrated by employing them in the preparation of a series of dithioureidopeptide esters. Boc-Gly-OH and Boc-Phe-OH derived isothiocyanates 9a and 9c have been obtained as single crystals and their structures solved through X-ray diffraction. They belong to the orthorhombic crystal system, and have a single molecule in the asymmetric unit (Z′ = 1). 9a crystallizes in the centrosymmetric space group Pbca, while 9c crystallizes in the noncentrosymmetric space group P212121.
- Sureshbabu, Vommina V.,Naik, Shankar A.,Hemantha,Narendra,Das, Ushati,Guru Row, Tayur N.
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supporting information; experimental part
p. 5260 - 5266
(2009/12/06)
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- Design and synthesis of dipeptidyl nitriles as potent, selective, and reversible inhibitors of cathepsin C
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A series of dipeptide nitriles with a thienyl alanine in P2 were identified as potent and selective cathepsin C inhibitors. Incorporation of a substituted cyclopropyl moiety in P1 effectively protects these derivatives against hydrolase activity in whole blood.
- Guay, Daniel,Beaulieu, Christian,Jagadeeswar Reddy,Zamboni, Robert,Methot, Nathalie,Rubin, Joel,Ethier, Diane,David Percival
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scheme or table
p. 5392 - 5396
(2010/05/02)
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- Primary amides as selective inhibitors of cathepsin K
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The nitrile warhead used in a series of cathepsin K inhibitors can be replaced by a less electrophilic primary amide. The accompanying loss of potency can be partially recovered by introducing a substituent α to the amide. The potency gain resulting from this addition is not achieved with the nitrile derivatives due to a different geometry of the cysteine adduct in the enzyme active site. This study led to the identification of the primary amide 2g, which is an inhibitory substrate, with an IC50 of 10 nM against cathepsin K and excellent selectivity versus the other cathepsins.
- Leger, Serge,Bayly, Christopher I.,Black, W. Cameron,Desmarais, Sylvie,Falgueyret, Jean-Pierre,Masse, Frederic,Percival, M. David,Truchon, Jean-Francois
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p. 4328 - 4332
(2008/02/10)
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- The aza-[2,3]-Wittig sigmatropic rearrangement of acyclic amines: Scope and limitations of silicon assistance
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The inclusion of a C-2 trialkylsilyl substituent into allylic amine precursors allows the base-induced aza-[2,3]-Wittig sigmatropic rearrangement to proceed in excellent yield and diastereoselectivity. The rearrangement precursors require a carbonyl-based nitrogen protecting group that must be stable to excess of strong base required for the reaction. The N-Boc and N-benzoyl group are very good at stabilizing the product anion and initiating deprotonation. The migrating groups (G) need to stabilize the intial anion by resonance and require G-CH3 pKa > 22 in order for the initial anion to be reactive enough for rearrangement. Products 7, 29b-d,f,g, and 23 are formed with high (10-20:1) anti diastereoselectivity. Product 23 containing the morpholine amide group is useful for preparing other carbonyl derivatives.
- Anderson,Flaherty,Swarbrick
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p. 9152 - 9156
(2007/10/03)
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- C-Alkylation of Peptides Containing Aminomalonate and (Amino)(cyano)acetate Residues
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N-Acetyl-, N-[(tert-butoxy)carbonyl](Boc)-, and N-[(benzyloxy)carbonyl](Z)-protected tri-, penta-, and heptapeptide methyl esters, 1-8, with a central aminomalonate (Ama) (allyl, methyl, benzyl, or tert-butyl) or (amino)(cyano)acetate (Aca) residue have been prepared by conventional techniques (Schemes 4-6). The new peptides with acidic backbone-bound CH groups can be C-alkylated with primary alkyl, allyl, and benzyl halides, under mildly basic conditions (1 equiv. MeONa or t-BuOK in THF); also, they can be added to Michael acceptors such as acrylates, acrylonitrile, methyl vinyl ketone, or nitrostyrene (catalytic amounts of alkoxide bases in THF) (Schemes 7-16). In most cases, the products, 48-100, are formed in excellent yields (average of 77%); one of the epimeric products prevails (2:1 to > 20:1), and the epimers have been separated, isolated in pure form, and fully characterized (without configurational assignments); addition of the co-solvent 3,4,5,6-tetrahydro-1,3-dimethylpyrimidin-2(1H)-one (DMPU) or of LiBr may improve or even reverse the ratio of epimeric products formed; the heptapeptide derivative 8 had to be solubilized for alkylations in THF by the addition of 30 equiv. of LiBr. Cleavage of the Ama groups (benzyl with H2/Pd-C, t-Bu with HCl/Et2O) gave carboxylate derivatives which are actually peptides containing the alkylated aminomalonic acid, the lower homolog of aspartic acid, as residue in the central position. These acids are quite resistant to decarboxylation which had to be achieved by heating at reflux in THF in the presence of 2 equiv. of LiBr and of catalytic amounts of pyridine (Schemes 17 and 18). A one-step removal of the allyl aminomalonate group is possible with Pd/PPh3/formate (Scheme 19). The resulting peptides, 101-115, were formed as separable 1:1 mixtures of two epimers. The CN group of the alkylated Aca residue can be removed reductively (Na/NH3; Scheme 20). The value of the new method is compared with that of existing methods of peptide-backbone modification.
- Matt, Thomas,Seebach, Dieter
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p. 1845 - 1895
(2007/10/03)
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- Trisubstituted β-lactams and oligo β-lactamamides
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Novel β-lactam monomers bearing various functional groups are prepared. The novel β-lactam monomers can be joined into oligomeric compounds via standard peptide linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen bonding. The oligomeric compounds are useful as diagnostic and research reagents.
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- DEPSIPEPTIDE ANALOGS OF THE ANTITUMOR DROG DISTAMYCIN CONTAINING THIAZOLE AMINO ACIDS RESIDUES
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Three compounds structurally related to the natural antiviral antitumor drugs netropsin and distamycin have been synthetized.They have been designed starting from 2-(aminomethyl)-thiazole-4 carboxylic acid, gly (Thz), a key element in the structure of hig
- Bailly, Christian,Houssin, Raymond,Bernier, Jean-Luc,Henichart, Jean-Pierre
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p. 5833 - 5844
(2007/10/02)
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- A Convenient and General Method for the Preparation of tert-Butoxycarbonylaminoalkanenitriles and Their Conversion to Mono-tert-butoxycarbonylalkanediamines
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A new method is described for the synthesis of tert-butoxycarbonylaminoalkanenitriles 3 by dehydration of the corresponding carboxamides 2 (prepared in two steps from aminoalkanoic acids) in the presence of trifluoroacetic anhydride and triethylamine.N-Boc-aminoalkanenitriles 3 are easily converted to mono-N-Boc-alkanediamines 4 under mild conditions avoiding the cleavage of the N-protective group.The monoprotected alkanediamines 4 are useful tools in affinity chromatography.
- Houssin, Raymond,Bernier, Jean-Luc,Henichart, Jean-Pierre
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p. 259 - 261
(2007/10/02)
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- 130. Poly(dipeptamidinium) Salts: Definition and Methods of Preparation
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Poly(dipeptamidines) are polypeptide derivatives in which the carbonyl oxygen of each second backbone amide group is replaced by an imine nitrogen (see A).So far, such derivatives have been unknown.Polyprotonated salts of them (= poly(dipeptamidinium) salts) are of interest in view of their intrinsic constitutional relationship to the structure of polynucleotides: the number of covalent bonds between neighboring centers of positive charge in poly(dipeptamidinum) salts is identical to the number of covalent bonds between neighboring centers of negative charge in natural polynucleotides (see D).Poly(dipeptamidinium) polycations and polynucleotide polyanions are constitutionally and electrostatically complementary structures.Since poly(dipeptamidines) are (formally) polymers of dipeptide nitriles, and, since they can be expected to give polypeptides on hydrolysis, the relationship mentioned above deserves attention and experimental study in context with the problem of designing chemical models of biogenesis.This paper describes methods for the chemical preparation, the spectral characterization, and some chemical properties of homodipeptidic poly(dipeptamidinium) salts in the L-alanyl-glycyl and L-phenylalanyl-glycyl series.The methods of preparation include a stepwise construction of defined lower oligomers (up to hexamer) as weel as, in the L-alanyl-glycyl series, a one-preparation poly-condensation procedure leading to polymers containing an average of ca. 20 dipeptamidinium units (Schemes 4,6 and 7).
- Moser, Heinz,Fliri, Anton,Steiger, Arthur,Costello, Gerard,Schreiber, Jakob,Eschenmoser, Albert
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p. 1224 - 1262
(2007/10/02)
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