- The Chemical Development of LB71350
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An efficient synthesis of the HIV-1 protease inhibitor LB71350 (1) is described. High diastereoselective epoxidation of the cis-allylic carbamate fragment of (5S)-[N-(benzyloxycarbonyl)-amino]-N-[2-methyl-(1R)-[(phenyl) carbonyl]-propyl]-6-phenylhex-(Z)-e
- Lee, Kyu Woong,So, Byungran,Cho, Sung Wook,Shin, Hyunik,Hwang, Sang Yeul,Kim, Chung Ryeol,Nam, Do Hyun,Chang, Jay Hyok,Choi, Sang Chul,Choi, Bo Seung,Choi, Hyeong-Wook,Lee, Ki Kon
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Read Online
- Probing α-Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary α-Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Br?nsted Bases
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The high tendency of α-amino aldehydes to undergo 1,2-additions and their relatively low stability under basic conditions have largely prevented their use as pronucleophiles in the realm of asymmetric catalysis, particularly for the production of quaternary α-amino aldehydes. Herein, it is demonstrated that the chemistry of α-amino aldehydes may be expanded beyond these limits by documenting the first direct α-alkylation of α-branched α-amino aldehydes with nitroolefins. The reaction produces densely functionalized products bearing up to two, quaternary and tertiary, vicinal stereocenters with high diastereo- and enantioselectivity. DFT modeling leads to the proposal that intramolecular hydrogen bonding between the NH group and the carbonyl oxygen atom in the starting α-amino aldehyde is key for reaction stereocontrol.
- García-Urricelqui, Ane,de Cózar, Abel,Mielgo, Antonia,Palomo, Claudio
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p. 2483 - 2492
(2020/12/25)
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- Regioselective Fluorination of α-Hydroxy-β-aminophosphonates by Using PyFluor
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We report a simple protocol for the synthesis of α-fluoro-β-aminophosphonates by the regioselective fluorination of α-hydroxy-β-aminophosphonates under mild conditions. The fluorination reactions were mediated by the PyFluor reagent and occurred with the retention of configuration. The main products of this reaction were a series of α-fluoro-β-aminophosphonates, which can be used as precursors in the preparation of medicinally important compounds (e.g., dipeptide analogues).
- Ka?mierczak, Marcin,Kubicki, Maciej,Koroniak, Henryk
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p. 3844 - 3852
(2018/07/31)
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- Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity
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Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.
- Wei, Binqing,Gunzner-Toste, Janet,Yao, Hui,Wang, Tao,Wang, Jing,Xu, Zijin,Chen, Jinhua,Wai, John,Nonomiya, Jim,Tsai, Siao Ping,Chuh, Josefa,Kozak, Katherine R.,Liu, Yichin,Yu, Shang-Fan,Lau, Jeff,Li, Guangmin,Phillips, Gail D.,Leipold, Doug,Kamath, Amrita,Su, Dian,Xu, Keyang,Eigenbrot, Charles,Steinbacher, Stefan,Ohri, Rachana,Raab, Helga,Staben, Leanna R.,Zhao, Guiling,Flygare, John A.,Pillow, Thomas H.,Verma, Vishal,Masterson, Luke A.,Howard, Philip W.,Safina, Brian
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supporting information
p. 989 - 1000
(2018/01/01)
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- Burgess Reagent Facilitated Alcohol Oxidations in DMSO
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The Burgess reagent ([methoxycarbonylsulfamoyl]triethylammonium hydroxide) has historically found utility as a dehydrating agent. Herein we show that, in the presence of dimethyl sulfoxide, the Burgess reagent efficiently and rapidly facilitates the oxidation of a broad range of primary and secondary alcohols to their corresponding aldehydes and ketones in excellent yields and under mild conditions, and can be combined with other transformations (e.g., Wittig olefinations). A mechanism similar to those described for the Pfitzner-Moffatt and Swern oxidations is proposed.
- Sultane, Prakash R.,Bielawski, Christopher W.
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p. 1046 - 1052
(2018/06/18)
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- Amino Aldehydes Revisited
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The enzymatic oxidation of amino alcohols was studied to address the long-standing problem of product stability. Amino aldehydes, highly sought and unstable compounds, can be generated under mild conditions if they are immediately protected. Utilizing a r
- Mestrom, Luuk,Bracco, Paula,Hanefeld, Ulf
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p. 7019 - 7025
(2017/12/28)
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- Discovery of Novel and Highly Selective Inhibitors of Calpain for the Treatment of Alzheimer's Disease: 2-(3-Phenyl-1H-pyrazol-1-yl)-nicotinamides
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Calpain overactivation has been implicated in a variety of pathological disorders including ischemia/reperfusion injury, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). Herein we describe our efforts leading to the ide
- Kling, Andreas,Jantos, Katja,Mack, Helmut,Hornberger, Wilfried,Drescher, Karla,Nimmrich, Volker,Relo, Ana,Wicke, Karsten,Hutchins, Charles W.,Lao, Yanbin,Marsh, Kennan,Moeller, Achim
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p. 7123 - 7138
(2017/09/07)
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- Aminooxylation Horner-Wadsworth-Emmons Sequence for the Synthesis of Enantioenriched γ-Functionalized Vinyl Sulfones
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An operationally simple protocol for the synthesis of γ-hydroxy vinyl sulfones has been developed using a proline-based aldehyde aminooxylation, followed by a vinyl sulfone forming Horner-Wadsworth-Emmons olefination. The adducts, formed in high enantiopurity, were subsequently converted to γ-azido vinyl sulfones, and azide-alkyne click chemistry enabled the synthesis of vinyl sulfone-based triazoles as potential nonpeptidic cysteine protease inhibitors. (Chemical Equation Presented).
- Doherty, William,Evans, Paul
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p. 1416 - 1424
(2016/03/01)
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- Immunomodulators
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The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
- -
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Paragraph 0503; 0504; 0505
(2016/08/29)
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- PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
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This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
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- A rapid and efficient one-pot method for the reduction of N-protected α-amino acids to chiral α-amino aldehydes using CDI/DIBAL-H
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N-Protected amino acids can be easily converted into chiral α-amino aldehydes in a one-pot reaction by activation with CDI followed by reduction with DIBAL-H. This method delivers Boc-, Cbz- and Fmoc-protected amino aldehydes from proteinogenic amino acids in very good isolated yields and complete stereointegrity.
- Ivkovic, Jakov,Lembacher-Fadum, Christian,Breinbauer, Rolf
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p. 10456 - 10460
(2015/11/10)
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- Substrate derived peptidic α-ketoamides as inhibitors of the malarial protease PfSUB1
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Peptidic α-ketoamides have been developed as inhibitors of the malarial protease PfSUB1. The design of inhibitors was based on the best known endogenous PfSUB1 substrate sequence, leading to compounds with low micromolar to submicromolar inhibitory activity. SAR studies were performed indicating the requirement of an aspartate mimicking the P1′ substituent and optimal P1-P4length of the non-prime part. The importance of each of the P1-P4amino acid side chains was investigated, revealing crucial interactions and size limitations.
- Kher, Samir S.,Penzo, Maria,Fulle, Simone,Finn, Paul W.,Blackman, Michael J.,Jirgensons, Aigars
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supporting information
p. 4486 - 4489
(2015/02/19)
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- Fukuyama reduction and integrated thioesterification/fukuyama reduction of thioesters and acyl chlorides using continuous flow
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Fukuyama reduction of thioesters has been achieved using a polymer-supported Pd[0] catalyst (Pd/XAD-4), and continuous flow conditions. The generality of this reaction is good with a range of aldehydes prepared in excellent yields. In addition, an integrated multistep thioesterfication/ Fukuyama reduction has been developed that allows acyl chlorides to be directly converted to the corresponding aldehydes. Integral to this process is the use of polymer-supported amine and isocyanate reagents to achieve thioesterification and scavenge unreacted thiol. In addition, catch-and-release purification has been employed to enable isolation of the aldehyde from silylthioether byproducts without the need for chromatographic purification.
- Asadi, Mousa,Bonke, Shannon,Polyzos, Anastasios,Lupton, David W.
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p. 2070 - 2074
(2014/06/24)
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- A mild multistep conversion of n-protected α-amino acids into N-protected β3-amino acids utilizing the Nef reaction
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Current methods of homologation of α-amino acids to β-amino acids have limitations. To overcome these shortfalls the Nef reaction has been utilized in the multistep synthesis of β3-amino acids from α-amino acids. In this approach, N-protected a
- Sleebs, Brad E.,Nguyen, Nghi H.,Hughes, Andrew B.
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supporting information
p. 747 - 751
(2013/05/08)
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- Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease
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Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 μM and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors.
- Gros, Guillaume,Martinez, Lorena,Gimenez, Anna Servat,Adler, Paula,Maurin, Philippe,Wolkowicz, Roland,Falson, Pierre,Hasserodt, Jens
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p. 5407 - 5413
(2013/09/02)
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- METHOD OF PRODUCING PYRONE AND PYRIDONE DERIVATIVES
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The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.
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Page/Page column 40
(2012/02/03)
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- Resolution and absolute configuration of some a-aminoacetals: En route to enantiopure N-protected a-aminoaldehydes
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The first successful resolution of rac-a-aminoacetals via diastereoisomeric salt formation with optically pure N-protected aminoacids is reported. The absolute configuration assignment of a-aminoacetal enantiomers is performed by an entirely non-racemizing chemical correlation method involving N-protection and a new efficient hydrolysis step followed by a reduction of the resulting N-protected a-aminoaldehyde intermediates. A racemization method of optically enriched a-aminoacetals is exemplified to allow valorisation of both enantiomers. Springer-Verlag 2011.
- Albalat-Serradeil, Muriel,Primazot, Geraldine,Wilhelm, Didier,Vallejos, Jean-Claude,Vanthuyne, Nicolas,Roussel, Christian
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p. 687 - 696
(2012/09/22)
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- Highly efficient, organocatalytic aerobic alcohol oxidation
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5-Fluoro-2-azaadamantane N-oxyl (5-F-AZADO) realizes a simple, organocatalytic aerobic alcohol oxidation system that has a wide scope under mild conditions at ambient pressure and temperature and is weakly acidic and halogen- and transition-metal-free. The oxoammonium nitrate (5-F-AZADO +NO3-) works as a bifunctional catalyst of 5-F-AZADO and NOx that enables the catalytic aerobic oxidation of alcohols by itself (a metal-salt-free system).
- Shibuya, Masatoshi,Osada, Yuji,Sasano, Yusuke,Tomizawa, Masaki,Iwabuchi, Yoshiharu
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supporting information; experimental part
p. 6497 - 6500
(2011/06/23)
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- Triazole-linked reduced amide isosteres: An approach for the fragment-based drug discovery of anti-Alzheimer's BACE1 inhibitors
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In the course of a β-site APP-cleaving enzyme 1 (BACE1) inhibitor discovery project an in situ synthesis/screening protocol was employed to prepare 120 triazole-linked reduced amide isostere inhibitors. Among these compounds, four showed modest (single digit micromolar) BACE1 inhibition. Our ligand design was based on a potent reduced amide isostere 1, wherein the P 2 amide moiety was replaced with an anti-1,2,3-triazole unit. Unfortunately, this replacement resulted in a 1000-fold decrease in potency. Docking studies of triazole-linked reduced amide isostere A3Z10 and potent oxadiazole-linked tertiary carbinamine 2a with BACE1 suggests that the docking poses of A3Z10 and 2a in the active sites are quite similar, with one exception. In the docked structures the placement of the protonated amine that engages D228 differs considerably between 2a and A3Z10. This difference could account for the lower BACE1 inhibition potency of A3Z10 and related compounds relative to 2a.
- Monceaux, Christopher J.,Hirata-Fukae, Chiho,Lam, Polo C.-H.,Totrov, Maxim M.,Matsuoka, Yasuji,Carlier, Paul R.
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supporting information; experimental part
p. 3992 - 3996
(2011/08/02)
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- Optically active N- and C-terminal building blocks for the synthesis of peptidyl olefin peptidomimetics
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Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. The N-terminal side of the C=C bond could be easily prepared in an optically pure form from α-amino acids. Synthesis of C-terminal building blocks in an optically pure form is more challenging. We developed a chemoenzymatic stereoselective approach to such optically active C-terminal building blocks to be assembled into peptidyl olefins by a variety of reactions. They include an electrophilic aldehyde and nucleophilic sulfone, phosphonium salt, phosphonate, and diselenide. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection- hydrolysis-functionalization or functionalization-hydrolysis- protection, determines the absolute stereochemistry of the final building blocks.
- Mirilashvili, Sima,Chasid-Rubinstein, Naama,Albeck, Amnon
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experimental part
p. 4671 - 4686
(2010/10/19)
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- Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration
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Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.
- Virlouvet, Mickael,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
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experimental part
p. 177 - 198
(2010/08/05)
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- Expedient solid-phase synthesis of both symmetric and asymmetric diol libraries targeting aspartic proteases
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C2-symmetric diols have been shown to be highly potent against HIV-1 protease (PR). However, gaining access to these compounds has been hampered by the need of multistep solution-phase reactions which are often tedious and inefficient. In this Letter, we have disclosed a solid-phase strategy for rapid preparation of small molecule-based, symmetric and asymmetric diols as potential HIV-1 protease inhibitors. Upon biological screening, we found one of them, SYM-5, to be a potent and selective inhibitor (Ki = 400 nM) against HIV-1 protease.
- Shi, Haibin,Liu, Kai,Leong, Wendy W.Y.,Yao, Shao Q.
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supporting information; experimental part
p. 3945 - 3948
(2010/03/30)
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- A novel and efficient synthesis of chiral C2-symmetric 1,4-diamines
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A novel and efficient method for synthesis of (R,R)- and (S,S)-C2-symmetric 1,4-diamines was established. The key steps are a combination of Pinacol Coupling and Corey-Winter olefination.
- Xu, Lianhong,Desai, Manoj C.,Liu, Hongtao
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scheme or table
p. 552 - 554
(2009/05/07)
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- Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase inhibitory properties
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The chemoenzymatic synthesis of a collection of pyrrolidine-type iminosugars generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C-α-substituted N-Cbz-2-aminoaldehydes derivatives, catalyzed by DHAP aldolases is reported. L-Fuculose-1-phosphate aldolase (FucA) and L-rhamnulose-1-phosphate aldolase (RhuA) from E. coli were used as biocatalysts to generate configurational diversity on the iminosugars. Alkyl linear substitutions at C-α were well tolerated by FucA catalyst (i.e., 40-70% conversions to aldol adduct), whereas no product was observed with C-α-alkyl branched substitutions, except for dimethyl and benzyl substitutions (20%). RhuA was the most versatile biocatalyst: C-α-alkyl linear groups gave the highest conversions to aldol adducts (60-99%), while the C-α-alkyl branched ones gave moderate to good conversions (50-80%), with the exception of dimethyl and benzyl substituents (20%). FucA was the most stereoselective biocatalyst (90-100% anti (3R,4R) adduct). RhuA was highly stereoselective with (S)-N-Cbz-2-aminoaldehydes (90-100% syn (i.e., 3R,4S) adduct), whereas those with R configuration gave mixtures of antilsyn adducts. For iPr and iBu substituents, RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high stereoselectivity. Molecular models of aldol products with iPr and iBu sub-stituents and as complexes with the RhuA active site suggest that the and adducts could be kinetically preferred, while the syn adducts would be the equilibrium products. The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of a-L-fucosidase (IC50 = 1-20 μM), moderate of α-L-rhamnosidase (IC50=7-150 μM), and weak of α-D-mannosidase (IC50 = 80-400 μM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were performed to understand both their binding capacity and the mode of interaction with the glycosidases.
- Calveras, Jordi,Egido-Gabas, Meritxell,Gomez, Livia,Casas, Josefina,Parella, Teodor,Joglar, Jesus,Bujons, Jordi,Clapes, Pere
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scheme or table
p. 7310 - 7328
(2010/03/24)
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- Synthesis of novel amino-acid-derived sulfinamides and their evaluation as ligands for the enantioselective transfer hydrogenation of ketones
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Novel chiral mono-sulfinyl diamines bearing a stereogenic sulfur atom were prepared in moderate to good yields starting from amino acids by means of a reductive amination of the corresponding amino aldehydes. Their potential as ligands for asymmetric catalysis was evaluated in the metal-catalyzed enantioselective transfer hydrogenation of alkyl-aryl ketones. The catalysts were generated in situ from sulfinamides 1a-i and arene complexes of rhodium and ruthenium, and the catalytic reductions led to the formation of chiral alcohols with up to 91% ee. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Zani, Lorenzo,Eriksson, Lars,Adolfsson, Hans
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scheme or table
p. 4655 - 4664
(2009/04/11)
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- COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS
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The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.
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Page/Page column 21-22
(2008/12/08)
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- COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTlVATING PROTEASE INHIBITORS
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The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.
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Page/Page column 51
(2008/12/08)
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- FKBP BINDING COMPOSITION AND PHARMACEUTICAL USE THEREOF
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A composition for binding FKBP proteins is disclosed, along with a method of treating conditions associated with neuronal degeneration, wherein said composition comprises a compound of formula I, wherein, R, R1, R2, R3 and
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- PROCESS OF DEACETALISATION OF ALPHA AMINOACETALS
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The invention relates to a process for the preparation of N-protected α-aminoaldehydes by deacetalization of the acetal functional group of corresponding N-protected α-aminoacetals using formic acid.
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Page/Page column 23-24
(2008/12/08)
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- Expanding the scope of PNA-encoded libraries: divergent synthesis of libraries targeting cysteine, serine and metallo-proteases as well as tyrosine phosphatases
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Seven PNA-encoded combinatorial libraries targeting proteases and phosphatases with covalent reversible and irreversible mechanism-based inhibitors were prepared. The libraries were synthesized using modified PNA monomers, which dramatically increase the water solubility of the libraries in biologically relevant buffers. The libraries were shown to selectively inhibit targeted enzymes.
- Debaene, Fran?ois,Da Silva, Julien A.,Pianowski, Zbigniew,Duran, Fernando J.,Winssinger, Nicolas
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p. 6577 - 6586
(2008/02/05)
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- FKBP BINDING COMPOSITION AND PHARMACEUTICAL USE THEREOF
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A composition for binding FKBP proteins is disclosed, along with a method of treating conditions associated with neuronal degeneration, wherein said composition comprises a compound of Formula (I), wherein, R, R1, R2, R3 a
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Page/Page column 87
(2010/02/15)
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- Procedure for the oxidation of β-amino alcohols to α-amino aldehydes
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A novel procedure for the mild oxidation of β-amino alcohols to α-amino aldehydes using commercially available manganese(IV) oxide is reported. There are several important advantages of the new method, such as high enantiopurity of the reaction and the absence of either over-oxidation or any reaction by-products during the process. A number of N-protected L-α-amino aldehydes was obtained. All new compounds were characterized by their NMR spectra and optical rotation data. Georg Thieme Verlag Stuttgart.
- Sergeev, Maxim E.,Pronin, Victor B.,Voyushina, Tatiana L.
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p. 2802 - 2804
(2007/10/03)
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- Convenient preparation of optically active N,N-bis(4-substituted-4- aminobutyl)amines
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An efficient and convenient method for the synthesis of chiral triamines with two substituents at the α position to the terminal amino group (spermidine analogues) is described. These chiral N,N-bis(4-substituted-4- aminobutyl)amines may have anticancer a
- Tsubaki, Kazunori,Kusumoto, Tomokazu,Hayashi, Noriyuki,Tanima, Daisuke,Fuji, Kaoru,Kawabata, Takeo
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p. 739 - 743
(2007/10/03)
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- New Odorless Protocols for the Synthesis of Aldehydes and Ketones from Thiol Esters
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Dodecanethiol esters derived from odorless dodecanethiol proved to be suitable substrates for Pd-catalyzed reduction with triethylsilane, coupling with organozinc reagents, and coupling with terminal acetylenes.
- Miyazaki, Tohru,Han-Ya, Yuki,Tokuyama, Hidetoshi,Fukuyama, Tohru
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p. 477 - 480
(2007/10/03)
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- HYDROXYMORPHOLINONE DERIVATIVE AND MEDICINAL USE THEREOF
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A compound represented by the following formula (I) wherein R1 and R2 are each a lower alkyl group optionally having substituents, which has a calpain inhibitory activity, or a salt thereof is provided.
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- Polymer-Supported Bisacetoxybromate(I) Anion - An Efficient Co-Oxidant in the TEMPO-Mediated Oxidation of Primary and Secondary Alcohols
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A polymer-bound reagent for the efficient oxidation of primary alcohols to aldehydes and secondary alcohols to ketones in the presence of a catalytic amount of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) is described. The oxidation process is particular mild and allows one to prepare aldehydes with α-chirality without racemization. This also includes the synthesis of α-aminoaldehydes. In most cases, work-up of this heavy metal-free oxidation is achieved by simple filtration followed by removal of the solvent. Insight into the role of the bromate(I) anion in the oxidation process was gained from the TEMPO-mediated oxidation of benzaldehyde in the presence of the hypochlorite anion loaded on an anion exchange resin.
- Bruenjes, Marco,Sourkouni-Argirusi, Georgia,Kirschning, Andreas
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p. 635 - 642
(2007/10/03)
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- An Ionic Liquid Mediated Efficient Oxidation of Alcohols Using o-Iodoxybenzoic Acid (IBX) - A Simple and Eco-friendly Protocol
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An environmentally benign ionic liquid is shown to be for the first time an excellent medium for mild and selective oxidation of alcohols using IBX at room temperature.
- Karthikeyan, Ganesan,Perumal, Paramasivan T.
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p. 2249 - 2251
(2007/10/03)
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- Novel 6-Hydroxy-3-morpholinones as cornea permeable calpain inhibitors
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A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and the hydroxy group of P2 site form a cyclic hemiacetal, was identified as calpain inhibitors. The placement of isobutyl group at the 2-position of the 3-morpholino
- Nakamura, Masayuki,Miyashita, Hiroyuki,Yamaguchi, Masazumi,Shirasaki, Yoshihisa,Nakamura, Yoshikuni,Inoue, Jun
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p. 5449 - 5460
(2007/10/03)
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- IgE antibody production inhibitors and autoimmune diseases inhibitors
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The present invention relates to an IgE antibody production inhibitor and an autoimmune disease suppressant containing a heterocyclic amide compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an activ
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- Reduction of ethanethiol esters to aldehydes
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Reduction of ethanethiol esters of α-amino acids to α-amino aldehydes by triethylsilane and catalytic palladium-on-carbon is described. α-Amino aldehydes with Boc, Cbz, or Fmoc protection could be obtained without racemization in high yield.
- Tokuyama, Hidetoshi,Yokoshima, Satoshi,Lin, Shao-Cheng,Li, Leping,Fukuyama, Tohru
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p. 1121 - 1123
(2007/10/03)
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- NOVEL THIAZINE OR PYRAZINE DERIVATIVES
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An object of the present invention is to synthesize novel compounds having 3-oxo-3, 4-dihydro-2H-1, 4-thiazine or 2-oxo-1, 2, 3, 4-tetrahydropyrazine as a main skeleton. The present invention relates to compounds represented by the following general formula [I] and salts thereof. In the formula, X is S or R6-(A2)n-N, R1 and R2 are H, alkyl, cycloalkyl or aryl, R3 and R4 are H, alkyl, cycloalkyl, aryl or aromatic heterocycles, R5 is H, alkyl, cycloalkyl, aryl or -A3-A4-R7, R6 is H, alkyl, cycloalkyl, OH, alkoxy, aryl, aryloxy or an aromatic heterocycle, R7 is H, alkyl, OH, alkoxy, aryl, aryloxy, amino, alkylamino, arylamino, an aromatic heterocycle or a nonaromatic heterocycle, A1 is alkylene, A2 is carbonyl or sulfonyl, A3 is alkylene, and A4 is carbonyl or oxalyl.
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- Efficient stereoselective synthesis of (2s,3s,5r)-(+)-preussin
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Allyltrimethylsilane reacted with N-carbobenzoxy-L-phenylalaninal to afford with high diastereoselectivity syn-adduct which was subsequently transformed into (2S, 3S, SR)-(+)-preussin.
- Krasiński, Antoni,Gruza, Henryk,Jurczak, Janusz
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p. 581 - 584
(2007/10/03)
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- A very mild and chemoselective oxidation of alcohols to carbonyl compounds
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matrixpresented Efficient oxidation of primary alcohols and β-amino alcohols to the corresponding aldehydes and α-amino aldehydes can be carried out at room temperature and in methylene chloride, using trichloroisocyanuric acid in the presence of catalytic TEMPO: aliphatic, benzylic, and allylic alcohols, and β-amino alcohols are rapidly oxidized without no overoxidation to carboxylic acids. Secondary carbinols are slowly oxidized so that the reaction is highly chemoselective.
- De Luca, Lidia,Giacomelli, Giampaolo,Porcheddu, Andrea
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p. 3041 - 3043
(2007/10/03)
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- A novel concept in combinatorial chemistry in solution with the advantages of solid-phase synthesis: Formation of N-betaines by multicomponent domino reactions
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Advantages of solid-phase and liquid-phase synthesis are combined in a new concept of combinatorial chemistry: a domino sequence comprising Knoevenagel and hetero-Diels-Alder reactions, with subsequent hydrogenation starting from protected aminoaldehydes, 1.3-dicarbonyl compounds, and enol ethers leads to N-heterocycles of high diversity with a betaine structure, which are isolated in highly pure form by precipitation with diethyl ether (see scheme), Cbz = benzylocycarbonyl, Bn = benzyl.
- Tietze, Lutz F.
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p. 903 - 905
(2007/10/03)
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- Novel inhibitors of HIV protease: Design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds
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A novel series of HIV protease inhibitors containing cyclic P1/P2 scaffolds has been synthesized and evaluated for biological activity. The trans 3,5-dibenzyl-2-oxo pyrrolidinone ring system resulted in a 50 pM enzyme inhibitor against HIV protease in vitro when combined with an indanolamine derived P'-backbone. This compound also shows comparable activity to currently marketed drugs in the MT-4 cell-based antiviral assay. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Spaltenstein, Andrew,Almond, Merrick R.,Bock, William J.,Cleary, Darryl G.,Furfine, Eric S.,Hazen, Richard J.,Kazmierski, Wieslaw M.,Salituro, Francesco G.,Tung, Roger D.,Wright, Lois L.
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p. 1159 - 1162
(2007/10/03)
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- Solid-phase synthesis of C-terminal peptide aldehydes from amino acetals anchored to a backbone amide linker (BAL) handle
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Peptide aldehydes were synthesized, starting from amino acetals, by a Solid-phase backbone amide linker (BAL) strategy. (C) 2000 Elsevier Science Ltd.
- Guillaumie,Kappel,Kelly,Barany,Jensen
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p. 6131 - 6135
(2007/10/03)
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- Heterocyclic amide compounds and medicinal uses thereof
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PCT No. PCT/JP97/03839 Sec. 371 Date Apr. 22, 1999 Sec. 102(e) Date Apr. 22, 1999 PCT Filed Oct. 22, 1997 PCT Pub. No. WO98/18794 PCT Pub. Date May 7, 1998A heterocyclic amide compound of the formula (I) wherein each symbol is as defined in the specification, a pharmacologically acceptable salt thereof, a pharmaceutical composition thereof and a pharmaceutical use thereof. The heterocyclic amide compound and a pharmacologically acceptable salt thereof of the present invention have superior inhibitory action on chymase group in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be used for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.
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- Synthesis of N-protected α-amino aldehydes from their morpholine amide derivatives
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A new method for the synthesis of N-protected α-amino aldehydes was developed. N-Protected α-amino amides of morpholine were easily prepared and then reduced with LiAlH4 to produce clean N-protected α-amino aldehydes. This new scheme of synthesis can be used with Boc, Z and Fmoc amino-protecting groups.
- Douat, Céline,Heitz, Annie,Martinez, Jean,Fehrentz, Jean-Alain
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- Peptidyl compounds
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Peptidyl compounds having an imidazole substituent have therapeutic utility via their inhibitory effect on metalloproteinases and tumour necrosis factor.
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