- A Phenylalanine Derivative Containing a 4-Pyridine Group Can Construct Both Single Crystals and a Selective Cu-Ag Bimetallohydrogel
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Metallohydrogels are attractive biomaterials, whereas formation of a selective bimetallogel in aqueous solution has rarely been explored. In this study, we show that a phenylalanine derivative containing a 4-pyridine group can not only assemble to form si
- Wei, Chuan-Wan,Wang, Xiao-Juan,Gao, Shu-Qin,Wen, Ge-Bo,Lin, Ying-Wu
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supporting information
p. 1349 - 1353
(2019/02/14)
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- Discovery of novel 20S proteasome inhibitors by rational topology-based scaffold hopping of bortezomib
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A series of structurally novel proteasome inhibitors 1–12 have been developed based rational topology-based scaffold hopping of bortezomib. Among these novel proteasome inhibitors, compound 10 represents an important advance due to the comparable proteasome-inhibitory activity (IC50 = 9.7 nM) to bortezomib (IC50 = 8.3 nM), the remarkably higher BEI and SEI values and the effectiveness in metabolic stability. Therefore, compound 10 provides an excellent lead suitable for further optimization.
- Xu, Yulong,Yang, Xicheng,Chen, Yiyi,Chen, Hao,Sun, Huijiao,Li, Wei,Xie, Qiong,Yu, Linqian,Shao, Liming
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supporting information
p. 2148 - 2152
(2018/05/25)
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- Biocatalytic Synthesis of Chiral N-Functionalized Amino Acids
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N-Functionalized amino acids are important building blocks for the preparation of diverse bioactive molecules, including peptides. The development of sustainable manufacturing routes to chiral N-alkylated amino acids remains a significant challenge in the pharmaceutical and fine-chemical industries. Herein we report the discovery of a structurally diverse panel of biocatalysts which catalyze the asymmetric synthesis of N-alkyl amino acids through the reductive coupling of ketones and amines. Reactions have been performed on a gram scale to yield optically pure N-alkyl-functionalized products in high yields.
- Hyslop, Julia F.,Lovelock, Sarah L.,Sutton, Peter W.,Brown, Kristin K.,Watson, Allan J. B.,Roiban, Gheorghe-Doru
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supporting information
p. 13821 - 13824
(2018/09/27)
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- Tuning of protease resistance in oligopeptides through: N -alkylation
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N-Methylation of amino acids is an effective way to create protease resistance in both natural and synthetic peptides. However, alkyl substituents other than N-methyl have not been extensively studied. Here, we prepare and examine a series of N-substituted peptides in which the size and length of the alkyl group is modulated. These design insights provide a unique and modular handle for tuning proteolysis in oligopeptides.
- Kaminker, Revital,Anastasaki, Athina,Gutekunst, Will R.,Luo, Yingdong,Lee, Sang-Ho,Hawker, Craig J.
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supporting information
p. 9631 - 9634
(2018/09/10)
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- Boric acid compound used as 20S proteasome inhibitor, and preparation method thereof
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The invention relates to the fields of pharmaceutical chemistry and medicine therapeutics, concretely relates to new boric acid compounds, and a preparation method and a use thereof, and especially relates to a boric acid compound used as a 20S proteasome inhibitor, and a preparation method thereof. The invention also discloses a boric acid compound represented by formula I, and a preparation method thereof. A result of bioactive screening test shows that the compound prepared in the invention has a proteasome inhibition function, and can be further used for preparing medicines for treating proteasome correlated diseases.
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Paragraph 0198; 0199; 0200
(2017/09/19)
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- Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
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Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
- Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 9067 - 9089
(2017/11/14)
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- Aminoacid-derivatized Cu (II) complexes: Synthesis, DNA interactions and in vitro cytotoxicity
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Two different series of copper complexes, [Cu(MFL)(FcAA)H2O] (C1-C4) and [Cu(MFL) (BzAA)H2O] (C5-C8), where FcAA = ferrocenyl amino acid mannich base conjugates and BzAA = benzaldehyde amino acid mannich base conjugates have been syn
- Singh, Rinky,Devi, P. Rama,Jana, Sharmita S.,Devkar, Ranjitsinh V.,Chakraborty, Debjani
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p. 157 - 169
(2017/09/30)
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- Concise, stereodivergent and highly stereoselective synthesis of cis-and trans-2-substituted 3-hydroxypiperidines-development of a phosphite-driven cyclodehydration
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A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.
- Huy, Peter H.,Westphal, Julia C.,Koskinen, Ari M.P.
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supporting information
p. 369 - 383
(2014/03/21)
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- Efficient, stereodivergent access to 3-piperidinols by traceless P(OEt)3 cyclodehydration
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A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a "traceless" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is developed.
- Huy, Peter H.,Koskinen, Ari M. P.
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p. 5178 - 5181
(2013/11/06)
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- Photocytotoxic ferrocene-appended (l-tyrosine)copper(II) complexes of phenanthroline bases
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Copper(II) complexes of ferrocene(Fc)-conjugated reduced Schiff base of l-tyrosine (Fc-TyrH), viz., [Cu(Fc-Tyr)(L)](ClO4), where L is 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2), dipyrido[3,2-a:2′,3′-c]phenazine (
- Goswami, Tridib K.,Gadadhar, Sudarshan,Karande, Anjali A.,Chakravarty, Akhil R.
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p. 1287 - 1298
(2013/07/11)
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- A facile synthesis of 1,5-disubstituted-2-aminoimidazoles: Antibiotic activity of a first generation library
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An efficient synthetic route to 1,5-disubstituted 2-aminoimidazoles from readily available amino acids and aldehydes has been developed. A library of simple analogues was synthesized and several compounds were shown to exhibit notable antibiotic activity
- Harris, Tyler L.,Worthington, Roberta J.,Melander, Christian
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p. 4516 - 4519
(2011/09/12)
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- A versatile catalyst for reductive animation by transfer hydrogenation
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An iridium catalyst enables the reductive amination of carbonyl groups with unprecedented substrate scope, selectivity, and activity using formic acid as the hydrogen source (see scheme) The catalyst system provides significant improvement over commonly used boron hydrides.
- Wang, Chao,Pettman, Alan,Basca, John,Xiao, Jianliang
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supporting information; experimental part
p. 7548 - 7552
(2010/12/19)
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- Resolution of racemic N-benzyl α-amino acids by liquid-liquid extraction: A practical method using a lipophilic chiral cobalt(III) salen complex and mechanistic studies
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The efficient resolution of racemic N-benzyl α-amino acids (N-Bn-AA) has been achieved by a liquid-liquid extraction process using the lipophilic chiral salen-cobalt(III) complex [CoIII(3)(OAc)]. As a result of the resolution by extraction, one enantiomer (S) of the N-benzyl α-amino acid predominated in the aqueous phase, while the other enantiomer (R) was driven into the organic phase by complexation to cobalt. The complexed amino acid (R) was then quantitatively released by a reductive (CoIII→Co II) counter-extraction with aqueous sodium dithionite or L-ascorbic acid in methanol. The reductive cleavage allowed to recover the [Co II(3)] complex in good yield, which could be easily re-oxidized to [CoIII(3)(OAc)] with air/AcOH and reused with essentially no loss of reactivity and selectivity. Investigation on the nitrogen substitution indicates that the presence of a single benzyl group on the amino acid nitrogen is important to obtain high enantioselectivity in the extraction process. The kinetic vs. thermodynamic nature of the resolution process was also investigated with an enantiomeric exchange experiment, which shows that the liquid-liquid extraction with [CoIII(3)-(OAc)] is an equilibrium process operating under thermodynamic control. In the absence of a suitable crystal structure of the [CoIII(3)(N-Bn-AA)] complexes, computational and spectroscopic studies were used to investigate how the N-benzyl α-amino acids are accommodated in the "binding pocket" of the chiral cobalt complex. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Dzygiel, Pawel,Reeve, Toby B.,Piarulli, Umberto,Krupicka, Martin,Tvaroska, Igor,Gennari, Cesare
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supporting information; experimental part
p. 1253 - 1264
(2009/04/07)
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- A practical approach to the resolution of racemic N-benzyl α-amino acids by liquid-liquid extraction with a lipophilic chiral salen-cobalt(III) complex
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(Chemical Equation Presented) Liquidating the assets: Coordination of one enantiomer from a racemic mixture of N-benzyl α-amino acids (N-Bn-AA) to the lipophilic chiral [CoIII(salen)(OAc)] complex results in its extraction into the organic phas
- Reeve, Toby B.,Cros, Jean-Philippe,Gennari, Cesare,Piarulli, Umberto,De Vries, Johannes G.
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p. 2449 - 2453
(2007/10/03)
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- Method for producing amines by homogeneously catalyzed reductive amination of carbonyl compounds
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The invention relates to the preparation of chiral or achiral amines by reaction of aldehydes or ketones with ammonia or primary or secondary amines in the presence of hydrogen and in the presence of homogeneous metal catalysts under mild conditions. Metal catalysts which can be used are complexes of late transition metals with chiral or achiral phosphorus-containing ligands.
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Page/Page column 16; 19-20
(2010/02/11)
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- The first highly enantioselective homogeneously catalyzed asymmetric reductive amination: Synthesis of α-N-benzylamino acids
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High-throughput screening considering a library of 96 chiral P-ligands involved in two types of RhI complexes was used for the identification of homogeneous catalysts for the highly enantioselective reductive amination of α-keto acids with benzylamine. After optimization of the reaction conditions and scale-up with a cationic Rh-Deguphos catalyst, a range of chiral α-amino acids could be produced by this new reaction in good yield and by up to 98% ee.
- Kadyrov, Renat,Riermeier, Thomas H.,Dingerdissen, Uwe,Tararov, Vitali,Boerner, Armin
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p. 4067 - 4070
(2007/10/03)
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- Sodium borohydride: A versatile reagent in the reductive N-monoalkylation of α-amino acids and α-amino methyl esters
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α-Amino acids and α-amino methyl esters are easily converted to their N-monoalkyl derivatives by a reductive condensation reaction using several carbonyl compounds in the presence of sodium borohydride. This reducing agent has shown a wide versatility with minor but essential procedural variations. The reaction allows the α-monodeuterium labeling of the new N-substituent by use of sodium borodeuteride.
- Verardo, Giancarlo,Geatti, Paola,Pol, Elena,Giumanini, Angelo G.
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p. 779 - 788
(2007/10/03)
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- A highly practical method for monobenzylation of amino acids
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Amino acids are cleanly monobenzylated at ambient temperature using benzyl chloride in water containing potassium carbonate.
- Shao, Hua-Wu,Wu, Yikang,Li, Rongxiu
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p. 1911 - 1915
(2007/10/03)
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- N-SUBSTITUTED AMINO ACID DERIVATIVES WITH HYPERALPHALIPOPROTEINAEMIC ACTIVITY
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A series of N-substituted amino acid derivatives was synthesized and the compounds were evaluated for their effects on serum total cholesterol, HDL cholesterol and triglycerides in experimental animals.Hyperalphalipoproteinaemic activity was found for some of these compounds tested, especially BRL 26314 (2) and related 3-aryl-2-aminopropionic acids.Structure-activity relationships are discussed.Keywords: N-substituted amino acid derivatives / hyperalphalipoproteinaemic activity
- Baggaley, Keith H.,Fears, Robin,Ferres, Harry,Geen, Graham R.,Hatton, Ian K.,et al.
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p. 523 - 532
(2007/10/02)
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- AN EFFICIENT ONE-STEP REDUCTIVE N-MONOALKYLATION OF α-AMINO ACIDS
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Reactions of protection-free α-amino acids with aldehydes or ketones in the presence of sodium cyanoborohydride afforded the N-monoalkylated amino acids in inorganic salt-free form.Application of this method to synthesis of N-alkyl derivatives of biologic
- Ohfune, Yasufumi,Kurokawa, Natsuko,Higuchi, Naoki,Saito, Masayuki,Hashimoto, Masaki,et al.
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p. 441 - 444
(2007/10/02)
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