- Mechanism of fluorescence quenching of tyrosine derivatives by amide group
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The difference between fluorescence lifetimes of the following amino acids: phenylalanine (Phe), tyrosine (Tyr), (O-methyl)tyrosine (Tyr(Me)), (3-hydroxy)tyrosine (Dopa), (3,4-dimethoxy)phenylalanine (Dopa(Me)2) and their amides was used to tes
- Wiczk, Wieslaw,Rzeska, Alicja,Lukomska, Joanna,Stachowiak, Krystyna,Karolczak, Jerzy,Malicka, Joanna,Lankiewicz, Leszek
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Read Online
- Mechanochemical Synthesis of Primary Amides
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Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation that was compatible with a variety of functional groups and maintained the integrity of a stereocenter α to carbonyl. This methodology was applied to α-amino esters and N-BOC dipeptide esters and also to the synthesis of rufinamide, an antiepileptic drug.
- Gómez-Carpintero, Jorge,Sánchez, J. Domingo,González, J. Francisco,Menéndez, J. Carlos
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p. 14232 - 14237
(2021/10/20)
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- Guanidine-containing compound as well as preparation method and application thereof
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The invention discloses a cyanoguanidine-containing compound as well as a preparation method and application thereof. The invention also discloses a composition containing the cyanoguanidine-structured compound (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention also discloses application thereof in preparation of analgesic drugs. The compounds of the invention are useful in the treatment of various pain.
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Paragraph 0038; 0042-0043
(2021/11/26)
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- Hybrid catalysis of 8-quinolinecarboxaldehyde and br?nsted acid for efficient racemization of α-amino amides and its application in chemoenzymatic dynamic kinetic resolution
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The combination of 8-quinolinecarboxaldehyde and benzoic acid proved to be an effective catalyst system for the racemization of N-unprotected α-aryl- or α-alkyl-substituted α-amino amides. Application of this system to chemoenzymatic dynamic kinetic resolution provided an efficient access to enantiomerically pure N-acetyl-α-amino amides in good to high yields.
- Kiyokawa, Mari,Nagato, Yuya,Ohmatsu, Kohsuke,Ooi, Takashi,Shirai, Yuto
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- Mapping the s1 and s1’ subsites of cysteine proteases with new dipeptidyl nitrile inhibitors as trypanocidal agents
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The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. A series of 26 new compounds were designed, synthesized, and tested against the recombinant cruzain (Cz) to map its S1/S1′ subsites. The same series was evaluated on a panel of four human cysteine proteases (CatB, CatK, CatL, CatS) and Leishmania mexicana CPB, which is a potential target for the treatment of cutaneous leishmaniasis. The synthesized compounds are dipeptidyl nitriles designed based on the most promising combinations of different moieties in P1 (ten), P2 (six), and P3 (four different building blocks). Eight compounds exhibited a Ki smaller than 20.0 nM for Cz, whereas three compounds met these criteria for LmCPB. Three inhibitors had an EC50 value of ca. 4.0 μM, thus being equipotent to benznidazole according to the antitrypanosomal effects. Our mapping approach and the respective structure-activity relationships provide insights into the specific ligand-target interactions for therapeutically relevant cysteine proteases.
- Cianni, Lorenzo,Lemke, Carina,Gilberg, Erik,Feldmann, Christian,Rosini, Fabiana,Rocho, Fernanda Dos Reis,Ribeiro, Jean F. R.,Tezuka, Daiane Y.,Lopes, Carla D.,de Albuquerque, Sérgio,Bajorath, Jürgen,Laufer, Stefan,Leit?o, Andrei,Gütschow, Michael,Montanariid, Carlos A.
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- ANALOGS THAT TARGET MITOCHONDRIAL DISEASES
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Disclosed are analogs of elamipretide (MTP-131). The compounds are useful for the treatment and prevention of ischemia-reperfusion injury (e.g., cardiac ischemia-reperfusion injury) or myocardial infarction.
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- HEMIAMINAL-TAG FOR PROTEIN LABELING AND PURIFICATION
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The invention pertains to the synthesis, isolation, and characterization of hemiaminal for selective labeling of peptides, proteins, antibodies, and organic fragments with -C(=0) CH2NH2 and derivatives with -CH2NH2 group over -C(=0) CHRNH2 group (where R≠H). The invention also pertains to the method of single-site immobilization of proteins through N-terminus Gly on solid phase. The invention includes late-stage tagging of N-terminus Gly with an affinity tag, 19F NMR probe, and a fluorophore and a method for metal-free protein purification and isolation of analytically pure proteins.
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Page/Page column 22; 24
(2018/06/30)
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- 3, 5-disubstituted hydantoin compound as well as preparation method and application thereof
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The invention provides a 3, 5-disubstituted hydantoin compound as well as a preparation method and an application thereof. The structure of the compound is shown in formula I in the description. The application of the 3, 5-disubstituted hydantoin compound shown in the formula I or solvates, hydrates or salts of the compound in preparation of medicines for treating Alzheimer's disease, vascular dementia and other dementia diseases with memory impairment also belongs to the protection scope. Animal experiments prove that the compound has the effect of saving memory of animal models, has high safety, does not have mutagenicity, can stay in blood for several hours after oral administration and intravenous injection, and can enter the brain.
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- Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase
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The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of the enzyme were characterized by crystallography, and the results provide further insight into the pharmacophore requirements for allosteric inhibition.
- Park, Jaeok,Leung, Chun Yuen,Matralis, Alexios N.,Lacbay, Cyrus M.,Tsakos, Michail,Fernandez De Troconiz, Guillermo,Berghuis, Albert M.,Tsantrizos, Youla S.
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p. 2119 - 2134
(2017/03/17)
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- SYNTHESIS OF ARYL CYCLOHEXANE CARBOXAMIDE DERIVATIVES USEFUL AS SENSATES IN CONSUMER PRODUCTS
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Synthesis methods to produce a series of carboxamides built off of an (S)-2-amino acid backbone or an (R)-2-amino acid backbone, depending upon the desired diastereomer of the end product.
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Paragraph 0060; 0139; 0141
(2017/03/21)
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- Synthetic method for chiral alpha-aminoamide compounds
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The invention provides a synthetic method for chiral alpha-aminoamide compounds, belongs to the technical field of organic synthetic methodology, and concretely relates to a synthetic method for chiral alpha-aminoamide compounds, wherein the method has a simple process, low costs and good economy. The method comprises the following steps: 1, performing ammonolysis: adding substituted chiral alpha-aminocarboxylate hydrochloride into concentrated ammonia water, performing stirring for 4-12h under a room temperature, wherein each 1mmol substituted chiral alpha-aminocarboxylate hydrochloride is corresponding to 2-8mL the concentrated ammonia water; 2, after a reaction is finished, performing distillation for removing ammonia water after the reaction to obtain crude products chiral alpha-aminoamide compounds; and 3, performing filtration on the obtained crude products chiral alpha-aminoamide compounds by adopting a manner of adding a solvent or performing purification on the obtained crude products chiral alpha-aminoamide compounds through a manner of column chromatography which uses ammonia water as a mobile phase to obtain the products chiral alpha-aminoamide compounds. Compared with the prior art, a large number of an ammonia gas for ammonolysis is not needed in the method, the process and post-treatment are simple, costs are low and reaction time is short.
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Paragraph 0042; 0043; 0044
(2018/01/11)
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- Carbohydrates as efficient catalysts for the hydration of α-amino nitriles
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Directed hydration of α-amino nitriles was achieved under mild conditions using simple carbohydrates as catalysts exploiting temporary intramolecularity. A broadly applicable procedure using both formaldehyde and NaOH as catalysts efficiently hydrated a variety of primary and secondary susbtrates, and allowed the hydration of enantiopure substrates to proceed without racemization. This work also provides a rare comparison of the catalytic activity of carbohydrates, and shows that the simple aldehydes at the basis of chemical evolution are efficient organocatalysts mimicking the function of hydratase enzymes. Optimal catalytic efficiency was observed with destabilized aldehydes, and with difficult substrates only simple carbohydrates such as formaldehyde and glycolaldehyde proved reliable.
- Chitale, Sampada,Derasp, Joshua S.,Hussain, Bashir,Tanveer, Kashif,Beauchemin, André M.
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p. 13147 - 13150
(2016/11/09)
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- Enantioselective oxidation of thioanisole to metyl phenyl sulfoxide by chiral compounds bearing N-Cl bond
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Chiral sulfoxides are used in asymmetric synthesis and are present in various biologically active compounds. Asymmetric synthesis of the sulfoxides has been performed by chiral metal complexes and non-metals containing peroxide and oxide moieties. In this study, a new metal free method has been developed to oxidize thioanisole into methyl phenyl sulfoxide with easily accessible chiral compounds carrying N-Cl bond. For this purpose, chiral amine and amide bearing reagents were synthesized and chlorinated by using N-chlorosuccinimide. In oxidation reactions, chiral information has been transferred from N-chloramines to sulfides. With chlorinated chiral reagents, we observed enantioenriched sulfoxide formation. Although the observed results are promising, the best chiral amines are yet to be found. This is the first report on such a reaction, to the best of our knowledge.
- Ipek, Halil,Akdag, Akin
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p. 1285 - 1293
(2015/08/18)
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- Characterization of an enantioselective amidase from Cupriavidus sp. KNK-J915 (FERM BP-10739) useful for enzymatic resolution of racemic 3-piperidinecarboxamide
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A novel amidase (CsAM) acting on (R,S)-N-benzyl-3-piperidinecarboxamide was purified from Cupriavidus sp. KNK-J915 (FERM BP-10739) and characterized. The enzyme acts on (R,S)-N-benzyl-3-piperidinecarboxamide S-selectively to yield (R)-N-benzyl-3-piperidinecarboxamide. Analytical gel filtration column chromatography and SDS-PAGE revealed that the enzyme is a tetramer with a subunit of approximately 47 kDa. It has a broad substrate spectrum against nitrogen-containing heterocyclic amides. Its optimal pH and temperature are 8.0-9.0 and 50 °C, respectively. The CsAM gene was cloned and sequenced, and it was found to comprise 1341 bp and encode a polypeptide of 46,388 Da. The deduced amino acid sequence exhibited 78% identity to that of a putative amidase (CnAM) from Cupriavidus necator JMP134. The cultured cells of recombinant Escherichia coli producing CnAM could be used for the S-selective hydrolysis of (R,S)-N-benzyl-3-piperidinecarboxamide but could not be used for the S-selective hydrolysis of (R,S)-3-piperidinecarboxamide because of its very low level of selectivity. In contrast, the cultured cells of recombinant E. coli producing CsAM could hydrolyze both (R,S)-N-benzyl-3-piperidinecarboxamide and (R,S)-3-piperidinecarboxamide with high S-selectivity.
- Nojiri, Masutoshi,Taoka, Naoaki,Yasohara, Yoshihiko
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p. 136 - 142
(2014/12/10)
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- Development and evaluation of novel phosphotyrosine mimetic inhibitors targeting the Src homology 2 domain of signaling lymphocytic activation molecule (SLAM) associated protein
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Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have incorporated a novel phosphotyrosine mimetic, which is an unusual amino acid carrying a cyclosaligenyl (cycloSal) phosphodiester moiety, into dipeptides to investigate the inhibitory effect on SH2 domain-containing proteins. A plate-based assay was also established to screen for inhibitors that disrupt the interaction between a phosphopeptide of SLAM (signaling lymphocytic activation molecule) and its interacting protein SAP (SLAM-associated protein). We identified a number of inhibitors with IC50 values in the range of 17-35 μM, implying that the cycloSal phosphodiester-carrying amino acid could mimic the phosphotyrosyl residue. Our results also raise the possibility of integrating the newly developed phosphotyrosine mimetic moiety into inhibitors designed for other SH2 domain-containing proteins.
- Chu, Chi-Yuan,Chang, Chun-Ping,Chou, Yun-Ting,Handoko,Hu, Yi-Ling,Lo, Lee-Chiang,Lin, Jing-Jer
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p. 2841 - 2849
(2013/06/04)
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- Microwave-assisted solution phase peptide synthesis in neat water
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An environmentally benign protocol for solution phase peptide synthesis has been developed in neat water using TBTU/HOBt/DIEA as a coupling combination under microwave irradiation. Key features of this procedure are the replacement of commonly used toxic organic solvents like DMF and NMP, the use of lower amounts of reactants, compatibility with both N-α-Boc- and N-α-Fmoc-protected amino acids and all commonly used side-chain protective groups, short reaction time, and racemization-free synthesis in high yield and purity. The Royal Society of Chemistry 2013.
- Mahindra, Amit,Nooney, Karthik,Uraon, Shrikant,Sharma, Krishna K.,Jain, Rahul
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p. 16810 - 16816
(2013/09/23)
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- Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes
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The aPKC [atypical PKC (protein kinase C)] isoforms ? and ζ play crucial roles in the formation and maintenance of cell polarity and represent attractive anti-oncogenic drug targets in Ras-dependent tumours. To date, few isoform-specific chemical biology
- Kjaeaer, Svend,Linch, Mark,Purkiss, Andrew,Kostelecky, Brenda,Knowles, Phillip P.,Rosse, Carine,Riou, Philippe,Soudy, Christelle,Kaye, Sarah,Patel, Bhavisha,Soriano, Erika,Murray-Rust, Judith,Barton, Caroline,Dillon, Christian,Roffey, Jon,Parker, Peter J.,Mcdonald, Neil Q.
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p. 329 - 342
(2013/06/05)
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- 2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors
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A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo γ-secretase activity were identified and described.
- Parker, Michael F.,Barten, Donna M.,Bergstrom, Carl P.,Bronson, Joanne J.,Corsa, Jason A.,Dee, Michael F.,Gai, Yonghua,Guss, Valerie L.,Higgins, Mendi A.,Keavy, Daniel J.,Loo, Alice,Mate, Robert A.,Marcin, Larry R.,McElhone, Katharine E.,Polson, Craig T.,Roberts, Susan B.,MacOr, John E.
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p. 6828 - 6831,4
(2020/09/02)
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- Thermodynamics of phenylacetamides synthesis: Linear free energy relationship with the pK of amine
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The effective equilibrium constants K′C expressed through the total concentrations of the reagents for the synthesis of N-phenylacetyl-derivatives in aqueous medium from phenylacetic acid and various primary amino compounds have been determined with penicillin acylase as a catalyst. Broad specificity of penicillin acylase (EC 3.5.1.11) to amino components made possible to investigate the acylation of primary amines with different structures and physicochemical properties. Analysis of different components of the effective standard Gibbs energy change ΔGC o′ has revealed favorable thermodynamics for the synthesis of phenylacetamides from unionized substrates forms, however the ionization of reactants carboxy and amino groups in aqueous solutions pushes the equilibrium position to the hydrolysis especially in case of highly basic amines. A linear correlation between the standard Gibbs energy change for amide bond formation from the unionized reagents species and the basicity of amino group was observed: ΔGTo=-3.56pKamine+7.71(kJ/mol). The established linear free energy relationship (LFER) allows to predict the thermodynamic parameters for direct condensation of phenylacetic acid with any amine of known pK. Condensation of phenylacetic acid and amines with pK value within 1.5-8.5 was shown to be thermodynamically favorable in homogeneous aqueous solution. .
- Guranda, Dorel T.,Ushakov, Gennadij A.,Yolkin, Petr G.,Svedas, Vytas K.
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experimental part
p. 48 - 53
(2012/05/19)
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- Carbamates of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects
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In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4′-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4′-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4′- demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.
- Chen, Shi-Wu,Gao, Yuan-Yu,Zhou, Ni-Ni,Liu, Jie,Huang, Wen-Ting,Hui, Ling,Jin, Yan,Jin, Yong-Xin
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p. 7355 - 7358
(2012/02/04)
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- Amino acid derived amides and hydroxamic acids as ligands for asymmetric transfer hydrogenation in aqueous media
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Amides and hydroxamic acids derived from α-amino acids were evaluated as ligands in combination with rhodium and iridium half-sandwich complexes in asymmetric transfer hydrogenation (ATH) of ketones. The reactions were performed in aqueous media using lithium formate as hydride source. The catalyst systems turned out to be highly efficient and ee's up to 90% were obtained.
- Ahlford, Katrin,Adolfsson, Hans
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scheme or table
p. 1118 - 1121
(2012/01/15)
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- Structure-based design of novel human Pin1 inhibitors (II)
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Following the discovery of a novel series of phosphate-containing small molecular Pin1 inhibitors, the drug design strategy shifted to replacement of the phosphate group with an isostere with potential better pharmaceutical properties. The initial loss in potency of carboxylate analogs was likely due to weaker charge-charge interactions in the putative phosphate binding pocket and was subsequently recovered by structure-based optimization of ligand-protein interactions in the proline binding site, leading to the discovery of a sub-micromolar non-phosphate small molecular Pin1 inhibitor.
- Dong, Liming,Marakovits, Joseph,Hou, Xinjun,Guo, Chuangxing,Greasley, Samantha,Dagostino, Eleanor,Ferre, RoseAnn,Johnson, M. Catherine,Kraynov, Eugenia,Thomson, James,Pathak, Ved,Murray, Brion W.
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supporting information; experimental part
p. 2210 - 2214
(2010/06/15)
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- Enantiopure trans -3-arylaziridine-2-carboxamides: Preparation by bacterial hydrolysis and ring-openings toward enantiopure, unnatural D -α-amino acids
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Several racemic trans-3-arylaziridine-2-carboxamides were prepared and then resolved by Rhodococcus rhodochrous IFO 15564-catalyzed hydrolysis. The resulting enantiopure (2R,3S)-3-arylaziridine-2-carboxamides are adequate substrates to undergo fully stereoselective nucleophilic ring-openings at the C-3 ring position to finally yield enantiopure, unnatural d-α- aminocarboxylic acids. Experimental evidence is provided that suggests the fate of the (2S,3R)-3-arylaziridine-2-carboxylic acids concomitantly formed during the resolution processes. In this context, the similar bacterial resolution of racemic 1-arylaziridine-2-carboxamides and -carbonitriles, previously investigated by our research group, has been partially re-examined.
- Moran-Ramallal, Roberto,Liz, Ramon,Gotor, Vicente
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experimental part
p. 6614 - 6624
(2010/11/17)
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- Induced-fit in the gas phase: Conformational effects on the enantioselectivity of chiral tetra-amide macrocycles
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The structure, stability, and reactivity of proton-bound diastereomeric [M?H?A]+ complexes between some amino acid derivatives (A) and several chiral tetra-amide macrocycles (M) have been investigated in the gas phase by ESI-FT-ICR and ESI-ITMS-CID mass spectrometry. The displacement of the A guest from the diastereomeric [M?H?A]+ complexes by reaction with the 2-aminobutane enantiomers (B) exhibits a distinct enantioselectivity with regards to the leaving amino acid A and, to a minor extent, to the amine reactant B. The emerging selectivity picture, discussed in the light of molecular mechanics calculations, provides compelling evidence that the most stable conformers of the selected chiral tetraamide macrocycles M may acquire in the gas phase a different conformation by induced fit on complexation with some representative amino acid derivatives A. This leads to the coexistence in the gas phase of stable diastereomeric [M?H?A] + eq-eq and ax-ax structures, in proportions depending on the configuration of A and M and characterized by different stability and reactivity toward the 2-aminobutane enantiomers. The enantioselectivity of the gas-phase A-to-B displacement in the diastereomeric [M?H?A]+ complexes essentially reflects the free energy gap between the homo- and heterochiral [M?H?A]+ complexes, except when the tetra-amidic host presents an additional macrocycle generated by a decamethylene chain. In this case, the measured enantioselectivity mostly reflects the stability difference between the relevant diastereomeric transition structures.
- Gasparrini, Francesco,Pierini, Marco,Villani, Claudio,Filippi, Antonello,Speranza, Maurizio
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p. 522 - 534
(2008/10/09)
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- Endomorphin-1 analogs with enhanced metabolic stability and systemic analgesic activity: Design, synthesis, and pharmacological characterization
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We synthesized four new analogs of endomorphin-1 by systematic chemical modifications. To identify the best possible drug candidates for clinical pain management and to investigate the potential contribution of these alterations to the biological activity, their pharmacological properties were determined. All of the analogs showed significantly enhanced metabolic stability. The fact that centrally mediated analgesia following peripheral administration was observed with one of the analogs suggested the approach design undertaken here had validity in the development of endomorphin-1 as a successful opioid drug for the clinic.
- Liu, Hongmei,Zhang, Bangzhi,Liu, Xuefeng,Wang, Changlin,Ni, Jingman,Wang, Rui
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p. 1694 - 1702
(2008/02/03)
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- Nitrile and amide biotransformations for the synthesis of enantiomerically pure 3-arylaziridine-2-carboxamide derivatives and their stereospecific ring-opening reactions
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(Chemical Equation Presented) Catalyzed by Rhodococcus erythropolis AJ270 (whole cell catalyst) under very mild conditions, a number of racemic trans-3-arylaziridine-2-carbonitriles and amides were efficiently transformed into enantiopure 2R,3S-3-arylazir
- Wang, Jin-Yuan,Wang, De-Xian,Pan, Jie,Huang, Zhi-Tang,Wang, Mei-Xiang
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p. 9391 - 9394
(2008/03/14)
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- Room-temperature debenzylation of N-benzylcarboxamides by N-bromosuccinimide
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A simple and highly efficient method has been developed with which to cleave the N-benzyl group on N-mono- or disubstituted carboxamides using N-bromosuccinimide (NBS) at room temperature. All the 31 substrates examined showed moderate to excellent deprotection yields. Our study also indicated that the debenzylation may involve an oxygen/light initiated free radical mechanism. Georg Thieme Verlag Stuttgart.
- Kuang, Liping,Zhou, Jing,Chen, Sheng,Ding, Ke
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p. 3129 - 3134
(2008/03/28)
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- Methods and compositions for treating amyloid-related diseases
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Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
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Page/Page column 139
(2010/11/24)
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- Biological activity of cholecystokinin (30-33) tetrapeptide analogues
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Analogues of the endogenous peptide corresponding to the 30-33 sequence of cholecystokinin (Trp-Met-Asp-Phe-NH2) were synthesized, and their biological activity was studied. It was shown that, in rats, the N-succinylated Nle2 analogu
- Proskuryakova,Bespalova,Pal'keeva,Petrichenko,Pankratova,Shokhonova,Anokhina
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p. 119 - 127
(2007/10/03)
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- Process for producing optically active alpha-amino acid and optically active alpha-amino acid amine
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The present invention provides a process for efficiently producing an optically active α-amino acid and an optically active α-amino acid amide. After contacting with cells or processed cells thereof having an ability to asymmetrically hydrolyse, a water solvent is substituted with at least one solvent selected from the group consisting of linear, branched, or cyclic alcohol having 3 or more carbon atoms and the optically active α-amino acid is preferentially precipitated from the alcohol solution. The addition of basic compounds, particularly potassium compounds to the alcohol solution containing the optically active α-amino acid amide, which is obtained after the separation of the optically active α-amino acid, enables the purification of the amide without the inclusion of amino acid into amino acid amide. Thus, the amide is subjected to the step of racemization and then recycled.
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- Allyltrichlorostannane additions to α-amino aldehydes: Application to the total synthesis of the aspartyl protease inhibitors L-682,679, L-684,414, L-685,434, and L-685,458
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The hydroxyethylene dipeptide isosteres L-682,679, L-684,414, L-685,434, and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-
- Dias, Luiz C.,Diaz, Gaspar,Ferreira, Andrea A.,Meira, Paulo R. R.,Ferreira, Edílson
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p. 603 - 622
(2007/10/03)
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- Practical and convenient enzymatic synthesis of enantiopure α-amino acids and amides
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Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of α-aryl- and α-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-α-amino acid amides 2 and L-(+)-α-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-α-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6542 - 6545
(2007/10/03)
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- Short total synthesis of aspartyl protease inhibitors L-685,434, L-682,679 and L-685,458
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Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti a
- Dias, Luiz C.,Ferreira, Andrea A.,Diaz, Gaspar
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p. 1845 - 1849
(2007/10/03)
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- Enantioselective enzyme catalysed ammoniolysis of amino acid derivatives. Effect of temperature
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The lipases from Candida antarctica (B type), Thermomyces lanuginosus and Pseudomonas alcaligenes catalysed the enantioselective ammoniolysis of free amino acid esters. In the ammoniolysis of phenylalanine methyl ester catalysed by T. lanuginosus lipase a
- Lopez-Serrano, Paloma,Wegman, Margreth A.,Van Rantwijk, Fred,Sheldon, Roger A.
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p. 235 - 240
(2007/10/03)
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- Catalytic Hydrolysis of Peptides by Cerium(IV)
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Oligopeptides are efficiently hydrolyzed by CeIV to the corresponding amino acids under mild conditions. The pseudo first-order rate constants for the hydrolysis of H-Gly-Phe-OH and H-Gly-Gly-OH at pH 7.0 and 50°C are 3.5 × 10-1 and 2.8 × 10-1 h-1, with [Ce(NH4)2(NO3)6]0 = 10 mM (the half-lives are 2.0 and 2.5 h). The catalytic activity of the CeIV is far greater than those of other lanthanide ions and nonlanthanide ions. No oxidative cleavage was observed under the reaction conditions. Catalytic turnover of the CeIV was also evidenced. The hydrolysis is fast especially when the substrates have no metal-coordinating side chains. Tripeptides and tetrapeptides are hydrolyzed at the similar rates as the dipeptides. In the hydrolysis of tripeptides, the amide linkage near the N-terminus is preferentially hydrolyzed. Neither the N-carbobenzyloxy derivative nor the amide of H-Gly-Phe-OH is hydrolyzed to a measurable extent, showing that both the terminal amino group and the carboxylate are coordinated to the CeIV ion. This complexation is further confirmed by 1H NMR spectroscopy. The CeIV ion is therefore one of the most active catalysts for peptide hydrolysis.
- Takarada, Tohru,Yashiro, Mono,Komiyama, Makoto
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p. 3906 - 3913
(2007/10/03)
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- Synthesis and properties of aminoacylamido-AMP: Chemical optimization for the construction of an N-acyl phosphoramidate linkage
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This paper describes the design and synthesis of a new type of aminoacyl-adenylate analogue (aa-AMPN) having an N-acyl phosphoramidate linkage where the oxygen atom of the mixed anhydride bond of aminoacyl-adenylate (aa-AMP) is replaced by an amino group. This new type of aa-AMP analogue is expected to be useful as material for studies on the recognition mechanism of the aminoacylation of tRNA and other biochemical reactions. The condensation of phosphoramidite derivatives of carboxamides with nucleoside derivatives failed, because the activated phosphoramidite derivatives reacted with not only the hydroxyl groups but also another reactive species. An alternative approach was examined by the reaction of 5'-O-phosphoramidite adenosine derivatives with carboxamide derivatives. The TBTr and TSE groups were chosen for protection of the amino group of amino acid amides and the phosphate group, respectively. Detailed studies revealed that the use of 5-(3,5-dinitrophenyl)-1H-tetrazole as an activating catalyst of phosphoramidites resulted in rapid condensation within 10 min to give fully protected aa-AMPN derivatives. No side reaction occurred. Deprotection of these products via a two-step procedure gave aa-AMPN derivatives in good yields. It also turned out that aa-AMPNs thus obtained are stable under both acidic and basic conditions, such as 0.1 M HCl (pH 1.0) and 0.1 M NaOH (pH 13.0).
- Moriguchi,Yanagi,Kunimori,Wada,Sekine
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p. 8229 - 8238
(2007/10/03)
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- Tachykinin antagonists
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A description is given of tachykinin receptor antagonists having general formula (I) STR1 their preparation and use in pharmaceutical formulations.
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- PEPTIDASE INHIBITORS
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This invention relates to analogs of peptidase substrates in which the nitrogen atom of the scissile amide group of the substrate peptide has been replaced by H, an aldehyde, a substituted carbonyl or a substituted malonyl moiety. These analogs of the pep
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- Chymotrypsin inhibitory conformation induced by amino acid side chain-side chain intramolecular CH/π interaction
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Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/π interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2]n-C6H5 (n = 0-4) have been assayed for chymotrypsin. They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (Ki = 3.6 × 10-6 M). The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition. The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically. The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active. When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (Ki = 6.1 × 107 M; this dipeptide is one of the most potent chymotrypsin inhibitors to date). 1H NMR conformational analyses of these dipeptide amide derivatives show the CH/π interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition. These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S1 site, while the hydrophobic core constructed by D-Leu-Phe CH/π interaction fits the chymotrypsin S2 or S1′ site.
- Shimohigashi, Yasuyuki,Maeda, Iori,Nose, Takeru,Ikesue, Koichi,Sakamoto, Hiroshi,Ogawa, Tomohisa,Ide, Yuzuru,Kawahara, Megumi,Nezu, Takashi,Terada, Yoshihiro,Kawano, Keiichi,Ohno, Motonori
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p. 2479 - 2485
(2007/10/03)
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- Synthesis of aromatic amino acid amides
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Aromatic amino esters, in toluene or water, react with aqueous ammonium hydroxide to give moderate to high yields of the corresponding amides.
- Ager, David J.,Prakash, Indra
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p. 3865 - 3868
(2007/10/03)
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- La pronase immobilisee sur poly(N-acryloylpiperidin-4-one): un catalyseur d'hydrolyse L-enantiospecifique des α-aminonitriles
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Pronase immobilized on poly(N-acryloylpiperidin-4-one) : a L-enantiospecific hydrolysis of α-aminonitriles with immobilized amidase. α-Aminonitriles are not substrates for pronase (an amidase) in the homogeneous phase but become substrates for pronase when it is immobilized on polymer matrix with ketonic sites (piperidin-4-one).In this paper we show that under low basic aqueous conditions (pH 10-11), the hydration of α-aminonitriles can be efficiently catalyzed by poly(N-acryloylpiperidin-4-one) crosslinked with 1,4-bis acryloylpiperazine (A(80:20)) in the presence of phosphate or borate buffers.These conditions comply with the hydrolysis of α-aminoamides by pronase immobilized on poly(N-acryloylpiperidin-4-one)crosslinked with 1,4-bis(acryloyl)piperazine (A(80:20/p).Thus, in a buffered borate solution at pH 10.5, α(DL)-aminonitrile is enantiospecifically hydrolyzed into α(D)-aminoamide and α(L)-amino acid. Key words: α-aminonitriles / α amino acids / L-enantiospecific hydrolysis / polymer-supported catalysis / nitrilasic activity
- Taillades, Jacques,Garrel, Laurence,Guillen, Franck,Collet, Helene,Commeyras, Auguste
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p. 119 - 127
(2007/10/02)
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- Auxiliary chiral ketones in the asymmetric synthesis of α-amino acids by Strecker reaction
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The asymmetric synthesis of α-aminoamides 1 R1CH(CONH2)NH2 1 = Ph-CH2, 1b: R1 = Pri, 1c: R1 = Ph> that leads to the corresponding α-amino acids is achieved by a classical Strecker reaction 1CHO, HCN, NH3> using an auxiliary chiral ketone (R2R'2CO) as a catalyst.In the presence of an aqueous solution of HCN and NH3, the (-)-5R-(methylethenyl)-3R-cyano-2R-methylcyclohexanone 2(-) leads to the 5R-(methylethenyl)-3R-cyano-2R-methyl-1R-cyano-cyclohexylamine 3 with 80percent stereoselectivity.Following condensation with R1CHO, this α-aminonitrile R2R'2C(CN)NH2 3 yields the corresponding iminonitrile which undergoes a second asymmetric addition of HCN yielding an asymmetric α-aminodinitrile 4 R2R'2C(CN)-NH-CHR1(CN) with stereoselectivity that varies betweeen 62percent (R1 = Ph) and 79percent (R1 = Ph-CH2).The α-aminodinitrile obtained as the major product undergoes regioselective hydration of the secondary aminonitrile moiety followed by the decomposition ("retro-Strecker") of the tertiary aminonitrile moiety yielding an optically active α-aminoamide (eg 78percent optical purity for 1a) and the auxiliary chiral ketone 2 and ketonic derivatives.Keywords - α-aminonitrile / α-amino acid / asymmetric synthesis
- Bousquet, C.,Tadros, Z.,Tonnel, J.,Mion, J.,Taillades, J.
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p. 513 - 520
(2007/10/02)
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- Novel peptidase inhibitors
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This invention relates to activated electrophilic ketone analogs of certain peptidase substrates which are useful in inhibiting serine-, carboxylic acid-and metallo-proteolytic enzymes, the inhibition of which will have useful physiological consequences i
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- Enzymatic hydrolysis of DL-phenylalaninamide with pronase immobilized on ketonic polymer.
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In the transformation of an aldehyde into an α-aminoacid (Strecker's reaction or related), we try to enantioselectively hydrolyse the α-aminonitrile intermediate using a catalyst obtained by the immobilization of pronase on chemically reactive polymer presenting piperidone groups.This catalyst should be able to simultaneously hydrate the α-aminonitrile and to enantioselectively hydrolyse the α-aminoamide obtained. First of all, we define the essential parameters of this reaction (pH, substrat concentration, catalyst mass) by a kinetic study.These parameters determine the activity of immobilized pronase in the enantioselective hydrolysis of DL-phenylalaninamide. immobilized enzyme / α-aminoamide / enantioselective hydrolysis / ketonic polymer
- Taillades, J.,Boussac, P.,Collet, H.,Brugidou, J.,Commeyras, A.
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p. 423 - 429
(2007/10/02)
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- Process for recimization of an optically active alpha-amino acid amides and process for producing optically active alpha-amino acids
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A process for optically isomerizing an optically active alpha-amino acid amide comprising heating a D-alpha-amino acid amide or an L-alpha-amino acid amide in the presence of a strongly basic compound; and a process for producing an L-alpha-amino acid, which comprises (1) subjecting a D,L-alpha-amino acid amide or a mixture of a major amount of a D-alpha-amino acid amide and a minor amount of an L-alpha-amino acid amide to the action of a microorganism having the ability to hydrolyze the L-alpha-amino acid to obtain a hydrolyzate containing the L-alpha-amino acid and D-alpha-amino acid, (2) separating the L-alpha-amino acid from the hydrolyzate and recovering the remaining D-alpha-amino acid amide. (3) heating all or part of the recovered D-alpha-amino acid amide in the presence of a strongly basic substance to obtain a D,L-alpha-amino acid amide or a mixture of a major amount of the D-alpha-amino acid amide and a minor amount of the L-alpha-amino acid amide, and (4) recycling the D,L-alpha-amino acid amide or the mixture to step (1) as part or all of the starting material.
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- Nouvelle voie d'acces aux alkylidene-3 piperazinediones-2,5
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The synthetic route to 3-alkylidene-2,5-piperazinediones has been studied.The condensation of stabilized phosphorus ylids with 5-substituted-2,3,6-piperazinetriones gives 3-alkylidene-6-substituted-2,5-piperazinediones in good yields.
- Person, Domonique,le Corre, Maurice
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p. 673 - 676
(2007/10/02)
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- A Modified Benzhydrylamine as a Handle Reagent for the Solid Phase Synthesis of Peptide Amides Based on the Fluorenylmethoxycarbonyl Method
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An easily preparable dimethoxybenzhydrylamine derivative, 3-(α-Fmoc-amino-4-methoxybenzyl)-4-methoxyphenyl propionic acid (Fmoc=fluoren-9-ylmethoxycarbonyl) is a useful precursor of the C-terminal amide, when applied to Fmoc-based solid phase peptide synthesis; as a cleavage reagent from the resine, thioanisole-mediated trimethylsilyl bromide in trifluoroacetic acid is recommended.
- Funakoshi, Susumu,Murayama, Eigoro,Guo, Lili,Fujii, Nobutaka,Yajima, Haruaki
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p. 382 - 384
(2007/10/02)
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