- GRANZYME B DIRECTED IMAGING AND THERAPY
-
Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
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Page/Page column 82; 105
(2019/09/04)
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- Chemo- and Enantioselective Pd/B Hybrid Catalysis for the Construction of Acyclic Quaternary Carbons: Migratory Allylation of O-Allyl Esters to α- C-Allyl Carboxylic Acids
-
We describe herein the asymmetric synthesis of α-allyl carboxylic acids containing an α-quaternary stereocenter by a chiral hybrid catalyst system comprising palladium and boron complexes. The reaction proceeded through palladium-catalyzed ionization of α,α-disubstituted O-allyl esters for the generation of chiral π-allyl palladium complex as an electrophile, boron-catalyzed enolization of the carboxylate part for the generation of chiral α,α-disubstituted carboxylic acid-derived enolates as a nucleophile, and enantioselective coupling between the thus-generated nucleophile and electrophile. Proper combinations of chiral ligands for the boron and palladium catalysts were crucial. The reaction proceeded chemoselectively at the α-position of the carboxylic acid group.
- Fujita, Taiki,Yamamoto, Tomohiro,Morita, Yuya,Chen, Hongyu,Shimizu, Yohei,Kanai, Motomu
-
supporting information
p. 5899 - 5903
(2018/05/14)
-
- Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives
-
Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.
- Wang, Tianli,Yu, Zhaoyuan,Hoon, Ding Long,Phee, Claire Yan,Lan, Yu,Lu, Yixin
-
p. 265 - 271
(2016/01/25)
-
- Chemical resolution of DL-phenylalanine methyl ester using N-acetyl-D-phenylglycine as resolving agent
-
An improved method for chemical resolution of DL-phenylalanine methyl ester using N-acetyl-D-phenylglycine as a resolving agent is described. This new resolving agent is readily available, non-toxic and easily recoverable from the insoluble diasteromeric salt. This method was used to obtain D-phenylalanine methyl ester with high optical purity of 98.1% and a high yield of 81.2%.
- Wang, Shuai-Shuai,Zou, Fang,Meng, Wen-Qi,Zhang, Jing-Zheng,Feng, Yan,Zhang, Ling,Liu, Yi
-
p. 159 - 161
(2015/06/02)
-
- Synthesis, enantioresolution, and activity profile of chiral 6-methyl-2,4-disubstituted pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists
-
A series of chiral pyridazin-3(2H)-ones was synthesized, separated as pure enantiomers, and evaluated for N-formyl peptide receptor (FPR) agonist activity. Characterization of the purified enantiomers using combined chiral HPLC and chiroptical studies (circular dichroism, allowed unambiguous assignment of the absolute configuration for each pair of enantiomers). Evaluation of the ability of racemic mixtures and purified enantiomers to stimulate intracellular Ca 2+ flux in FPR-transfected HL-60 cells and human neutrophils and to induce β-arrestin recruitment in FPR-transfected CHO-K1 cells showed that many enantiomers were potent agonists, inducing responses in the sub-micromolar to nanomolar range. Furthermore, FPRs exhibited enantiomer selectivity, generally preferring the R-(-)-forms over the S-(+)-enantiomers. Finally, we found that elongation of the carbon chain in the chiral center of the active compounds generally increased biological activity. Thus, these studies provide important new information regarding molecular features involved in FPR ligand preference and report the identification of a novel series of FPR agonists.
- Cilibrizzi, Agostino,Schepetkin, Igor A.,Bartolucci, Gianluca,Crocetti, Letizia,Dal Piaz, Vittorio,Giovannoni, Maria Paola,Graziano, Alessia,Kirpotina, Liliya N.,Quinn, Mark T.,Vergelli, Claudia
-
experimental part
p. 3781 - 3792
(2012/08/28)
-
- Efficient kinetic resolution of amino acids catalyzed by lipase AS 'Amano' via cleavage of an amide bond
-
Herein the efficient kinetic resolution of non-natural alpha-amino acids catalyzed by lipase AS 'Amano' via cleaving the amide bond is reported. The starting materials were the corresponding amino acid amides and the amino acids were generated with ees of up to 99% with E values of >600. These results indicated that the lipase AS 'Amano' could be a powerful amide hydrolase for the kinetic resolution of amino acid starting from the corresponding amino acid amides.
- Wang, Bo,Liu, Yanfeng,Zhang, Dela,Feng, Yuhong,Li, Jiacheng
-
p. 1338 - 1342,5
(2020/09/16)
-
- Preparation of cross-linked enzyme aggregates of l-aminoacylase via co-aggregation with polyethyleneimine
-
l-Aminoacylase from Aspergillus melleus was co-aggregated with polyethyleneimine and subsequently cross-linked with glutaraldehyde to obtain aminoacylase-polyethyleneimine cross-linked enzyme aggregates (termed as AP-CLEA). Under the optimum conditions, AP-CLEA expressed 74.9% activity recovery and 81.2% aggregation yield. The said method of co-aggregation and cross-linking significantly improved the catalytic stability of l-aminoacylase with respect to temperature and storage. AP-CLEA were employed for enantioselective synthesis of three unnatural amino acids (namely: phenylglycine, homophenylalanine and 2-naphthylalanine) via chiral resolution of their ester-, amide- and N-acetyl derivatives. The enantioselectivity of AP-CLEA was the highest for hydrolysis of amino acid amides; was moderate for hydrolysis of N-acetyl amino acids and was the least for hydrolysis of amino acid esters. Furthermore, AP-CLEA were found to retain more than 92% of the initial activity after five consecutive batches of (RS)-homophenylalanine hydrolysis suggesting an adequate operational stability of the biocatalyst.
- Vaidya, Bhalchandra K.,Kuwar, Suyog S.,Golegaonkar, Sandeep B.,Nene, Sanjay N.
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experimental part
p. 184 - 191
(2012/03/22)
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- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
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Page/Page column 99
(2012/02/15)
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- Convenient method for reduction of C-N double bonds in oximes, imines, and hydrazones using sodium Borohydride-Raney ni system
-
(Chemical Equation Presented) A practical method has been developed for reduction of C-N double bond in oximes, imines, and hydrazones with sodium borohydride catalyzed by Raney Ni. The reactions were carried out in basic aqueous solution, and the desired products were obtained in moderate yields after a simple procedure. This method can be applied to synthesize simpler aliphatic or aromatic amines and its analogs. Copyright Taylor & Francis Group, LLC.
- Yang, Yihua,Liu, Shouxin,Li, Junzhang,Tian, Xia,Zhen, Xiaoli,Han, Jianrong
-
p. 2540 - 2554
(2012/07/27)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS5A protein
- -
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Page/Page column 134
(2011/07/30)
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- The influence of molecular structure and crystallization time on the efficiency of diastereoisomeric salt forming resolutions
-
Reciprocal resolutions between compounds (racemates and enantiomers) with similar structures have been examined. Amongst structurally similar compounds (so called relative structures) several N-acyl amino acids and amino acid esters were investigated. A part of the resolving agent or the racemic compound could be replaced by an achiral compound with a relative structure and an additive could occasionally improve significantly the efficiency of the resolution. Both the kinetic and the thermodynamic controls were observed as governing factors of the reciprocal resolutions.
- Palovics, Emese,Schindler, Jozsef,Faigl, Ferenc,Fogassy, Elemer
-
experimental part
p. 2429 - 2434
(2010/12/25)
-
- Formation and hydrolysis of amide bonds by lipase A from Candida antarctica; Exceptional features
-
Various commercial lyophilized and immobilized preparations of lipase A from Candida antarctica (CAL-A) were studied for their ability to catalyze the hydrolysis of amide bonds in N-acylated α-amino acids, 3-butanamidobutanoic acid (β-amino acid) and its ethyl ester. The activity toward amide bonds is highly untypical of lipases, despite the close mechanistic analogy to amidases which normally catalyze the corresponding reactions. Most CAL-A preparations cleaved amide bonds of various substrates with high enantioselectivity, although high variations in substrate selectivity and catalytic rates were detected. The possible role of contaminant protein species on the hydrolytic activity toward these bonds was studied by fractionation and analysis of the commercial lyophilized preparation of CAL-A (Cat#ICR-112, Codexis). In addition to minor impurities, two equally abundant proteins were detected, migrating on SDS-PAGE a few kDa apart around the calculated size of CAL-A. Based on peptide fragment analysis and sequence comparison both bands shared substantial sequence coverage with CAL-A. However, peptides at the C-terminal end constituting a motile domain described as an active-site flap were not identified in the smaller fragment. Separated gel filtration fractions of the two forms of CAL-A both catalyzed the amide bond hydrolysis of ethyl 3-butanamidobutanoate as well as the N-acylation of methyl pipecolinate. Hydrolytic activity towards N-acetylmethionine was, however, solely confined to the fractions containing the truncated form of CAL-A. These fractions were also found to contain a trace enzyme impurity identified in sequence analysis as a serine carboxypeptidase. The possible role of catalytic impurities versus the function of CAL-A in amide bond hydrolysis is further discussed in the paper. The Royal Society of Chemistry 2010.
- Liljeblad, Arto,Kallio, Pauli,Vainio, Marita,Niemi, Jarmo,Kanerva, Liisa T.
-
scheme or table
p. 886 - 895
(2010/06/20)
-
- HEPATITIS C VIRUS INHIBITORS
-
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
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Page/Page column 149
(2010/12/26)
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- Benzimidazole and imidazole inhibitors of histone deacetylases: Synthesis and biological activity
-
A series of N-hydroxy-3-[3-(1-substituted-1H-benzoimidazol-2-yl)-phenyl]-acrylamides (5a-5ab) and N-hydroxy-3-[3-(1,4,5-trisubstituted-1H-imidazol-2-yl)-phenyl]-acrylamides (12a-s) were designed, synthesized, and found to be nanomolar inhibitors of human histone deacetylases. Multiple compounds bearing an N1-piperidine demonstrate EC50s of 20-100 nM in human A549, HL60, and PC3 cells, in vitro and in vivo hyperacetylation of histones H3 and H4, and induction of p21waf. Compound 5x displays efficacy in human tumor xenograft models.
- Bressi, Jerome C.,Jong, Ron de,Wu, Yiqin,Jennings, Andy J.,Brown, Jason W.,O'Connell, Shawn,Tari, Leslie W.,Skene, Robert J.,Vu, Phong,Navre, Marc,Cao, Xiaodong,Gangloff, Anthony R.
-
experimental part
p. 3138 - 3141
(2010/09/03)
-
- Regioselective synthesis of tetrasubstituted pyrroles by 1,3-dipolar cycloaddition and spontaneous decarboxylation
-
We developed a novel regioselective synthesis of tetrasubstituted pyrroles via the classic 1,3-dipolar cycloaddition of α,β-unsaturated benzofuran-3(2H)-one and azlactones (1) followed by spontaneous decarboxylation. The complete regiochemical control of tetrasubstituted pyrroles was confirmed by the orthogonal synthesis of complementary regioisomers (7a and 7b) simply by using different azlactones (1a and 1b, respectively).
- Kim, Yongju,Kim, Jonghoon,Park, Seung Bum
-
supporting information; experimental part
p. 17 - 20
(2009/08/07)
-
- Lipase activity of Lecitase Ultra: characterization and applications in enantioselective reactions
-
The general properties of Lecitase Ultra, a phospholipase manufactured and marketed by Novozymes, Denmark, have been studied after purification by ultrafiltration. The enzyme has a molecular mass of 35 KD, pH-optimum of 8.5, and appears to possess a single active site which exhibits both the lipase and phospholipase activities that increase in the presence of Ca2+ and Mg2+ ions. The enzyme is inhibited by heavy metal ions and surfactants, and does not accept p-nitrophenyl acetate and glycerol triacetate. Substrates, such as glycerol tributyrate and p-nitrophenyl palmitate, esters of N-acetyl-α-amino acids and α-hydroxy acids are readily accepted. Amino acids with aliphatic residues, such as alanine, isoleucine, and methionine, are hydrolyzed with high enantioselectivity for the l-enantiomer (E >100), but amino acids with aromatic residues such as phenylalanine and phenylglycine, and esters of α-hydroxy acids are hydrolyzed with low enantioselectivity (E = 1-5). Immobilization of the enzyme in a gelatin matrix (gelozyme) leads to a marginal improvement in the enantioselectivity for these substrates. However, a dramatic improvement in enantioselectivity is observed for ethyl 2-hydroxy-4-oxo-4-phenylbutyrate (E value increases from 4.5 to 19.5 with S-selectivity). Similarly, glycidate esters, such as ethyl trans-(±)-3-phenyl glycidate and methyl trans-(±)-3-(4-methoxyphenyl) glycidate, are selectively hydrolyzed with a remarkable selectivity towards the (2S,3R)-enantiomer providing unreacted (2R,3S)-glycidate esters (ee >99%, conversion 52-55%) by the immobilized enzyme.
- Mishra, Mithilesh Kumar,Kumaraguru, Thenkrishnan,Sheelu, Gurrala,Fadnavis, Nitin W.
-
experimental part
p. 2854 - 2860
(2010/04/05)
-
- METHOD FOR INHIBITING PROLIFERATION OF TUMOR CELLS
-
Disclosed are methods for synergistically inhibiting the proliferation of tumor cells by contacting the tumor cells with a MEK inhibitor compound and erlotinib, either sequentially or simultaneously. Also disclosed are methods for inhibiting the proliferation of tumor cells in a human, by administering to the human, sequentially or simultaneously, an amount of erlotinib and a MEK inhibitor compound, wherein the amounts are effective, in combination, to synergistically inhibit the proliferation of the tumor cells in the human.
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Page/Page column 13
(2008/12/08)
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- Manganese catalysed asymmetric cis-dihydroxylation with H2O 2
-
High turnover enantioselective alkene cis-dihydroxylation is achieved with H2O2 catalysed by manganese based complexes containing chiral carboxylato ligands. The Royal Society of Chemistry.
- De Boer, Johannes W.,Browne, Wesley R.,Harutyunyan, Syuzanna R.,Bini, Laura,Tiemersma-Wegman, Theodora D.,Alsters, Paul L.,Hage, Ronald,Feringa, Ben L.
-
supporting information; experimental part
p. 3747 - 3749
(2009/02/07)
-
- Efficient ligand-free, palladium-catalyzed amidocarbonylation in ionic liquids: Facile synthesis of N-acyl-α-arylglycines
-
A ligand-free, palladium-catalyzed amidocarbonylation reaction of aromatic aldehyde, acetamide, and CO in ionic liquids [C4mim]PF6, [C6mim]PF6, [C8mim]PF6, and [C6mim]BF4 as solvents is developed. The yields decreased in the order [C6mim]PF6 > [C8mim]PF6 > [C4mim]PF6 > [C6mim]BF4, and substrate concentration affected the catalytic activity of amidocarbonylation. The excellent yield with up to 98% in amidocarbonylation of benzaldehyde was obtained using 15 mol% LiBr · H2O and 6 mol% H2SO4 at 80°C. This reaction could proceed smoothly, resulting in several functionalized ortho-, meta-, and para-substituted N-acyl-α-phenylglycines in moderate to good yields, and o-tolualdehyde and m-tolualdehyde as substrates were amidocarbonylated for the first time in [C6mim]PF6. A significant dependence of product yield on both substituent position and electronic effect of aromatic aldehyde was observed. The ligand-free synthetic method and convenient separation of the products highlighted the versatility of this newly developed methodology. Copyright Taylor & Francis Group, LLC.
- Zhao, Qing-Lu,Yang, Min,Wang, Lai-Lai
-
experimental part
p. 4460 - 4473
(2009/04/07)
-
- Substituted hydantoins
-
The present invention relates to compounds of the formula methods for the preparation thereof, and methods for their use. The compounds are useful in treating diseases characterized by the hyperactivity of MEK. Accordingly the compounds are useful in the treatment of diseases, such as cancer, cognitive and CNS disorders, and inflammatory/autoimmune diseases.
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Page/Page column 13
(2008/06/13)
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- METHOD OF AMIDOCARBONYLATION REACTION
-
A novel method of an amidocarbonylation reaction among an aldehyde compound, an amide compound, and carbon monoxide, which comprises using a palladium-supporting crosslinked-polymer composition containing palladium clusters having a major-axis length of 20 nm or shorter to conduct the amidocarbonylation reaction. Thus, an N-acyl-±-amino acid can be more efficiently and selectively synthesized in a clean reaction system. Also provided is a catalyst for use in the method.
- -
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Page/Page column 11
(2008/06/13)
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- Palladium-catalyzed amidocarbonylation improved by recyclable ionic liquids
-
Two types of ionic liquids (halide anion ionic liquids and Brensted acidic ionic liquids) were first applied to improve the palladium-catalyzed amidocarbonylation. Both the palladium catalyst and the ionic liquids could be recycled at least five times without significant loss in catalytic activity. Georg Thieme Verlag Stuttgart.
- Zhu, Bingchun,Jiang, Xuanzhen
-
p. 2795 - 2798
(2008/02/11)
-
- A study of amidocarbonylation reactions catalyzed by Pd/HZSM-5
-
A HZSM-5-supported palladium catalyst, which was prepared by the conventional impregnation method, was utilized in amidocarbonylation reactions. Several important parameters were optimized to give moderate to excellent yields. The catalyst recycling of Pd/HZSM-5, for the first time, was achieved for at least four run times without depreciation of catalytic activity. The studies of TEM images revealed that agglomeration of the palladium species of Pd/ HZSM-5 catalyst was avoided after reaction, which was quite different from the case of Pd/C catalyst.
- Ke, Wu Yang,Xuan, Zhen Jiang
-
p. 806 - 809
(2007/10/03)
-
- Asymmetric synthesis of N-protected amino acids by the addition of organolithium carboxyl synthons to ROPHy/SOPHy-derived aldoximes and ketoximes.
-
A new asymmetric synthesis of alpha-amino acids is described in which the key step is the highly diastereoselective addition of organolithium carboxyl synthons (2-furyllithium, phenyllithium, vinyllithium) to (R)- and (S)-O-(1-phenylbutyl) oximes to give hydroxylamines, with vinyllithium being the most satisfactory nucleophilic reagent. Subsequent reductive cleavage of the N-O bond in hydroxylamines, followed by N-protection, and oxidative cleavage of the carboxyl precursor gave a range of N-protected amino acids and esters. The method was exemplified by the synthesis of a range of derivatives of non-proteinogenic amino acids such as 4-bromophenylalanine, tert-leucine, norvaline, cyclohexyl- and aryl-glycines, 2-amino-8-oxodecanoic acid (Aoda) and alpha-methylvaline.
- Cooper, Tracey S,Laurent, Pierre,Moody, Christopher J,Takle, Andrew K
-
p. 265 - 276
(2007/10/03)
-
- Efficient synthesis of N-acyl-α-amino acids via polymer incarcerated palladium-catalyzed amidocarbonylation
-
A novel polymer incarcerated Pd catalyst (PI Pd 7c) was synthesized from amide-containing polymer 6b, and this catalyst was shown to be effective in amidocarbonylation, which is a versatile one-pot method for the preparation of N-acyl-α-amino acids. The reactions proceeded smoothly with a wide variety of substrates, and no leaching of the Pd metal to the reaction mixture was detected.
- Akiyama, Ryo,Sagae, Takahiro,Sugiura, Masaharu,Kobayashi, Shu
-
p. 3806 - 3809
(2007/10/03)
-
- Application of aminoacylase I to the enantioselective resolution of α-amino acid esters and amides
-
Aminoacylase I from Aspergillus melleus, a readily available and inexpensive enzyme mainly used in the industrial production of enantiopure L-amino acids from their N-acetyl derivatives, is shown to hydrolyze the esters and amides of natural and non-natural amino acids with high enantioselectivity (for the ester hydrolysis, E is up to 76, in case of amides E >300). The reaction rates of amide and ester hydrolysis are comparable, and in some cases these conversions proceeded even faster than 'traditional' aminoacylase- catalyzed hydrolysis of N-acetyl derivatives thus providing new possibilities for the resolution of the corresponding racemates. This novel approach provides an alternative route for the biocatalytic production of optically active amino acids and their derivatives.
- Youshko, Maxim I.,Van Langen, Luuk M.,Sheldon, Roger A.,Svedas, Vytas K.
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p. 1933 - 1936
(2007/10/03)
-
- Platinum-catalyzed amidocarbonylation
-
The first example of platinum-catalyzed amidocarbonylation of aldehydes with amides and carbon monoxide is described. In contrast to precedent palladium catalysis, a remarkable ligand acceleration by phosphines was observed. Furthermore, an optically active N-acetyl amino acid was partially epimerized under the platinum-catalyzed conditions, while faster racemization was observed under the palladium catalysis.
- Sagae, Takahiro,Sugiura, Masaharu,Hagio, Hiroyuki,Kobayashi, Shu
-
p. 160 - 161
(2007/10/03)
-
- Synthesis of 2-[4′-(Ethylcarbamoyl)phenyl]-N-acetylglycine, the proposed structure for giganticine
-
A compound (1) with the structure proposed for giganticine, an antifeedant principle isolated from the root bark of Caloropis gigantea, has been successfully synthesized by two independent methods. Comparison of physical properties and spectroscopic data of 1 with giganticine revealed that they are different compounds. All available evidence suggests that the proposed structure of giganticine is incorrect.
- Suparpprom,Vilaivan
-
p. 1114 - 1116
(2007/10/03)
-
- N-Acyl imine and enamide intermediates in the palladium-catalyzed amidocarbonylation reaction
-
N-Acyl imines and enamides have been synthesized and subjected to the reaction conditions for palladium-catalyzed amidocarbonylation of aldehydes. These compounds were competent substrates resulting in the formation of N-acyl amino acids; however, the presence of water was found to be necessary. Direct study of the same amidocarbonylation reaction revealed that enamides could be detected during the course of the reaction. A slight enhancement in the yield of the amidocarbonylation is observed in the presence of radical inhibitors ruling out a meaningful radical pathway. The results are most consistent with a mechanism involving complex equilibration of the starting materials to a number of intermediates which can converge to a haloamidal that subsequently undergoes a palladium insertion.
- Freed, Dana A.,Kozlowski, Marisa C.
-
p. 3403 - 3406
(2007/10/03)
-
- Rhodium-catalysed racemisation of N-acyl α-amino acids
-
The first transition metal-catalysed racemisation of N-acyl α-amino acids, which is of importance for kinetic resolution processes, is described. Enantiomerically pure N-acyl α-amino acids were efficiently racemised under mild conditions using various rhodium complexes as catalysts, e.g. [Rh(cod)Cl]2, in the presence of phosphines. (C) 2000 Elsevier Science Ltd.
- Hateley, Martin J.,Schichl, Daniel A.,Kreuzfeld, Hans-J?rn,Beller, Matthias
-
p. 3821 - 3824
(2007/10/03)
-
- A new improved palladium-catalyzed amidocarbonylation
-
A new and improved variant of the palladium-catalyzed amidocarbonylation to yield N-acyl-α-amino acids is described. Using Pd/C as catalyst the products were prepared in good to excellent yields (up to 98 %). Advantages of the Pd/C-catalyst with regard to former catalyst systems are demonstrated by the preparation of N-substituted non-natural amino acids which are of current interest as structural units of peptoids.
- Beller, Matthias,Moradi, Wahed A.,Eckert, Markus,Neumann, Helfried
-
p. 4523 - 4526
(2007/10/03)
-
- Pronase catalysed peptide syntheses
-
A mixture of proteases from Streptomyces griseus (pronase), displaying a very broad substrate tolerance in the hydrolysis of peptides, has been studied for the first time systematically regarding their substrate specificity in peptide synthesis. It is demonstrated that pronase can be employed successfully for the formation of dipeptides with yields up to 95%. Pronase has also been employed successfully as catalyst for the enzyme assisted synthesis of a hexapeptide.
- Lobell, Mario,Schneider, Manfred P.
-
p. 319 - 325
(2007/10/03)
-
- Enantioselective hydrolytic reactions of rice bran lipase (RBL): A first report
-
Enantioselectivity has been observed in the hydrolysis of racemic N-acetyl amino acid esters with rice bran lipase (RBL). The enzyme shows selectivity towards the (S)-enantiomer. Products with high enantiomeric excess (e.e. >99%) are obtained depending upon the hydrophobicity of the amino acid as well as that of the leaving group.
- Fadnavis,Jadhav, Vasudev
-
p. 2361 - 2366
(2007/10/03)
-
- Reaction of organolead triacetates with 4-ethoxycarbonyl-2-methyl-4,5-dihydro-1,3-oxazol-5-one. The synthesis of α-aryl- and α-vinyl-N-acetylglycines and their ethyl esters and their enzymic resolution
-
4-Ethoxycarbonyl-2-methyl-4,5-dihydro-1,3-oxazol-5-one 7, which may be readily obtained from diethyl acetamidomalonate, undergoes high-yielding arylation and vinylation at the 4-position with organolead triacetates to give compounds which may be hydrolysed to give either the α-aryl- or α-vinyl-N-acetylglycine or the corresponding ethyl ester. The kinetic resolution of a number of these derivatives by enzymic hydrolysis of either the amide or ester function has been demonstrated.
- Morgan, Jacqueline,Pinhey, John T.,Sherry, Christopher J.
-
p. 613 - 619
(2007/10/03)
-
- Palladium-catalyzed amidocarbonylation - A new, efficient synthesis of N-acyl amino acids
-
For the first time palladium catalysts have been used successfully for the amidocarbonylation reaction. The activity of the cobalt catalysts that were used exclusively beforehand has now been exceeded by an order of magnitude, and the reaction can be performed under far milder conditions. Palladium-catalyzed amidocarbonylation reactions can now be used for the synthesis of a much wider range of N-acyl amino acids.
- Beller,Eckert,Vollmuller,Bogdanovic,Geissler
-
p. 1494 - 1496
(2007/10/03)
-
- -
-
Treatment of the readily available (S)-(+) and (R)-(-) enantiomers of 2-aminobutan-1-ol 1 with sodium hydride followed by benzyl chloride, or a substituted benzyl halide, afforded the corresponding O-benzyl bases 4-7 in good yields. These new bases are recommended for the large scale resolution of racemic acids. For instance, they proved efficient for the practical resolutions of α-methylsuccinic acid (±)-9, N-acetylphenylglycine (±)-11, N-acetyl-(4-hydroxyphenyl) glycine (±)-14 and N-chloroacetyl-(4-hydroxyphenyl) glycine (±)-15.
- Touet, Joel,Faveriel, Laurent,Brown, Eric
-
p. 1709 - 1720
(2007/10/02)
-
- Reaction of Organolead Triacetates with 4-Ethoxycarbonyl-2-methyloxazol-5-one. The Synthesis of α-Aryl and α-Vinyl N-Acetylglycine Ethyl Esters and Their Enzymic Resolution.
-
An efficient synthesis of the moisture-sensitive compound, 4-ethoxycarbonyl-2-methyloxazol-5-one, has been achieved.This compound undergoes high-yielding arylation and vinylation at the 4-position with organolead triacetates to give compounds which in water are converted to α-aryl and α-vinyl N-acetylglycine ethyl esters.These α-substituted glycine derivatives may be kinetically resolved in very good yield and high enantiomeric excess by enzymic hydrolysis of either the ester group or the amide function of the corresponding carboxylic acids.
- Morgan, Jacqueline,Pinhey, John T.
-
p. 9625 - 9628
(2007/10/02)
-
- A novel tea-bag methodology for enzymatic resolutions of α-amino acid derivatives in reverse micellar media
-
A novel tea bag methodology for resolution of methyl esters of N-acetyl- α-amino acids in reverse micellar medium of bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) in isooctane-chloroform using immobilized enzymes or microbial cells is presented. The methodology effectively solves the problems of substrate solubility, product separation and surfactant recycling and provides products in high yields (80 to 90%) and excellent optical purities (% ee 97 to >99%).
- Bhalerao,Rao,Fadnavis
-
p. 2109 - 2118
(2007/10/02)
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- O-Benzyl derivatives of (S)-(+) and (R)-(-)-2-aminobutan-1-ol as new resolving agents for racemic acids. Practical resolutions of N-acyl derivatives of phenylglycine and 4-hydroxyphenylglycine
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Treatment of the readily available (S)-(+) and (R)-(-)-2-aminobutan-1-ol 1 with sodium hydride followed by benzyl chloride, or a substituted benzyl halide, afforded the corresponding O-benzyl bases 2-5 in high yields. These new bases are recommended for the large scale resolution of racemic acids. For instance, they proved efficient for the practical resolution of N-acetylphenylglycine (±)-7, N-acetyl-(4-hyroxylphenyl)glycine (±)-9 and N-chloroacetyl-(4-hydroxyphenyl) glycine (±)-10.
- Touet, Joel,Faveriel, Laurent,Brown, Eric
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p. 2957 - 2960
(2007/10/02)
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- Racemization of Optically Active Aromatic N-Acetylamino Acids and Asymmetric Transformation of N-Acetyl-2-(4-hydroxyphenyl)glycine via Salt Formation with Optically Active α-Methylbenzylamine
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The racemization rates of N-acetyl-(S)-tyrosine, N-acetyl-(S)-phenylalanine, N-acetyl-(R)-2-(4-hydroxyphenyl)glycine , N-acetyl-(R)-2-phenylglycine, and N-acetyl-(S)-alanine were measured by use of (RS)-α-methylbenzylamine as base-catalyst.The first-order rate constant for racemization tended to increase with an increase in the polar substituent constant of the N-acetylamino acid side chain.The racemization appeared to be subject to the inductive effect by the side chain.An asymmetric transformation of (RS)-AcHpg by using (R)-MBA, based on the result of racemization, gave an optically pure salt of (R)-AcHpg with (R)-MBA by successive use of the filtrate as the solvent.Optically pure (R)-2-(4-hydroxyphenyl)glycine was separated from the salt in 87-90percent yield based on the starting (RS)-AcHpg.In addition, the asymmetric transformation of (R)-AcHpg was achieved by using (S)-MBA to give optically pure (S)-Hpg in 80percent yield after purification of the salt of (S)-AcHpg with (S)-MBA followed by hydrolysis.
- Shiraiwa, Tadashi,Sakata, Shinji,Natsuyama, Hisashi,Fujishima, Keiko,Miyazaki, Hideya,et al.
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p. 965 - 970
(2007/10/02)
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- Enzymes in organic synthesis: Use of subtilisin and a highly stable mutant derived from multiple site-specific mutations
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A subtilisin mutant (subtilisin 8350) derived from subtilisin BPN' via six-specific mutations (Met50Phe, Gly169Ala, Asn76Asp, Gln206Cys, Tyr217Lys, and Asn218Ser) was found to be 100 times more stable than the wild-type enzyme in aqueous solution at room temperature and 50 times more stable than the wild type in anhydrous dimethylformamide. Kinetic studies using ester, thio ester, and amide substrates, and the transition-state analogue inhibitor Boc-Ala-Val-Phe-CF3, indicate the both the wild-type and the mutant enzymes have very similar specificities and catalytic properties. The inhibition constant (K(i)) = 5.0 μM) for the wild-type enzyme is approximately 5 times that of the mutant enzyme (K(i)) = 1.1 μM), suggesting that the mutant enzyme binds the reaction transition state more strongly than the wild-type enzyme. This result is consistent with the observed rate constants for the corresponding ester and amide substrates; i.e. the k(cat)/k(m) values for the mutant are larger than those for hhe wild-type enzyme. Application of the mutant enzyme and the wild-type enzyme to organic synthesis has been demonstrated in the regioselective acylation of nucleosides in anhydrous dimethylformamide (with 65-100% regioselectivity at the 5'-position), in the enantioselective hydrolysis of N-protected and unprotected common and uncommon amino acid esters in water (with 85-98% enantioselectivity for the L-isomer), and in the synthesis of di- and oligopeptides via aminolysis of N-protected amino acid and peptide esters. The enzymatic peptide synthesis was carried out under high concentrations of DMF (~50%) to improve substrate solubility and to minimize enzymatic peptide cleavage. Low enantioselectivity was observed in the enzymatic transformation of non-amino acid alcohols and acids.
- Wong,Chen,Hennen,Bibbs,Wang,L iu,Pantoliano,Whitlow,Bryan
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p. 945 - 953
(2007/10/02)
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- Novel β-lactam antibiotics
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Antibacterially active and animal growth-promoting novel β-lactam compounds of the formula STR1 in which R1 represents the radical STR2 Y representing N or CR9, or Y--R7 representing >C=O or >C=N--R7, Z representing O, S, or NR10, and R2 represents hydrogen or a protective group.
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- A general and accurate nmr determination of the enantiomeric purity of α-aminoacids and α-aminoacid derivatives
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Derivatization of α-aminoacids, α-aminoesters and α-aminolactones as N-acetyl derivatives allow the accurate NMR determination of the enantiomeric purity. In these conditions the major coordination site with a chiral shift reagent will correspond to the NMR observation site. Experimental factors leading to the highest ΔΔδ values are ascertained. No straightforward correlation with absolute configurations can be established.
- Calmes, Monique,Daunis, Jacques,Jacquier, Robert,Verducci, Jean
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p. 2285 - 2292
(2007/10/02)
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