- Chemical dynamic kinetic resolution and S/R interconversion of unprotected α-amino acids
-
Reported herein is the first purely chemical method for the dynamic kinetic resolution (DKR) of unprotected racemic α-amino acids (α-AAs), a method which can rival the economic efficiency of the enzymatic reactions. The DKR reaction principle can be readily applied for S/R interconversions of α-AAs, the methodological versatility of which is unmatched by biocatalytic approaches. The presented process features a virtually complete stereochemical outcome, fully recyclable source of chirality, and operationally simple and convenient reaction conditions, thus allowing its ready scalability. A quite unique and novel mode of the thermodynamic control over the stereochemical outcome, including an exciting interplay between axial, helical, and central elements of chirality is proposed. A new player for DKR: Dynamic kinetic resolution of α-amino acids has been achieved upon complexation with nickel(II) and a chiral ligand derived from optically active bis(naphthyl)amine under thermodynamic control, thus affording excellent diastereoselectivities and chemical yields. The S to R interconversion of α-amino acids is also described.
- Takeda, Ryosuke,Kawamura, Akie,Kawashima, Aki,Sato, Tatsunori,Moriwaki, Hiroki,Izawa, Kunisuke,Akaji, Kenichi,Wang, Shuni,Liu, Hong,Ace?a, José Luis,Soloshonok, Vadim A.
-
-
Read Online
- Tetracyclic compound as plasma kallikrein inhibitor and application thereof
-
The invention provides a tetracyclic plasma kallikrein inhibitor compound which is novel in structure, good in activity and high in selectivity, and can be widely applied to prevention or treatment of diseases related to plasma kallikrein activity.
- -
-
-
- Tricyclic compound as plasma kallikrein inhibitor and application thereof
-
The invention provides a tricyclic plasma kallikrein inhibitor compound which is novel in structure, good in activity and high in selectivity. The tricyclic plasma kallikrein inhibitor compound can be widely applied to prevention or treatment of diseases related to plasma kallikrein activity.
- -
-
-
- Tetracyclic compound as plasma kallikrein inhibitor and application thereof
-
The invention provides a tetracyclic plasma kallikrein inhibitor compound which is novel in structure, good in activity and high in selectivity, and can be widely applied to prevention or treatment of diseases related to plasma kallikrein activity.
- -
-
Paragraph 0138; 0140; 0143-0144
(2021/06/23)
-
- Enantioselective inclusion of pyrene-1-sulfonate salts of α-amino acids with crystals of α-cyclodextrin
-
Enantioselective inclusion of α-amino acids with crystals of α-cyclodextrin (α-CD) has been achieved by converting the amino acids into sulfonate salts with pyrene-1-sulfonic acid (PyS). For example, crystals of α-CD selectively include L-leucine/PyS (1:1) salt in a host/guest ratio of ~1 with 92%ee from a solution of the racemic salt in ethanol/N-methylformamide (91:9) at 40 °C. Under conditions optimized for individual amino acids, the PyS salts of valine, phenylalanine, and methionine are also included with good enantioselectivities (up to 86%ee). Mechanistic studies for the inclusion of leucine/PyS salt reveals that the enantioselectivity originates from the difference in stability between the inclusion complexes of D- and L-leucine/PyS salts with α-CD in crystals.
- Hattori, Tetsutaro,Kitamoto, Yuichi,Maeda, Tetsuya,Miyoshi, Ikuko,Morohashi, Naoya
-
-
- β,γ-diamino acids as building blocks for new analogues of Gramicidin S: Synthesis and biological activity
-
We describe here the synthesis and biological activity study of a pair of diastereomeric analogues of Gramicidin S using β,γ-diamino acids as β-turn mimic. The synthesis of the orthogonally protected β,γ-diamino acids was achieved in 6 steps starting from D-alanine. The analogues were then synthesized in solution phase and on solid phase. Biological activity tests showed that, compared with Gramicidin S, both analogues exerted diminished hemolytic activity while they retained interesting antibacterial activity.
- Wan, Yang,Stanovych, Andrii,Gori, Didier,Zirah, Séverine,Kouklovsky, Cyrille,Alezra, Valérie
-
supporting information
p. 122 - 128
(2018/03/06)
-
- Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts
-
Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.
- Sabatini, Marco T.,Karaluka, Valerija,Lanigan, Rachel M.,Boulton, Lee T.,Badland, Matthew,Sheppard, Tom D.
-
supporting information
p. 7033 - 7043
(2018/05/04)
-
- Substrate specificity of an actively assembling amyloid catalyst
-
In the presence of Zn2+, the catalytic, amyloid-forming peptide Ac-IHIHIQI-NH2, was found to exhibit enhanced selectivity for hydrophobic p-nitrophenyl ester substrates while in the process of self-assembly. As opposed to the substrate p-nitrophenyl acetate, which was more effectively hydrolyzed with Ac-IHIHIQI-NH2 in its fully fibrillar state, the hydrophobic substrate Z-L-Phe-ONp was converted with a second-order rate constant more than 11-times greater when the catalyst was actively assembling. Under such conditions, Z-L-Phe-ONp hydrolysis proceeded at a greater velocity than the more hydrophilic and otherwise more labile ester Boc-L-Asn-ONp. When assembling, the catalyst also showed increased selectivity for the L-enantiomer of Z-Phe-ONp. These findings suggest the occurrence of increased interactions of hydrophobic moieties of the substrate with exposed hydrophobic surfaces of the assembling peptides and present valuable features for future de novo design consideration.
- Heier, Jason L.,Mikolajczak, Dorian J.,B?ttcher, Christoph,Koksch, Beate
-
-
- Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity
-
Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [3H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [3H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy.
- Zou, Mu-Fa,Keck, Thomas M.,Kumar, Vivek,Donthamsetti, Prashant,Michino, Mayako,Burzynski, Caitlin,Schweppe, Catherine,Bonifazi, Alessandro,Free, R. Benjamin,Sibley, David R.,Janowsky, Aaron,Shi, Lei,Javitch, Jonathan A.,Newman, Amy Hauck
-
p. 2973 - 2988
(2016/05/19)
-
- Glycosylation mediated - BAIL in aqueous solution
-
The use of Br?nsted acid ionic liquid (BAIL) as a catalyst for the activation of unreactive and unprotected glycosyl donors has been demonstrated for the first time in aqueous solution.
- Delacroix, Sébastien,Bonnet, Jean-Pierre,Courty, Matthieu,Postel, Denis,Van Nhien, Albert Nguyen
-
-
- Self-assembly of a catalytic multivalent peptide-nanoparticle complex
-
Catalytically active peptide-nanoparticle complexes were obtained by assembling small peptide sequences on the surface of cationic self-assembled monolayers on gold nanoparticles. When bound to the surface, the peptides accelerate the transesterification
- Zaramella, Davide,Scrimin, Paolo,Prins, Leonard J.
-
supporting information; experimental part
p. 8396 - 8399
(2012/07/14)
-
- Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities
-
Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.
- King, Amber M.,Salomé, Christophe,Dinsmore, Jason,Salomé-Grosjean, Elise,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Kohn, Harold
-
supporting information; experimental part
p. 4815 - 4830
(2011/10/01)
-
- A bismuth(III)-catalyzed friedel-crafts cyclization and stereocontrolled organocatalytic approach to (-)-platensimycin
-
A high yielding route to the (-)-platensimycin core is communicated. This entailed the discovery of Bi(OTf)3 to catalyze a Friedel-Crafts cyclization of a free lactol, supplemented by LiClO4 to suppress the Lewis basicity of the sulfonate group. After TBAF-promoted cyclodearomatization, a diastereoselective conjugate reduction of a dienone was achieved by adopting amine-based organocatalytic rationales to reverse the inherent steric control of the substrate.
- Eey, Stanley T.-C.,Lear, Martin J.
-
supporting information; experimental part
p. 5510 - 5513
(2011/03/18)
-
- 1,4-Cyclohexadiene with Pd/C as a rapid, safe transfer hydrogenation system with microwave heating
-
A method for the rapid, safe hydrogenation of alkenes and deprotection of benzyl ethers and carboxybenzyl amides is described using catalytic transfer hydrogenation under microwave heating conditions. Commonly available Pd/C catalyst is extremely effective with 1,4-cyclohexadiene as the hydrogen transfer source. In general, the reactions are complete within five minutes at 100 °C.
- Quinn, John F.,Razzano, Dana A.,Golden, Kathryn C.,Gregg, Brian T.
-
scheme or table
p. 6137 - 6140
(2009/04/05)
-
- Multicomponent diversity and enzymatic enantioselectivity as a route towards both enantiomers of α-amino acids-a model study
-
A model study on a new, enantioconvergent method for the synthesis of chiral, nonracemic α-amino acids is presented. α-Acetoxyamides obtained in a Passerini multicomponent reaction are selectively hydrolyzed by Wheat Germ lipase. Studies on conversion of the thus obtained, enantiomerically enriched α-hydroxyamides into α-aminoamides are presented. Products of these reactions are then hydrolyzed to give α-amino acids.
- Szymanski, Wiktor,Ostaszewski, Ryszard
-
p. 2667 - 2671
(2007/10/03)
-
- α-Chymotrypsin-catalyzed peptide synthesis in frozen aqueous solution using N-protected amino acid carbamoylmethyl esters as acyl donors
-
A kinetically controlled peptide synthesis catalyzed by α-chymotrypsin was performed in frozen aqueous solution (ice, -24 °C). The yield of the peptide was significantly improved by the use of the carbamoylmethyl (Cam) ester as the acyl donor instead of the conventional ethyl ester. The peptide yield increased up to ca. 90% when N-benzyloxycarbonyl (CBZ)-Phe-OCam and H-Phe-NH2 were used as the acyl donor and nucleophile, respectively. Such an improvement of the peptide yield in ice was also observed in the coupling of other CBZ-amino acid Cam esters as acyl donors. Furthermore, this approach was applied to the synthesis of peptides containing d-amino acids. The peptides such as CBZ-d-Phe-Phe-NH2, CBZ-Phe-d-Phe-NH2 and CBZ-d-Phe-d-Phe-NH2 were also obtained in excellent to moderate yields in ice. A high diastereoselectivity towards the l-l peptide was observed when the racemic amino acid Cam ester was used as the acyl donor in ice.
- Salam, Sayed Mohiuddin Abdus,Kagawa, Ken-Ichi,Kawashiro, Katsuhiro
-
-
- Diastereoselective cationic tandem cyclizations to N-heterocyclic scaffolds: Total synthesis of (-)-dysibetaine PP
-
Herein, we report a short and diastereoselective synthesis of the natural product (-)-dysibetaine PP. The key step in the synthetic sequence is a novel highly diastereoselective tandem-cyclization reaction of an enantiomerically pure dipeptide. This cyclization methodology is applied in the synthesis of a broader range of N-heterocyclic scaffolds.
- IJzendoorn, Denis R.,Botman, Peter N. M.,Blaauw, Richard H.
-
p. 239 - 242
(2007/10/03)
-
- The preparation and alkylation of a butanedione-derived chiral glycine equivalent and its use for the synthesis of α-amino acids and α,α-disubstituted amino acids
-
A benzyloxycarbonyl protected glycine equivalent 2 has been prepared in enantiopure form and has been used in the synthesis of both α-substituted amino acids and α,α-disubstituted amino acids. The process involved deprotonation to form the corresponding enolates which underwent stereoselective alkylation with various electrophiles and upon hydrolysis gave the corresponding amino acid derivatives as enantiomerically pure products.
- Harding, Christopher I.,Dixon, Darren J.,Ley, Steven V.
-
p. 7679 - 7692
(2007/10/03)
-
- Fairly marked enantioselectivity for the hydrolysis of amino acid esters by chemically modified enzymes
-
The hydrolysis (deacylation) of enantiomeric substrates by the chemically modified enzymes decanoyl-α-chymotrypsin and decanoyl-trypsin was studied. Reaction activity for decanoyl-α-chymotrypsin was lower than that for the native enzyme, although intriguingly the enantioselectivity was markedly enhanced as compared with the native enzyme. In particular, the apparently complete enantioselective catalysis was attained for the hydrolytic cleavage of p-nitrophenyl N-dodecanoyl- D(L)-phenylalaninates. The enhancement of enantioselectivity, however, was not observed for decanoyl-trypsin. These results suggest that the chemically modified α-chymotrypsin by addition of hydrophobic groups has promoted enantioselectivity for the hydrolysis of hydrophobic esters.
- Yano, Yoshihiro,Shimada, Kenji,Okai, Jiro,Goto, Koichi,Matsumoto, Yoko,Ueoka, Ryuichi
-
p. 1314 - 1318
(2007/10/03)
-
- A 2,3-butanedione protected chiral glycine equivalent--a new building block for the stereoselective synthesis of enantiopure N-protected alpha-amino acids.
-
A new chiral glycine equivalent 7 has been synthesised from glycidol using a chiral memory protocol, and its use in the synthesis of N-Z protected alpha-amino acids was demonstrated in a series of diasteroselective lithium enolate alkylation reactions and subsequent acid hydrolyses.
- Dixon, Darren J,Harding, Christopher I,Ley, Steven V,Tilbrook, D Matthew G
-
p. 468 - 469
(2007/10/03)
-
- Enantioselective Enzymatic Cleavage of N-Benzyloxycarbonyl Groups
-
A new enzymatic process for the enantioselective cleavage of N-benzyloxycarbonyl (Cbz) groups from protected amino acids and related compounds has been developed. The Cbz-deprotecting enzyme was isolated from cell extracts of Sphingomonas paucimobilis SC 16113 and purified to homogeneity. The purified protein has a molecular weight of 155,000 daltons and a subunit size of 44,000 daltons.
- Patel, Ramesh N.,Nanduri, Venkata,Brzozowski, David,McNamee, Clyde,Banerjee, Amit
-
p. 830 - 834
(2007/10/03)
-
- Cyclodextrin-mediated deacylation of amino acid esters with marked stereoselectivity.
-
With respect to the hydrolysis (deacylation) of Z-D(L)-amino acid esters (N-(benzyloxycarbonyl)-D(L)-amino acid p-nitrophenyl esters) mediated by alpha-, beta- and gamma-cyclodextrins (CyDs), a remarkably high enantioselectivity (L/D=9.0) was observed for the deacylation of Ala substrate with gamma-CyD. The kinetic results on the basis of the Michaelis-Menten principle indicate that the enantioselectivity should be mainly originated in the deacylation process of substrates following the formation of gamma-CyD-substrate (1 : 1) complexes. The computer modeling (molecular mechanics) studies on the inclusion complexes are also described.
- Goto, Koichi,Nakashima, Kentaro,Tanoue, Osamu,Nukushina, Satoshi,Toudo, Isao,Imamura, Chikara,Ihara, Yasuji,Matsumoto, Yoko,Ueoka, Ryuichi
-
p. 1283 - 1285
(2007/10/03)
-
- Enantioselective hydrolysis of amino acid esters by apomyoglobin: Perfect kinetic resolution of a phenylalanine derivative
-
Apoprotein of horse-heart myoglobin promoted enantioselective hydrolysis of 4-nitrophenyl esters of amino acids, which allowed nearly perfect kinetic resolution of racemic N-Boc-phenylalanine ester (Boc-Phe-ONp).
- Tomisaka,Ishida,Konishi,Aida
-
p. 133 - 134
(2007/10/03)
-
- Facile and selective cleavage of allyl ethers, amines and esters using polymethylhydrosiloxane-ZnCl2/Pd(PPh3)4
-
Allyl deprotection to liberate free hydroxy, amino and acid groups from the corresponding allyl ethers, amines and esters is achieved under mild conditions. The reagent combination employed for this transformation is polymethylhydrosiloxane (PMHS), ZnCl2 and Pd(PPh3)4.
- Chandrasekhar,Raji Reddy,Jagadeeshwar Rao
-
p. 3435 - 3438
(2007/10/03)
-
- Simple and efficient preparation of (R)- and (S)-enantiomers of α-carbon deuterium-labelled α-amino acids
-
A procedure for the synthesis of (R)- and (S)-enantiomers of α-carbon deuterium-labelled α-amino acids, exemplified for (R)- and (S)-[2-2H1]-Leu is described. Starting from the respective (S)- or (R)-enantiomer or from the racemic mixture of an α-amino acid the selective proton exchange at the α-carbon is carried out by racemization via a Schiff base in monodeuterated acetic acid as solvent which serves as deuterium source. After N-protection the racemic mixture is liquid chromatographically separated into the individual (R)- and (S)-enantiomers on preparative scale employing a chiral anion exchanger based on carbamoylated quinine as chiral selector. After deprotection the enantiomerically pure products can be obtained in good yields.
- Mitulovi, Goran,Laemmerhofer, Michael,Maier,Lindner, Wolfgang
-
p. 449 - 461
(2007/10/03)
-
- Inhibitors of β-amyloid protein production
-
This invention relates to compounds and pharmaceutical compositions, and methods for inhibiting or preventing the amyloid protein deposits in the brain which are associated with Alzheimer's disease and aged Down's syndrome patients. More particularly, it relates to the treatment of Alzheimer's disease.
- -
-
-
- Enantioselective hydrolysis of an α-amino acid ester in sugar-derived surfactant micelles
-
p-Nitrophenyl ester of D-phenylalanine hydrogen bromide was hydrolyzed much faster than that of the corresponding L-isomer in the micelles formed with sugar-derived surfactants such as N-dodecylmaltobionamide. The enantioselectivity was largely affected by the alkyl chain length as well as the structure of the sugar part of the surfactant.
- Kida, Toshiyuki,Isogawa, Kazuhiko,Zhang, Wanbin,Nakatsuji, Yohji,Ikeda, Isao
-
p. 4339 - 4342
(2007/10/03)
-
- Empirical rules for the enantiopreference of lipase from Aspergillus niger toward secondary alcohols and carboxylic acids, especially α-amino acids
-
Lipase from Aspergillus niger (ANL, Amano lipase AP) catalyzes enantioselective hydrolysis and acylation reactions. To aid in the design of new applications of this lipase, we propose two empirical rules that predict which enantiomer reacts faster. For secondary alcohols, a rule proposed previously for other lipases also works for ANL, but with lower reliability (77%, 37 of 48 examples). For carboxylic acids, we examined both crude and partially-purified ANL because commercial ANL contains contaminating hydrolases. Partial purification removed a contaminating amidase and increased the enantioselectivity of ANL toward many α-amino acids, including cyclic amino acids. Unlike other lipases, ANL readily accepts positively-charged substrates and shows the highest enantioselectivity towards α-amino acids. Although a rule based on the sizes of the substituents could not predict the fast-reacting enantiomer, a rule limited to α-amino acids did predict the fast-reacting enantiomer. We estimate that the charged α-amino group contributes a factor of 40-100 (ΔΔ≠ = 2.2-2.7 kcal/mol) to the enantioselectivity of ANL towards carboxylic acids.
- Janes, Lana E.,Kazlauskas, Romas J.
-
p. 3719 - 3733
(2007/10/03)
-
- Relaxing substrate specificity in antibody-catalyzed reactions: Enantioselective hydrolysis of N-Cbz-amino acid esters
-
For a catalytic antibody to be generally useful for organic synthetic chemistry, it must be able to accept a broad range of substrates, yet retain high selectivity. In this work, we propose a hapten design to endow antibody catalysts with two opposing qualities, such as high enantioselectivity and broad substrate specificity. Racemic hapten 2 induced two separate classes of catalytic antibodies to hydrolyze either the L- or D-isomers of N-Cbz-amino acid esters 1. In the kinetic resolution of racemic ester 9, antibodies 7G12 and 3G2 gave 96% ee of L-10 and 94% ee of D-10, respectively. In addition, antibody 7G12 displayed broad substrate specificity, hydrolyzing the L-esters of Ala (1a), Leu (1b), Norleu (1c), Met (1d), Phe (1e), Val (1f), and phenylglycine (1g) with high enantioselectivity. Antibody 3G2 also hydrolyzed the D-isomers of these esters without sacrificing the enantioselectivity. This observation suggests that the use of haptens that fit snugly into the antigen-combining site, and leave the linker moiety outside, is an effective approach for the generation of catalytic antibodies with high selectivity and broad substrate applicability.
- Tanaka, Fujie,Kinoshita, Keiko,Tanimura, Ryuji,Fujii, Ikuo
-
p. 2332 - 2339
(2007/10/03)
-
- Enantioselectivity enhancement of ester cleavage by a β-sheet polypeptide containing catalytic triads in a serine protease
-
Catalytic activity and enantioselectivity of Poly(Asp-Leu-His-Leu-Ser-Leu) with a β-sheet structure for the hydrolysis of chiral phenylalanine p-nitrophenyl esters were compared with those of the peptide hexamer, under various conditions. The relationship
- Fukushima, Yasumasa
-
p. 2269 - 2274
(2007/10/03)
-
- Poststatin, a new inhibitor of prolyl endopeptidase. V. Endopeptidase inhibitory activity of poststatin analogues
-
Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The α-ketone was essential and the S configuration was preferable to the R configuration in the β-substituted-β-amino-α-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P4 position and proline into the P2 position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)-3-amino-2-oxovaleryl-D- leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.
- Tsuda, Makoto,Muraoka, Yasuhiko,Nagai, Machiko,Aoyagi, Takaaki,Takeuchi, Tomio
-
p. 890 - 899
(2007/10/03)
-
- Chiral Lipophilic Ligands. 1. Enantioselective Cleavage of α-Amino Acid Esters in Metallomicellar Aggregates
-
Several chiral ligands (1a,b, 2a-d), their marked lipophilic structure featuring a binding subunit comprising a 2-substituted pyridine, a tertiary amine, and a hydroxyl, have been synthesized and their complexes with Cu(II), Zn(II), or Co(II) ions investigated in homomicellar or comicellar aggregates as enantioselective catalysts of the cleavage of p-nitrophenyl esters of α-amino acids (Phe, Phg, Leu).Rate accelerations up to 3 orders of magnitude over the Cu(II) catalyzed hydrolysis and enantioselectivities ranging from 3.2 to 11.6 have been observed.In each case explored, the chiral ligand reacts faster with the enantiomeric substrate of oposite absolute configuration.Several pieces of evidence indicate that the effective cleavage process in micellar aggregates involves the following: (a) the formation of a ternary (ligand-metal ion-substrate) complex; (b) within such a complex, a nucleophilic attack of the ligand hydroxyl on the substrate to give a transacylation intermediate; and (c) the metal ion promoted hydrolysis of the transacylation intermediate with a relatively fast turnover of the catalyst.Such a mode of action does not operate outside or in the absence of micellar aggregates: in this case, the hydroxyl is displaced by water that acts as the nucleophile in a slower (less enantioselective) process.The enantioselectivity of the transacylation process appears to be little affected by the steric interaction between the substituents at the chiral center of the amino acid ester and of the ligand.We suggest that the enantioselectivity arises from a different hydration, due to steric reasons, of the diastereomeric complexes comprising the two enantiomers of the substrate.As a consequence, the relevance of the competing mechanisms of cleavage of the ester, the first one, faster, involving the hydroxyl and the second one, slower, involving a Cu(II)-bound water molecule, may be different.In the case of the less hydrated, more hydrophobic R-S or S-R complex the former, faster, mode of cleavage may be more relevant than in the case of the more hydrated, less hydrophobic, S-S or R-R complex.
- Scrimin, Paolo,Tecilla, Paolo,Tonellato, Umberto
-
p. 4194 - 4201
(2007/10/02)
-
- Synthesis of a 14-membered cyclic peptide model of the CFG rings of ristocetin A and observations on atropdiastereoisomerism
-
Two routes for the synthesis of a 14-membered heterodetic cyclic peptide as a model for the CFG ring system of the antibiotic ristocetin A (2) are described. The key aryl ether bonds for this molecule were constructed by using the reaction of phenoxides from (hydroxyaryl)glycine derivatives with tricarbonyl(3-methoxy-2-methylchlorobenzene)manganese hexafluorophosphate (11). This coupling reaction can be performed in the presence of protected amino acids and dipeptides without racemization of the sensitive arylglycine. Stereoselective introduction of the F-ring glycine side chain was accomplished by reaction of the aryl ether manganese complexes with Schollkopf's bislactim glycine enolate equivalent. The product(s) from this reaction were demetalated and aromatized by treatment with N-bromosuccinimide. Deprotection of the aromatized compounds followed by cycloamidation furnished two atrodiastereomeric cyclic peptides corresponding to the target molecule, the structures of which were assigned on the basis of 2D-NMR NOESY experiments coupled with molecular modeling. One of the product molecules corresponds closely to the structure that has been proposed for the CFG ring system of ristocetin, except for the orientation of the w3 amide group.
- Pearson,Shin
-
p. 2314 - 2323
(2007/10/02)
-
- Mechanism of Enantioselective Ester Cleavage by Histidine-Containing Dipeptides at a Micellar Interface
-
Chiral p-nitrophenyl esters derived from the amino acid phenylalanine are cleaved by histidine-containing dipeptides at a micellar interface.High enantioselectivities (up to kL/kD = 30.4 at 0 deg C) are observed.Both the substrates and the catalysts contain an alternating sequence of hydrophobic and hydrophilic groups.Due to the need for hydration of the hydrophilic groups, the hydrophobic groups cannot dissolve completely into the micellar hydrocarbon phase.The kinetic data suggest that the micellar interface is capable of discriminating between transition states that have different hydrophilic and hydrophobic properties.One of the diastereomeric transition states is characterized by a hydrogen bond between the amide CO group of the ester and an NH group of the histidine-containing dipeptide.Upon formation of this hydrogen bond these polar CO and NH groups lose their hydrophilicity which allows the transfer of the adjacent apolar groups to the micellar hydrocarbon phase.The other diastereomeric transition state cannot form this hydrogen bond and the hydrophobic groups remain hydrated.Consequently, the latter transition state is of higher energy.The kinetic data reveal that it is important to prevent steric hinderance between the reactants in order to allow the unhindered formation of the hydrogen bond.
- Cleij, Marco C.,Drenth, Wiendelt,Nolte, Roeland J. M.
-
p. 3883 - 3891
(2007/10/02)
-
- 3,5-substituted 4,5-dihydroisoxazoles as transglutaminase inhibitors
-
The present invention is directed to certain 3,5 substituted, 4,5-dihydroisoxazoles, and methods for their use. These compounds are transgulatminase inhibitors, and are particularly effective in the inhibition of epidermal transglutaminase and the treatment of acne.
- -
-
-
- Porcine Pancreatic Lipase Catalyzed Enantioselective Hydrolysis of Esters of N-Protected Unusual Amino Acids
-
Porcine pancreatic lipase catalyzed the highly enantioselective hydrolysis of a kind of α-substituted carboxylic esters, i.e., the 2,2,2-trifluoroethyl esters of the N-benzyloxycarbonyl derivatives of unusual amino acids.
- Miyazawa, Toshifumi,Iwanaga, Hitoshi,Ueji, Shinichi,Yamada,Takashi,Kuwata, Shigeru
-
p. 2219 - 2222
(2007/10/02)
-
- Optical Resolution of Unusual Amino-Acids by Lipase-catalysed Hydrolysis
-
The 2-chloroethyl esters of the N-benzyloxycarbonyl (Z) derivatives of several unusual amino-acids are converted by Aspergillus niger lipase into enantiomerically enriched Z-amino-acids with fairly high optical purities, the L-enantiomers being preferentially hydrolysed.
- Miyazawa, Toshifumi,Takitani, Tadanori,Ueji, Shinichi,Yamada, Takashi,Kuwata, Shigeru
-
p. 1214 - 1216
(2007/10/02)
-
- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
-
A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
-
p. 1125 - 1128
(2007/10/02)
-
- Membrane Matrix for the Hydrolysis of Amino Acid Esters with Marked Enantioselectivity
-
The stereoselective hydrolysis of the long-chain substrate (p-nitrophenyl n-dodecanoyl-D(L)-phenylalaninate, D(L)-S12) in surfactant aggregates has been found to be easily controlled by changing the reaction temperature, amino acid sequence in peptide cat
- Ueoka, Ryuichi,Matsumoto, Yoko,Moss, Robert A.,Swarup, Shanti,Sugii, Atsushi,et al.
-
p. 1588 - 1595
(2007/10/02)
-
- Amino alcohols as C-Terminal Protecting Groups in Peptide Synthesis
-
The synthesis of peptides using amino alcohols as C-terminal protecting groups is described.C-Terminal protection of amino acid could be accomplished by reduction of the terminal carboxyl group to a hydroxymethyl group, and regeneration of the carboxyl group could be achieved by Jones' oxidation.This method was applied to the formation of di- and tripeptides.
- Kashima, Choji,Harada, Kazuo,Fujioka, Yoko,Maruyama, Tatsuya,Omote, Yoshimori
-
p. 535 - 540
(2007/10/02)
-
- PAPAIN-ASSISTED RESOLUTION OF NATURAL AND XENOBIOTIC α-AMINO ACIDS
-
A new and convenient method for the preparation of pure enantiomers of α-amino acids is described.Industrial papain, catalyzes the synthesis of L-Z-amino acid ethyl esters in ethanolic medium, with good yields.These esters are obtained from DL-Z-amino acids with 100percent optical purity.Unreactive D-Z-amino acids are readily isolated from reaction medium.Physical constants of natural and xenobiotic L-Z-amino acid esters and D-Z-amino acids are described.
- Moriniere, J. L.,Danree, B.,Lemoine, J.,Guy, A.
-
p. 441 - 444
(2007/10/02)
-
- HYDROLYSE ENANTIOSELECTIVE D'ESTERS D'AMINOACIDE CATALYSEE PAR L'IMIDAZOLE DANS DES MICELLES INVERSES CHIRALES.1300
-
This paper reports the study of the imidazole catalyzed hydrolysis of enantiomeric pairs of three aminoacid esters in reversed micelles prepared from water, heptane and a combination of both racemic or chiral surfactants and of both racemic or chiral (S)2-octanol as cosurfactants.The enantioselectivity observed is important in the combination of chiral surfactant with racemic cosurfactant, and small in the combination of racemic surfactant with chiral cosurfactant, when ω = 20 (ω = / ).This enantioselectivity is also affected by the nature of the cosurfactant, the size of micelles and the nature of the substrate.The results prove that the reaction occurs effectively in a chiral microenvironment, the micelle membrane, and indicate that the cosurfactant is actually present in this membrane.
- Andriamanampisoa, R.,Boyer, B.,Lamity, G.,Roque, J. P.
-
-
- Stereoselective Micellar Catalysis. Part V. Deacylation Behaviour in the Cleavage of Enantiomeric Esters by Optically Active Catalysts containing the Imidazolyl Group
-
The rate constants of both acylation and deacylation in the cleavage of the enantiomers of amino acid p-nitrophenyl esters catalysed by optically active catalysts containing the imidazolyl group have been determined in the presence of surfactant micelles
- Ihara, Yasuji,Okamoto, Mari,Kawamura, Yoeko,Nakanishi, Eiji,Nango, Mamoru,Koga, Joichi
-
p. 607 - 612
(2007/10/02)
-
- UTILISATION DES HYDROLASES EN CHIMIE ORGANIQUE: SYNTHESE DE LIAISONS ESTER ET AMIDE CATALYSEE PAR LA PAPAINE INDUSTRIELLE
-
The use of hydrolases in organic chemistry: synthesis of amide and ester bonds catalyzed by industrial papain.Industrial papain, which is readily available, catalyzed the synthesis of L-Z-alanine ethyl ester (L-ZAEt) in organic medium, under different conditions, with good yields.L-ZAEt was obtained from DL-Z-alanine with 100 percent optical purity.We studied the effects of pH, the solvent/substrate and papain/substrate ratios and the type of organic solvent added, on the L-ZAEt yield.Unreactive D-ZA was also easily isolated from the aqueous phase with good optical purity.This attractive method has been applied to other N-Z-amino acid esters with the same succes.This procedure has been developed for the preparation of peptides using carboxylic or phosphonic substrates.These peptides have anti-bacterial activity. enzymatic catalysis / papain / chymopapain / stereospecific esterification of carboxylic amino acids / dipeptides / phosphonopeptides / anti-bacterial activity
- Moriniere, Jean-Luc,Danree, Bernard,Guy, Alain
-
p. 347 - 358
(2007/10/02)
-
- Conversion of Serine β-Lactones to Chiral α-Amino Acids by Copper-Containing Organolithium and Organomagnesium Reagents
-
A method for the synthesis of optically pure α-amino acids has been developed.Mono- and di-N-protected α-amino-β-lactones 3a (L, R1=H, R2=COOCH2Ph (Z)), 3b (D, R1=H, R2=Z), 3c (L, R1=CH2Ph, R2=Z), and 3d (D, R1=CH2Ph, R2=Z) are readily produced by cyclization of the corresponding serine derivatives 2 under modified Mitsunobu conditions without loss of optical purity.Stereochemical integrity was demonstrated by conversion of 3 to 2-methoxy-2-(trifluoromethyl)phenylacetate esters 6 and analysis by HPLC, (19)F NMR, and (1)H NMR.Reaction of 3 with organolithium-derived cuprate reagents (R2CuLi or R2Cu(CN)Li2) at low temperature produces N-protected α-amino acids by attack at the β-methylene group.Yields of di-N-protected amino acids are generally higher (ca. 50-75percent), but some decrease in enantiomeric excess (ee) can occur (0-27percent).In contrast, the mono-N-protected β-lactones 3a and 3b give slightly lower yields (ca. 44-62percent) but negligible decrease in ee (0-1.7percent) with the exception of Ph2Cu(CN)Li2 (67percent loss of ee).However, the use of Cu(I)-catalyzed Grignard (RMgCl) additions gives better yields (44-83percent), complete retention of optical purity ( 99.4percent), and fewer side products.Reductive removal of the protecting groups in a single step (H2/Pd-C or Na/NH3) affords the free α-amino acids in 91-99percent yield.Their stereochemical purity was determined by conversion to the corresponding N-(-)-camphanoyl methyl esters and analysis by gas chromatography and (1)H NMR spectroscopy.
- Arnold, Lee D.,Drover, John C. G.,Vederas, John C.
-
p. 4649 - 4659
(2007/10/02)
-
- Pharmaceutical composition having an excellent absorption property
-
A compound represented by the formula: STR1 wherein R1 is a hydrogen atom, a fluorine atom, a nitro group, a hydroxyl group or a hydroxyl group protected by an esterifying group; X is CO or SO2 ; --Y-- is a straight bond, a lower alkylene group, a substituted or unsubstituted vinylene group, or group having the formula --CH2 --O-- or --O--CH2 --; R2 is a substituted or unsubstituted phenyl or naphthyl group, or R2 --Y--CO is N-benzyloxycarbonylphenylalanyl, N-benzyloxycarbonyl-4-fluorophenylalanyl or N-(m-methoxycinnamoyl)-phenylalanyl group; or a non-toxic salt thereof is disclosed along with pharmaceutical compositions containing these compounds and methods of using these compositions to increase the rate of absorption of medicines.
- -
-
-
- Enantioselectivity in Chiral Inverted Micelles and Co-surfactant Localization in Microemulsion
-
The enantioselectivity observed in a study of the imidazole-catalysed hydrolysis of enantiomeric pairs of three amino acids in chiral reversed micelles proves that the reaction takes place in the micelle membrane.
- Andriamanampisoa, Ramarofidy,Boyer, Bernard,Lamaty, Gerard,Roque, Jean Pierre
-
p. 597 - 598
(2007/10/02)
-
- Preparation of optically active alpha-hydroxynitriles
-
Preparation of certain optically-active alpha-hydroxynitriles or a mixture enriched therein comprises treating an aldehyde with hydrogen cyanide in a substantially water-immiscible, aprotic solvent in the presence of a cyclo(D-phenylalanyl-D-histidine) as a catalyst.
- -
-
-
- Allylic Selenides in Organic Synthesis: New Methods for the Synthesis of Allylic Amines
-
Oxidative rearrangement of allylic selenides in the presence of various amine nucleophiles provides synthetic access to a variety of allylic amine derivatives.The stereochemical outcome of these reactions has been investigated, and is consistent with a -sigmatropic rearrangement mechanism.Several D-α-amino acids and racemic β,γ-unsaturated α-amino acids were prepared in this manner.A variant of this process employing an achiral allylic selenide and chiral amide afforded protected allylic amines in low diastereoisomeric excess.
- Shea, Regan G.,Fitzner, Jeffrey N.,Fankhauser, John E.,Spaltenstein, Andreas,Carpino, Philip A.,et al.
-
p. 5243 - 5252
(2007/10/02)
-