- Syntheses of Polypeptides by Hidrogenolysis of N-Benzyloxycarbonyl-Amino Acid Anhydrides
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When anhydrides of N-benzyloxycarbonyl-DL-aspartic acid (Z-DL-Asp), Z-L-Asp, N-Z-DL-glutamic acid (Z-DL-Glu), Z-L-Glu and N-Z-3-aminoglutaric acid (Z-β-Agl) were hydrogenolyzed in N,N-dimethylformamide (DMF), polypeptides were obtained in high yields.Hydrogenolyses of Z-DL-Glu and Z-L-Glu in dioxane gave pyroglutamic acid.
- Munegumi, Toratane,Meng, Yan-Quing,Harada, Kaoru
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- On the racemisation of aspartic anhydride during its preparation
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Due to the possible differentiation of both carboxyl groups, N-protected aspartic anhydride is a useful starting material in synthesis. However, most methods published in the literature for its formation lead to partial racemisation, which is generally not mentioned. Herein we report a comparison between the main methods published, with accurate measurements of the enantiomeric purity of this compound.
- Buron, Frederic,Deguest, Geoffrey,Bischoff, Laurent,Fruit, Corinne,Marsais, Francis
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- Economical synthesis of tert-butyl (S)-3-aminopyrrolidine-1-carboxylate from L-aspartic acid
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3-Aminopyrrolidine building block was used as the intermediate for many pharmaceutically active substances. Starting from L-aspartic acid, optically active (S)-tert-butyl-3-aminopyrrolidine-1-carboxylate was synthesized, and the reaction conditions were optimized in each step. The procedure of each step was discussed in detail and could be useful for the industrial preparation. This process was featured by readily available starting material, mild reaction conditions, easy work-up, and economy.
- Han, Zhi-Jian,Li, Yang-Bing,Gu, Bao-Hong,Li, Yu-Min,Chen, Hao
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- Regioselective opening of N-Cbz glutamic and aspartic anhydrides with carbon nucleophiles
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Depending on the experimental conditions, aspartic and glutamic anhydrides can be opened regioselectively with Grignard reagents, thus giving access to different isomers of chiral amino-ketoesters.
- Deguest, Geoffrey,Bischoff, Laurent,Fruit, Corinne,Marsais, Francis
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- Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase
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The antifungal activity of 5-hydroxy-4-oxo-l-norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV-containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI-1640 medium, with minimal inhibitory concentration values in the 32 to 64?μg?mL?1 range. This activity was not affected by multidrug resistance that is caused by overexpression of genes encoding drug efflux proteins. The mechanism of antifungal action of HONV dipeptides involved uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. The relative transport rates determined the anticandidal activity of HONV dipeptides.
- Skwarecki, Andrzej S.,Schielmann, Marta,Martynow, Dorota,Kawczyński, Marcin,Wi?niewska, Aleksandra,Milewska, Maria J.,Milewski, S?awomir
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- Environmentally Benign CO2-Based Copolymers: Degradable Polycarbonates Derived from Dihydroxybutyric Acid and Their Platinum-Polymer Conjugates
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(S)-3,4-Dihydroxybutyric acid ((S)-3,4-DHBA), an endogenous straight chain fatty acid, is a normal human urinary metabolite and can be obtained as a valuable chiral biomass for synthesizing statin-class drugs. Hence, its epoxide derivatives should serve as promising monomers for producing biocompatible polymers via alternating copolymerization with carbon dioxide. In this report, we demonstrate the production of poly(tert-butyl 3,4-dihydroxybutanoate carbonate) from racemic-tert-butyl 3,4-epoxybutanoate (rac-tBu 3,4-EB) and CO2 using bifunctional cobalt(III) salen catalysts. The copolymer exhibited greater than 99% carbonate linkages, 100% head-to-tail regioselectivity, and a glass-transition temperature (Tg) of 37 °C. By way of comparison, the similarly derived polycarbonate from the sterically less congested monomer, methyl 3,4-epoxybutanoate, displayed 91.8% head-to-tail content and a lower Tg of 18 °C. The tert-butyl protecting group of the pendant carboxylate group was removed using trifluoroacetic acid to afford poly(3,4-dihydroxybutyric acid carbonate). Depolymerization of poly(tert-butyl 3,4-dihydroxybutanoate carbonate) in the presence of strong base results in a stepwise unzipping of the polymer chain to yield the corresponding cyclic carbonate. Furthermore, the full degradation of the acetyl-capped poly(potassium 3,4-dihydroxybutyrate carbonate) resulted in formation of the biomasses, β-hydroxy-γ-butyrolacetone and 3,4-dihydroxybutyrate, in water (pH = 8) at 37 °C. In addition, water-soluble platinum-polymer conjugates were synthesized with platinum loading of 21.3-29.5%, suggesting poly(3,4-dihydroxybutyric acid carbonate) and related derivatives may serve as platinum drug delivery carriers.
- Tsai, Fu-Te,Wang, Yanyan,Darensbourg, Donald J.
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supporting information
p. 4626 - 4633
(2016/05/19)
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- Synthesis of models of the BC ring systems of MPC1001 and MPC1001F
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Piperazinedione 13, representing the BC rings of the anti-prostate cancer fungal metabolite MPC1001, was prepared by a route in which a sulfur-stabilized carbanion derived from 22 cyclizes onto the terminal ester of the pendant chain attached to N1. Another model, 14, was synthesized by cyclization of an α-ketoamide nitrogen onto an ester; 14 represents the BC rings of MPC1001F.
- Dong, Shuai,Indukuri, Kiran,Clive, Derrick L. J.,Gao, Jin-Ming
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supporting information
p. 8271 - 8274
(2016/07/06)
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- Synthesis and anticonvulsant evaluation of (R)-and (S)-3-carbobenzyloxy- amino-1-oxysuccinimides
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A series of (R)-and (S)-3-carbobenzyloxy-amino-1-oxysuccinimides (5a-d) [(S)-3-carbobenzyloxy-amino-1-benzoyloxysuccinimde, (R)-3-carbobenzyloxy-amino- 1-acetyloxysuccinimde, (R)-3-carbobenzyloxy-amino-1,4-nitrobenzoyloxysuccinimde, (R)-3-carbobenzyloxyamino-1,4-fluorobenzoyloxysuccinimde] were synthesized and investigated their anticonvulsant activities in maximal electric shock seizure test and pentylenetetrazole induced seizure test.
- Lee, Do-Hun
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p. 5948 - 5950
(2013/07/26)
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- A PREPARATION METHOD OF SITAGLIPTIN
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The present invention relates to a preparation method of sitagliptin, and more particularly, to a method of preparing sitagliptin using L-aspartic acid having a (R)-beta amino acid structure by mild amide formation, by the use of industrially applicable halo isopropylmagnesium, and by removal of amine protecting group using Pd/C and H2 and carbonyl reduction using reducing agent.
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Page/Page column 12
(2012/11/13)
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- Total synthesis of tryprostatins A and B
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Three distinct synthetic routes to the 2-prenyl tryptophan core skeleton of tryprostatins and their total syntheses are described. The strategies include a traditional gramine-mediated coupling reaction, Fuerstner indole synthesis, and our radical-mediated indole synthesis from o-alkenylphenyl isocyanide. The establishment of reliable conditions for the radical-mediated construction of indoles via a low-temperature radical initiator V-70 (2,2′-azobis(4- methoxy-2,4-dimethylvaleronitrile)) led to the highly efficient syntheses of tryprostatins A and B.
- Yamakawa, Takayuki,Ideue, Eiji,Iwaki, Yuzo,Sato, Ayumu,Tokuyama, Hidetoshi,Shimokawa, Jun,Fukuyama, Tohru
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scheme or table
p. 6547 - 6560
(2011/09/20)
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- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of one or more mitotic kinesins are disclosed.
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Page/Page column 56
(2010/11/27)
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- 4-SULFONYL-SUBSTITUTED BENZOYLALANINE DERIVATES USEFUL AS KYNURENINE-AMINOTRANSFERASE INHIBITORS
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The invention relates to compounds of formula (I), in which R, R' and R" are as defined in the disclosure and the pharmaceutically acceptable esters thereof. The compounds of the invention reduce the synthesis of kynurenic acid thus inhibiting the enzyme kynurenine aminotransferase and can be used for the preparation of medicaments for the treatment of those psychiatric and neurological diseases which benefit from an increase in glutamatergic and/or cholinergic neurotransmission, such as depression, bipolar illness, anxiety, Alzheimer's disease. Furthemore, the compounds of the invention are useful for stimulating attention, memory and other cognitive processes in normal individuals of any age, including children, adolescents and the elderly.
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Page/Page column 4
(2010/10/19)
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- Aqueous phase mono-protection of amines and amino acids as N-benzyloxycarbonyl derivatives in the presence of β-cyclodextrin
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A simple and selective protection of amines/amino acids with Cbz-Cl has been achieved in aqueous phase with catalytic amounts of β-cyclodextrin in high yields at room temperature. This reaction proceeds without the formation of any by-products and has advantages over existing methods.
- Pavan Kumar,Somi Reddy,Narender,Surendra,Nageswar,Rama Rao
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p. 6393 - 6396
(2007/10/03)
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- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of one or more mitotic kinesins are disclosed.
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Page/Page column 268-270
(2008/06/13)
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- Easy saponification by metal silanolates: Application in SPPS and in (S)-5-hydroxynorvaline preparation
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Alkali metal trimethylsilanolates, TMSO-, M+, has been used for efficient conversion of methyl esters into their corresponding anhydrous acid salts under mild non-aqueous conditions. This strategy has been applied to SPPS for the preparation of neurotoxin cyclic analogues and in (S)-5-hydroxynorvaline synthesis.
- Minta, Ewelina,Boutonnet, Cédric,Boutard, Nicolas,Martinez, Jean,Rolland, Valérie
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p. 1795 - 1797
(2007/10/03)
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- Control of hydrolysis and condensation activities of thermolysin by ultrasound irradiation
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Hydrolysis and condensation reactions of peptides catalyzed by thermolysin can be reversibly controlled by on/off ultrasound irradiation depending on its frequency region. Copyright
- Kawasaki, Takayoshi,Hoshino, Yu,Ishizu, Yukari,Mizushiro, Yu,Okahata, Yoshio
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p. 1602 - 1603
(2007/10/03)
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- First Practical Protection of α-Amino Acids as N, N-Benzyloxycarbamoyl Derivatives
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The consecutive treatment of N-Cbz amino protected compounds with LiHMDS and CbzCl provides a practical method for the preparation of N,N-benzyloxycarbamoyl (N,N-di-Cbz) derivatives in good yield. When α-amino acids are used the protection occurs without racemization. The method is compatible with a wide range of other functional and protecting groups. The procedure is also valid for the synthesis of mixed N,N-carbamoyl derivatives.
- Hernandez, J. Nicolas,Martin, Victor S.
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p. 3590 - 3592
(2007/10/03)
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- Geometrical optimisation of 1,1′-binaphthalene receptors for enantioselective molecular recognition of excitatory amino acid derivatives
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A series of optically active 1,1′-binaphthalene-derived receptors with N-(pyridine-2,6-diyl)acetamide [CONH(py)] H-bonding sites in the 6,6′-positions has been prepared for the enantioselective complexation of the N-carbobenzyloxy (Cbz)-protected excitatory amino acids aspartic (Asp) and glutamic (Glu) acid via two COOH ... CONH(py) H-bonding arrays and additional secondary bonding interactions. The conformational homogeneity of the receptors is enhanced by locking the dihedral angle θ about the chirality axis through the C(1)-C(1′) bond of the 1,1′-binaphthalene moiety either by bridging the 2,2′-positions or by attaching bulky substituents to these centres. Computer modelling has shown that bridging is more efficient in locking this dihedral angle than the introduction of bulky substituents, and these predictions have been confirmed by 1H NMR binding studies in CDCl3 and in CDCl3-CD3OD 99.8:0.2. Plots of the enantioselectivity Δ(ΔG°) (difference in stability between diastereoisomeric complexes) in the recognition by the bridged receptors as a function of the enforced dihedral angle θ are peak-shaped, and the highest values have been measured in CDCl3 (300 K) for the complexation of the enantiomers of N-Cbz-Asp [Δ(ΔG°) = 6.9 kJ mol-1] and N-Cbz-Glu [Δ(ΔG°) = 5.2 kJ mol-1] by (R)-21 (θ = 86 ± 4°). The more stable diastereoisomeric complexes are highly structured, and tight host-guest bonding has been confirmed by the observation of up to five intermolecular NOEs. Enforcing the conformational homogeneity by bridging represents a new general principle for improving the chiral recognition potential of 1,1′-binaphthalene receptors.
- Lustenberger, Philipp,Martinborough, Esther,Mordasini Denti, Tiziana,Diederich, Francois
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p. 747 - 761
(2007/10/03)
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- Peptidic ketones as interleukin-1β-converting enzyme inhibitors
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: STR1 wherein R1 is (CR5 R6)n, (CR5 R6)n -aryl, (CR5 R6)n -heteroaryl, X-(CR5 R6)n, X-(CR5 R6)n -aryl or X-(CR5 R6)n -heteroaryl wherein aryl and heteroaryl may be optionally substituted; X is O or NR5 ; R5 and R6 are independently H or lower alkyl; R2 is H, halo, lower alkyl or (CR5 R6)n -aryl; R3 and R4 are independently H or alkyl; A is a D or L isomer of an amino acid selected from the group consisting of alanine, valine, leucine, isoleucine, proline, phenylalanine, glycine, tyrosine, methionine, asparagine, glutamine, aspattic acid, glutamic acid, lysine, arginine, histidine and β-thienylalanine; Z is CH2 or O; and n is 0-4; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1β protease activity in a mammal utilizing the compounds and compositions.
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- Enzymic synthesis design and enzymic synthesis of aspartame
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An enzymic synthesis of aspartame (H-Asp-Phe-OMe) has been designed and realized based on the structure-activity study of thermolysin and penicillin amidase hydrolysis of its p-substituted phenylacetyl derivatives. These compounds meet the structural and energetic requirements of two enzymic binding sites. The peptide sweetener has been prepared by thermolysin - catalyzed condensation of the p-substituted phenylacetyl-Asp-OH and H-Phe-OMe follwed by penicillin amidase - catalyzed deprotection of the resulted aspartame precursors.
- Stoineva,Galunsky,Lozanov,Ivanov,Petkov
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p. 1115 - 1122
(2007/10/02)
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- L-aspartic acid bis(trimethylsilyl) ester: A convenient starting material for the acylation of L-aspartic acid
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Reaction of L-aspartic acid with excess of bis(trimethylsilyl)amine under reflux provides optically pure L-aspartic acid bis(trimethylsilyl) ester in quantitative yield. This silyl ester reacts with a variety of acylating reagens in tetrahydrofuran to give N-protected aspartic acids and dipeptides in good yields without racemization.
- Castano, Ana M.,Echavarren, Antonio M.
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p. 3377 - 3384
(2007/10/02)
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- Improved efficiency and selectivity in peptide synthesis: Use of triethylsilane as a carbocation scavenger in deprotection of t-butyl esters and t-butoxycarbonyl-protected sites
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The use of triethylsilane as a carbocation scavenger in the presence of trifluoroacetic acid in dichloromethane leads to increased yields, decreased reaction times, simple work-up and improved selectivity for the deprotection of t-butyl ester and t-butoxycarbonyl sites in protected amino-acids and peptides in the presence of other acid-sensitive protecting groups such as the benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, O- and S-benzyl and t-butylthio groups.
- Mehta, Anita,Jaouhari, Rabih,Benson, Timothy J.,Douglas, Kenneth T.
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p. 5441 - 5444
(2007/10/02)
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- 3,5-substituted 4,5-dihydroisoxazoles as transglutaminase inhibitors
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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.
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- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
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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
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p. 1125 - 1128
(2007/10/02)
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- Method for reductive elimination of protecting groups
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The invention provides a novel and efficient method for the elimination of protecting groups, e.g. benzyloxycarbonyl group, from a protected amino acid, peptide or derivative thereof having at least one functional group protected by a protecting group, e.g. a lower alkyl ester of N-benzyloxycarbonyl-α-L-aspartyl-L-phenylalanine by catalytic hydrogen reduction to produce free amino acid, peptide or derivative thereof. In contrast to the conventional procedures in which the reaction is carried out in a solvent dissolving both the starting compound and the product compound or a solvent dissolving the starting compound but not dissolving the product compound, the inventive method utilizes a binary two-phase reaction medium composed of water and an organic solvent not freely miscible with water such as toluene. The reaction takes place in the organic phase containing the starting compound dissolved and the catalyst dispersed therein whereas the reaction product which is water-soluble is smoothly and successively transferred into the aqueous phase so that advantages are obtained in the unexpectedly high yield of the product as well as in the easiness of handling the reaction mixture after completion of the reaction.
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- 3-Alkoxycarbonyl-2-oxazolones and Their Homopolymers as Highly Preservable Amino-Protecting Reagents. tert-Butoxy-carbonylation and Benzyloxycarbonylation of Amino Groups
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Highly preservable amino protecting reagents derived from the 2-oxazolone moiety as a common activating mediator have been developed. 3-Alkoxycarbonyl-2-oxazolones serve as easily handled reagents for amino protection, including tert-butoxycarbonylation, benzyloxycarbonylation, p-methoxybenzyloxycarbonylation, methoxycarbonylation and ethoxycarbonylation.For example, high yield N-protection of α-amino acids has been smoothly performed by the use of 3-tert-butoxycarbonyl and 3-benzyloxycarbonyl-2-oxazolones in aqueous solution at room temperature.A series of homopolymers, poly(3-alkoxycarbonyl-2-oxazolone), is readily obtainable by radical-initiated chain reaction of the corresponding 4,5-unsubstituted oxazolone monomers (except for the tert-butoxy derivate, which failed to give polymeric compounds), and these were successfully used for amino protection as well.Use of the polymer reagents greatly simplifies the purification procedure, though a longer reaction time is required.Keywords - 3-alkoxycarbonyl-2-oxazolone; poly(2-alkoxycarbonyl-2-oxazolone); 3-tert-butoxycarbonyl-2-oxazolone; 3-benzyloxycarbonyl-2-oxazolone; amino protection
- Kunieda, Takehisa,Higuchi, Tsunehiko,Abe, Yoshihiro,Hirobe, Masaaki
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p. 2174 - 2181
(2007/10/02)
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- DEVELOPMENT OF CHIRAL β-DICARBONYL EQUIVALENTS. ENANTIODIVERGENT ALKYLATION OF ASPARTIC ACID.
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L-Aspartic acid has been converted to derivatives which undergo alkylation reactions with stereoselectivities that are enantiomerically complimentary.
- McGarvey, Glenn J.,Hiner, Roger N,Matsubara, Yoshio,Oh, Taeboem
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p. 2733 - 2736
(2007/10/02)
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