- Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
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A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
- Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
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p. 5790 - 5795
(2021/03/08)
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- MACROCYCLIZATION OF PEPTIDOMIMETICS
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The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H.
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Page/Page column 36; 41-42
(2019/10/19)
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- NS5B polymerase inhibitor
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The invention discloses a compound represented by a formula shown in the description, or medicinal salts thereof. The compound has a better hepatitis C treatment effect than sofosbuvir, has similar toxic and side effects with the sofosbuvir, and does not have obvious untoward effects.
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- A synthetic amino acid N-methylation method and its product and application (by machine translation)
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The invention belongs to the technical field of amino acid polypeptide synthesis, discloses a synthetic amino acid N-methylation method and its product and application. This method passes the benzyl protection of a carboxyl group of the amino acid, trifluoroacetyl protection of the amino group, after methylation, get N-methylation of the amino acid. N obtained by the method of this invention-methyl (trifluoro-acetyl)-amino acid benzyl ester, can be directly used for polypeptide synthesis N-methyl structure having the amino acid benzyl ester product, and it has good selective deprotection of, its N the C-end-to-end and selectively deprotected. With foreign Ag 2 O/CH 3 I/Boc method (hypertoxic, high cost) and NaH / (CH 3 O) 2 SO 2 method compared with (hypertoxic), and the like, the method of the invention high yield, the use of the virulent reagent-free, safe and non-toxic, the operation is simple, common reagent to the raw material, the cost is low, and the structure strong pertinence, racemation a low possibility of the product obtained, it has broad industrial prospects. (by machine translation)
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Paragraph 0053; 0054; 0055
(2016/11/09)
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- Enantioselective synthesis of 1,2,4-triazolines by chiral iron(ii)-complex catalyzed cyclization of α-isocyano esters and azodicarboxylates
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Enantioselective cyclization of α-isocyano esters with azodicarboxylates catalyzed by FeII-N,N′-dioxide complexes has been developed. Under mild conditions, a variety of 1,2,4-triazoline derivatives was obtained in high yields and enantioselectivities.
- Wang, Min,Liu, Xiaohua,He, Peng,Lin, Lili,Feng, Xiaoming
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supporting information
p. 2572 - 2574
(2013/04/10)
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- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
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The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
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supporting information
p. 6824 - 6830
(2013/06/26)
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- N-aminosulfamide peptide mimic synthesis by alkylation of aza-sulfurylglycinyl peptides
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N-Aminosulfamides are peptidomimetics in which the CαH and the carbonyl of an amino acid residue are both respectively replaced by a nitrogen atom and a sulfonyl group. Aza-sulfurylglycinyl tripeptide analogs were effectively synthesized from amino acid building blocks by condensations of N-protected amino hydrazides and p-nitrophenylsulfamidate esters. The installation of N-alkyl chains and access to other aza-sulfuryl amino acid residues were effectively achieved by chemoselective alkylation.
- Turcotte, Stephane,Bouayad-Gervais, Samir H.,Lubell, William D.
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supporting information; body text
p. 1318 - 1321
(2012/05/20)
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- Esterification of unprotected a-Amino acids in ionic liquids as the reaction media
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Ionic liquid 1,3-dimethylimidazolium methanesulfonate was used to prepare a-amino acids benzylic esters from unprotected amino acids and benzyl chloride. Esterification of several amino acids was achieved with satisfactory yields: by-products can be removed by a simple work-up procedure to afford the pure product. The described method is simple, mild, rapid and save.
- Biondini, Daniele,Brinchi, Lucia,Germani, Raimondo,Goracci, Laura,Savelli, Gianfranco
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experimental part
p. 39 - 44
(2010/08/22)
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- Synthesis and RNase A inhibition study of C2-symmetric bis-isochromenyl sulfones
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A new class of C2-symmetric bis-isochromene derivatives with 3,3′-linkage has been synthesized from bis-propargyl sulfones. The method involves treatment of the sulfones with triethylamine to form the isochromene derivatives presumably via the intramolecular Michael addition to the intermediate bis-allenic sulfones. Interestingly, the product expected from the Garratt-Braverman pathway was not obtained. The bis-isochromene 7d displayed RNase A inhibition activity, much stronger than the isochromene 8 and bis-isocoumarin 9.
- Mitra, Tapobrata,Dutta, Sansa,Basak, Amit
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supporting information; experimental part
p. 2828 - 2831
(2010/07/06)
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- A class of novel conjugates of substituted purine and Gly-AA-OBzl: Synthesis and evaluation of orally analgesic activity
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Aimed at the chemotherapy of chronic pain two kinds of analgesic pharmacophores, substituted purine and Gly-AA-OBzl, were coupled via a five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9- (tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC2H 5 into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl into this position leads to significant increase of the analgesic activity.
- Kang, Guifeng,Zhao, Ming,Zhang, Xiaoyi,Peng, Li,Li, Chunbo,Mao, Wei,Ye, Weidong,Peng, Shiqi
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supporting information; experimental part
p. 6157 - 6160
(2010/12/19)
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- METHOD FOR PRODUCING ASYMMETRIC COPPER COMPLEX CRYSTAL
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A method of producing an asymmetric copper complex crystal comprising reacting an optically active salicylidene amino alcohol compound with a copper compound, then, performing a crystallization treatment in the presence of an alcohol solvent.
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Page/Page column 11
(2009/07/25)
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- A novel naphthylmethyleneimino-type photocleavable protecting group for primary amines
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A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties. Georg Thieme Verlag Stuttgart.
- Igarashi, Tetsutaro,Shimokawa, Masaru,Iwasaki, Miyuki,Nagata, Kensaku,Fujii, Masato,Sakurai, Tadamitsu
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p. 1436 - 1440
(2008/02/13)
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- Synthesis and cytotoxic activities of β-carboline amino acid ester conjugates
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β-Carboline represents a class of compounds with potent anti-tumor activity by intercalating with DNA. To further enhance the cytotoxic potency and bioavailability of β-carboline, a series of novel β-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were tested using a panel of human tumor cell lines. In addition, the membrane permeability of these compounds was evaluated in vitro using a Caco-2 cell monolayer model. The β-carboline amino acid ester conjugates demonstrated improved cytotoxic activity compared to the parental β-carbolines. In particular, the Lys/Arg conjugates were the most potent analogs with an IC50 value of 4 and 1 μM against human cervical carcinoma cells. The low interaction energy of Arg conjugate based on molecular modeling may contribute to its enhanced cytotoxicity. Taken together, this study provided new insights into structure-activity relationships in the β-carboline amino acid ester conjugates and identified the β-carboline Lys/Arg conjugates as promising lead compounds for further in vivo biological and molecular evaluation.
- Zhao, Ming,Bi, Lanrong,Wang, Wei,Wang, Chao,Baudy-Floc'h, Michele,Ju, Jingfang,Peng, Shiqi
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p. 6998 - 7010
(2007/10/03)
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- Mimicking enzymatic transaminations: Attempts to understand and develop a catalytic asymmetric approach to chiral α-amino acids
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Attempts are made to build a bridge between asymmetric catalysis and enzymatic reactions by mechanistic investigations and the development of a catalytic and enantioselective approach to amination of α-keto esters by primary amines catalyzed by chiral Lewis acids as a model for transamination enzymes. Different Lewis acids can catalyze the half-transamination of α-keto esters using primary amine nitrogen sources such as pyridoxamine and 4-picolylamine. The mechanistic studies of the Lewis-acid catalyzed half-transamination using deuterium-labelled compounds show the incorporation of deuterium atoms in several positions of the α-amino acid derivative, indicating that the enol of the α-keto ester plays an important role along the reaction path. The catalytic enantioselective reactions are dependent on the pKa-value of the solvent since enantioselectivities were only obtained in solvents with high pKa-values relative to methanol. However, stronger acidic conditions generally gave better yields, but poor enantioselectivities. A series of chiral Lewis acids were screened as catalysts for the enantioselective half-transamination reactions and moderate yields and enantioselectivities of up to 46% ee were obtained.
- Bachmann, Stephan,Knudsen, Kristian Rahbek,Jorgensen, Karl Anker
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p. 2044 - 2049
(2007/10/03)
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- (α-aminophosphino) peptide derivatives, method for making same and therapeutic applications thereof
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The invention concerns compounds derived from (α-aminophosphino) peptides, of general formula (I), in which R1and R2each represents a hydrogen atom or taken together form an imine with the adjacent nitrogen atom; R3represents an alkyl group, an alkenyl group, a phenyl group, a benzyl group, all these groups capable of being substituted or not, a hydrogen atom, a cycloalkyl group, a cycloalkylmethyl group or finally, a methyl group substituted by a heterocyclic, aromatic or saturated group; R4represents a phenyl group, a benzyl group, these groups capable of being substituted or not, a hydrogen atom, an alkyl group, analkenyl group or a cycloalkyl group; R5represents an alkyl group, an alkenyl group, a phenyl group, a benzyl group, all these groups capable of being substituted or not, a hydrogen atom, a cycloalkyl, cycloalkylmethyl group or finally a methyl group substituted by a heterocyclic, aromatic or saturated group; R6, R7and R8can in particular represent a hydrogen atom, an alkyl group, a phenyl group substituted or not . . . n is equal to 0 or 1, in the form of enantiomers, diastereoisomers or racemic mixtures, their salts, their method of preparation and their therapeutic applications.
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- (α-aminophosphino) peptides derivative and compositions containing same
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The invention concerns (α-aminophosphino) peptide derivative compounds of general formula (I) wherein: R1and R2represent each a hydrogen atom or together form an imine with the adjacent nitrogen atom; R3represents an alkyl
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- Synthesis of novel amino acid carbohydrate hybrids via Mitsunobu glycosylation of nitrobenzenesulfonamides
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Amino acid derived 2-nitrobenzenesulfonamides were successfully condensed under Mitsunobu conditions with the primary alcohol of various saccharide and nucleoside derivatives to furnish the fully protected hybrids in excellent yield. One such hybrid was i
- Turner, John J.,Filippov, Dmitri V.,Overhand, Mark,Van der Marel, Gijs A.,Van Boom, Jacques H.
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p. 5763 - 5767
(2007/10/03)
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- Solution-phase automated synthesis of tripeptide derivatives
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An improved general method for automated synthesis of tripeptides was developed, in which methanesulfonic acid (MSA) was used in place of trifluoroacetic acid (TFA), thus making it possible to avoid, 1) corrosion of the apparatus by strong acid vapor, 2) formation of emulsions, and 3) use of the restricted solvent, dichloromethane. As an application of the automated synthesis apparatus, 216 fragment tripeptide derivatives were synthesized systematically using the MSA method, in excellent yield and with increased efficiency.
- Kuroda,Hattori,Kitada,Sugawara
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p. 1138 - 1146
(2007/10/03)
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- The (2-phenyl-2-trimethylsilyl)ethoxycarbonyl (Psoc) group - A novel amino protecting group
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A novel silicon containing protecting group has been developed based on the known 2-(trimethylsilyl)ethyl system. The new protecting group is cleaved under very mild conditions by treatment with tetra-n-butylammonium fluoride in CH2Cl2 much more rapidly than the 2-(trimethylsilyl)ethoxycarbonyl group, leading to less side reactions.
- Wagner,Heiner,Kunz
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p. 1753 - 1756
(2007/10/03)
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- The synthesis of pure Amadori rearrangement products
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The term "Maillard reaction" is used to describe a complex set of reactions in foods leading to flavour generation and non-enzymatic browning.The first step in this process is the so-called Amadori rearrangement: a reducing saccharide and a peptide fragment react to form an Amadori Rearrangement Product (ARP).To be able to do model studies on flavour generation, gram amounts of pure ARP are required.In the present study, glucose-derived ARPs were synthesised from specifically protected and activated starting compounds.After deprotection and purification, pure ARPs were obtained.This is the first time that ARPs of dipeptides have been isolated.
- Noomen, S. N.,Breel, G. J.,Winkel, C.
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p. 321 - 324
(2007/10/02)
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- Application of a unique automated synthesis system for solution-phase peptide synthesis
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An automated synthesis system, which is suitable for repetitive syntheses using similar reaction procedures, was used to synthesize systematically a library of all possible dipeptides (25) and tripeptides (125) from 5 protected amino acids. The apparatus has also been applied to the automated synthesis of 10 fragment tripeptide derivatives that are constituents of the hormone PACAP-27. The measured molecular optical rotation values of the library of 125 tripeptides were found to correlate well with calculated values obtained by summation of the molecular optical rotation values for the constituent amino acids.
- Sugawara,Kobayashi,Okamoto,Kitada,Fujino
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p. 1272 - 1280
(2007/10/02)
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- SYNTHESIS AND CHIROPTICAL PROPERTIES OF MODEL PEPTIDES SUITABLE FOR THE IMMUNOLOGICAL CHARACTERIZATION OF BRANCHED POLYPEPTIDES WITH THE GENERAL FORMULA POLYm)>
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Over the last 10 years we have developed a new group of branched polypeptides with significant immunomodulatory activity, corresponding to the general formula poly (i 1, m ca. 3).The humoral immune response of four inbred mouse strains
- Mezoe, Gabor,Hudecz, Ferenc,Kajtar, Judit,Szekerke, Maria
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p. 803 - 812
(2007/10/02)
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- ENANTIOSELECTIVE HYDROLYSIS BY BAKER'S YEAST - II. ESTERS OF N-ACETYL AMINO ACIDS
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D-N-Acetyl amino acid esters were obtained via enantioselective hydrolysis of their racemates by use of fermenting yeast.Evidence is given that proteinases are the enzymes involved.
- Glaenzer, B. I.,Faber, K.,Griengl, H.
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p. 771 - 778
(2007/10/02)
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- Chirally Selective Hydrolysis of D,L-Amino Acid Esters by Alkaline Protease
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Alcalase selectively catalyses the hydrolysis of D,L-amino acid methyl and benzyl ester to provide L-amino acid and D-amino acid ester with high optical purity.
- Chen, Shui-Tein,Wang, Kung-Tsung,Wong, Chi-Huey
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p. 1514 - 1516
(2007/10/02)
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- Relative Partial Molar Enthalpies and Apparent Molar Volumes of Dipeptides in Aqueous Solution
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Enthalpies of dilution at 25 deg C of aqueous solutions of the dipeptides glycylglycine, glycylalanine and alanylalanine have been determined and used to calculate the partial molar enthalpies of the solvent water in the solutions.The partial molar volumes of these dipeptides are also reported.The results are discussed in terms of the likely solute-solvent interactions.
- Dyke, Shaun H.,Hedwig, Gavin R.,Watson, Ian D.
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p. 321 - 332
(2007/10/02)
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