- NDTP Mediated Direct Rapid Amide and Peptide Synthesis without Epimerization
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Herein, we explored an unprecedented mild, nonirritating, conveniently available, and recyclable coupling reagent NDTP, which could activate the carboxylic acids via acyl thiocyanide and enable the rapid amide and peptide synthesis at very mild conditions
- Bao, Guangjun,He, Zeyuan,Li, Jingyue,Li, Yiping,Liu, Yuyang,Ma, Wen,Sun, Wangsheng,Wang, Peng,Wang, Rui,Xie, Junqiu,Yu, Changjun
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supporting information
(2022/01/28)
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- The photoredox-catalyzed hydrosulfamoylation of styrenes and its application in the novel synthesis of naratriptan
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The hydrosulfamoylation of diverse aryl olefins provides facile access to alkylsulfonamides. Here we report a novel protocol utilizing radical-mediated addition and a thiol-assisted strategy to achieve the hydrosulfamoylation of diverse styrenes in modest to excellent yields under mild and economic reaction conditions. The methodology was found to provide an efficient and convenient approach for the synthesis of the anti-migraine drug naratriptan and it also can be used for the late-stage functionalization of natural products or medicines.
- Chen, Miaomiao,Ding, Xin,Gao, Yongyue,He, Xingxing,Kang, Jin,Lu, Aidang,Wang, Qingmin,Wang, Ziwen,Zhang, Mingjun
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supporting information
p. 9140 - 9143
(2021/09/14)
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- METHOD FOR PRODUCING CARBOXYLIC ACID AMIDE COMPOUND, AND CATALYST AND FLOW PRODUCTION SYSTEM
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PROBLEM TO BE SOLVED: To provide a new production method that allows a dehydration condensation reaction between carboxylic acid and amine, and a catalyst. SOLUTION: A method for producing a carboxylic acid amide compound includes the step for causing a r
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Paragraph 0081-0087
(2021/09/03)
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- New cysteine protease inhibitors: Electrophilic (Het)arenes and unexpected prodrug identification for the trypanosoma protease rhodesain
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Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SNAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly active prodrug inhibitor, the liberated carboxylic acid represents a highly potent inhibitor of rhodesain (Ki = 4.0 nM). The simulations indicate that, after the cleavage of the ester, the carboxylic acid leaves the active site and re-binds to the enzyme in an orientation that allows the formation of a very stable π-complex between the catalytic dyad (Cys-25/His-162) of rhodesain and the electrophilic aromatic moiety. The reversible inhibition mode results because the SNAr reaction, which is found in an alkaline solvent containing a low molecular weight thiol, is hindered within the enzyme due to the presence of the positively charged imidazolium ring of His-162. Comparisons between measured and calculated NMR shifts support this interpretation.
- Barthels, Fabian,Distler, Ute,Engels, Bernd,Hellmich, Ute A.,Johe, Patrick,Jung, Sascha,Kühlborn, Jonas,Klein, Philipp,Opatz, Till,Schirmeister, Tanja,Tenzer, Stefan,Wagner, Annika,Waigel, Waldemar
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supporting information
(2020/03/27)
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- Naphthoquinones as covalent reversible inhibitors of cysteine proteases—studies on inhibition mechanism and kinetics
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The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4‐naphthoquinones with a dipeptidic recognition motif (HN‐L‐Phe‐L‐Leu‐OR) in the 2‐position and an electron‐withdrawing group (EWG) in the 3‐positio
- Barthels, Fabian,Distler, Ute,Engel, Volker,Engels, Bernd,Hellmich, Ute A.,Johe, Patrick,Klein, Philipp,Le, Thien Anh,Opatz, Till,Schirmeister, Tanja,Schmid, Paul,Tenzer, Stefan,Wagner, Annika
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supporting information
(2020/05/16)
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- Method of producing peptide
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The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active
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Page/Page column 31-32
(2014/05/20)
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- Synthesis of a novel series of L-isoserine derivatives as aminopeptidase N inhibitors
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A series of novel L-isoserine derivatives were synthesised and evaluated for their ability to inhibit aminopeptidase N (APN)/CD13. In our preliminary biological results, some of these compounds possessed a potent inhibitory activity against the APN. Within this series, compound 14b not only showed similar enzyme inhibition (IC50 of 12.2μM) compared with the positive control bestatin (half maximal inhibitory concentration (IC 50) of 7.3μM), but also had a potent antiproliferative activity against human cancer cell lines cells.
- Yang, Kanghui,Fen, Jinghong,Fang, Hao,Zhang, Lei,Gong, Jianzhi,Xu, Wenfang
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p. 302 - 310
(2012/07/02)
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- Preparation and conformational study of CF3-containing enkephalin-derived oligopeptide
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Incorporation of (2S,3S)-4,4,4-trifluorothreonine (F3-Thr) instead of Thr in the enkephalin-derived hexapeptide led to the apparent conformational alteration due to the strong electron-withdrawing effect of the trifluoromethyl group by comparison with the original compound on the basis of their various NMR measurements.
- Kitamoto, Takamasa,Marubayashi, Shunsuke,Yamazaki, Takashi
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p. 1888 - 1894
(2008/09/18)
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- Introduction of F3-Threonine to the Hexapeptide, DSLET: Investigation of the Effect of Fluorine Atoms toward Peptidic Conformations
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Introduction of trifluoromethyl-containing threonine to the target hexapeptide, Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), led to the apparent conformational alteration due to the electron-withdrawing effect of the CF 3 group when compared with the ori
- Kitamoto, Takamasa,Marubayashi, Shunsuke,Yamazaki, Takashi
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p. 1264 - 1265
(2008/02/05)
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- MW-enhanced high-speed deprotection of Boc group using p-TsOH and concommitant formation of N-Me-amino acid benzyl ester p-TsOH salts
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A high-speed, complete deprotection of Boc group from Boc amino acids and protected peptide esters employing p-TsOH in toluene under microwave irradiation is found to be complete in 30s. The deprotection can be carried out in methanol and acetonitrile also. Under the present conditions, C-peptide benzyl esters and O-benzyl ethers have been found to be stable. This has permitted us to carry out the synthesis of [Leu]enkephalin employing the Boc/Bzl-group strategy. Further more, it has been found that both Nα-Fmoc and N α-Z groups are completely stable. The present conditions can be extended for the concomitant removal of the Boc group and the formation of C-benzyl amino acid esters as well. This has been utilized for the synthesis of N-Me amino acid benzyl esters starting from Boc-N-Me amino acids in a single step. Copyright Taylor & Francis, Inc.
- Suresh Babu, Vommina V.,Patil, Basanagoud S.,Vasanthakumar, Ganga-Ramu
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p. 1795 - 1802
(2007/10/03)
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- Peptide amides and amide dimers useful as muscle relaxants
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Peptide amide and amide dimer muscle relaxants represented by the formulae: STR1 wherein: R is lower alkyl; R1 and R2 independently selected from the group consisting of hydrogen, lower alkyl, allyl, propargyl, aryl lower alkyl and c
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- Transesterifications with 1,8-Diazabicycloundec-7-ene/Lithium Bromide (DBU/LiBr) - Also Applicable to Cleavage of Peptides from Resins in Merrifield Syntheses
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A mixture of the amidine base 1,8-diazabicycloundec-7-ene (DBU) and LiBr (preferably 0.5 and 5 equiv., resp.) turns out to be a highly efficient catalyst (at 0-25 deg C) for saponifications (in THF/H2O) and transesterifications (in ROH).The scope and limitations of the method are determined using ca. two dozens of different ester/alcohol combinations (Schemes 2 and 3).The investigation is focused on peptides as substrates.Under carefully controlled conditions, no epimerization occurs with N-Boc- and N-Z-protected peptide esters, when methyl, ethyl, isopropyl, or allyl esters are the products, as shown for peptides containing up to six amino acids, with Ala, Leu, MeLeu, Asp(OEt), or Tyr at the C-terminus (Scheme 3 and Tables 1 and 2).Hydrolytic and transesterifying detachments of Boc-Leu-Ala-Gly-Val-OR and Boc-Leu-Ala-Gly-Phe-OR (R = H, Me) from PAM and Wang resins (1-8 h at 0-25 deg C, 2 equiv. of DBU, 5 equiv. of LiBr) can be achieved by this method without epimerization of the C-terminal stereogenic center; a comparison with other methods (HF, Ti(OR)4) is given (Schemes 4 and 5).Possible protecting-group strategies involving the DBU/LiBr method are discussed (Table 3).Extensive experimental details are given.
- Seebach, Dieter,Thaler, Adrian,Blaser, Denis,Ko, Soo Y.
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p. 1102 - 1118
(2007/10/02)
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- SYNTHESIS OF ENKEPHALINS BY THE METHOD OF POLYMERIC ACTIVATED ESTERS BASED ON 4-HYDROXY-3-NITROBENZOPHENONE
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Leucine- and methionine-enkephalins have been synthesized by the successive growth of the peptide chain from the C-end by the method of polymeric activated esters based on 4-hydroxy-3-nitrobenzophenone with yields of 90 and 70percent, respectively, calculated on the initial C-terminal amino acid.Polystyrene with 2percent of divinylbenzene was used as the polymeric matrix.Using the synthesis of methionine-enkephalin as an example, the possibility has been shown of using polymeric activated esters for the synthesis of peptides with a free carboxy group.
- Grigor'ev, E. I.,Chernova, S. V.
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p. 468 - 474
(2007/10/02)
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- AMINO ACIDS AND PEPTIDES. VIII. A WATER - SOLUBLE ACTIVE ESTER, PHENOLSULFONIC ACID DERIVATIVE
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N-protected amino acid 4-phenolsulfonic acid derivative esters, such as 2,6-dibromo-4-sulfophenyl ester sodium salt, 2,6-dichloro-4-sulfophenyl ester potassium salt and 2-nitro-4-sulfophenyl ester sodium salt, were prepared.These esters are water - soluble active esters, and were applied for rhe synthesys of Leu-enkephalin.Keywords - water - soluble active ester; 2,6-dichloro-4-sulfophenyl ester; 2,6-dibromo-4-sulfophenyl ester; 2-nitro-4-sulfophenyl ester; peptide synthesis; Leu-enkephalin
- Kawasaki, Koichi,Tsuji, Toshiki,Maeda, Misuko,Matsumoto, Tatsuya,Hirase, Katsuhiko
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p. 1044 - 1048
(2007/10/02)
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- Bitter Taste of H-Val-Val-Val-Pro-Pro-Phe-Leu-OH Corresponding to the Partial Sequence (Positions 82-88) of Bovine β-Casein, and Related Peptides
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A heptapeptide, H-Val-Val-Val-Pro-Pro-Phe-Leu-OH, corresponding to the partial sequence of bovine β-casein, positions 82-88, was synthesized and its bitter taste was measured.Its threshold value of bitterness was 0.14 mM.We previously reported that H-Arg-
- Shinoda, Ichizo,Okai, Hideo,Fukui, Sakuzo
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p. 1255 - 1260
(2007/10/02)
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- N-Hydroxy Amides. III. Active Esters of Polystyrene-bound 1-Hydroxy-2-pyrrolidinone and Their Use in Peptide Synthesis
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A polymer-bond cyclic N-hydroxy amide has been prepared by reaction of aminomethylated copoly(styrene-2percent divinylbenzene) with 1-hydroxy-5-oxo-3-pyrrolidinecarboxylic acid using dicyclohexylcarbodiimide (DCC) as a condensing agent.Several N-blocked α-amino acids have been loaded on this resin by use of DCC.The amino acid resin can be utilized for peptide synthesis.Repetitive usage of the resin in the form of esters and facile synthesis of a biologically active pentapeptide, Leu5-enkephalin, show the usefulness of the polymer-bound 1-hydroxy-2-pyrrolidinone.
- Akiyama, Masayasu,Shimizu, Kazuyuki,Aiba, Seiichi,Katoh, Hiroaki
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p. 1421 - 1425
(2007/10/02)
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- Studies on Amino Acids and Peptides. Part 6. Methods for Introducing Thioamide Bonds into the Peptide Backbone: Synthesis of the Four Monothio Analogues of Leucine Enkephalin
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A methodology for preparing peptide analogues in which a thioamide bond replaces the normal amide bond is described.Thus, the synthesis of the three leucine enkephalin analogues 4>-, 2>-, and 1>-leucine enke
- Clausen, Kim,Thorsen, Michael,Lawesson, Sven-Olov,Spatola, Arno F.
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p. 785 - 798
(2007/10/02)
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- PEPTIDE SYNTHESIS BY USING PHENYLPHOSPHONIC ESTER AS A COUPLING REAGENT
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Synthesis of peptides containing various functions was efficiently accomplished by treatment of the tetrabutylammonium salts of N-protected amino acids (or peptides) with amino acid esters in the presence of bis(o- or p-nitrophenyl) phenylphosphonate.Synthesis of leucine-enkephalin was successfully achieved by the above method employing a (3+2) or (4+1) fragment coupling approach.
- Watanabe, Yutaka,Morito, Naoya,Kamekawa, Ken-ichi,Mukaiyama, Teruaki
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- Europium Ion Coordination with γ-Carboxyglutamic Acid Containing Ligand Systems
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Measurements of europium(III) ion luminescence decay constants, k, were made on solutions of Eu3+ complexed to each of the three γ-carboxyglutamic acid containing peptides, Z-Gly-Gla-Gly-OEt (XV), Z-Gla-Ser-OMe (IV), and Z-Gla-Gla-OMe (III), us
- Sarasua, Martha M.,Scott, Mary E.,Helpern, Joseph A.,Kortenaar, Paul B. W. Ten,Boggs, Norman T.,et al.
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p. 3404 - 3412
(2007/10/02)
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