- PROCESS AND INTERMEDIATES FOR SYNTHESIS OF PEPTIDE COMPOUNDS
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Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.
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Paragraph 0166; 0167
(2019/02/13)
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- A mechanochemical approach to access the proline-proline diketopiperazine framework
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Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline-proline dipeptides under solvent-free conditions. A deprotection-cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro-Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill.
- Pétry, Nicolas,Benakki, Hafid,Clot, Eric,Retailleau, Pascal,Guenoun, Farhate,Asserar, Fatima,Sekkat, Chakib,Métro, Thomas-Xavier,Martinez, Jean,Lamaty, Frédéric
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supporting information
p. 2169 - 2178
(2017/11/16)
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- PROCESSES FOR SYNTHESIS OF DIPYRROLIDINE PEPTIDE COMPOUNDS
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Disclosed is a new process for preparing dipyrrolidine peptide compounds such as, for example, GLYX-13. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.
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Paragraph 0092-0097
(2017/12/27)
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- Prolylprolinol-catalyzed asymmetric michael addition of aliphatic aldehydes to nitroalkenes
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Several novel prolylprolinol catalysts have been designed and synthesized. This type of compound showed high catalytic efficiency on pro-moting the direct addition of unmodified aldehydes to nitroalkenes. Among the catalysts surveyed, the least bulky memb
- Lu, Dengfu,Gong, Yuefa,Wang, Weizhou
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supporting information; experimental part
p. 644 - 650
(2010/06/20)
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- Structures, sensory activity, and dose/response functions of 2,5-diketopiperazines in roasted cocoa nibs (Theobroma cacao)
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The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and i
- Stark, Timo,Hofmann, Thomas
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p. 7222 - 7231
(2007/10/03)
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- Chemical Characterization of Diketopiperazines in Beer
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Diketopiperazines (DKPs) corresponding to cyclic dipeptides have been detected in a variety of natural products as well as in processed foods, beverages, and food and beverage ingredients. A series of seven proline-based diketopiperazines, namely, cyclo(Ala-Pro), cyclo(Val-Pro), cyclo(Ile-Pro), cyclo(Leu-Pro), cyclo(Met-Pro), cyclo(Phe-Pro), and cyclo(Pro-Pro), has now been identified in beer. A marketplace cross-section of five commercial beers was studied, involving products manufactured in different countries using distinctly different raw materials and brewing styles; maximum concentrations of individual diketopiperazines in various beers ranged from below detection limit to approximately 24 ppm. The flavor characteristics of these compounds were described variously as bitter, mouth coating, drying, astringent, salty, metallic, and grainy when evaluated in water at concentrations ranging from 10 to 50 ppm. However, it is questionable whether or not the diketopiperazines reported here make a significant contribution to either the aroma or taste of most beers.
- Gautschi, Markus,Schmid, Joachim P.,Peppard, Terry L.,Ryan, Thomas P.,Tuorto, Raymond M.,Yang, Xiaogen
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p. 3183 - 3189
(2007/10/03)
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- Amino acids and peptides. XVI. Synthesis of N-terminal tetrapeptide analogs of fibrin α-chain and their inhibitory effects on fibrinogen/thrombin clotting
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N-Terminal tetrapeptide analogs of fibrin α-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p-nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect.
- Kawasaki,Hirase,Miyano,Tsuji,Iwamoto
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p. 3253 - 3260
(2007/10/02)
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- KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
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The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
- Hoogwater, D. A.,Peereboom, M.
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p. 5325 - 5332
(2007/10/02)
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- RATES OF PEPTIDE FORMATION INVOLVING IMINO ACID RESIDUES
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The determination of the rates for peptide coupling in tetrahydrofuran between Z-Aaa-OPcp (Aaa = Ala, (NMe)Ala, Pro, Thz, Pip and (S)Pip) and H-Bbb-OMe (Bbb = (NMe)Ala, Pro, Thz, Pip and (S)Pip) allowed us to evaluate the relative reactivities between these members, either as active components or as amino components.The reactivity of Pro (either as the active species or the amino component) equals that of (NMe)Ala.The reactivity of Pip and (S)Pip as imino components is low while the activation energy is raised by an amount that roughly equals the energy increment needed for bringing the carboxylate grouping from the equatorial to the axial position The reactivities of these six-membered residues are also appreciably low when being the active components during peptide coupling.The presence of a ring-sulfur atom at γ-position of nitrogen additionally decreases the rate for peptidation, especially if (S)Pip is the imino component.
- Wante, Dirk P. M.,Anteunis, Marc J. O.
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- ASYMMETRIC SYNTHESIS BASED ON CHIRAL DIAMINES HAVING PYRROLIDINE RING
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Various highly stereoselective asymmetric reactions based on chiral diamines having pyrrolidine ring are described.Some of these reactions have been successfully applied to the syntheses of natural products.
- Mukaiyama, Teruaki
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p. 4111 - 4119
(2007/10/02)
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