- Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
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Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
- Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
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p. 30720 - 30728
(2019/10/28)
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- A Fmoc - Thr (tBu) - OH preparation method (by machine translation)
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The invention discloses a Fmoc - Thr (tBu) - OH of the preparation method, relates to the field of chemical technology. The method comprises: methanol, thionyl chloride, Thr are mixed, the reaction produces Thr?OMe?HCl solution; to the Thr?OMe?HCl solution enters dichloromethane, and inject the isobutene, at the same time add sulfuric acid to maintain the acidic environment, reaction (tBu) Thr??OMe solution; will be Thr??OMe solution (tBu) saponification by alkali Thr?(tBu), then add Fmoc - OSu reaction to obtain the elementary product Fmoc - Thr (tBu) - OH; the taste for the Fmoc - Thr (tBu) - OH to obtain the Fmoc - Thr (tBu) - OH product. The method can effectively shorten the production steps, can improve the production efficiency and yield, is suitable for modern industrial production. (by machine translation)
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Paragraph 0031-0038
(2019/02/04)
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- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
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The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
- Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
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p. 10575 - 10582
(2013/02/22)
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- Derivates of Polyethylene Glycol Modified Thymosin Alpha 1
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Pharmaceutical compositions that include thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol, and their pharmaceutical acceptable salts, are generally disclosed. Also, new methods used to prepare these thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol are generally provided. The presently disclosed compounds and their salts can be prepared administered to humans to treat immune disease and can also be used in adjuvant treatment.
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- GLP-2 compounds, formulations, and uses thereof
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The present invention relates to novel human glucagon-like peptide-2 (GLP-2) peptides and human glucagon-like peptide-2 derivatives which have a protracted profile of action as well as polynucleotide constructs encoding such peptides, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.
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- (2-Phenyl-2-trimethylsilyl)ethyl (PTMSE) esters - A novel carboxyl protecting group
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A novel silicon-containing protecting group based on the known 2- (trimethylsilyl)ethyl system has been developed for the protection of the carboxylic group, e.g. in peptide chemistry. The new protecting group can be cleaved by treatment with tetra-n-butylammonium fluoride much more rapidly than the known 2-(trimethylsilyl)ethyl group, leading to less side reactions.
- Wagner, Michael,Kunz, Horst
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p. 400 - 402
(2007/10/03)
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- Treating disorders by application of insulin-like growth factors and analogs
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A method of enhancing the survival of neuronal cells in a mammal, the cells being at risk of dying, the method including the step of administering to the mammal one of the following substances: IGF-I; a functional derivative of IGF-I; IGF-II; a functional derivative of IGF-II; IGF-III; or a functional derivative of IGF-III.
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- Mild, selective cleavage of amino acid and peptide β-(trimethylsilyl)ethoxymethyl (SEM) esters by magnesium bromide
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Magnesium bromide etherate has been previously shown to cleave β-(trimethylsilyl)ethoxymethyl (SEM) esters of aliphatic acids. This methodology has now been extended to amino acid and peptide derivatives in the presence of protecting groups typically encountered in peptide chemistry, including the Boc, Cbz, Fmoc and Troc carbamates as well as benzyl-, tert-butyl- and tert-butyldimethylsilyl ethers. The stability of fluoride sensitive protecting groups to magnesium bromide allows for added selectivity in the removal of SEM esters in organic synthesis.
- Chen, Wei-Chuan,Vera, Matthew D.,Joullie, Madeleine M.
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p. 4025 - 4028
(2007/10/03)
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- Angiopeptin cyclopeptide compounds
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The invention relates to a compound selected from those of formula (I) (SEQ ID NO:1): STR1 in which R1, R2, X1 and X2 are as defined in the description, useful as inhibitor of the proliferation component of vascular smooth muscle cells.
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- Application of t-Butyldimethylsilyl Ethers of Serine, Threonine and Tyrosine in Peptide Synthesis
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The utility of Tbdms (t-butyldimethylsilyl) ethers, prepared conveniently in a one pot procedure from Nα-Fmoc (9-fluorenylmethoxycarbonyl) and Nα-Z (benzyloxycarbonyl) hydroxyamino acids, is demonstrated: peptide bond formation and esterification to 4-alkoxybenzylalcohol resin are achieved readily with these derivatives.The lability of the Tbdms ethers to various reagents enables selective deprotection of the hydroxyl side-chains assembly, desirable, e.g., for phosphorylation of glycosylation.
- Fischer, Peter M.
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p. 7605 - 7608
(2007/10/02)
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- Urethane-protected amino acid-N-carboxyanhydrides
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Urethane-protected NCAs and MTAs are prepared by reacting an NCA or NTA with a haloformate in an inert diluent, under anhydrous conditions and in the presence of a tertiary nitrogen-containing base having an atom or functional group sufficiently electron rich and positioned relative to the nitrogen of said base so as to render said atom or group capable of complexing with the H--N group of said N-carboxyanhydride or N-thiocarboxyanhydride but able to generate N-carboxyanhydride or N-thiocarboxyanhydride anionic complexes capable of reacting with the haloformate.
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- Urethane-protected amino acid-N-carboxyanhydrides
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The invention relates to urethane-protected amino acid-N-carboxyanhydride and N-thiocarboxyanhydride compounds which are useful in peptide, polypeptide and protein synthesis. Disclosed herein is the preparation and use of these novel compounds.
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- A New Synthesis of Thymosin α1
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Thymosin α1, an N-acetylated octacosa thymus peptide, isolated first from thymosin fraction 5, is synthesized by the solid phase method using the p-benzyloxybenzyl alcohol/polystyrene/divinylbenzene resin, Nα-Fmoc-amino acids and those with tert-butyl or Boc side chain protection.All couplings are performed with the Bop reagent.The peptide is purified by a combination of gel chromatography and preparative HPLC, its purity checked by amino acid analysis and analytical HPLC, and the biological activity tested by the E-rosette assay.
- Echner, Hartmut,Voelter, Wolfgang
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p. 1095 - 1098
(2007/10/02)
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