83150-76-9Relevant articles and documents
Use of trichloroacetimidate linker in solid-phase peptide synthesis
Yan, Liang Zeng,Mayer, John P.
, p. 1161 - 1162 (2003)
A solid-phase method for the preparation of C-terminal amino-alcohol-containing peptides using activated Wang resin is presented. A diverse set of (fluorenylmethoxy)carbonyl (Fmoc) protected amino alcohols was found to load rapidly and efficiently. The synthetic utility of this approach was demonstrated through the direct synthesis of the peptide drug octreotide with excellent yield and purity. These results suggest that the use of trichloroacetimidate activated resins offers an attractive alternative in the preparation of this class of peptides.
Rapid Photolysis-Mediated Folding of Disulfide-Rich Peptides
Patil, Nitin A.,Karas, John A.,Wade, John D.,Hossain, Mohammed Akhter,Tailhades, Julien
, p. 8599 - 8603 (2019/06/04)
Structure–activity relationship studies are a highly time-consuming aspect of peptide-based drug development, particularly in the assembly of disulfide-rich peptides, which often requires multiple synthetic steps and purifications. Therefore, it is vital to develop rapid and efficient chemical methods to readily access the desired peptides. We have developed a photolysis-mediated “one-pot” strategy for regioselective disulfide bond formation. The new pairing system utilises two ortho-nitroveratryl protected cysteines to generate two disulfide bridges in less than one hour in good yield. This strategy was applied to the synthesis of complex disulfide-rich peptides such as Rho-conotoxin ρ-TIA and native human insulin.
METHOD FOR PRODUCTION OF OCTREOTIDE
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Paragraph 0060, (2016/10/08)
PROBLEM TO BE SOLVED: To provide a method for producing high-purity octreotide with high yields in a liquid phase synthesis method. SOLUTION: The present invention provides a method for producing octreotide or a salt thereof by using an acetal compound represented by formula (3) or a salt thereof as an intermediate, desorbing the amino protective group R1a, repeating condensation reaction with a protected amino acid and desorption of a protective group, and further performing oxidation reaction thereof. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
Synthesis of peptide alcohols on the basis of an O-N acyl-transfer reaction
Tailhades, Julien,Gidel, Marie-Aude,Grossi, Benjamin,Lecaillon, Jennifer,Brunel, Luc,Subra, Gilles,Martinez, Jean,Amblard, Muriel
experimental part, p. 117 - 120 (2010/04/04)
(Figure Presented) Getting the better of troublemakers: C-terminal peptide alcohols cannot be synthesized by conventional solidphase peptide synthesis (SPPS) because of the absence of a free carboxylic group to attach to the resin. This problem was circumvented by anchoring a β-amino alcohol residue to the resin to provide a starting point for SPPS. An intramolecular O-N acyl shift completed the synthesis of the desired peptides (see scheme).
Electrophilic S-trifluoromethylation of cysteine side chains in α- and β-peptides: Isolation of trifluoromethylated sandostatin (octreotide) derivatives
Caponea, Stefania,Kieltschb, Iris,Floegela, Oliver,Lelaisa, Gerald,Togni, Antonio,Seebach, Dieter
body text, p. 2035 - 2056 (2009/02/08)
The new electrophilic trifluoromethylating 1-(trifluoromethyl)-benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF3 groups to the S-atom of cysteine side chains of α- and β-peptides (up to 13-residues-long; products 7-14). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2-position). The products are purified by chromatography, and identified by 1H-, 13C-, and 19F-NMR spectroscopy, by CD spectroscopy, and by high-resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin-labelling, imaging, PET) are discussed.
Process for the formation of disulfide bonds in cyclic peptides
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Page/Page column 1-3, (2008/06/13)
A non-oxidative process is described for the formation of an intramolecular disulfide bond in precursors of the peptide or peptidomimetic type; said process comprises the preparation of a linear intermediate containing an —SH group in the S-sulfonate form and a second —SH group which is obtainable in the free form by means of acid treatment.
The use of hydrogen peroxide for closing disulfide bridges in peptides
Sidorova,Molokoedov,Az'muko,Kudryavtseva,Krause,Ovchinnikov,Bespalova
, p. 101 - 110 (2007/10/03)
The use of hydrogen peroxide for the formation of disulfide bridges was studied in 15 peptides of various lengths and structures. The oxidation of peptide thiols by hydrogen peroxide was shown to proceed under mild conditions without noticeable side reactions of Trp, Tyr, and Met residues. Yields of the corresponding cyclic disulfides were high and mostly exceeded those obtained with other oxidative agents, in particular, iodine. It was established that the use of hydrogen peroxide in organic medium also provided sufficiently high yields when large-scale syntheses of oxytocin and octreotide (up to 10 g) were carried out.
Direct solid-phase synthesis of octreotide conjugates: Precursors for use as tumor-targeted radiopharmaceuticals
Hsieh, Hsing-Pang,Wu, Ying-Ta,Chen, Shui-Tein,Wang, Kung-Tsung
, p. 1797 - 1803 (2007/10/03)
Somatostatin analogues, such as octreotide, are useful for the visualization and treatment of tumors. Unfortunately, these compounds were produced synthetically using complex and inefficient procedures. Here, we describe a novel approach for the synthesis of octreotide and its analogues using p-carboxybenzaldehyde to anchor Fmoc-threoninol to solid phase resins. The reaction of the two hydroxyl groups of Fmoc-threoninol with p-carboxybenzaldehyde was catalyzed with p-toluenesulphonic acid in chloroform using a Dean-Stark apparatus to form Fmoc-threoninol p-carboxybenzacetal in 91% yield. The Fmoc-threoninol p-carboxybenzacetal acted as an Fmoc-amino acid derivative and the carboxyl group of Fmoc-threoninol p-carboxybenzacetal was coupled to an amine-resin via a DCC coupling reaction. The synthesis of protected octreotide and its conjugates were carried out in their entirety using a conventional Fmoc protocol and an autosynthesizer. The acetal was stable during the stepwise elongation of each Fmoc-amino acid as shown by the averaged coupling yield (>95%). Octreotide (74 to 78% yield) and five conjugated derivatives were synthesized with high yields using this procedure, including three radiotherapy octreotides (62 to 75% yield) and two cellular markers (72 to 76% yield). This novel approach provides a strategy for the rapid and efficient large-scale synthesis of octreotide and its analogues for radiopharmaceutical and tagged conjugates.
Dihydropyran-2-carboxylic acid, a novel bifunctional linker for the solid-phase synthesis of peptides containing a C-terminal alcohol
Hsieh, Hsing-Pang,Wu, Ying-Ta,Chen, Shui-Tein,Wang, Kung-Tsung
, p. 649 - 650 (2007/10/03)
Dihydropyran-2-carboxylic acid, a novel compound used to link an amino alcohol and an amine resin, is utilised for the solid-phase synthesis of peptide alcohols via the Fmoc strategy; this bifunctional linker was effectively applied to the synthesis of Octreotide.
