536721-25-2Relevant articles and documents
A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides
Pedersen, Simon S.,Donslund, Aske S.,Mikkelsen, Jesper H.,Bakholm, Oskar S.,Papp, Florian,Jensen, Kim B.,Gustafsson, Magnus B. F.,Skrydstrup, Troels
, p. 7114 - 7123 (2021/03/03)
A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.
IMPROVED PROCESSES FOR THE PREPARATION OF PEPTIDE INTERMEDIATES/MODIFIERS
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, (2020/10/21)
The present application relates to improved processes for the preparation of peptide intermediates/modifier compounds of Formula (I) and their use in the synthesis of peptide derivatives. The present application further provides the compound of Formula I with high chemical purity of >98% and chiral purity of >99% and its use to make pharmaceutical peptide like Liraglutide.
Preparation method of high-purity liraglutide side chain
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, (2019/07/04)
The invention discloses a preparation method of a high-purity liraglutide side chain, palmitic acid, N-hydroxysuccinimide and N, N'-diisopropylcarbodiimide are used as starting materials to react to obtain Palmitoyl-OSu, Palmitoyl-Glu-OtBu, Liraglutide side chain crude product Palmitoyl-Glu (OSu)-OtBu in sequence; the reaction solution is filtered, the obtained filtrate is washed with an acidic aqueous solution, and an organic phase is concentrated the until being dry; the organic phase is recrystallized by using an alkane and a fatty alcohol or a mixed solvent of the alkane and the fatty alcohol to obtain the high-purity liraglutide side chain. The method for preparing the high-purity liraglutide side chain is simple to operate, the synthesis period is short, the cost is low, the after-treatment is easy, the product purity can reach 99.41%, and the method can effectively remove HOSU, DIU, tetradecanoic acid impurities, L5-S2 and octadecanoic acid impurities and other unknown impurities, and is beneficial to large-scale production.