- Water-removable ynamide coupling reagent for racemization-free syntheses of peptides, amides, and esters
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A novel ynamide coupling reagent, the by-product of which can be removed by water, was reported. It promotes the direct coupling between carboxylic acids and amines, alcohols or thiols to provide amides, peptides, esters and thioesters, respectively. No detectable racemization was observed for all the coupling reactions of carboxylic acids containing an α-chiral center. Importantly, a simple acidic aqueous work-up removed the by-product readily to afford pure coupling products in good to excellent yields without the use of column chromatography, thus making this method more environmentally benign, user friendly and cost-effective. The robustness of the water-removable ynamide coupling reagent was further exemplified by the racemization/epimerization-free synthesis of carfilzomib, in which no column chromatography purification was involved for the entire 12-step synthesis.
- Liu, Tao,Zhang, Xue,Peng, Zejun,Zhao, Junfeng
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p. 9916 - 9921
(2021/12/24)
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- Allenone-Mediated Racemization/Epimerization-Free Peptide Bond Formation and Its Application in Peptide Synthesis
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Allenone has been identified as a highly effective peptide coupling reagent for the first time. The peptide bond was formed with an α-carbonyl vinyl ester as the key intermediate, the formation and subsequent aminolysis of which proceed spontaneously in a racemization-/epimerization-free manner. The allenone coupling reagent not only is effective for the synthesis of simple amides and dipeptides but is also amenable to peptide fragment condensation and solid-phase peptide synthesis (SPPS). The robustness of the allenone-mediated peptide bond formation was showcased incisively by the synthesis of carfilzomib, which involved a rare racemization-/epimerization-free N to C peptide elongation strategy. Furthermore, the successful synthesis of the model difficult peptide ACP (65-74) on a solid support suggested that this method was compatible with SPPS. This method combines the advantages of conventional active esters and coupling reagents, while overcoming the disadvantages of both strategies. Thus, this allenone-mediated peptide bond formation strategy represents a disruptive innovation in peptide synthesis.
- Wang, Penghui,Wang, Xuewei,Wang, Zhengning,Zhao, Junfeng
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p. 10374 - 10381
(2021/07/26)
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- PURIFICATION METHOD OF CARFILZOMIB
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The present invention relates to a process for purification of carfilzomib free from its impurities using preparative high performance liquid chromatography (prep-HPLC).
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Page/Page column 12-15
(2021/01/22)
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- PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.
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- PROCESS FOR MAKING CARFILZOMIB
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The present invention relates to a process for preparation of Carfilzomib of formula (I).
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Page/Page column 17-18
(2018/03/28)
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- AN IMPROVED PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.
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- PROCESS FOR THE PREPARATION OF (2S)-N-((S)-1-((S)-4-METHYL-1-((R)-2-METHYL OXIRAN-2-YL)-1-OXOPENTAN-2-YLCARBAMOYL)-2-PHENYLETHYL)-2-((S)-2-(2-MORPHOLINO ACETAMIDO)-4-PHENYLBUTANAMIDO)-4-METHYLPENTANAMIDE
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The present invention relates to process for the preparation of (2S)-N-((S)-l -((S)-4-methyl-1 -((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4 -methylpentanamide represented by the following structural formula-1.
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- METHODS OF MAKING CARFILZOMIB AND INTERMEDIATES THEREOF
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Racemization-free methods are disclosed for the synthesis of carfilzomib. Novel intermediates and methods of making carfilzomib employing fragment condensation using the novel intermediates are disclosed. Amorphous carfilzomib and methods of making same are disclosed.
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- CRYSTALLINE PEPTIDE EPOXY KETONE PROTEASE INHIBITORS AND THE SYNTHESIS OF AMINO ACID KETO-EPOXIDES
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The invention relates to crystalline peptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions. This invention also relates to methods for the preparation of amino acid keto-epoxides. Specifically, allylic ketones are stereoselectively converted to the desired keto epoxides.
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- Compounds for enzyme inhibition
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Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.
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Page/Page column 31-32
(2008/06/13)
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