- Improved synthesis of unnatural amino acids for peptide stapling
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The procedures for the synthesis of various α-alkenyl and alkyne amino acids were systematically optimized in light of enhancing atom economy, reducing hazardous reagent usage, and simplifying workup. By starting with Boc-Pro-OH and coupling with EDCI/DMAP followed by alkylation, chiral auxiliary was synthesized with high yield and enantioselectivity. For alkylation of the chiral complex, tBuONa was found and proved by quantitative calculation to be superior to tBuOK in generating more nucleophilic enolate salt, thereby can significantly enhance yield under room temperature. Final Fmoc protection was also dramatically facilitated in one-pot sequential manner by adding EDTA-2Na as the nickel chelator. Synthesis of α-bisalkenyl amino acid was also accomplished by achiral complex approach with high yield and efficacy. Accordingly, five most commonly used N-Fmoc protected α-alkenyl and alkynyl amino acids were synthesized and characterized.
- Li, Bo,Zhang, Jie,Xu, Yongjuan,Yang, Xiaoxiao,Li, Li
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supporting information
p. 2374 - 2377
(2017/05/29)
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- Synthesis of ω-(hetero)arylalkynylated α-amino acid by sonogashira-type reactions in aqueous media
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(Chemical Equation Presented) Mild conditions are described that allow the palladium-catalyzed cross-coupling of Cα-alkynylated glycine with a wide variety of electron-rich and electron-poor aryl and heteroaryl halides in aqueous media.
- Brea, Roberto J.,Lopez-Deber, M. Pilar,Castedo, Luis,Granja, Juan R.
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p. 7870 - 7873
(2007/10/03)
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- A Biocatalytic Route to Enantiomerically Pure Unsaturated α-H-α-Amino Acids
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A set of both enantiomeric forms of non-proteinogenic, unsaturated α-H-α-amino acids was efficiently synthesized using a biocatalytic pathway. This route involved the straightforward synthesis of the required unsaturated amino acid amides, followed by resolution with an aminopeptidase present in Pseudomonas putida ATCC 12633 and/or a genetically modified organism, leading to the (S)-acids and (R)-amides. Undesired amino acid racemase activity was identified in the wild-type strain, which was absent in the newly developed organism. The (R)-amides were hydrolyzed under mild conditions using an amidase present in whole cells from Rhodococcus erythropolis NCIMB 11540 to the (R)-acids. The viability of this procedure was demonstrated with the multi-gram synthesis of a variety of unsaturated amino acids in excellent enantiopurity.
- Wolf, Larissa B.,Sonke, Theo,Tjen, Kim C. M. F.,Kaptein, Bernard,Broxterman, Quirinus B.,Schoemaker, Hans E.,Rutjes, Floris P. J. T.
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p. 662 - 674
(2007/10/03)
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- Synthesis and evaluation of ω-borono-α-amino acids 1 as active-site probes of arginase and nitric oxide synthases
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Enantiomerically pure ω-borono-α-amino acids of various chain lengths have been synthesized according to a general methodology involving condensation of alkenyl and alkynyl bromides with NiII complex of the Schiff base derived from glycine and (S)-2-[N′-(N-benzylprolyl)amino]benzophenone, hydroboration of the intermediate ω-unsaturated α-amino acids with diisopinocampheylborane, and oxidation with acetaldehyde. Some of these compounds act as potent inhibitors of rat liver and murine macrophage arginases, demonstrating that distance between the B(OH)2 and α-amino acid groups is a key determinant for their interaction with arginase. In contrast, they are without effect on neuronal and inducible NO synthases. The Royal Society of Chemistry 2000.
- Collet, Sylvain,Carreaux, Francois,Boucher, Jean-Luc,Pethe, Stephanie,Lepoivre, Michel,Danion-Bougot, Renee,Danion, Daniel
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p. 177 - 182
(2007/10/03)
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