- Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins
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Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was the discovery of a new sterically encumbered bis(oxazoline) ligand backbone, thus offering a de novo technology for accessing enantioenriched sp3-sp3 linkages via sp3 C-N functionalization. Our protocol is distinguished by its broad scope and generality across a wide number of counterparts, even in the context of late-stage functionalization. In addition, an enantioselective deaminative remote hydroalkylation reaction of unactivated internal olefins is within reach, thus providing a useful entry point for forging enantioenriched sp3-sp3 centers at remote sp3 C-H sites.
- Cai, Yue-Ming,Martin, Ruben,Rui, Xi-Yan,Shang, Ming,Sun, Shang-Zheng,Wang, Jia-Bao,Yao, Hong-Qing,Zhang, De-Liang
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supporting information
p. 1130 - 1137
(2022/02/05)
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- Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L
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Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.
- Aggarwal, Anupriya,Ashhurst, Anneliese S.,Bedding, Max J.,Beretta, Laura,Drelich, Aleksandra,Gerwick, William H.,Hook, Vivian,Larance, Mark,Li, Linfeng,McKerrow, James H.,Meek, Thomas D.,O'Donoghue, Anthony J.,Payne, Richard J.,Pwee, Dustin,Skinner, Danielle,Stoye, Alexander,Tang, Arthur H.,Tseng, Chien-Te,Turville, Stuart,Yoon, Michael C.,Fajtová, Pavla
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supporting information
(2021/11/18)
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- Chemoenzymatic Synthesis of Optically Pure l- and d-Biarylalanines through Biocatalytic Asymmetric Amination and Palladium-Catalyzed Arylation
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A chemoenzymatic approach was developed and optimized for the synthesis of a range of N-protected nonnatural l- and d-biarylalanine derivatives. Starting from 4-bromocinnamic acid and 4-bromophenylpyruvic acid using a phenylalanine ammonia lyase (PAL) and an evolved d-amino acid dehydrogenase (DAADH), respectively, both enantiomers of 4-bromophenylalanine were obtained and subsequently coupled with a panel of arylboronic acids to give the target compounds in high yield and optical purity under mild aqueous conditions.
- Ahmed, Syed T.,Parmeggiani, Fabio,Weise, Nicholas J.,Flitsch, Sabine L.,Turner, Nicholas J.
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p. 5410 - 5413
(2015/09/15)
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- PEPTIDYL NITRIL COMPOUNDS AS DIPEPTIDYL PEPTIDASE I INHIBITORS
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The invention relates to compounds of Formula (I) and its use as a selective dipeptidyl peptidase I inhibitor, as well as pharmaceutical compositions comprising said compounds, and methods of treatment involving said compounds.
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Page/Page column 26
(2015/03/28)
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- PEPTIDYL NITRILCOMPOUNDS AS PEPTIDASE INHIBITORS
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The invention relates to compounds of Formula (II) and their use in theraphy as peptidase inhibitors.
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Page/Page column 112
(2012/09/22)
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- Asymmetric synthesis of N-protected amino acids by the addition of organolithium carboxyl synthons to ROPHy/SOPHy-derived aldoximes and ketoximes.
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A new asymmetric synthesis of alpha-amino acids is described in which the key step is the highly diastereoselective addition of organolithium carboxyl synthons (2-furyllithium, phenyllithium, vinyllithium) to (R)- and (S)-O-(1-phenylbutyl) oximes to give hydroxylamines, with vinyllithium being the most satisfactory nucleophilic reagent. Subsequent reductive cleavage of the N-O bond in hydroxylamines, followed by N-protection, and oxidative cleavage of the carboxyl precursor gave a range of N-protected amino acids and esters. The method was exemplified by the synthesis of a range of derivatives of non-proteinogenic amino acids such as 4-bromophenylalanine, tert-leucine, norvaline, cyclohexyl- and aryl-glycines, 2-amino-8-oxodecanoic acid (Aoda) and alpha-methylvaline.
- Cooper, Tracey S,Laurent, Pierre,Moody, Christopher J,Takle, Andrew K
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p. 265 - 276
(2007/10/03)
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