- A self-assembling NHC-PD-loaded calixarene as a potent catalyst for the Suzuki-Miyaura cross-coupling reaction in water
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Nanoformulated calix[8]arenes functionalized with N-heterocyclic carbene (NHC)palladium complexes were found to be efficient nano-reactors for Suzuki-Miyaura cross-coupling reactions of water soluble iodo- and bromoaryl compounds with cyclic triol arylborates at low temperature in water without any organic co-solvent. Combined with an improved one-step synthesis of triol arylborates from boronic acid, this remarkably efficient new tool provided a variety of 40-arylated phenylalanines and tyrosines in good yields at low catalyst loading with a wide functional group tolerance.
- Abdellah, Ibrahim,Couvreur, Patrick,Desma?le, Didier,Huc, Vincent,Martini, Cyril,Mougin, Julie,Pecnard, Shannon,Peramo, Arnaud
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- Selective modification of a native protein in a patient tissue homogenate using palladium nanoparticles
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We have developed new benign palladium nanoparticles able to catalyze the Suzuki-Miyaura cross-coupling reaction on human thyroglobulin (Tg), a naturally iodinated protein produced by the thyroid gland, in homogenates from patients' tissues. This represents the first example of a chemoselective native protein modification using transition metal nanoobjects in near-organ medium.
- Peramo, Arnaud,Dumas, Ana?lle,Remita, Hynd,Beno?t, Mireille,Yen-Nicolay, Stephanie,Corre, Rapha?l,Louzada, Ruy A.,Dupuy, Corinne,Pecnard, Shannon,Lambert, Benoit,Young, Jacques,Desma?le, Didier,Couvreur, Patrick
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supporting information
p. 15121 - 15124
(2019/12/26)
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- Tertiary-butoxycarbonyl (Boc) – A strategic group for N-protection/deprotection in the synthesis of various natural/unnatural N-unprotected aminoacid cyanomethyl esters
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A number of cyanomethyl esters of natural/unnatural aminoacids with un-protected amino functionality were synthesized because of their synthetic and medicinal importance. Critical N-Boc deprotection methods in the presence of labile (hydrolytic sensitivity) cyanomethyl functionality were screened thoroughly and it was found that readily available 4M HCl in 1,4-dioxane solution (2–4 equiv); acetonitrile, 0 °C, 2–4 h was a suitable condition. This condition was generalized and successfully applied to a variety of alkyl, alkynyl, aryl, heteroaryl, benzyl, azido, spiro amino acid cyanomethylesters irrespective of the nature of the amine (primary or secondary) and the distance between the amine and ester group to achieve final deprotected amino esters with high yield, and purity compared to other commonly known N-protecting groups (Cbz, Fmoc, Ac, Bn, Bz etc.). It was also demonstrated that N-Boc protected aminoacid cyanomethylesters are stable enough to carry out further functionalization compared to N-unprotected counterparts.
- Karmakar, Ananta,Basha, Mushkin,Venkatesh Babu,Botlagunta, Murali,Malik, Noormohamed Abdul,Rampulla, Richard,Mathur, Arvind,Gupta, Arun Kumar
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supporting information
p. 4267 - 4271
(2018/11/03)
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- Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
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As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki= 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki= 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki= 8.45 μM), which was the same as positive control Gossypol (Ki= 7.54 μM).
- Wan, Yichao,Liu, Tingting,Li, Xiaoxian,Chen, Chen,Fang, Hao
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p. 138 - 152
(2016/12/22)
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- PLGA-PEG-supported Pd nanoparticles as efficient catalysts for Suzuki-Miyaura coupling reactions in water
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Chemical transformations that can be performed selectively under physiological conditions are highly desirable tools to track biomolecules and manipulate complex biological processes. Here, we report a new nanocatalyst consisting of small palladium nanoparticles stabilized on the surface of PLGA-PEG nanoparticles that show excellent catalytic activity for the modification of biological building blocks through Suzuki-Miyaura cross-coupling reactions in water. Brominated or iodinated amino acids were coupled with aryl boronic acids in phosphate buffer in good yields. Interestingly, up to 98% conversion into the coupled amino acid could be achieved in 2 h at 37°C using the stable, water-soluble cyclic triolborate as organometallic partner in the presence of only 1 mol% of palladium. These results pave the way for the modification of biomolecules in complex biological systems such as the intracellular space.
- Dumas, Ana?lle,Peramo, Arnaud,Desma?le, Didier,Couvreur, Patrick
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p. 252 - 257
(2016/06/01)
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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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- Suzuki-Miyaura Diversification of Amino Acids and Dipeptides in Aqueous Media
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The Suzuki-Miyaura derivatisation of free amino acids, peptides and proteins is an attractive area with considerable potential utility for medicinal chemistry and chemical biology. Here we report the modification of unprotected and Boc-protected aromatic amino acids and dipeptides in aqueous media, enabling heteroarylation and vinylation. We systematically investigate the impact of the peptide backbone and adjacent amino acid residues upon the reaction. Our studies reveal that although asparagine and histidine hinder the reaction, by utilising dppf, a ferrocene-based bidentate phosphine ligand, cross coupling of halophenylalanine or halotryptophan adjacent to such a residue could be enabled. Our studies reveal dppf to have good compatibility with all unprotected, proteinogenic amino acid side chains.
- Willemse, Tom,Van Imp, Karolien,Goss, Rebecca J. M.,Van Vlijmen, Herman W. T.,Schepens, Wim,Maes, Bert U. W.,Ballet, Steven
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p. 2055 - 2070
(2015/11/24)
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- Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors
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A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, α-ketoamide, bisulfite adduct, and α-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities.
- Prior, Allan M.,Kim, Yunjeong,Weerasekara, Sahani,Moroze, Meghan,Alliston, Kevin R.,Uy, Roxanne Adeline Z.,Groutas, William C.,Chang, Kyeong-Ok,Hua, Duy H.
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p. 6317 - 6320
(2013/11/19)
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- A convenient catalyst for aqueous and protein Suzuki-Miyaura cross-coupling
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(Figure Presented) A phosphine-free palladium catalyst for aqueous Suzuki-Miyaura cross-coupling is presented. The catalyst is active enough to mediate hindered, ortho-substituted biaryl couplings but mild enough for use on peptides and proteins. The Suzuki-Miyaura couplings on protein substrates are the first to proceed in useful conversions. Notably, hydrophobic aryl and vinyl groups can be transferred to the protein surface without the aid of organic solvent since the aryl- and vinylboronic acids used in the coupling are water-soluble as borate salts. The convenience and activity of this catalyst prompts use in both general synthesis and bioconjugation.
- Chalker, Justin M.,Wood, Charlotte S. C.,Davis, Benjamin G.
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supporting information; experimental part
p. 16346 - 16347
(2010/01/29)
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- PHOSPHONO SUBSTITUTED TETRAZOLE DERIVATIVES AS ECE INHIBITORS
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The present invention relates to the N-phosphonomethyl substituted compounds of formula STR1
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- Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors
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The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described.In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo.Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys.Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment.A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements.Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a.Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.
- Ksander, Gary M.,Ghai, Raj D.,deJesus, Reynalda,Diefenbacher, Clive G.,Yuan, Andrew,et al.
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p. 1689 - 1700
(2007/10/02)
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- PHOSPHONO/BIARYL SUBSTITUTED AMINO ACID DERIVATIVES
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The present invention relates to the N-phosphonomethyl-biaryl substituted amino acid derivatives of formula I STR1 wherein X represents a direct bond, C 1-4-alkylene or C 2-C 4-alkenylene; R and R' represent independently hydrogen, carbocyclic aryl, 6-tet
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