- Synthesis of water-soluble hypervalent iodine reagents for fluoroalkylation of biological thiols
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New open-chain and water-soluble hypervalent iodine reagents were synthesized and used for the transfer of fluoroalkyl groups to sulfur atoms of cysteine and cysteine-containing peptides under biocompatible conditions. Some of the reagents displayed excellent reactivity despite their limited stability in aqueous media. In reactions with a short cysteine-containing peptide, in addition to the expected S-fluoroalkylated product, a range of side-products were obtained. The amount of side-products depended on the conditions used (type of reagent, concentration, and pH). With highly activated hypervalent iodine reagents, a new reactive mode was observed-reaction with disulfides to form fluoroalkyl thiols.
- Klimánková, Iveta,Hubálek, Martin,Matou?ek, Václav,Beier, Petr
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supporting information
p. 10097 - 10102
(2019/12/23)
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- Chemoselective Synthesis of N-Terminal Cysteinyl Thioesters via β,γ-C,S Thiol-Michael Addition
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Dehydroalanine (ΔAla) is a highly electrophilic residue that can react efficiently with sulfur nucleophiles to furnish cysteinyl analogues. Herein, we report an efficient synthesis of N-terminal cysteinyl thioesters, suitable for S,N-acyl transfer, based on β,γ-C,S thiol-Michael addition. Both ionic and radical-based methodologies were found to be efficient for this process.
- Petracca, Rita,Bowen, Katherine A.,McSweeney, Lauren,O'Flaherty, Siobhan,Genna, Vito,Twamley, Brendan,Devocelle, Marc,Scanlan, Eoin M.
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supporting information
p. 3281 - 3285
(2019/05/10)
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- Rapid cross-metathesis for reversible protein modifications via chemical access to se-allyl-selenocysteine in proteins
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Cross-metathesis (CM) has recently emerged as a viable strategy for protein modification. Here, efficient protein CM has been demonstrated through biomimetic chemical access to Se-allyl-selenocysteine (Seac), a metathesis-reactive amino acid substrate, via dehydroalanine. On-protein reaction kinetics reveal a rapid reaction with rate constants of Seac-mediated-CM comparable or superior to off-protein rates of many current bioconjugations. This use of Se-relayed Seac CM on proteins has now enabled reactions with substrates (allyl GlcNAc, N-allyl acetamide) that were previously not possible for the corresponding sulfur analogue. This CM strategy was applied to histone proteins to install a mimic of acetylated lysine (KAc, an epigenetic marker). The resulting synthetic H3 was successfully recognized by antibody that binds natural H3-K9Ac. Moreover, Cope-type selenoxide elimination allowed this putative marker (and function) to be chemically expunged, regenerating an H3 that can be rewritten to complete a chemically enabled "write (CM)-erase (ox)-rewrite (CM)" cycle.
- Lin, Yuya A.,Boutureira, Omar,Lercher, Lukas,Bhushan, Bhaskar,Paton, Robert S.,Davis, Benjamin G.
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supporting information
p. 12156 - 12159
(2013/09/23)
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- Reversible and Diastereospecific Insertion of 2-Acetamidoacrylic Methyl Ester into the Metal-Hydrogen Function of Chiral Clusters
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The chiral hydrido metal clusters (μ3-RC)CoMM'Cp(CO)8H (R = Me, Ph; M = Ru, Os; M'= Mo, W) (1a-5a) react with the prochiral alanine precursor 2-acetamidoacrylic methyl ester by insertion into the M-H function and substitution of a CO group.In a diastereospecific reaction cluster adducts 1b-5b with a five-membered M-C-N-C-O ring are formed which contain an M-C ?-bond involving a tertiary carbon atom.This has been confirmed by a crystal structure determination of the RuCoMo compound 1b.Deuteration experiments have ascertained that the reaction is of the Markownikow-type.The enamide substrate is regenerated with CO or PPh3, it is not hydrogenerated with H2.A partial enantiomer separation of the insertion products is possible by chromatography over triacetylcellulose.The subsequent elimination of the enamide by CO or PPh3 is accompanied by nearly quantitative racemisation of the cluster. - Key Words: Clusters, hydrido metal / Insertion, diastereospecific
- Mani, Darjusch,Schacht, Hans-Thomas,Powell, Anne K.,Vahrenkamp, Heinrich
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p. 2245 - 2252
(2007/10/02)
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- Reversible and diastereospecific olefin insertion into a cluster Ru-H unit. Formation of metallacycles with tertiary carbon-ruthenium σ bonds
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The chiral hydrido metal clusters (μ3-RC)Ru-CoMCp(CO)8H with R = Me or Ph and M = Mo or W react reversibly with the prochiral alanine precursor acetamido acrylic acid methyl ester according to a Markownikow-type insertion of the X2C=CH2 substrate into a Ru-H bond. The cluster products formed consist of only one pair of the possible diastereoisomers rendering the reaction diastereospecific. The resulting σ-alkyl cluster complexes contain a Ru-C-N-C-O metallacycle with a tertiary carbon atom bound to ruthenium.
- Mani, Darjusch,Schacht, Hans-Thomas,Powell, Anne,Vahrenkamp, Heinrich
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p. 1360 - 1361
(2008/10/08)
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- INTRINSIC REACTIVITIES IN THE ALKYLATIONS OF PROTECTED AMINO ACIDS BY (R)- AND (S)-METHYLOXIRANE
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A comparative study is described of the reactions between protected amino acids and the enantiomeric methyloxiranes .At 45 deg C in methanol the relative rates of the reactions with either (1a) or (1b) are (5a) ca. (3a) > (2a>.The reaction of (1a)/(1b) with (2a) is dramatically accelerated (>/= 100-fold) by triethylamine, because of the conversion of (2a) into its thiolate.The products from (1a)/(1b) + (2a) thiolate are (R,αR)- and (S,αR)-N-acetyl-S-(2-hydroxy-propyl)-L-cysteine methyl ester .These products undergo a slow further reaction with methyloxirane leading via a β-elimination to N-acetyldehydroalanine methyl ester and bis-(2-hydroxypropyl) sulphide.The products from (1a)/(1b) + (3a) are (R,αS)- and (S,αS)-N-(2-hydroxypropyl)-L-valine methyl ester .These products also undergo a slow further reaction with methyloxirane leading to an NN-bis-(2-hydroxypropyl)valine methyl ester and derived morpholone (R,R,αS)-NN-bis-(2-hydroxypropyl)valine methyl ester (3f) and δ-lactone (3h)>.The reactions of (1a) or (1b) with (5a) give, via the products of mono-N-alkylation in the imidazole ring α-benzoyl-Nτ-(2-hydroxypropyl)-L-histidine methyl ester (5d) and its N?-isomer (5e) from (1b) + (5a)>, a mixture α-benzoyl-N?Nτ-bis-(2-hydroxypropyl)-L-histidinylimidazolium carboxylates (6d) + (6e) from excess of (1b) + (5a)>.The generation of methoxide during the reactions described is responsible for the β-elimination leading to a dehydroalanine derivative and for the epimerisation during the formation of (6d) + (6e).Kinetic studies show that for none of the substrates (2a), (3a), or (5a) is there significant enantioselectivity in their reactions with the enantiomers of methyloxirane.The relevance of the present study to the toxicology of methyloxiranes is discussed.
- Ellis, Martin K.,Golding, Bernard T.,Watson, William P.
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p. 1737 - 1744
(2007/10/02)
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