- A simple and versatile method to synthesize N-acyl-benzotriazoles
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An efficient method for the synthesis of N-acyl-benzotriazoles from a wide variety of protected amino acids, as well as from compounds frequently used in drug discovery such as biotin and N-Fmoc polyethylene glycol, has been developed. The reaction of car
- Laconde, Guillaume,Amblard, Muriel,Martinez, Jean
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supporting information
p. 341 - 343
(2019/01/04)
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- Unexpected Reactivity of N-Acyl-Benzotriazoles with Aromatic Amines in Acidic Medium (ABAA Reaction)
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Despite the large number of methods for the synthesis of amides, formation of the amide bond from aromatic amines has always been a challenge for organic chemists due to their weak nucleophile character. We describe here a new efficient method of amide formation from N-Acyl-Benzotriazoles and Aromatic Amines (ABAA reaction) including aniline derivatives, in acidic conditions. This reaction is selective for aromatic amines, since aliphatic amines did not react under the same experimental conditions. Using the ABAA reaction, we have synthesized a series of aromatic amide compounds including labelled enzyme substrates, in excellent yield. The ABAA reaction also allowed the one-pot synthesis of Nordiazepam, which is a precursor of the anxiolytic Diazepam (Valium). This procedure opens new ways of synthesis of amides from aromatic amines, as well as of heterocyclic structures.
- Laconde, Guillaume,Amblard, Muriel,Martinez, Jean
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- Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors
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The synthesis of vinyl sulfones and (α,β-unsaturated) nitriles from carboxylic acids was realized through oxidative decarboxylation with 1,4-dicyanoanthracene as an organic photoredox catalyst. Various types of C-radicals are generated and used to construct three different classes of potential covalent protease inhibitors. The procedure is functional group tolerant and applicable to natural products and druglike scaffolds. It may serve for the rapid construction of screening candidates as demonstrated by a three-step synthesis of the known protease inhibitor K11777.
- Kammer, Lisa Marie,Lipp, Benjamin,Opatz, Till
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p. 2379 - 2392
(2019/01/21)
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- Chemical ligation of S-scylated cysteine peptides to form native peptides via 5-, 11-, and 14-membered cyclic transition states
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Cysteine-containing dipeptides 3a-l, (3b+3b′) (compound numbers in parentheses are used to indicate racemic mixtures; thus (3b+3b′) is the racemate of 3b and 3b′), and tripeptide 13 were synthesized in 68-96% yields by acylation of cysteine with N-(Pg-α-aminoacyl)- and N-(Pg-α-dipeptidoyl)benzotriazoles (where Pg stands for protecting group in the nomenclature for peptides throughout the paper) in the presence of Et3N. Cysteine-containing peptides 3a-l and 13 were S-acylated to give S-(Pg-α-aminoacyl)dipeptides 5a-l and S-(Pg-α-aminoacyl) tripeptide 14 without racemization in 47-90% yields using N-(Pg-α- aminoacyl)benzotriazoles 2 in CH3CN-H2O (7:3) in the presence of KHCO3. (In our peptide nomenclature, the prefixes di-, tri-, etc. refer to the number of amino acid residues in the main peptide chain; amino acid residues attached to sulfur are designated as S-acyl peptides. Thus we avoid use of the prefix "iso".) Selective S-acylations of serine peptide 3k and threonine peptide 3l containing free OH groups were thus achieved in 58% and 72% yield, respectively. S-(Pg-α-aminoacyl)cysteines 4a,b underwent native chemical ligations to form native dipeptides 3f,i via 5-membered cyclic transition states. Microwave irradiation of S-(Pg-α-aminoacyl)tripeptide 15 and S-(Pg-α-aminoacyl)tetrapeptide 17 in the presence of NaH2PO4/Na2HPO 4 buffer solution at pH 7.8 achieved chemical ligations, involving intramolecular migrations of acyl groups, via 11- and 14-membered cyclic transition states from the S-atom of a cysteine residue to a peptide terminal amino group to form native peptides 19 and 20 in isolated yields of 26% and 23%, respectively.
- Katritzky, Alan R.,Tala, Srinivasa R.,Abo-Dya, Nader E.,Ibrahim, Tarek S.,El-Feky, Said A.,Gyanda, Kapil,Pandya, Keyur M.
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experimental part
p. 85 - 96
(2011/04/12)
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- Benzotriazole-assisted solid-phase assembly of Leu-Enkephalin, amyloid β segment 34-42, and other "difficult" peptide sequences
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Microwave-assisted solid-phase syntheses of six "difficult" peptides, H-VVSVV-NH2 (3), H-VVVSVV-NH2(4), H-VIVIG-OH (5), H-TVTVTV-NH2 (6), H-VKDGYI-NH2 (7), and H-VKDVYI-NH2 (8), were achieved utilizing N-(Fmoc-α-aminoacyl) benzotriazoles. Extension to the syntheses of Leu-enkephalin (9) and amyloid-β (34-42) (10) demonstrates that this strategy comprises an efficient route to new and known "difficult" peptides.
- Katritzky, Alan R.,Haase, Danniebelle N.,Johnsons, Jodie V.,Chung, Alfred
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body text
p. 2028 - 2032
(2009/08/07)
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- N-Tfa- and N-Fmoc-(α-aminoacyl)benzotriazoles as chiral C-acylating reagents under Friedel-Crafts reaction conditions
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Chiral N-Tfa- and N-Fmoc-protected (α-aminoacyl)benzotriazoles 1a-j undergo Friedel-Crafts-type reactions with indole, N-methylindole, pyrrole, N-methylpyrrole, and benzene in the presence of AlCl3 in efficient two-step sequences leading to ena
- Katritzky, Alan R.,Jiang, Rong,Suzuki, Kazuyuki
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p. 4993 - 5000
(2007/10/03)
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