- Enzymatic C-terminal amidation of amino acids and peptides
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Herein, we describe two versatile and high yielding enzymatic approaches for the conversion of semi-protected amino acid and peptidyl C-terminal α-carboxylic acids into their corresponding amides. In the first approach, the lipase Candida antarctica lipase-B (Cal-B), and in the second approach, the protease Subtilisin A, are used, respectively. We found that by using the ammonium salt of the α-carboxylic acid instead of separate ammonia sources, the enzymatic amidation reactions proceeded much faster without side reactions and gave near to quantitative yields of products.
- Nuijens, Timo,Piva, Elena,Kruijtzer, John A.W.,Rijkers, Dirk T.S.,Liskamp, Rob M.J.,Quaedflieg, Peter J.L.M.
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experimental part
p. 3777 - 3779
(2012/09/22)
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- Basic proline-amide derivatives of GE 2270 and GE 2270-like antibiotics
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PCT No. PCT/EP96/00407 Sec. 371 Date Jul. 31, 1997 Sec. 102(e) Date Jul. 31, 1997 PCT Filed Feb. 1, 1996 PCT Pub. No. WO96/24607 PCT Pub. Date Aug. 15, 1996The present invention refers to basic amides derivatives of GE 2270 and GE 2270-like antibiotics of general formula (1), wherein the group GE represents the antibiotic core molecule. The amide derivatives of antibiotic GE 2270 of formula (I) are antimicrobial agents mainly active against gram positive bacteria.
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- Derivatives of antibiotic GE2270 factors C2a, D2 and E
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Mono- or di-substituted derivatives of GE2270 factors C2a, D2 and E of general formula (I), wherein W represents a moiety of formula (a), (b) or (c), R1 and R2 representing a variety of substituents, X1 is methyl, X2 is a --CH2 --W1 moiety and X3 is methylamino or amino, or X1 is a --CH2 --W1 moiety, X2 is methoxymethylene and X3 is methylamino, with the proviso that when X3 is amino, then W must be 2-(aminocarbonyl)-pyrrolidinyl; with the further proviso that when W is 2-(aminocarbonyl)-pyrrolidinyl, then W1 cannot be hydroxy; and the pharmaceutically acceptable salts thereof. The mono- or di-substituted derivatives of antibiotic GE 2270 of formula (I) are antimicrobial agents mainly active against gram positive bacteria. STR1
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- Protein backbone modification by novel C(α)-C side-chain scission
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α-Ketoamide (-NH-CO-CO-) units in intact peptides are generated from Ser/Thr residues via Ru(VIII)-catalyzed C(α)-C side-chain scission. Facets associated with this novel α-carbon modification have been probed with 75 peptides chosen to represent every possible peptide environment. The reactions were carried out at room temperature with in situ generated Ru(VIII) in biphasic (CH3CN/CCl4/pH 3 phosphate buffer, 1:1:2 v/v) medium. Whereas Ser/Thr residues placed at the C-terminal end in peptides undergo N-C bond scission leading to des-Ser/Thr peptide amides - thus acting as Gly equivalents in simulating the α-amidating action of pituitary enzymes - those located at the N-terminal or nonterminal or even at the C-terminal position (protected as amide) were found to undergo oxidative C-C bond scission (involving C(α) and C side-chain bond), resulting in the generation of α-ketoamide (-NH-CO-CO-) units in the intact peptide backbone. The difference in the products arising from C(α)-C side-chain scission of Ser/Thr esters and amides is rationalized on the basis of a common mechanism involving either oxaloesters [PeP-NH-CO-COX; X = OMe] or oxalamides [X = NH2 or NH-Pep] arising from the oxidation of initially formed carbinolamide intermediates [Pep-NH-CH(OH)-COX], wherein, while the former are shown to undergo hydrolysis to terminal amides [Pep-NH2], the oxalamides are found to be stable to hydrolysis. Ancillary noteworthy findings are those of peptide bond scission when contiguous Ser-Ser/Thr-Thr residues are present and the oxidative cleavage at C-terminal Tyr/Trp sites generating des amides. The oxidative methodology presented here is mild, simple, and practical and proceeds with chiral retention. The insensitivity of a large number of amino acid residues, such as Gly, Ala, Leu, Asn, Gln, Asp, Glu, Pro, Arg, Phe, Lys, Val, and Aib, and N-protecting groups, such as Boc, Z, and Bz, toward Ru(VIII) under the experimental conditions should make this methodology practical and useful. Sulfur-containing amino acids Cys and Met get oxidized to sulfones in the products.
- Ranganathan,Vaish,Shah
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p. 6545 - 6557
(2007/10/02)
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- Branched amides of L-aspartyl-D-amino acid dipeptides
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Amides of L-aspartyl-D-amino acid dipeptides of the formula STR1 and physiologically acceptable cationic and acid addition salts thereof wherein Ra is CH2 OH or CH2 OCH3 ; R is a branched member selected from the group consisting of fenchyl, diisopropylcarbinyl, d-methyl-t-butylcarbinyl, d-ethyl-t-butylcarbinyl, di-t-butylcarbinyl, 2-methylthio-2,4-dimethylpentan-3-yl, STR2 where at least one of R3, R4, R5, R6 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms, X is O, S, SO, SO2, C=O or CHOH; m is zero or 1-4, n and p are each zero, 1, 2 or 3 where the sum of n+p is not greater than 3 and the sum of the carbon atoms in R3, R4, R5 and R6 is not greater than six, and when both of R3 and R4 or R5 and R6 are alkyl they are methyl or ethyl, STR3 where one of R7, R8, R9 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms and the sum of the carbon atoms in R7, R8 and R9 is not greater than six, m and q are the same or different and each have the values previously defined for m; STR4 where each of R12 and R13 are methyl or ethyl, or R12 is hydrogen and R13 is alkyl having from one to four carbon atoms, Z is O or NH and t is 1 or 2, STR5 where W is 1-4, R14 and R16 are each alkyl having from one to four carbon atoms, R15 is H, OH, methyl or ethyl and the sum of the carbon atoms in R14, R15 and R16 is not greater than six and when both of R14 and R15 are alkyl they are methyl or ethyl, and STR6 where R17 and R19 are alkyl having from one to four carbon atoms, R18 and R20 are H or alkyl having one to two carbon atoms, A is OH and B is H, OH or CH3 and taken together A and B are STR7 where the sum of the carbon atoms in R17, R18, R19 and R20 is not greater than six and when both of R17 and R18 or R19 and R20 are alkyl they are methyl or ethyl; said amides are potent sweeteners having advantages over the prior art, edible compositions containing them, methods for their use in edible compositions and novel amide intermediates useful in their production.
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- Dichlorotris(dimethylamino)phosphorane as a Dehydratisation Reagent for the Preparation of N-Protected Amino Acid Amides
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Besides for the synthesis of peptides and activated esters dichlorotris(dimethylamino)phosphorane (2) now proved to be an excellent reagent for the preparation of N-protected amino acid amides.
- Appel, Rolf,Hiester, Ernst
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p. 2037 - 2040
(2007/10/02)
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