Activation carboxyl groups

Carboxylate groups activated with NHS esters are highly reactive toward amine nucleophiles. In the mid-1970s, NHS esters were introduced as reactive ends of homobifunctional crosslinkers (Bragg and Hou, 1975 Fomant and Fairbanks, 1976). Their excellent reactivity at physiological pH quickly established NHS esters as viable alternatives to the imidoesters predominating at the time (Section 2, this chapter). 

PROTOCATECHUATE 4,5-DIOXYGENASE CARBOXYLESTERASES Carboxyl group activation,... 

A second advantage of preparing peptides by sequential acylation of support-bound amines arises from the fact that activated A -acyl amino acids readily form oxa-zolones, which quickly racemize under basic conditions, such as in the presence of excess amine. Hence, carboxyl group activation of support-bound peptides in the presence of an amine will readily lead to racemization (Figure 16.2). 

Polypeptide chains with a predetermined amino acid sequence can be synthesized by chemical methods involving carboxyl-group activation. 

NCAs are well known forms of a-amino acids which present the amino group protected and the carboxylic group activated for a peptide coupling step. The most common access to NCAs is based on dehydration procedures of a-amino acids involving carbonic acid equivalents, which has limited the method to proteinogenic... 

The lactyl carboxyl group was unmasked by exposure of the phenylsulfonylethyl ester to DBU. Carboxyl group activation of muramic acid derivative 21 was achieved by conversion to the corresponding NHS ester (N-hydroxysuccinimide, EDCI, DMF). The pentapeptide fragment 10 was readily prepared in quantity using standard peptide synthesis protocols [Scheme 7]. Addition of a DMF solution of pentapeptide 10 to a solution of PrNEt2 and the NHS ester deriving from 21 provided the protected muramyl pentapeptide 9 in excellent overall yield. 

Figure 1. Covalent binding of amino acids to proteins using a water-soluble carbodiimide as a carboxyl group activating reagent (50, 51)...

Alternative syntheses of p-lactams which circumvent the use of acid halides involve carboxyl group activating reagents (equations 33-35). These are more practical when the corresponding acid chlorides are unstable or unsafe. ... 

Bis(trifluoromethyl)oxazol-5(2//)-ones are carbonyl-group protected, carboxyl-group activated, a-oxoacid derivatives that undergo reaction with benzene-1,2-diamine to yield quinoxa-lin-2(1 7)-one or its 3-alkyl- or 3-aryl-substituted derivatives. ... 

The aforementioned method for carboxyl group activation proceeds via intermediate 6a, which is then subjected to an intramolecular attack by the secondary alcohol. Among the noteworthy aspects of this synthesis were the rapid entry into the system and the specific formation of the (jE)-olefin geometry. 

After the C-terminal amino acid is attached to the resin, the f-BOC protecting group is removed (Section 23.9). The next amino acid, with its amino group protected with f-BOC and its carboxyl group activated with DCC, is added to the column. 

Figure 2.2 Modern solid phase peptide synthesis. Process begins with a-N terminal Fmoc deprotection of resin bound C-terminal amino acid residue with piperidine (mechanism illustrated). Peptide link formation follows (typical solvent Al-methylpyrrolidone [NMP]) by carboxyl group activation with dicyclohexylcarbodiimide (DCC) (mechanism illustrated) in presence of hydroxybenzotriazole (HOBt). HOBt probably replaces DCC as an activated leaving group helping to reduce a-racemization during peptide link formation. Other effective coupling agents used in place of DCC/HOBt are HBTU 2-(lH-benzotriazol-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate Py-BOP benzotriazole-l-yl-oxy-tns-pyrrolidino-phosphonium hexafluorophosphate. The Process of a-N deprotection, and peptide link formation, continues for as many times as required (n-times), prior to global deprotection and resin removal.

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