Acylation water-soluble carbodiimide

FIGURE 1.16 Purified symmetrical anhydrides of iV-alkoxycarbonylamino acids obtained using a soluble carbodiimide.15 The reagent ethyl-(3-dimethylaminopropyl)-carbodiimide hydrochloride,14 also known as WSCD (water-soluble carbodiimide), the NW -dialkylurea, and the iV-acyl-iV,iV -dialkylurea are soluble in water and thus can be removed from a reaction mixture by washing it with water. 

Interestingly, reaction of hyaluronic acid with EDC in the presence of primary amines affords only theN-acyl urea derivatives, as proven by C- and N-labeling experiments. Water soluble carbodiimides are also used in the depolymerization of polyuronides via reduction of their carbodiimide activated carboxyl groups. ... 

Fig. 6.22.B Synthesis ofrc-N2Sp-antihody by formation of " Tc-4,. i-bis(thioacetamido)pcntanoatc, which is con cited to an active ester by water-soluble carbodiimide and finally conjugated to antibody (Ab) via acylation of amino groups [195]...

Reaction of (233), or its 6-mercapto analogue, with a water soluble carbodiimide resulted in an intramolecular acylation at N-3 followed by a spontaneous hydroxylation at C-2 and opening of the pyrimidine ring to give (137) in 67% yield <85H(23)2669>. Treatment of (234) in refluxing ethanol gave (235) <90JCS(Pl)3003>. 

Direct covalent linkage of nucleic acids to carbon nanotubes for cell uptake experiments has been reported by only a few investigators. The most direct procedure involved activation of the carboxyl functional group on oxidized carbon nanotubes by the water soluble carbodiimide l-[3-(dimethylpropyl]-3-ethylcarbodiimide (EDC) followed by incubation with nucleic acid. The nucleic acid became associated with the carbon nanotubes, presumably through acylation of nucleobase amino groups as illustrated in Fig. 18.9. 

Another potential problem with DCC is that at the completion of the reaction some DCU remains in solution with the product, necessitating additional purification. Water-soluble carbodiimide derivatives such as l-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide Metho-p-toluenesulffonate and l-Ethyl-3-(3 -dimethylaminopropyl)carbodiimide Hydrochloride (EDCI) obviate this problem, as they are removed by a simple extraction. Many newer coupling agents have been developed for peptide synthesis and other acylation reactions. These include Benzotriazol-l-yloxytris(dimethylamino)phosphonium Hexafluorophosphate (BOP)," 0-Benzotriazol-l-yl-N,N,N, N -tetramethyluronium Hexafluorophosphate (HBTU)," Bis(2-oxo-3-oxazolidinyl)phosphinic Chloride (BOP-Cl), and (1 //-1,2,3-benzotriazol-1 -yloxy)tris(pyrTolidino)phosphonium hexafluorophosphate (PyBOP). In addition to linear and polymeric amides, lactams of various ring sizes have been synthesized using these methods (eq 1)."... 

RCO2H, R OH, DCC/DMAP, EtjO, 25°C, l-24h, 70-95% yield. This method is suitable for a large variety of hindered and unhindered acids and alcohols. The use of Sc(OTf)3 as a cocatalyst improves the esterification of 3° alcohols. Carboxylic acids that can form ketenes with DCC react preferentially with aliphatic alcohols in the presence of phenols whereas those that do not show the opposite selectivity. In some sterically congested situations the 0-acyl urea will migrate to an unreactive A-acyl urea in competition with esterification. Carbodi-imide I was developed to make the urea by-product water soluble and thus easily washed out. Isoureas are prepared from a carbodiimide and an alcohol which upon reaction with a carboxylic acid give esters in excellent yield. A polymer supported version of this process has been developed. This process has been reviewed. Note that DCC is a potent skin irritant in some individuals. 

Carbodiimide method, a procedure for peptide bond formation using carbodi-imides, R-N=C=N-R, such as dicyclohexyl carbodiimide (DCC), diisopropyl carbodiimide (DIC) and water-soluble carbodi-imides. The carbodiimide reacts in a one-pot procedure with the carboxylate anion of the carboxy component to form a highly reactive O-acylisourea intermediate. The former reacts immediately with the amino function of the amino component to yield the desired peptide derivative and the urea byproduct. Indeed, a more complex mechanism must be taken into consideration. Unwanted side reactions are racemization via the oxazolone mechanism and formation of the unreactive N-acylurea by base-catalyzed acyl migration from the isourea oxygen to nitrogen. The side reactions can be diminished by preparing the O-acylisourea at 0 °C... 

Retronamine and monocrotaline antibodies were used to detect retronecine and monocrotaline. In an attenqit to inqnove on the relatively high I50 value of our anti-retronecine (1.68 put), we conjugated retronamine, a synthetic derivative of retronecine, to BS A by acylation of the retronamine primary anaine with hexanedioic anhydride giving a hapten intermediate which was then coupled to BSA by water-soluble l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC). The tertiary nitrogen of monocrotaline was alkylated with the N-hydroxysuedninoide ester of 4-bromocrotonic acid giving a hapten intermediate which was then coupled to BSA via N-acylation of the lysine primary amines. 

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