N, A"-Dicyclohexylcarbodiimide

Coupling of the two amino acids is achieved by N, A/ -dicyclohexylcarbodiimide (DCCI)-promoted amide bond formation between the free amino group of leucine benzyl ester and the free carboxyl group of Z-protected alanine. 

More extensive studies118 have shown that a-mercaptocarboxylic acids, ethyl nitrite, and N.N1 -dicyclohexylcarbodiimide with a catalytic amount of sulfuric acid yield meso-ionic l,3,2-oxathiazole-5-ones (169), presumably via intermediate S-nitroso derivatives (170). 

Step 3 The resin-bound C-terminal amino acid is coupled to an N-protected amino acid by using A,A -dicyclohexylcarbodiimide. Excess reagent and iV,iV -dicyclohexylurea are washed away from the resin after coupling is complete. 

The checkers obtained a yield of 1.44 g (19%), and observed only a trace of JV, /V -dicyclohexylurea precipitate during addition of the carbodiimide. They attribute the low yield to contamination of their nitrogen gas with water, a condition discovered after the experiments were completed. The submitters note that, over the 30-min addition period, water in the nitrogen gas would hydrolyze the moisture sensitive N, Al -dicyclohexylcarbodiimide and would thus reduce the yield. 

In one method, treatment of a solution containing the N-protected and the C-protected amino acids with A, A -dicyclohexylcarbodiimide (DCCI) leads directly to peptide bond formation ... 

Af,Af -diisopropylcarbodiimide (DIC), A, A -dicyclohexylcarbodiimide (DCC), N-(3-dimethylaminopropyl)-A -ethylcarbodiimide (EDCI), and TsCl (p-toluenesnlfonyl chloride), and found that the addition of DIC markedly increased the yield of the desired resin 32. This intermediate is subsequently cyclized to yield 2-mercaptobenzoxazole 34, which combines with the Merriheld resin 1 to afford the polymer-bound benzoxazole 32 (Scheme 10.6, path c). 

In addition to the general usefulness of this class of compounds, the popularity of this chemistry is largely due to the facile preparation of the starting materials (Scheme 7). The most straightforward method of preparation of Barton esters of types I to IV is acylation by activation of the corresponding carboxylic acid (paths A and B). Accordingly, the hydroxamic acid sodium salt can be O-acylated with the acyl chlorides or, alternatively, the free hydroxamic acid can be condensed with primary carboxylic acids in the presence of N,W -dicyclohexylcarbodiimide and dimethylaminopyridine (DMAP). Likewise, condensation of the free thiohydroxamic acid or the corresponding sodium salt with the mixed anhydride formed from the acid and isobutyl chloroformate in the presence of N-methylmorpholine has proven to... 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

Section 27 17 Peptide bond formation between a protected ammo acid having a free carboxyl group and a protected ammo acid having a free ammo group can be accomplished with the aid of N N dicyclohexylcarbodiimide (DCCI)... 

Photosensitive functions are in many cases also heat sensitive, so the preparation of photosensitive polyimides needs smooth conditions for the condensations and imidization reactions. Some chemical reactants, which can be used for polyamide preparation, have been patented for the synthesis of polyimides and polyimide precursors. For example, chemical imidization takes place at room temperature by using phosphonic derivative of a thiabenzothiazoline.102 A mixture of N -hydroxybenzotriazole and dicyclohexylcarbodiimide allows the room temperature condensation of diacid di(photosensitive) ester with a diamine.103 Dimethyl-2-chloro-imidazolinium chloride (Fig. 5.25) has been patented for the cyclization of a maleamic acid in toluene at 90°C.104 The chemistry of imidazolide has been recently investigated for the synthesis of polyimide precursor.105 As shown in Fig. 5.26, a secondary amine reacts with a dianhydride giving meta- and para-diamide diacid. The carbonyldiimidazole... 

Mono(guanidinate) complexes of lanthanum and yttrium have been synthesized as illustrated in Scheme 58.The lanthanum compounds were made starting from La[N(SiMe3)2]3 and dicyclohexylcarbodiimide. Both mono (guanidinate) derivatives are monomeric in the solid state with a four-coordinate La center. ... 

Alkali metal derivatives of 2-(trimethylsilyl)aminopyridines can be further derivatized by insertion of 1,3-dicyclohexylcarbodiimide. Functionalized guani-dinates are formed in this reaction via a 1,3-silyl shift. Scheme 170 illustrates the reaction sequence as well as the preparation of an aluminum complex of the modified ligand, which exhibits pseudo jS-diketiminate binding of the metal center, thus exemplifying the coordinative versatility of this new multi-N-donor system. ... 

Abbreviations DEPC, diethylpyrocarbonate DCCD, Af.iV -dicyclohexylcarbodiimide EEDQ, N-ethyoxycarbonyl-2-ethoxy-1,2-dihydroquinoline NEM, A-ethylmaleimide PAO, phenylarsine oxide NPM, IV-phenylmaleimide PLP, pyridoxal phosphate DIDS, diisothiocyanostilbene disulfonate PITC, phenylisothiocyanate. 

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