Dextrane imidazolides

Starch esters have been obtained by reactions of starch and carboxylic or sulfonic acid imidazolides in aqueous NaOH or nonaqueous solutions, as described in reference [226]. The esterification of dextran with butyric or palmitic acid using CDI in DMSO or formamide is discussed in reference [174]. 

A method with an enormous potential for dextran modification is the homogeneous one-pot synthesis after in situ activation of the carboxylic acids with CDI, which is a rather well known technique in general organic chemistry and was published in 1962 [ 197]. It is especially suitable for the functionalisation of the biopolymers, because during conversion the reactive imidazolide of the acid is generated and only CO2 and imidazole are formed as by-products (Fig. 29). 

Basic investigations on conditions for coupling by use of butyric acid and dextran confirm that the imidazolide is formed within 2 h. The reaction at room temperature for 17 h results in butyrate content of 92% of the acid applied. Only 0.25% N is found in the product. The solvent has a pronounced influence for dextran the solvent of choice is the mixture formamide/DMF/CH2Cl2 [189]. 4-Pyrrolidinopyridine is used as catalyst in this process. 

Although CDI was applied as early as 1972 as reagent for the esterification of starch and dextran, it has only scarcely been used up to now. Its renaissance during the last few years may be due to the fact that it became an affordable commercially available product. Among the first attempts for the esterification of polysaccharides via CDI is the binding of amino acids onto dextran. Besides CDI, -(thiocarbony diimidazole can be utilised to obtain the corresponding imidazolide [198]. The amino acids bound via this path are glycine, L-leucine, L-phenylalanine, L-histidine and L-alanyl-L-histidine. They are protected with N-trifluoroacetyl, N-benzyloxycarbonyl... 

Succinic esters of dextran have been prepared and transformed into the corresponding imidazolides, which react smoothly with alcohols or amines to yield the corresponding polymeric esters or amides. These activated amides may be of value for the preparation of polymer-drug adducts with a main backbone degradable to safe metabolites in the body fluids. 

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