Amino group modification alkylation

Figure 18. Reversible reductive alkylation of amino groups. Amino groups are alkylated first by treatment with (a) glycolaldehyde or (b) acetol in the presence of sodium borohydride. Reversal of the modification is effected by treating the modified amino group with 10-20mM NalOh for 30 min (85).

Chlorobenzene is employed in the synthesis of certain amino-containing vat dye intermediates. When reacted with phthalic anhydride, the product is 2-chloroanthraquinone, which, with ammonia, is converted readily into 2-aminoanthraquinone (61). Other routes include replacement of halogen by amino groups, with ammonia or ammonium salts of urea, and alkyl- and aryl amines to afford secondary amines. Modification of the amino group by alkylation, with dimethyl sulfate, alkyl halides or esters of toluenesul-fonic acids, is of synthetic value. Arylation of the amino groups is of importance only in the reaction between aminoanthraquinones and nitro- or chloroanthraquinones to yield dianthraquinonylamines, or anthrimides48. For example, the reaction between 62 and 63 yields 64, which can then be converted into carbazole 65, Cl Vat Brown R (Scheme 14). Amination of haloanthraquinones such as l-amino-4-bromoanthraquinone-2-sulfonic acid (bromamine acid) (66), prepared from 1-aminoanthraquinone, is of industrial use. 

Quinazolines undergo many of the same reactions as pyrimidines, such as the modification of an amino group. Gangjee and co-workers reported the reductive alkylation of diaminoquinazolinones 141 with various aryl carbonyl compounds 142, which regioselectively produced quinazolinones 143 <00JHC1097>. 

Furthermore, Weiss and coworkers66 developed also a method of diazotizing aminocyclopropenium salts with nitrosyl salts in the presence of two equivalents of trimethylchlorosilane to trap the water produced. In a modification of this method the authors showed that the use of the terf-butylated amine was an advantage, as the risk of oxidation of the alkylated amino group by the nitrosyl ion is less than in the case of the primary amine. This method would also appear to be suitable for the diazotization of other sensitive amines. 

Chemical modification of proteins has been extensively studied over the years to identify which amino acids are involved in catalysis. Much less work has been carried out on its influence on enzyme stability. Chemical modification of proteins may yield stabilization, destabilization or no effect at all. Martinek and Berezin (1978) reported the dependence of the thermostability of chymotrypsin on the degree of alkylation of its amino groups up to 30% alkylation the stability rose slightly at 90% substitution stability increased markedly, with a maximum (110-fold) at 95% stability fell to nearly initial values when 100% amino groups were modified. (With these modifications, the optimum pH of the errzyme can change and one must therefore be cautious in comparing two different... 

The availability of different types of amino groups allows a variety of reactions typical for amines which are suitable for the derivatization of PEI. Reaction partners can be aldehydes, ketones, alkyl halides, isocyanates and thioisocyanates, epoxides, cyanamides, guanides, ureas, acids, and anhydrides. The synthesis and chemical modification reactions of PEI will be discussed in the next sections. 

Reversible Modifications. Reversibility of a modification is frequently a desired characteristic in order to regain the protein in its original native form. A variety of methods (I) is available for this purpose. Sometimes a further intermediate modification is necessary as used recently in the reductive alkylation of amino groups with an a-hydroxy aldehyde or ketone and subsequent removal of the hydroxyalkyl group by periodate cleavage (85) (see Figure 18). 

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