Other Acylated Aminoacids

Several reactions are occurring in this step that have been elucidated by others (1). First, an a-ketoester is the initial condensation product of an N-acyl-aminoacid and an alkyl oxalyl chloride via a Dakin-West reaction. Second, at reflux temperatures isomeric enol esters are formed that directly condense with hydrazine to form a triazinone intermediate followed by the second ring closure. Other purines have been prepared in an analogous reaction pathway (2). 

High yields and S -O-regioselectivity can be obtained in the acylation of libonucleosides using subtilisin as catalyst if pyridine is used as solvenL When the acetoxime esters of Cbz-glycine and Cbz- -alanine were used as acyl donors, Candida antarcHca lipase catalysed the formation of S -O-aminoacyl derivatives of ribo- and 2 -deoxyiibonocleosides, whilst use of Pseudomonas cepacia lipase gave reaction at 0-3 in 2 -deoxyribonucleosides (the same selectivities as observed in previous work see Vol. 27, p. 266). The enzymes would not accq>t donaminoacid derivatives could not be used. ... 

Preparation of optically active P-aminoesters, P-aminonitriles, and P-aminocarbox-amides are of special relevance for the synthesis of enantiomerically pure P-aminoacids compounds of special relevance in several areas of medicinal chemistry. The resolution of P-aminoesters can be carried out by acylation of the amino groups or by other biocatalytic reactions of the ester groups, such as hydrolysis, transesterification, or aminolysis. The resolution of ethyl ( )-3-aminobutyrate... 

Other important derivatives for the preparation of (i-aminoacids are the corresponding P-aminonitriles. Lipase-catalyzed N-acylations of racemic cis-2-aminocyclopentane and cyclohexane carbonitriles with 2,2,2-trifluoroethyl butanoate have been successfully carried out in organic solvents and ionic liquids [53], PSL yielding better results than CALB (Scheme 7.29). 

Other derivatives to obtain P-aminoacids are the corresponding carboxamides. Thus, for the preparation of all enantiomers of as and traws-2-aminocydopentane-and cydohexanecarboxamides, the best results obtained are using this acyl donor and CALB [54]. An unexpected change in enantiopreference accompanied by low enantioselectivity was observed when PSL (ds-cydohexane substrate) or CALA (ds-cyclopentane and cydohexane substrates) replaced CALB (Scheme 7.30). 

Hydrolase-catalyzed enantioselective N-acylation is an important tool for the preparation of enantiopure a- and P-aminoacids. It has been observed that the reactions of many amino acid esters with ester acyl donors catalyzed by CALB is sometimes complicated by interesterification reactions. CALA has, however, emerged as a very chemoselective catalyst in favor of N-acylation of P-aminoesters. Some reviews on CALA and other hydrolases as catalysts for N-acylations of aminoesters are available [109, 126, 127]. 

Amino acylases catalyse the hydrolysis of N-acyl-L-aminoacids (Figure 6.28) but not of the corresponding D-isomers. This reaction is comparable to that catalysed by penicillin acylase which in fact shows a similar selectivity when hydrolysing amides other than penicillin G. If the racemic mixture of an amino acid is first acylated and is then treated with the acylase, the product will be a mixture of optically pure L-amino acid and predominantly D-acyl amino acid. These are easily separated on the basis of their solubilities at the isoelectric point of the amino acid. The pure L-amino acid can be crystallized from the mixture leaving the residual acyl amino acid to be racemized and recycled through the process. 

The dependency of bacterial RNA synthesis on protein synthesis which has been called "stringent control" has been demonstrated to take place under conditions such as aminoacid-starvation, nitrogen starvation, phosphate and Mg" starvation, energy deprivation and in strains mutated in amino-acyl-t-RNA synthetases. In all these conditions the synthesis of r-RNA and t-RNA is inhibited as far as the m-RNAs are concerned, some m-RNAs are inhibited, whereas the synthesis of others is enhanced" ". ... 

---