N. V. Nikiforova, A. Belyaev, L. Radina
Dec 1, 1989
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Journal
Pharmaceutical Chemistry Journal
Abstract
One of the groups of compounds utilized clinically for the treatment of tumor disease is the 2chloroethylnitrosoureas (CNUs) of the general formula CICH2CHzNXCONYR (I) [1], where (Ia) indicates that X = NO, Y = H; (Ib) indicates that X = H, Y = NO, R indicates radicals of different chemical type. When the CNUs are isolated by the nitrosation of the unsymmetrical l-(2-chloroethyl)-3-alkylureas, the mixture of the positional isomers (Ia) and (Ib) of the nitroso groups is generally formed [4-6]; these may differ significantly both in their stability and in their biological activity. There are no data in the literature on the comparative study of the stability of the positional isomers of the alkylnitrosoureas; the antitumor activity was only studied for isomers of the structure (Ia) whereby it is considered that the isomers (Ib) do not possess biological activity [7]. In this connection, there is interest in the study of the properties of the individual isomers and the reasons determining the preferential formation of one or the other of the isomers. In the given communication, we describe the synthesis and properties of the methyl esters of N-[(2chloroethyl)nitrosocarbamoyl]glycyl-L-leucine (IIIa) and N-[(2-chloroethyl)carbamoyl]-N-nitrosoglycyl-L-leucine (IIIb) which differ in the position of the nitroso group. The isomer (IIIa) was obtained by regioselective synthesis in the interaction of the dipeptide (II) and pentachlorophenyl N-(2-chloroethyl)-N-nitrosocarbamate (IV) in ethyl acetate: