engleski

Efficient five-step synthetic pathway toward biologically active carbamates

Compounds containing a carbamate group have found their application in various fields ; they are valuable intermediates and protecting groups for amines in organic synthesis, linkers in combinatorial chemistry, and biologically active compounds such as insecticides or drugs and prodrugs. The use of carbamates as drugs has attracted much attention since some recent studies have shown that the incorporation of a carbamate group into the structure of biologically active compounds could lead to an improvement of their biological activity. More precisely, compounds bearing a carbamate group are characterized by conformational and metabolic stability, the ability to pass through cell membranes, and for some carbamates through the blood-brain barrier, which has led to the fact that carbamate groups have become a desirable part of the structure of many pharmacologically important compounds. Therefore, in recent years considerable efforts have been invested in the design of biologically active carbamate derivates as well as in the development of efficient methodologies for the synthesis of new carbamates. Our goal was to prepare a series of aromatic amino alcohols with carbamate moiety on the phenyl ring with varying carbamate moieties, as well as a varying amine group. We have applied a five-step synthetic pathway for the preparation of these biologically active carbamates starting from 3, 5- dihidoxyacetophenone. We successfully synthesized 27 carbamates with an alkyl chain of different size (diethyl, ethyl/methyl or 1- pyrrolidine) on the nitrogen atom of a carbamate group, and a different amine moieties (aniline, piperidine, p- toluidine, cyclohexylamine, tert-amylamine, 1- adamantylamine, tert-butylamine, 2- phenylethylamine, 1-phenylethylamine). For all of the synthesized carbamates, the cholinesterase inhibition potency will be determined as a key feature of drugs for treating Alzheimer’s disease.

synthesis, carbamates, cholinesterases

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