M. A. Tlekhusezh, Z. I. Tyukhteneva, L. Badovskaya
Mar 1, 1999
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Influential Citations
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Journal
Pharmaceutical Chemistry Journal
Abstract
3-Amino-4-hydroxybutanamides, being polyfunctional derivatives ofy-hydroxybutyric acid, can be used for the targeted synthesis of heterocyclic compounds, including structures containing oxazolidine rings. As is known, both 7-hydroxybutyric acid and many of the substances containing oxazolidine fragments possess antimicrobial properties [1 -4] . 4-Hydroxybutanamides can be considered as prodrugs subjected to lactonization immediately in the organism, which leads to certain biological effects [5, 6]. However, there is still no commonly accepted opinion as to whether 7hydroxybutyric acid occurs in the organism in an open form or as a cyclic y-butyrolactone [5, 7, 8]. We have used 3-benzylamino-4-hydroxy-N-benzylbutanamide (I) to synthesize a series of new carbamoyl-containing oxa(thia)zolidines (II, IIIa, IIIb) and 4-hydroxy-3-dialkylamino-N-butanamides (IVa, IVb) and studied their antimicrobial properties. 3-Benzyl-4-(N-benzylcarbamoylmethyl)-2-oxo1,2,3-oxathiazolidine (II) is readily formed from the reaction between compound I and thionyl chloride in benzene at room temperature in the presence of triethylamine [9]. 3-Benzyl-4-(N-benzylcarbamoylmethyl)-2-aryl1,3-oxathiazolidines (IIla, IIIb) were synthesized by boiling compound I with aromatic aldehydes in chloroform in the presence ofp-toluenesulfonic acid and molecular sieves [10]. The properties and spectroscopic characteristics of compound II were presented in [9], and compounds IIIa, IIIb were reported in [ 10]. Alkylation of compound I with bromoacetic acid ethyl ether or with ot-bromobutyric acid led to the previously undescribed dialkylamino derivatives, which were isolated in the form of hydrobromides: 3-N-(ethoxycarbonylmethyl)benzylamino-4-hydroxy-N-benzylbutanamide (IVa) and 3-N-(1carboxylpropyl)benzylamino-4-hydroxy-N-benzylbutanami de (IVb).