Phosphoramidate Derivatives of AZT as Inhibitors of HIV: Studies on the Carboxyl Terminus

Novel phosphoramidate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials carry carboxy-protected, amino acids, and are designed to act as membrane-soluble prodrugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In particular, variation in the carboxy terminus region is studied. For alkyl phosphates small changes in the structure of the amino ester lead to marked changes in biological activity. However, for analogous aryl phosphates there is little dependence on the structure of the ester. This suggests a different mechanism of action for these two categories of phosphate prodrug.

ORGANIC COMPOUNDS OF SAMARIUM: II. REACTIONS OF SAMARIUM ISOPROPOXIDE WITH ETHYL ACETOACETATE

The reactions of samarium isopropoxide with ethyl acetoacetate have been carried out in benzene medium in different stoichiometric ratios and the compounds of the type Sm(OPri)2 (Etacac), Sm(OPri)(Etacac)2, and Sm(Etacac)3 have been isolated in quantitative yields. However, the reaction of samarium isopropoxide with excess of the acetoacetic ester lead to the formation of Sm(Etacac)3.Etacac, which on heating under reduced pressure at 110 °C for [Formula: see text] loses its addition molecule of ester. The reactions are exothermic and the amount of heat liberated also increases with the increase in the concentration of the ester.The interchange reactions of the products Sm(OPri)2(Etacac) and Sm(OPri)(Etacac)2 with t-butyl alcohol have also been carried out; they are endothermic reactions. The compounds Sm(OBut)2(Etacac) and Sm(OBut)(Etacac)2 have been obtained in quantitative yields from the reaction mixture. All the products are stable up to 200 °C at 0.5 mm, but at higher temperature they decompose to deep-red solids. Molecular weight determinations show that they are dimeric in nature.