THE DESIGN AND SYNTHESIS OF NUCLEOSIDE TRIPHOSPHATE ISOSTERES AS POTENTIAL INHIBITORS OF HIV REVERSE-TRANSCRIPTASE

We describe the synthesis of a variety of lipophilic isosteres of nucl eoside triphosphates as potential anti-HIV agents. The citrate molecul e proved to be a good mimic of triphosphate by modelling in terms of c harge and spatial distribution. Several lipophilc derivatives of citra te were conjugated to the precedented anti-HIV nucleoside d4T via este r and amide linkages. A novel synthesis of 5'-amino-d4T is included. I ntramolecular rearrangement of several amide-linked isosteres are also reported, along with an alternative synthetic strategy to the desired amide-linked isosteres. (C) 1997 Elsevier Science Ltd.