NEW NUCLEOSIDE CONJUGATES WITH PHOSPHOLIP IDS - SYNTHESIS AND ANTI-HIV ACTIVITY OF 1-HEXADECYL-2-ACYL-SN-GLYCERO-3-PHOSPHONUCLEOSIDES

New nucleoside-phospholipid conjugates were synthesized based on 1,2-d isubstituted glycerides and nucleosides. These contain rac-1-hexadecyl -2-palmitoyl(or 2-methylcarbamoyl)-sn-glycero-3-phosphat as the phosph olipid component and 2',3'-didehydro-3'-deoxythymidine, 1-(Z-5-hydroxy pentene-2 yl)thymine, or 2',3'-isopropylideneuridine as a nucleoside c omponent. The conjugates were synthesized by three different ways: fro m 1-hexadecyl-2-acyl-sn-glycero-3-phospodichlorides, 3-phosphatidic ac ids, or -3-H-phosphonates. When subjected to mild alkaline hydrolysis, conjugates containing a 2-palmitoyl group formed conjugates with the lysophospholipid component that had not yet been described. All the co njugates obtained were amorphous compounds stable at room temperature. Their hemolytic and anti-HIV activities were determined. Some conjuga tes were found to completely inhibit in vitro HIV-1 reproduction in lo wer doses than the corresponding nucleosides.