The synthesis and NMR investigation on novel boron derivatives of stavudine

Preparation and spectroscopic properties of novel boron-containing derivatives of anti-HIV agent stavudine are presented, The new compounds, (5′-O-(4,4,5,5-tetramethyl-1,3,2-dioxaboronate)-2′-3′-didehydro-2′-3′-dideoxythymidine and 5′-O-(dihydroxyboronate)-2′-3′-didehydro-2′-3′-dideoxythymidine), were prepared by direct reaction between stavudine and reagents containing BH moieties – pinacolborane and borane–dimethylsulfide complexes, respectively. The boron coordination equilibrium of those compounds was analyzed by water titration monitored by NMR. Results of the DFT calculations and NMR experiments pointed to structural and electronic similarity of tetrahedral boron complexes to phosphate group.

Graphical abstractPreparation and spectroscopic properties of novel boron-containing derivatives of anti-HIV agent stavudine are presented, The new compounds, (5′-O-(4,4,5,5-tetramethyl-1,3,2-dioxa-boronate)-2′-3′-didehydro-2′-3′-dideoxythymidine and 5′-O-(di-hydroxyboronate)-2′-3′-didehydro-2′-3′-dideoxythymidine), were prepared by direct reaction between stavudine and reagents containing BH moieties – pinacolborane and borane–dimethylsulfide complexes, respectively. The boron coordination equilibrium of those compounds was analyzed by water titration monitored by NMR. Results of the DFT calculations and NMR experiments pointed to structural and electronic similarity of tetrahedral boron complexes to phosphate group.Figure optionsDownload full-size imageDownload as PowerPoint slide