Solution phase synthesis of ISIS 2922 (Vitravene) by the modified H-phosphonate approach
Abstract
The synthesis of Vitravene, a 21-mer oligonucleotide phosphorothioate (d[Gp(s)Cp(s)Gp(s)Tp(s)Tp(s)Tp(s)Gp(s)Cp(s)Tp(s)Cp(s)Tp(s)Tp(s)Cp(s)Tp(s)Tp(s)Cp(s)Tp(s)Tp(s)Gp(s)Cp(s)G]) by the modified H-phosphonate approach in solution is reported. The synthetic strategy adopted involves the use of only four different trimer building blocks. The dimer and trimer blocks are prepared by a novel four component procedure in which the coupling agent (