Synthesis of oligodeoxynucleoside methylphosphonates utilizing the tert-butylphenoxyacetyl group for exocyclic amine...

Oligodeoxynucleoside methylphosphonates were synthesized using methylphosphonamidite monomers incorporating the base labile tert-butylphenoxyacetyl (t-BPA) protecting group on the exocyclic amines of dA, dC, and dG. Synthesis of the oligodeoxynucleoside methylphosphonates required only a small change in oxidation solution from standard DNA synthesis. The increased lability of the t-BPA group over the standard benzoyl and isobutyryl protection permitted the use of milder basic deprotection conditions. Deprotection of the nucleoside bases and release from support was best accomplished by a short treatment with ammonia saturated methanol. This procedure resulted in minimal backgone degradation with no base modifications. Analysis of the resultant oligodeoxynucleoside methylphosphonates by reverse phase HPLC and MALDI-TOF mass spectroscopy are described.