Nucleoside H-Phosphonates. XI. A Convenient Method for the Preparation of Nucleoside H-Phosphonates

The Prooligonucleotide Approach: Synthesis of Mixed Phosphodiester and SATE Phosphotriester Prooligonucleotides Using H-Phosphonate and Phosphoramidite Chemistries

“…[3Ϫ5] The prooligo group. [5] Results and Discussion However, we have shown that two Me-SATE prooligos (12mers) were fully demasked by carboxyesterases in cell ex-Synthesis of Mixed Phosphodiester SATEtract with a half-life of about 21 h. [5] This prompted us to Phosphotriester Prohexathymidines synthesize mixed phosphodiester/SATE phosphotriester prooligos so as to obtain compounds with an optimal bal-To establish the optimal conditions for the synthesis of mixed prooligos using both phosphoramidite and H-phosphonate chemistries, [11] we prepared eight prohexathymid- ages were introduced using a thymidine SATE phos-ing block [12] by means of H-phosphonate chemistry (Figure 2). In this of each phosphodiester or phosphorothioate linkage forpaper, we report the synthesis of mixed prooligos with ming a corresponding phosphotriester linkage.…”

“…The eight prooligos were synthesized, starting from Hphosphonate thymidine [12] and Me-or tBu-SATE thymid-duced using an H-phosphonate monoester thymidine build- purified by reversed-phase HPLC and characterized by mass spectrometry (electrospray ionization in negative mode) (Figure 1). HPLC profiles of prooligos 1, 3, 5, and 7 showed a small additional peak with a retention time greater than that of the corresponding prooligo ( Figure 3).…”

Synthetic studies on nucleoside 5'-H-phosphonate monoesters under Mitsunobu reaction conditions

“…The method works well both for pyrimidine and purine nucleosides and can be considered and as an alternative procedure [19][20][21] for the preparation of H-phosphonate monoesters. 31 P NMR studies shown that also H-phosphonate diesters can be efficiently formed under the Mitsunobu coupling conditions.…”

“…18 Since Hpyrophosphonate in pyridine is known to act as a phosphonylating agent for nucleosides, 19 we could not exclude a possibility that this can be a reactive species involved in the reaction investigated. To verify this assumption, H-pyrophosphonate (generated in situ from phosphonic acid and pivaloyl chloride in pyridine) 19 was allowed to react with nucleoside 1a in pyridine.…”

“…To verify this assumption, H-pyrophosphonate (generated in situ from phosphonic acid and pivaloyl chloride in pyridine) 19 was allowed to react with nucleoside 1a in pyridine.…”