RESUMEN
We have developed a robust solid-phase protocol which allowed the synthesis of chimeric oligonucleotides modified with phosphodiester and O-methylphosphonate linkages as well as their P-S and P-N variants. The novel O-methylphosphonate-derived modifications were obtained by oxidation, sulfurization, and amidation of the O-methyl-(H)-phosphinate internucleotide linkage introduced into the oligonucleotide chain by H-phosphonate chemistry using nucleoside-O-methyl-(H)-phosphinates as monomers. The H-phosphonate coupling followed by oxidation after each cycle enabled us to successfully combine H-phosphonate and phosphoramidite chemistries to synthesize diversely modified oligonucleotide strands.
Asunto(s)
Amidas/química , Oligonucleótidos/síntesis química , Fosfatos/química , Ácidos Fosfóricos/química , Oligonucleótidos Fosforotioatos/síntesis química , Técnicas de Síntesis en Fase Sólida , Dimerización , Estructura Molecular , Oligonucleótidos/químicaRESUMEN
This unit comprises the straightforward synthesis of protected 2'-deoxyribonucleoside-O-methyl-(H)-phosphinates in both 3'- and 5'-series. These compounds represent a new class of monomers compatible with the solid-phase synthesis of oligonucleotides using H-phosphonate chemistry and are suitable for the preparation of both 3'- and 5'-O-methylphosphonate oligonucleotides. The synthesis of 4-toluenesulfonyloxymethyl-(H)-phosphinic acid as a new reagent for the preparation of O-methyl-(H)-phosphinic acid derivatives is described. © 2017 by John Wiley & Sons, Inc.
Asunto(s)
Oligonucleótidos/síntesis química , Compuestos Organofosforados/química , OrganofosfonatosRESUMEN
The straightforward synthesis of sodium 4-toluenesulfonyloxymethyl-(H)-phosphinate and (H)-phosphinomethylisothiouronium tosylate as new reagents for the preparation of O- and S-methyl-(H)-phosphinic acid derivatives, respectively, is described. The reactivity of both reagents was demonstrated by the preparation of protected 2'-deoxyribonucleoside-O-methyl-(H)-phosphinates in the 5'- and 3'-series and 2',5'-dideoxyribonucleoside-5'-S-methyl-(H)-phosphinates. These compounds represent a new class of monomers compatible with the solid phase synthesis of oligonucleotides by H-phosphonate chemistry, as it was proved with the synthesis of a fully phosphonate heptamer.