Study on reactivity and protection of the alpha-hydroxyphosphonate moiety in 5'-nucleotide analogues: formation of the 3'-O-P-C(OH)-C4' internucleotide linkage.
The recently described epimeric nucleosidyl-5'-C-phosphonates (alpha-hydroxyphosphonates) represent novel nucleotide analogues that can be incorporated into chimeric oligonucleotides by the phosphotriester condensation method. In order to prepare suitable protected monomer(s) we have studied condensation reaction between protected 2'-deoxythymidine and 2'-deoxythymidinyl-5'-C-phosphonate, both as model compounds, in dependence on the nature of the 5'-hydroxyl protecting group. We have found that the O-acetyl group is unstable in the presence of TPSCl or MSNT used as condensing agents for activation of the phosphorus moiety. This instability negatively influences the scope of the condensation process. On the other hand, introduction of the O-methoxycarbonyl group gave excellent results. The O-methoxycarbonyl group does not participate in the condensation process, and its quantitative introduction into the nucleotide analo gues is accomplished using a novel acylating agent, methoxycarbonyl tetrazole.
Králíková
Sárka
S
Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic.
Masojídková
Milena
M
Budĕsínský
Milos
M
Rosenberg
Ivan
I
D008956:Models, Chemical; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry*; D011740:Pyrimidine Dimers / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
D009711:Nucleotides; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D063065:Organophosphonates; D011740:Pyrimidine Dimers; C074618:5'-deoxythymidine; D013936:Thymidine