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Individual Isomers of Dinucleoside Boranophosphates as Synthons for Incorporation into Oligonucleotides: Synthesis and Configurational Assignment
Author(s) -
Sergueeva Zinaida A.,
Sergueev Dmitri S.,
Ribeiro Anthony A.,
Summers Jack S.,
Ramsay Shaw Barbara
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000705)83:7<1377::aid-hlca1377>3.0.co;2-s
Subject(s) - synthon , chemistry , stereochemistry , stereospecificity , oligonucleotide , structural isomer , silylation , nucleotide , phosphonate , linkage isomerism , dna , catalysis , organic chemistry , biochemistry , gene , metal
Individual isomers of the protected boranophosphates 5a and 5b , i.e. , the N 6 ‐benzyl‐2′‐deoxy‐5′‐ O ‐(4,4′‐dimethoxytrityl)adenosin‐3′‐yl 2′‐deoxy‐4‐ O ‐(4‐nitrophenyl)uridin‐5′‐yl boranophosphates, were synthesized via stereospecific silylation and boronation of their H ‐phosphonate precursors. 2D‐NMR Spectroscopic studies yielded an initial assignment of the isomer configuration, which was further confirmed unambiguously by a parallel chemical synthesis. Deprotection of the `dimers' 5a and 5b yielded the individual [ P ( R )]‐ and [ P ( S )]‐isomers 7a and 7b , respectively, i.e. , the 2′‐deoxyadenosin‐3′‐yl 2′‐deoxycytidin‐5′‐yl boranophosphates. Their substrate properties toward phosphodiesterase I were identical to those of the previously characterized isomers of dithymidine boranophosphate. The protected `dimers' 5a and 5b can be used as synthons to incorporate the boranophosphate linkage with a defined configuration to selected positions of an oligonucleotide chain.