Diastereocontrolled synthesis of dinucleoside phosphorothioates using a novel class of activators, dialkyl(cyanomethyl)ammonium tetrafluoroborates.
A novel class of activators, dialkyl(cyanomethyl)ammonium tetrafluoroborates 1a-c, has been developed and applied to the condensations of diastereopure 5'-O-tert-butyldiphenylsilylthymidine 3'-cyclic phosphoramidites 3a-d with 3'-O-tert-butyldimethylsilylthymidine (4a). Among them, the condensation of 3a with 4a in the presence of 1a completed within 5 min and gave only one diastereoisomer of the corresponding phosphite 5a. After sulfurization and deprtection, almost diastereopure (Rp)-TpsT 7 was obtained (d.r. = 99:1). Next the 5'-O-(DMTr)nucleoside 3'-phosphoramidites 8a-d containing thymine, N6-benzoyladenine, N4-benzoylcytosine, and N2-phenylacetylguanine have been synthesized and allowed to condense with 3'-O-protected thymidine and 2'-deoxyadenosine. The 5'-O-DMTr group and the N-acyl groups of the nucleobases were compatible with the reaction conditions and the condensations completed quickly with excellent diastereoselectivity.
Oka
Natsuhisa
N
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, Kashiwa, Chiba 277-8562, Japan.
Wada
Takeshi
T
Saigo
Kazuhiko
K
D000605:Amino Alcohols / Q000737:chemistry; D001881:Borates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013872:Thionucleosides / Q000138:chemical synthesis*
D000605:Amino Alcohols; D001881:Borates; D009943:Organophosphorus Compounds; D000644:Quaternary Ammonium Compounds; D013872:Thionucleosides; C434331:phosphoramidite