Synthesis of 2'-C-alpha-(hydroxyalkyl) and 2'-C-alpha-alkylcytidine phosphoramidites: analogues for probing solvent interactions with RNA.
Nucleoside analogues bearing 2'-C-alpha-(hydroxyalkyl) and 2'-C-alpha-alkyl substitutes have numerous applications in RNA chemistry and biology. In particular, they provide a strategy to probe the interaction between the 2'-hydroxyl group of RNA and water. To incorporate these nucleoside analogues into oligonucleotides for studies of the group II intron (Gordon, P. M.; Fong, R.; Deb, S.; Li, N.-S.; Schwans, J. P.; Ye, J.-D.; Piccirilli, J. A. Chem. Biol. 2004, 11, 237), we synthesized six new phosphoramidite derivatives of 2'-deoxy-2'-C-alpha-(hydroxyalkyl)cytidine (36: R = -(CH2)2OH; 38: R = -(CH2)3OH; 40: R = -(CH2)4OH) and 2'-deoxy-2'-C-alpha-alkylcytidine (37: R = -CH2CH3; 39: R = -(CH2)2CH3; 41: R = -(CH2)3CH3) from cytidine or uridine via 2'-C-alpha-allylation, followed by alkene and alcohol transformations. Phosphoramidites 36 and 37 were prepared from cytidine in overall yields of 14% (10 steps) and 7% (11 steps), respectively. Phosphoramidites 38 and 39 were prepared from uridine in overall yields of 30% (10 steps) and 13% (11 steps), respectively. Phosphoramidites 40 and 41 were synthesized from uridine in overall yields of 21% (13 steps) and 25% (14 steps), respectively.
Li
Nan-Sheng
NS
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. nli@uchicago.edu
Piccirilli
Joseph A
JA
D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D009943:Organophosphorus Compounds; D014867:Water; D003562:Cytidine; D012313:RNA