Dioxaphosphorinane-Constrained Nucleic Acid Dinucleotides as Tools for Structural Tuning of Nucleic Acids

Scheme 6

Synthesis of xylo-ε,ζ-Dioxaphosphorinane-Constrained Nucleic Acid dinucleotides (xylo-ε,ζ-D-CNA). Reagents and conditions: (i) TBDMSCl, AgNO₃, Pyr, THF, 74%, (ii) Dess-Martin periodinane, Pyr, DCM, rt, 87%, (iii) t-butyldimethylsilyl-methyl-ketene, BF₃·Et₂O, DCM, −78°C, 57%, (iv) DIBAH, DCM, 0°C, 2 h then rt 12 h, 46%, (v) TsCl, Pyr, CHCl₃, 64%, (vi) 3′-O-t-Butyldiphenylsilylthymidine-5′-O-phosphoramidite (2 eq), tetrazole, acetonitrile then collidine, I₂/H₂O, 65%, (vii) K₂CO₃, DMF, rt., 81%, and (viii) TBAF (3.3 eq), THF, rt, 74%.