Synthesis of enantiomeric-pure cyclohexenyl nucleoside building blocks for oligonucleotide synthesis

Lipases were used for the resolution of (±) (4aR, 7R, 8aS)-2-phenyl-4a,7,8,8a-tetrahydro-4H-1,3-benzodioxine. This separation was carried out on preparative scale and used for the synthesis of eight phosphoramidites of cyclohexenyl nucleosides (d- and l-series).     

Crystal structure of a nucleoside analog: 1-(R)-[6-(R)-hydroxymethyl-1,4-dioxan-2-yl] uracil

The title compound (C₉H₁₂N₂O₅,M _r =228.2) crystallizes in the trigonal space groupP3₁,21 witha=b=9.438(3) andc=19.775(3) Å,V=1525.5 ų,D _x =1.490 gm cm^–3,Z=6,=0.12 mm^–1,F(000)=720.0,T=293 K. The structure was solved by direct methods and refined by full-matrix least-squares calculations to anR value of 0.044 on 843 unique observed reflections. The dioxane ring adopts a chair conformation. The crystal structure is stabilized by N-HO hydrogen bonds and C-HO close contacts.     

Crystal structure of a nucleoside analog: 2′,3′-dideoxy-3′-fluoro-5-bromocytidine

The title compound crystallizes in the orthorhombic space groupP2₁2₁2₁ witha=5.084(1),b=14.322(3),c=16.065(2)Å,Z=4. The structure was solved by the heavy atom method and refined by full-matrix least-squares calculations to a finalR value of 0.033 for 1106 unique observed reflections. The N-glycosidic torsion anglex has a value of –153.7(4)°, in the anti-range. The sugar pucker is²T₃ withP=175(1)° and=30(1)°. The C4-C5 conformation is + sc with =46.7(7)°. The structure is stabilized by N-HN, N-HO and O-HO hydrogen bonds and C-HO close contacts.