(±)-1-{8′-(tert-Butyldiphenylsilyloxymethyl)-1′,7′-dioxaspiro[5.5]undecan-2′-yl}uridine

Abstract

The crystal structure of the title compound, C30H38N2O5Si, has been investigated to establish the relative stereochemistry at the spiro ring junction and the two anomeric centres. Each of the O atoms in the tetra­hydro­pyran rings adopts an axial position on the neighbouring ring. This bis­-diaxial conformation is adopted, thus gaining maximum stablization from the anomeric effect. The silyl-protected hydroxy­methyl and uracil substituents adopt equatorial positions on their associated tetra­hydro­pyran rings, thereby minimizing unfavourable steric inter­actions. The dimeric (2′R*,6′R*,8′R*)- and (2′S*,6′S*,8′S*)-uridine units are connected to each other across crystallographic inversion centres via inter­molecular N—H⋯O hydrogen bonds.

Synthesis of spiroacetal-nucleosides as privileged natural product-like scaffolds

“…Recrystallisation of uridine 15d from dichloromethane-hexane afforded pale yellow needles that allowed structural determination by X-ray crystallography. 31 The results were consistent with the above NMR analysis which established that the spiroacetal rings adopted a bis-anomerically stabilised conformation and both the uracil and TBDPS-protected hydroxymethyl substituent occupied the equatorial positions on their respective tetrahydropyran rings (Fig. 5).…”

“…5 X-Ray crystal structure of uridine 15d with displacement ellipsoids drawn at the 50% probability level. 31 Only the equatorial substituted nucleoside analogues 15a-h were isolated from the nucleosidation step. This may be due to the destabilising steric interactions exerted by the bulky TBDPSprotected hydroxymethyl group if the nucleoside occupied an axial position.…”