Using conformationally locked nucleosides to calibrate the anomeric effect: Implications for glycosyl bond stability.
Steric and electronic parameters such as the anomeric effect (AE) and gauche effect play significant roles in steering the North ⇆ South equilibrium of nucleosides in solution. Two isomeric oxa-bicyclo[3.1.0]hexane nucleosides that are conformationally locked in either the North or the South conformation of the pseudorotational cycle were designed to study the consequences of having the AE operational or not, independent of other parameters. The rigidity of the system allowed the orientation of the orbitals involved to be set in "fixed" relationships, either antiperiplanar where the AE is permanently "on", or gauche where the AE is impaired. The consequences of these two alternatives were subject to high-level calculations and measured experimentally by x-ray crystallography, hydrolytic stability of the glycosyl bond, and pKa values.
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, NIH.
Hyung Ryong
HR
Moon
Maqbool A
MA
Siddiqui
Guangyu
G
Sun
Igor V
IV
Filippov
Nicholas A
NA
Landsman
Yi-Chien
YC
Lee
Kristie M
KM
Adams
Joseph J
JJ
Barchi
Jeffrey R
JR
Deschamps
Marc C
MC
Nicklaus
James A
JA
Kelley
Victor E
VE
Marquez