Improved Understanding of Conformational Preferences of

Furanosides: Potential Energy Surface Scans of Permethylated Pentofuranosides

Brian Dow, Chris Ruark, and Dr. Jonathan RhoadMissouri Western State University, St. Joseph, MO

Introduction Conformational preferences of furanosides are of

interest in many biological systems including DNA structure and synthesis and the components of bacterial cell walls. Because these rings are so flexible, understanding the conformational preferences is difficult.

To gain a better understanding of their conformation preferences, thorough scans have been performed of the ring potential energy subsurface with respect to phase angle and amplitude of all the permethylated pentofuranosides including rotational conformations of the exocyclic C4-C5 bond. Theoretical 3JH-H coupling constants were calculated and compared to experimental results.

Computational Methods All calculations were performed with the Guassian ’03 program using the B3LYP

method of calculation at the 6-311G** level of theory. Lyxose and xylose in the alpha and beta conformations were studied with the exocyclic rotamer frozen in 60° intervals. They were scanned for a global energy minimum on the potential energy surface as described by Alton & Sundaralingam1. The two lowest scans with different exocyclic rotamer positions for each alpha or beta version of lyxose and xylose were studied and compared.

The pseudorotational wheel above displays the various conformations that the ring can be in. At zero degrees the ring is in the 3T2 twist conformation which means that there are two atoms (the 2nd and 3rd carbon) out of the plane of the rest of the ring with one atom (the 3rd carbon) positioned above the plane and one atom (the 2nd carbon) positioned below the plane. At 18 degrees the phase angle changes to the 3E conformation which is an envelope with only one atom out of the plane (the third carbon here). As it goes around the wheel the conformations switch atoms (i.e. 36 degrees is a 4T3 twist conformation) until the complement phase angles are reached (i.e. the complement of 3E is E3 where the third carbon is below the plane). The amplitude of these phase angles determine how far out of the plane these affected atoms are.

α-Lyxose Phase Angle Scans

Alpha Lyxose 120° Rotamer PESAlpha Lyxose 60° Rotamer PES

β-Lyxose Phase Angle Scans

Beta Lyxose 240° Rotamer PESBeta Lyxose 60° Rotamer PES

α-Xylose Phase Angle Scans

Alpha Xylose 60° Rotamer PES Alpha Xylose 180° Rotamer PES

β-Xylose Phase Angle Scans

Beta Xylose 60° Rotamer PES Beta Xylose 180° Rotamer PES

Conclusion

The results of the computational methods show a greater stereocontrol at the 3-methoxy position than at the 2-methoxy position. The scans also show that both the 3-methoxy and 2-methoxy substituents prefer to be in the pseudoaxial position. These results do not differ greatly with formyl protecting groups except in the case of anchimeric assistance.

The Woerpel group at the university of California’s experimental research proposed the rule of “inside attack”2 where the nucleophile attacks the cation on the inside of the preferred 3E conformation, but their results could only be verified completely if the second carbon’s protecting group was pseudoequatorial3. The computations deviate from this result.

References

1. Altona C., Sundaralingam M, 1973,“Conformational Analysis of the Sugar Ring in Nucleosides and Nucleotides.  Improved Method for the Interpretation of Proton Magnetic Resonance Coupling Constants.”, Journal of the American Chemical Society, v.95 i.7 p.2933-44

2. Becke, A.D. J. Chem. Phys. 1993, 98  5648-5652. 2. Lee, C.; Yang, W.; Parr, R.G. Phys. Rev. B 1988, 37 785-789.