Stereodirecting effect of the pyranosyl C-5 substituent in glycosylation reactions.
The stereodirecting effect of the glycosyl C-5 substituent has been investigated in a series of d-pyranosyl thioglycoside donors and related to their preferred positions in the intermediate (3)H(4) and (4)H(3) half-chair oxacarbenium ions. Computational studies showed that an axially positioned C-5 carboxylate ester can stabilize the (3)H(4) half-chair oxacarbenium ion conformer by donating electron density from its carbonyl function into the electron-poor oxacarbenium ion functionality. A similar stabilization can be achieved by a C-5 benzyloxymethyl group, but the magnitude of this stabilization is significantly smaller than for the C-5 carboxylate ester. As a result, the preference of the C-5 benzyloxymethyl to occupy an axial position in the half-chair oxacarbenium ions is much reduced compared to the C-5 carboxylate ester. To minimize steric interactions, a C-5 methyl group prefers to adopt an equatorial position and therefore favors the (4)H(3) half-chair oxacarbenium ion. When all pyranosyl substituents occupy their favored position in one of the two intermediate half-chair oxacarbenium ions, highly stereoselective glycosylations can be achieved as revealed by the excellent beta-selectivity of mannuronate esters and alpha-selectivity of 6-deoxygulosides.
Dinkelaar
Jasper
J
Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
de Jong
Ana Rae
AR
van Meer
Robert
R
Somers
Mark
M
Lodder
Gerrit
G
Overkleeft
Herman S
HS
Codée
Jeroen D C
JD
van der Marel
Gijsbert A
GA
D003198:Computer Simulation; D006031:Glycosylation; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics; D013865:Thioglycosides / Q000737:chemistry
D011714:Pyrans; D013865:Thioglycosides