ja9724957_si_001.pdf (773.43 kB)
Synthesis of Asialo GM1. New Insights in the Application of Sulfonamidoglycosylation in Oligosaccharide Assembly: Subtle Proximity Effects in the Stereochemical Governance of Glycosidation
journal contribution
posted on 1998-02-04, 00:00 authored by Ohyun Kwon, Samuel J. DanishefskyThe total synthesis of asialo GM1 (1a) has
been accomplished. Using related chemistry, the
methyl
glycoside of the asialo compound (1b) has also been
synthesized. These kinds of compounds have been
identified as potential ligands for bacterial and viral infection
sites. A simpler structure, which has also been
identified for its infection attracting structure in the context of
glycopeptides and glycolipids (methyl glycoside
2), has also been synthesized. The key common phase in
the syntheses involves the sulfonamidoglycosidation
reaction which is used to create a β-linkage leading to a galNAc
residue joined to the C4 hydroxyl group of
a galactose unit either as a monosaccharide (see compound 2)
or as C4‘ in the context of a lactosyl moiety.
During the course of these studies there was encountered an
unusual “proximal hydroxyl” directing effect.
Thus, when C4 on the galactose ring of an
azaglycosylating donor bears a free hydroxyl (see, for
instance,
compound 13), β-glycoside formation predominates.
When this hydroxyl group is blocked, the process
tends
in the direction of α-glycoside formation (see compound
32). These findings were explained as arising
from
a critical intramolecular hydrogen bond between the C4
axial hydroxyl of the galactose donor and its proximal
pyranosidal ring oxygen. This interaction stabilizes conformations
from which β-glycosidation predominates.