one stereoisomer can be formed. Reviewing the â-mannoside
literature, we felt the most promising avenue to explore was
the methodology developed by Ito: the oxidation of meth-
oxy-substituted benzyl ethers by agency of 2,3-dichloro-4,5-
dicyanoquinone (DDQ) to form mixed acetals (Figure 2A).8d
Figure 2. (A) Ito’s mixed acetal methodology for the formation
of â-mannosides. (B) General IAD scheme for formation of a 1,1-
R,R-glycosidic linkage.
Figure 1. Trehalose (1), sulfolipid-1 (2), trehalose 6,6′-dimycolate
(3), and oligosaccharide 4.
In our case, the anomeric configuration of intermediate
mixed acetal 6 will be guaranteed by the use of acceptor
monosaccharide 5, in which the R-anomer is fixed (Figure
2B). Upon activation of the glycosyl donor by alkylation,
the intermolecular tether will deliver the acceptor to the
R-face of the donor, thus ensuring the formation of the
second R-anomer, yielding trehalose derivative 7.
Toward this goal, known selectively protected glucose
derivative 89 was glycosylated with 4-methoxybenzyl alcohol
(PMBOH), involving a glycosyl iodide intermediate devel-
oped by Gervay and Hadd,9 to give 9 with complete anomeric
selectivity (Scheme 1). Compound 9 was then oxidized with
DDQ under strict anhydrous conditions and the resulting
benzylic cation was trapped by known thioglucoside 1010 in
a one-pot procedure. The crude reaction mixture containing
mixed acetal 11 was activated with methyl trifluoromethane-
sulfonate (MeOTf) to give desymmetrized trehalose deriva-
tive 12 as one stereoisomer in 40% yield. The remainder of
the material was mostly starting materials due to incomplete
oxidation of 9. Niether R,â nor â,R products were observed.
molecules such as SL-1.7c-f Indeed, the best of these methods
only produced R,R-trehalose in a yield of 39% with ap-
preciable formation of R,â and â,R side products.7c Therefore,
a high-yielding, stereoselective method for the formation of
1,1-R,R-glycosidic linkages remains an important goal. Thus,
we turned our attention to the intramolecular aglycone
delivery (IAD) methodology developed for the synthesis of
â-mannosides.8 Using IAD, the donor and acceptor molecules
are oriented with a linker prior to activation such that only
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