SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 417

formation of -KDN glycosides with essentially complete stereoselectivity in high

yield. More important, and as with oxazolidinone-protected donors, the formation of
2,3-glycal, normally a major by-product in the formation of sialic acid glycosides, was
avoided through the use of this protecting group.

a

12.6. URONIC ACID GLYCOSIDES

Uronic acids occur in nature in the alginates, which are made of varying combinations
of L -guluronic and D -mannuronic acid residues. Because of their thickening and
gel-forming capacities, alginates have found extensive application in the food or
coating material industries. It has been more recently discovered that such oligo-
saccharides have immunomodulating properties owing to their binding to Toll-like
receptors (TLRs), which are key players in mammanlian immunity [121].
Using Crich's activation conditions for -mannoside synthesis, van der Marel

and coworkers demonstrated a high level of

b

-selectivity in the formation of
mannuronic acid glycoside series [122]. In this chemistry, coupling of a mannuronic
ester or a mannosaminuronic ester thioglycoside proceeded in high yield and selec-
tivity with various glycosyl acceptors (Scheme 12.40) [123].
Reminiscent of the benzylidene-directed

b

-mannosylation, in the mannosazide
series the arming benzyl group at O- 3 proved highly

b

-directing, whereas O- 3 b

acylated compounds gave rise to -products exclusively. Studies directed at the

mechanism of b -selectivity led to two hypotheses (Scheme 12.41). In the first one,
the formation of an axial triflate is followed by a direct S N 2-like substitution or a
S N 1-type substitution pattern on an oxocarbenium ion that favored 3 H 4 half-chair

a

MeO 2 C
AcO

R

1. Ph 2 SO, Tf 2 O
CH 2 Cl 2 , -80°C

O

R

MeO 2 C
AcO

O

O BnO

BnO O

2.

OH

BnO
BnO

SPh

O

BnO
BnO

BnO

OMe

BnO

OMe

R = OBn
R = N 3

R = OBn (81%, β/α >10:1)

R = N 3 (69%, β/α = 1:0)

SCHEME 12.40 b -Selectivity in the synthesis of various mannuronic esters.

MeO 2 C Nu

MeO 2 C

OBn

OBn

H

O

O OTf

N 3

N 3

OTf N 3

OAc MeO 2 C

AcO

OAc

RO H O

eq OTf OR

BnO

S N 1-like

OBn

CO 2 Me

N 3

O

S N 2-like

N 3 N 3

3 H 4

OTf OAc

MeO 2 C
AcO

MeO 2 C
AcO

Ph 2 SO, Tf 2 O

O O

N 3

MeO 2 C
AcO

BnO CH 2 Cl 2 , -80°C BnO N 3

OAc
CO 2 Me

ROH O

SPh OTf O

ax OTf BnO

BnO

OR

OTf

4 H 3

S N 1-like

SCHEME 12.41 van der Marel's explanation for b -selectivity.