Biomedical Engineering Reference
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O(NBz)
BzO
OBz
(NBz)O
(NBz)O
O(NBz)
OBn
BzO
OBz
BnO
O
(ClBn)O
OBn
O
TrocHN
BnO
HO
STol
HO
STol
O
(ClBn)O
(13)
O
TrocHN
O
(850)
O
O
STol
O
BnO
STol
BnO
1. NIS, TfOH, CH
2
Cl
2
, -20°C, “one pot” (67%)
2. Deprotection (95%)
OLev
OH
(6)
(4000)
OBn
OH
HO
OBn
HO
HO
OH
HO
OH
O
BnO
OBn
STol
OBn
O
O
OBn
O
O
O
AcHN
O
HO
BnO
OPMP
BnO
H
O
O
O
(72,000)
OBn
O
1. NIS, TfOH, CH
2
Cl
2
, -40°C to rt, “one pot” (62%)
2. Functional group adjustment (45%)
OH
O
OH
O
HO
OH
OH
O
O
OH
O
HO
OPMP
HO
OH
SCHEME 12.20
Globo-H synthesis via a programmable reactivity-based one-pot strategy.
parentheses in Scheme 12.20). With this strategy, oligosaccharides containing three to
sixmonosaccharides are rapidly assembled inminutes or hours bymixing the selected
building blocks in sequence, with the most reactive one first. No intermediate workup
and purification are required except for the final deprotection/isolation step. In
principle, this type of protocol may be applied to the one-pot preparation of
increasingly long oligosaccharide chains, but it is limited in practice by the increas-
ingly long reaction times required as the sequence progresses, that is, by the neces-
sarily decreasing reactivity of the donors with increased chain length. Nevertheless,
this strategy allowed Wong and coworkers to achieve the synthesis of a Globo-H
derivative via sequential selective glycosylations, relying on the decreasing reactiv-
ities of glycosyl acceptors [77].
Seeking to extend the scope of this method, Huang and coworkers, building
on earlier work byBoonswith sterically differentiated thioglycosides [78], introduced a
series of thioglycoside donors whose reactivity was differentiated not by the use of
armed or disarmed protecting groups but by the presence of increasingly electron-
withdrawing groups in the thioglycoside moiety [79]. Thus, sequential activation of
thioglycosides substituted from
p
-methoxyphenyl to
p
-bromophenyl to
p
-nitrophenyl
withNIS/TfOHallowed the formation of an intermediate trisaccharide (Scheme 12.21).
OR
BzO
O
BzO
S
OBz
X
R = H, TBDPS
X = NEt
2
, OMe, NHAc, Br, NO
2
, N
3
OTBDPS
BzO
O
O
BzO
OTBDPS
BzO
BzO
OBz
Donor 1
Donor 2
Acceptor
O
O
S
BzO
O
BzO
NIS, TfOH
CH
2
Cl
2
, -60°C
NIS, TfOH
CH
2
Cl
2
, -60°C
p
-TolSCl, AgOTf
CH
2
Cl
2
, -50°C to rt
BzO
OBz
OBz
2
O
OMe
BzO
BzO
OMe
OH
OH
BzO
BzO
OH
BzO
O
O
O
BzO
S
BzO
S
BzO
OBz
OBz
BzO
OMe
NO
2
Br
Donor 1
Donor 2
Acceptor
SCHEME 12.21
One-pot synthesis of a
b
-(1
!
6)-galactan by Huang and coworkers.
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