Biomedical Engineering Reference
In-Depth Information
OBn
OBn
FmocO
BnO
OBn
O
O
O
O
OPiv
O
OPiv
O
FmocO
O
P
OBu
OBu
O
P
OBu
BnO
O
P
OBu
OBu
FmocO
BnO
OBn
OBu
Donor 1
Donor 2
Donor 3
NPh
OBn
OBn
BnO
BnO
BnO
O
O
O
O
CF
3
NPh
CCF
3
O
PivO
OPiv
O
FmocO
O
P
OBu
OBn
OFmoc
TCAHN
OBu
Donor 4
Donor 5
Donor 6
1. Donor 1, TMSOTf, CH
2
Cl
2
, -15°C
2. Piperidine (20% in DMF)
3. Donor 2, TMSOTf, CH
2
Cl
2
, -15°C
4. Piperidine (20% in DMF)
OBn
OBn
BnO
BnO
O
O
O
FmocO
BnO
TCAHN
O
OBn
OBn
HO
5. Donor 3, TMSOTf, CH
2
Cl
2
, -15°C
6. Piperidine (20% in DMF)
7. Donor 4, TMSOTf, CH
2
Cl
2
, -15°C
8. Piperidine (20% in DMF)
O
OPiv
O
OPiv
O
O
BnO
BnO
1. Donor 5, TMSOTf, CH
2
Cl
2
, -15°C
2. Piperidine (20% in DMF)
3. Donor 6, TMSOTf, CH
2
Cl
2
, -15°C
4. Grubb's catalyst (first generation)
ethylene atmosphere, CH
2
Cl
2
OBn
OBn
BnO
BnO
OBn
BnO
O
O
O
O
O
BnO
BnO
TCAHN
O
OBn
O
OBn
O
OPiv
O
OPiv
O
O
PivO
OPiv
O
OBn
BnO
BnO
30% overall yield
SCHEME 12.23
Solid-phase synthesis of Globo-H.
12.4.
1,2-cis-AXIAL GLYCOSIDES
As the
-gluco- and galactopyranosides
constitute a class of 1,2-
cis
-glycosides for whose synthesis classical neighboring
group participation cannot be employed. Owing to the axial nature of the bond to be
formed and the ability to benefit from the kinetic anomeric effect, the challenge is less
formidable than in the case of the manno- and rhamnosides, but the attainment of
complete selectivity still poses considerable problems. Examples abound of the use of
fully armed galactopyranosyl donors, bearing only ether type protecting groups,
giving excellent
-manno- and rhamnopyranosides, the
b
a
-selectivity. These couplings rely on the highly armed nature of
the galactopyranosyl donors, which is a function of the axial nature of the C4-O4
bond [81] and its interaction with the pyranosyl ring oxygen [84], but such high
selectivity is rare in the glucopyranose series. Solvent mixtures containing diethyl
ether or dioxane are a feature of many such 1,2-
cis
-axial glycosidic bond forming
reactions based on the general hypothesis that the ether solvent participates through
the formation of an
a
-glycosyl diethyl oxonium ion. To our knowledge,
such ions, while certainly possible, have yet to be demonstrated spectroscopically in
glycosylation reactions, but related glycosyl dialkyl sulfonium ions have been iden-
tified in reactions conducted in the presence of dialkyl sulfides [85].
a
-directing
b
12.4.1. Armed Galactosyl Donors
The use of fully armed galactosyl donors has been nicely illustrated in the synthesis
of the Globo-H by Boons and Zhu [61], Danishefsky and coworkers [68a]
(Scheme 12.24), Huang and coworkers (Scheme 12.19) [79], and Wong and
Search WWH ::
Custom Search