Biomedical Engineering Reference
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of the chloroacetate group, the two tetrasaccharides assembled in this manner were
conjoined by activation of 1,6-anhydro bridge by means of silver triflate. The high
a
-selectivity seen in these couplings in contrast to the previous Ag
2
CO
3
-mediated
step is a function of the soluble nature of AgOTf [6b,7] and doubtless the presence of
the ester at
O-
3 [6a,[8]]. Afinal 1,2-
cis
-axial glycosidic bondwas also introducedwith
help of a soluble silver promoter. The synthesis was completed after deprotection,
reduction of the azido group, and sulfation. A feature of this synthesis, as with the
latter approaches to heparin and heparin analogues [9] by Boons and coworkers [10],
Hsieh-Wilson and coworkers [11], and other groups [12], is its modular approach and
the apposite use of protecting groups. The relatively classical nature of the chemistry
is signaled by the employment of silver-based promoters, especially the insoluble
silver carbonate, with its obvious disadvantages of long reaction times and frequently
poor reproducibility.
12.1.2. Moenomycin Pentasaccharide Synthesis
A second example of a highly refined application of classical methods is Kahne's
synthesis of the pentasaccharide from the antibiotic moenomycin (Scheme 12.2),
BnO
CO
2
TMSE
CO
2
Ph
O
PMP
O
O
O
TCPN
O
O
HO
OTMSE
+
HO
+
S
S
BnO
Ph
SPh
AcO
Ph
PhO
2
CO
HO
O
OBz
NTCP
OH
1. Tf
2
O, DTBMP
ADMB, CH
2
Cl
2
-78°C to 0°C (75%)
2. m-CPBA, CH
2
Cl
2
-78°C to 0°C (70%)
1. Tf
2
O, DTBMP
ADMB, CH
2
Cl
2
, -42°C (84%)
2. Bu
2
BOTf, BH
3
.THF, -60°C (83%)
BnO
CO
2
TMSE
TCPN
Ph
HO
O
OBz
S
O
BnO
O
O
HO
CO
2
Ph
PhO
2
CO
1. Tf
2
O, DTBMP
ADMB, CH
2
Cl
2
, -60°C (50%)
2. Acetylation/PMB-deprotection (73%)
O
PMBO
HO
O
NTCP
O
OTMSE
DTBMP =
AcO
t
-Bu
N
t
-Bu
MeO
HO
ADMB =
CO
2
Ph
PhO
2
CO
MeO
O
BnO
CO
2
TMSE
TCPN
HO
Cl
O
NTCP
O
O
HO
O
O
OTMSE
O
AcO
Cl
BnO
O
NTCP =
N
OBz
Cl
OBn
O
Cl
Tf
2
O, DTBMP
ADMB, EtCN, -78°C
76%
O
BnO
BnO
BnO
OH
O
S
O
O
Ph
HO
HO
CONH
2
HO
H
2
NOCO
O
AcHN
OBn
OH
HN
HO
O
OH
NHAc
O
O
O
BnO
HO
CO
2
Ph
O
OH
HO
O
O
BnO
PhO
2
CO
O
HO
O
O
HO
BnO
O
BnO
CO
2
TMSE
TCPN
O
O
P
OH
Steps
O
NTCP
OTMSE
O
OBz
HO
O
O
O
O
BnO
O
AcO
O
CO
2
H
Moenomycin
SCHEME 12.2
Synthesis of moenomycin by Kahne and coworkers.
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