Peptide-Based Drug Design

196 Cudic and Burstein
AcO AcO
AcO AcO
OAc
O
OAc
OAc
NH 2 x HCl
O
OAc
NHTroc
1) Zn/HOAc
OAc
2) Ac2O AcO
AcO
O O
NHAc
1) C6H5CHO 2) pyridine/Ac2O AcO
AcO
OAc
O OAc
N=CHC6H5 1) Fmoc-Ser-OH/Fmoc-Thr-OH
OAc
2) BF3-OEt2 AcO
AcO
O O
NHTroc
R
NHFmoc
COOH
Ser
R
H
Thr CH3 1) HCl/acetone
2) Troc-Cl
R
NHFmoc
COOH
Fig. 7. Synthesis of Fmoc-Ser/Thr-OH building blocks containing glycosylated O-�-
GlcNAc (62).
and the method does not require extensive experience in synthetic carbohydrate
chemistry. 1,2-trans-1-O-acetylated saccharides have been used for preparation
of �-O-glycosides in the d-galactose and glucose series (Fig. 7) and for the
synthesis of �-d-mannosides (62) (Fig. 8).
3.2.2.1. SYNTHESIS OF �-PERACETYLATED SUGARS (WITH PYRIDINE AS
CATALYST)
1. Add acetic anhydride (10 eq, 2 eq per OH group) into dry pyridine (approx 10 mL
pyridine for 1 g of sugar) and cool down the reaction mixture to 0 ◦ C(see Note 5).
2. Add sugar (1 eq) and stir the solution until it dissolves completely at 0 ◦ C.
3. Let solution stand overnight at room temperature.
OAc
AcO
AcO
OAc
O
OAc
Fmoc-Ser/Thr-OH
BF .
3 Et2O Ser
R
H
Thr CH3 OAc OAc
AcO
AcO
O
O
R
NHFmoc
CO 2 H
Fig. 8. Synthesis of Fmoc-Ser-OH (62) and Fmoc-Thr-OH (75) building blocks
containing glycosylated 1-O-�-Man.