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PGO
OPG
N
HFmoc
OPG
PGO
OPG
O
HO
OBn
O
PG O
O
O
PGO
PGO
PGO
O
R
A
B
C
HO
OH
OH
O
O
HO
O
HO
O
HO
AcHN
HO
O
HO
Mucin related F1
αα
antigen
N
H
2
AcHN
O
OH
12
R = H
13
R = Me
O
R
Scheme 4 Building blocks used in the synthesis of mucin related F1
a
antigen via two
different strategies: convergent (AþB, then C) or ''cassette'' (BþC, then A) approaches.
Scheme 5 The ''cassette'' approach for glycopeptide synthesis and its application for the
preparation of mucin-related antigen clusters.
that can be further coupled to a target carbohydrate bearing a glycosyl
donor moiety at its reducing end (Scheme 5). This suitably protected O-
glycosyl amino acid can be also used as a building block (''cassette'') in
solution or solid-phase peptide synthesis (SPPS) en route to larger glyco-
peptide fragments. Admittedly, the cassette protocol requires a sacrifice in
overall convergence. However by taking this approach, the nontrivial issues
associated with achieving high levels of a-stereocontrol in the direct for-
mation of the O-linkage between the Ser/Thr side chain hydroxyl group and
the fully elaborated, already complex saccharide donor can be circum-
vented. The clear advantage of this method is the need to only solve the
very dicult O-linkage problem once for a given ''reducing end'' and to
exploit that capability for building on the desired clustered system.
Scheme 5 demonstrates the logic of the cassette strategy, which together
with our glycal assembly methods, has been successfully implemented in
the preparation of several trimeric clustered mucin-related antigens, in-
cluding Tn(c),
16
TF(c),
16
STn(c),
17
and Le
y
(c).
18
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