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Scheme 11 Synthesis of the STn cluster 51 via the cassette approach. (a) TMSOTf, THF,
4 Å mol. sieves, 40
1
C[R
=
Me, X
=
OP(OBn), 37%]; AgOTf, DTBP, CaSO
4
, THF, 78
1
C
[R
=
H, X
=
Cl, 50%]; (b) AcSH, pyr, 87%; (c) AcOH/H
2
O (4 : 1); (d) Ac
2
O, Et
3
N, DMAP,
CH
2
Cl
2
, 84% (2 steps); (e) H
2
, Pd/C, MeOH/H
2
O, quant.
achieved via the convergent approach (see Scheme 1) to form a cluster of
three glycodomains as a mimic portion of the CD43 glycopeptide.
12
3.1.4 The Lewis
y
-clustered glycopeptide. Blood group antigens are
presented as terminal carbohydrates moieties on glycolipids and mucin-
like glycoproteins in many epithelial cells and their secretions. The en-
hanced presentation of cell surface Lewis
y
(Le
y
) blood group antigen,
both in glycolipid (Le
y
-ceramide) and mucin forms on many human
tumor cells (colon, lung, breast, and ovary) can serve as a marker in a
variety of cancers. The Le
y
determinant has been previously identified as
an important epitope for eliciting antibodies against colon and liver
carcinomas.
26
It has also recently been implicated as a marker in meta-
static prostate cancer and was found to be overexpressed in ovarian
tumors.
27
In pursuit of a fully synthetic, homogeneous Lewis
y
antigen in
a mucin context, the total synthesis of a Le
y
-clustered glycopeptide was
then accomplished by further extension of the cassette methodology.
18
Le
y
glycal 52 was prepared as shown (Scheme 12), and converted to the
thioethyl or pentenyl glycoside donors 53 or 54, respectively.
In the [5
þ
1] cassette coupling event, NIS/TfOH-promoted glycosyla-
tion of either pentasaccharide donor with building block acceptor 23,
followed by functional group manipulation afforded the a-O-Ser linked
hexasaccharide 55. Mucin construction required peptide couplings of
highly complex glycosylamino acids. In this case, HOAt/HATU method-
ology allowed for ecient assembly of the protected linear heptapeptide
mucin model 56 (Scheme 12).
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