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O
O
N
O
O
40
41
FIGURE 9.15
Linkers used in the synthesis of dimeric sucroses by click approach.
the cavity is rather small, so strong repulsion between the triazole proton and the
benzyloxy group at the C1
-position makes this structure not very favored.
If this assumption is correct, enlargement of the cavity should result in the for-
mation of the mechanistically favored 1,4-isomer exclusively. Indeed, the “click”
cyclization of the elongated azidoacetylene
38
catalyzed with Cu(I) species led to the
expected monomer
39
in good yield. The elongated azidoacetylene
38
was prepared
by a rather classical approach taking advantage from the high affinity of the termi-
nal fructose hydroxyl group at the C6
toward silylating agents and further standard
transformations (Fig. 9.14) [50].
To prepare more complex symmetrical sucrose macrocycles, we decided to connect
two sucrose molecules via dialkyne linkers
40
and
41
(Fig. 9.15) obtained from
catechol or lutidine by standard methodology [51].
Each linker might react efficiently with two molecules of sucrose that were func-
tionalized with an azide at one of the terminal positions. Coupling of sucrose azide
42
(readily available from the mono-silylated derivative
32
) with both linkers under the
click reaction conditions (Cu(I)-cat/DIPEA/acetonitrile for
40
; CuSO
4
, sodium ascor-
bate, t-BuOH/H
2
Ofor
41
) afforded the C2-symmetrical precursors of macrocycles:
43
and
44
in good yields (Fig. 9.16) [51].
Further steps leading to macrocycles included activation of both terminal hydroxyl
groups as mesylates and subsequent reaction with ethylene diamine. The last step
was very demanding [51].
The dimesylate derived from
43
did not react with ethylene diamine under the
standard conditions (Fig. 9.17). The product
45
could be obtained only in the presence
of the template, (
R
)-(-)-2-phenylglycine methyl ester hydrochloride. This template
was also effective in the cyclization of the dimesylate derived from
44
; without
the template, the yield of the corresponding macrocycle was very low, while in the
presence of this amino acid derivative 25% of the product
46
was obtained.
9.2 CONCLUSION
A few examples of the preparation of sucrose macrocycles by “click” methodology
shown here point out the usefulness of this approach in the synthesis of such complex
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