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O
11b
n
O
O
1. NaH/THF
2. Ts(OCH
2
CH
2
)
n+1
O
Ts
OR
(or)
O
O
BnO
22
30-50% yield
O
OBn
BnO
OBn
OBn
de-protected
sucrose
macrocycles
48.
R = BOM
49.
R = Bn
H
2
/Pd/C
n = 1-3
O
O
O
O
OH
H
O
OBn
O
O
O
O
BnO
O
O
OBn
O
OBn
BnO
OBn
O
OBn
O
BnO
OBn
22
O
BnO
OBn
OBn
50
Scheme 11 Synthesis of sucrose-based crown ether analogs.
ester functions - provided diol 56. Activation of the hydroxyl groups
followed by reaction with benzylamine afforded macrocycle 57 with the
three nitrogen atoms in the ring. Macrocycles with larger cavity having
two nitrogen atoms were also prepared from 'homologated diol' 52 as
shown in Scheme 12.
33
We were also able to prepare macrocycles with
four nitrogen atoms. The amine 54 was reacted either with di-tosylate 59a
or 59b to afford target compounds 60 and 61.
34
All compounds presented till now had the nitrogen atoms protected. It
would be advantageous to prepare such macrocycles with the un-
protected nitrogen atom(s), which might allow to modify the properties
of the ring by placing proper substituent (electro-withdrawing or electro-
donating) at the nitrogen atom(s). Simple removal of the benzyl group
protecting the nitrogen atom(s) in macrocycles: 53, 57, 58, 60 and 61 was
not possible, since the sucrose core was also protected by benzyls; an-
other methodology should be, therefore, elaborated.
This goal was achieved starting from mono-substituted sucrose de-
rivative 23. Alkylation of the 6
0
-OH with tert-butyl bromoacetate and
subsequent reduction of both: nitrile and ester functions afforded ami-
noalcohol 62. Treatment of this derivative with the Garegg's reagent
(triphenylphosphine/iodine/imidazole) provided an unstable iodide 63,
which cyclized under the reaction conditions furnishing macrocycle 64
with the secondary amino group. The nitrogen atom could be substituted
with various groups (to 65; Scheme 13).
35
Other inconvenience of our standard methodology of the synthesis of
macrocycles was, that it allowed to prepare only symmetrical' derivatives,
i.e. with identical heteroatoms (either oxygen or nitrogen) at the glucose
and fructose parts. Recently we have proposed the method for
the preparation of macrocyclic sucrose-based derivatives differing in
heteroatom at both sub-units (Scheme 14).
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