Sucrose as chiral platform in the synthesis of macrocyclic receptor - Carbohydrate Chemistry: Chemical and Biological Approaches - page 243

SH

H S

S S

6

OBn

6'

oxidation

6 6'

1. MsCl

O

22

O

BnO

Fruc
3xOBn

Gluc
3xOBn

reduction

2. NaSH

O OBn

36

BnO

OBn

OBn

35

Fruc
3xOH

Gluc
3xOH

SH

TBDPSO

6 6'

S
S

H

1. I 2
2. F (-)

OBn

H

O

O

24

BnO

6

6'

O OBn

Fruc
3xOBn

Gluc
3xOBn

BnO

37

OBn

38

OBn

Scheme 8 Synthesis of sulphur derivatives of sucrose from hexa-O-benzylated substrate.

3 Synthesis and properties of sucrose based
macrocycles
In the most stable conformation of free sucrose in the solid state (for-
mula A in Fig. 3) the terminal positions of both sub-units are close to
each other. It is a result of strong hydrogen bonds between 6 0 -OH and
ring oxygen atom of the glucose part and 1 0 -OH and 2-OH.
The dynamic structure of sucrose in solution - as determined by NMR
- is slightly different and can be depicted as equilibrium between B and C
(Fig. 3); in the preferred conformation B these terminal positions are also
in close vicinity. 29
Can they be connected, therefore, via a linker? Surely, it cannot be
realized directly on free sucrose, because of the presence of many hy-
droxyl groups with similar reactivity. Can this be done, therefore, for
partially protected sucrose (i.e. 13 or 22)? The answer may be yes, if these
derivatives exist (preferably) in conformation of type B, which was not,
however, known.
If the answer is YES, the route to crown and aza-crown ethers (and their
analogs) with sucrose scaffold is open. Sugars are convenient and easily
accessible starting platforms for the preparation of chiral macrocyclic
receptors. This is true for monosaccharides (as mentioned already in the
INTRODUCTION) however, much less is known about chiral macrocycles
with di-saccharide scaffold.
Our first paper dealing with this problem, tried to answer the question:
how long should be the linker connecting both terminal positions of two
subunits of sucrose? We have found that minimum four carbon atom
unit is able to connect the 6,6 0 -positions. 30 Reaction of 13a with 1,4-
di-iodobutane afforded macrocycle 39. Both terminal positions (C-6 and
C-6 0 ) could be also connected via the RCM approach which is shown in
Scheme 9. Di-allyl derivative 40, easily prepared from diol 22, was con-
verted into macrocycle 41 with the Grubbs catalyst. Alternatively, reaction
of diol 22 with pentenoyl acid chloride afforded di-ester 42, which also
underwent the RCM reaction to afford olefin 43. 20 We were able to
deprotect the sucrose backbone and obtain the corresponding 'free'
polyhydroxylated macrocyclic derivatives (Scheme 9).