7567
Synthesis of 9 from 4 proceeded through such three stages as phenylthioglycoside
formation the configurational inversion at C-3 and C-3’ utilizing participation of the
neighboring acetamido groups
replacement of N-protection with phthaloyl groups.
contain some problem because most of usual
The above reaction sequence
aminosugar thioglycosidations had been conducted using N-phthaloyl derivatives,7 but not
N-acetyl ones.8 We succeeded in developing an efficient way to change 4 into the
thioglycoside derivative 5. Thus, 4 was treated with
in the presence of
CDC13) 4.58 (d,
H-l), in 87% yield. Apparently, this reaction must have proceeded
at
mp 300°C;
H-l’), 4.67 (d,
via an oxazoline intermediate 65 because it was detectable on t. 1. c. in the course of the
reaction and a similar treatment with
resulted in 5 in good yield. Use of
After Zemplen de-0-acetylation of 5,
benzylidenation
(4eq.) of 6 separately derived from 4
instead of
resulted in a lower yield of 5.
the resulting pentaol was subjected to successive
and tritylation
3.65
pyridine-DMP) to give 7, mp
H-3’). 3.73
CHCl3);
H-3). The two hydroxyl groups of 7 were sulfonylated by treatment with
and the resulted dimesylate was solvolyzed in the presence of
methoxyethanol, giving 8 with &o-configuration, mp 169°C;
in pyridine
in aq.
4.03
H-3’), 4.20
determined by these
H-3). in good yield. The &o-configuration of 8 was
spectral data. The lower chemical shift and smaller coupling
constants of two protons at C-3 and
positions of 8 than those of 7 indicate the presence
of axially oriented hydroxyl groups. In order to prepare for the stereoselective glycosidation
reaction expected, N-acetyl groups were replaced with phthaloyl groups. After removal of
the O-protecting group of 8 under acidic conditions, N-acetyl groups were hydrolyzed under
basic conditions and the resulted compound was successively treated with phthalic anhydride
in methanol and
Glycosyl acceptor 11 was derived from the cyclitol derivative 10. which used to be the
final intermediate in the course of our previous synthesis of allosamizoline. After
in pyridine, giving the synthon 9,
in 41% overall yield.
unsuccessful attempts for benzylations under conventional basic conditions, 10 underwent
smooth 0-benzylation by treatment with benzyl 2, 2, 2-trichloroacetimidate in acidic
condition
giving a fully protected compound, from which I-
butyldimethylsilyl group was removed with dil.
61% yield.
to afford 11, mp 119°C
in
Coupling between the glycosyl donor 9 and the acceptor 11 was conducted by the
Fraser-Reid’s procedure. Thus, 9 and 11 (3.0 mole eq.) were treated with
succinimide (2.5 eq.) and
protected allosamidin derivative 12,
in the presence of MS 4A in
at
giving fully
4.93 (dd,
2.28 (m, H-5), 2.66 (s,
5.76 (t, H-3’), 5.98 (d,
5.53 (t,
H-l’), 6.04 (d,
H-l”), in 40% yield.14 Finally, removal of all protecting groups
After simultaneous hydrolysis of
phthaloyl and 0-acetyl groups had been conducted under mild conditions by the action of
from 12 was performed in a continuous manner.