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An expeditious enantiodivergent synthesis of chiral oxepanes from D-glucose by the application of intramolecular 1,3-dipolar nitrone cycloaddition
00404039193 56.00 + .OO
Tank&m Latcrs. Vol. 34. No. 22. pp. 3585-3588.1993 Printedin Great Brimin
An Expeditious from
Pergamon Press Ltd
Enantiodivergentsynthesis
D-Glucose
by the
1,3-Dipolar Seaua Datta,
Application Nitrone
Partha Chattopedhyey,
Indian Institute
of of
Chiral
Oxepanes
Intramolecular
Cycloaddition
Banjen Rukhopadhyay and Auup Bhattacherjya*
of Chemical Biology, Calcutta
4 Raja S. C. Mullick Road,
700032,
India
and a chiral oxepane, Abstract : The enantiomers of an oxepanoisoxazolidine potentially useful as precursors for naturally occurring oxepanes, were synthesised from D-glucose involving intramolecular 1,3-dipolar nitrone cycloaddition. The ‘chiron’ chiral
precursor
particularly
usually
of
a
profiles
of
desirable
application
of
a
chiral
a precursor enable
both
the
results
the
this
via
a large
synthesis
synthesis
of
of
an opticallyactive
in a particular active
enantiomers of
compound
for
the
biologically
to
be
would
be
but
due to its number of
as
drug,
Thus
preparation
similar
easy availability
the
a of
routes
from
physiological
more both
economic
the
from
a
D-glucose
single
chiral
utilised
a scheme
via similar
and
enantiomers
has been extensively
compounds, we envisioned
compounds
compound from a
However, in many cases,
a
evaluated. the
closely
chiral
enantiomeric
enantiomer.
compound such
need
approach separate
Since D-glucose
precursor.
to
approach’
which
as will
routes.
-X
X
R’O
3 4
--)_
M -
2 -R203
OR’
t
3
I_
Y
-OR’
RG
Y
or
4 -OR3 L
-Y
D-Glucose
4
2
The general sets
of
[X-C-4-C-3-Y] tions
scheme
enantiomeric
to
derivable
synthesis
depicted
chirons from the
3
I Schrmr
via.
in
1 was
borne
out
of
the
recognition
of
two
[X-C-Z-C-3-C-4-Y ] / [X-C-4-C-3-C-Z-Y ] and [X-C-Z-C-3-Y]/
D-glucose.
enantiomeric
Scheme
I
Hence compounds
3585
it
is
possible
1 and
2 or
by proper 3 and
4
chemical (Scheme
manipula1)
from
D-
3586
glucose.
Herein
D-glucose which
we demonstrate
to the enantiomeric
incorporate
importance
of
activity
of
interest
as
two (C-4/C-2
the
chiral
naturally a
the
and C-3)
oxepane
occurring
reproductive
amenable to modifications
application
of
oxepanoisoxazolidines
medicine.
necessary
7 and 12,
chiral
centres
derivatives
oxepanes
the strategy
stems
like
of
The substitution
for a total
and a chiral
D-glucose
from
soapatanol’
the
significant in
of zoapatanol
7,
of
oxepane 13
(Scheme 2).
The
biological
which has generated pattern
synthesis
by the conversion
immense
12 and 13 is
and its
analogues.
D-Glucose 7: cdlDt
fI,_b,e,!
104.3.
,
OAc
.‘O
c 6:
b
R=
II
f
,
12
: Cdlg- 103.7.
NHAc I
,+@:R=CHO
1
6n
lo:R=CH=N<
AcO-
h -I
‘0-
13 : a NaOMe,MeOH b NaI04, H20, 25’C c NaBH4, EtOH d Ac20, pyridine e AcOH-Hz0 (3:1), 66°C f BnNHOH,benzene, 3A-mol.sieve 4 4% H2S04, CH3CN, H20, 2Y’C h cyclohexene,Pd-C, EtOH. Reagents
Scheme 2 The key reaction cycloaddition
of
employed in this
nitrones
derived
allyl-1,2:5,6-diisopropylideneglucose via
the E-benzylnitrone
63 with known3 absolute
of
synthesis
involved
the intramolecular 1,3-dipolar 3,4 . Thus, 3-0from 0-allylcarbohydrate derivatives (5) easily obtained5 from D-glucose was converted
3-0-allylglucose to the optically active oxepane derivative stereochemistry. A sequence of reactions involving deacetylation,
3587
oxidativc finally 7
cleavage
with
isolaticn
as the acetate
from 6.
yield’
The retention
was apparent
constants
of the relevant
In s separate cleavage
was converted
effected
by heating
only
isolable
product8
to
its
to
the
methylene
of
reduced
with
fulfilling
bridge
of
enantiodivergent to the optically
the isoxazolidine
yield7
mass
without -in as the
isoxasolidine
for
synthesis
according is
spectra
establishment
the
final
deprotected,
and finally
times,
step
cleaved
acetylated.
but also
enantiomers.
was
bridge
as in 11 as well
the
of
the
The resulting +I RHR, optical
the confirmation
as the completion
of 7 and 12 from D-glucose.
Finally
12 was
oxepane 136 by the reductive
to the aforementioned
of
with sodium
equal and opposite
This constituted
Thus a formal enantiodivergent
grateful
The till
from 11) and 7 not only had superimposable
GC retention
Thanks are due to hr.
for
used
116 was obtained
group.
was deferred
pure tetrasubstituted
ring.
Acknowledgement : S.D.
methylene
bridge
the methylene
converted
Fellowship.
to a5 followed
The latter,
10 which underwent cycloaddition
11 was successively
the crtteria
expedient,
wss also achieved
9.
That 11 was a bridged
sodium borohydride
and identical
the stereochemistry
Banerjee
the
1Z6 (23.8% overall
IR, mass spectra
of
76 in 20% overall
5 was deprotected
aldehyde
The oxepanoisoxazolidine
from 8).
Thus, the isoxazolidine
rotations
the
E-benzylnitrone
(55% yield
due
diacetate
and
from the appearance of a one-proton doublet at 6 2.64 and a one1 at 6 2.34 in its H NMRspectrum as well as a tripl.et at 6 26.9 in the
stereochemistry metaperiodate,
to
in benzene.
proton multiplet 1.3 C RMR spectrum synthesis.
to the oxepanoisoxazolidine
2) the common precurscr
sodium metaperiodate
situ
discernible
sodium borohydride
of 6 and 7.
(Scbae
purification,
clearly
with
of
protons
route
with
gave rise
reduction
the stereochemistry at the chiral centres during the 1 from the closely similar H RHR chemical shifts and coupling
reactions
by
sodium metaperiodate,
synthesis
of a chiral
of
of an readily
cleavage oxepane
scheme.
to the CSIR, India for the award of a Senior Research P.P.
and to RSIC,
Ghosh Lucknow,
Destidar, India,
Dr. for
R.C.
Yadev
elemental
for
NHFl, Mr.
A.
analysis.
RRFRRRNCRS ANDNOTES 1. 2. 3. 4. 5. 6.
S. Hanessian, Oxford: 1983:
The
Total
Synthesis
of
Natural
Products
:
The
Chiron
Approach;
23-26. Kocienski, P:;‘iove, C.; Witby, R. Tetrahedron 1989, 2, 3839-3848. Bhattacharjya, A.; Chattopadhyay, P.; McPhail, A.T.; McPhail, D.R. J. Chem. Soe., Chem. Commun. 1990, 1508-1509; corrigendum, ibid, 1991, 136. Collins, P.M.; Ashwood, M.S.; Wright, S.Hx Kennedy, D.J. Tetrahedron Lett. 1990, 2, 2055-2058. Smith, III, A.B.; Rivero, R.A.; Hale, K.J.; Vaccaro, H.A. J..Am.-Chem. Sot. 1991, 113, 2092-2112. Sal.ient data for 7,-U, 12 and 13 : DD.
7 : m.p. 94’-95’C; (c,
0.27,
[a],
+104.3”
(c,
0.23,
CHC13); 12 : m.p. 94’-95OC;
CHC13); 7 or 12 : HRMS,~12 : 349.1512
(KBr) : 1731,
1238 and 1060 cm-1;
1H NHR (CDC13) :6 2.04
2.04-2.44
(m, lH),
3.96-4.32
(m, 3H), 4.04 (d, J=12 Hz, lH),
[a],
-103.7’
(C18Hz306N, m/p : 349.1526);
2.58 (d, J=32 Hz, l.H), 3.56-3.72 4.64 (br.d,
(8,
3H), 2.10
(8,
IR ?H),
(m, 3H), 3.82 (d, 5112 Hz, lH), J=8 Hz, IH), 4.90 (d, 516 Hz,
and 7.36
(br.s,
(t),
72.3
(s),
170.0
(d),
1.46
(s,
3H),
3H),
3.70
(d,
lH),
4.62
(br.d,
(d),
and
1.36.7
(6);
13
23.2 169.3
2.08
The
formation
cycloaddition found
to
be
(d),
1738 2.08 (br.d,
49.3
(d),
170.1
in
these
to diols any
could insoluble
(s)
5.86
(d,
(Received in UK 23 February 1993)
(d),
27.7
128.3 [al,
(d,
4.12
(d,
J=12
136.8 CHC13);
: 61.28
lH),
(8,
4.42
(d,
(br.s, 72.3
(t),
78.3
1.11.5
(s),
127.5
(d),
128.4
(d),
129.0
+21O
(c,
1.0,
CHC~~);
1H);
13C NMR (CDC13)
71.1
J=12,8
(d),
E/E
: 6 1.96
Hz,
71.7
5H);
(m, J=4 Hz,
7.32
; ‘H NMR (CDC13)
IH),
13C NMR
(FAB)
(d), (d)
: 346
(8,
3H),
2.04
3.9-4.5
(m,
5H),
:620.6
(t),
3H),
3.56-3.84
(d),
(dd,
(2q),
20.8
(q),
(d),
78.1
(d),
73.8
(6).
viz. without
common organic
(d),
1.0,
62.5
-9
1H) and
3.46
reactions
Hz,
63.5
(t),
(III, 2H),
and 170.4
1.28.8 (c,
(d),
62.0
[aI
(t),
(d),
5~12 Hz, IH),
cm
62.1
63.1
-100.8”
and 1653
J=8 Hz,
(t),
‘l-l NMR (CDC13)
2.64
J=4 Hz,
(d),
be ascertained in
lH),
(t),
pyranoisoxazolidine
ethylacetate.
127.4
(q),
126’-127’C;
lH),
26.9
were used
not
2C.7
: 333.1577);
(br.8,
104.1
(q),
(d),
Hz,
143°-1440C;
m.p.
:
(s),
of
I-H), (q),
84.4
(t),
169.5
reduction
Hz, 26.5
and 6.16
33.7
m/e --
4.08
3H),
The intermediates their
: m.p.
Hz, IH),
(8,
(m,2H)
(s),
78.8
11
J=l;,lO,S
: 3284,
IR (KBr)
(q),
(d),
(8);
(C18H230,N,
J=lO
~520.6
73.8
(ddd,
(q),
82.3
5.0-5.4
8.
J-12
(d),
(s,
(t),
2.34
6 25.9
6~),
NMR (CDC13)
and 170.4
79.5
(M+l);
7.
72.8
(8)
‘3C
: 333.1526
HRMS, -m/z
(CDC13);
5H);
daprotection, puriffcation arising
since
the
solvents
oxidation for
out
of
material such
as
next an
to
aldehydes
and
steps. alternative
obtained chloroform,
besides
mode
of
11 was
methanol
and
Tank&m Latcrs. Vol. 34. No. 22. pp. 3585-3588.1993 Printedin Great Brimin
An Expeditious from
Pergamon Press Ltd
Enantiodivergentsynthesis
D-Glucose
by the
1,3-Dipolar Seaua Datta,
Application Nitrone
Partha Chattopedhyey,
Indian Institute
of of
Chiral
Oxepanes
Intramolecular
Cycloaddition
Banjen Rukhopadhyay and Auup Bhattacherjya*
of Chemical Biology, Calcutta
4 Raja S. C. Mullick Road,
700032,
India
and a chiral oxepane, Abstract : The enantiomers of an oxepanoisoxazolidine potentially useful as precursors for naturally occurring oxepanes, were synthesised from D-glucose involving intramolecular 1,3-dipolar nitrone cycloaddition. The ‘chiron’ chiral
precursor
particularly
usually
of
a
profiles
of
desirable
application
of
a
chiral
a precursor enable
both
the
results
the
this
via
a large
synthesis
synthesis
of
of
an opticallyactive
in a particular active
enantiomers of
compound
for
the
biologically
to
be
would
be
but
due to its number of
as
drug,
Thus
preparation
similar
easy availability
the
a of
routes
from
physiological
more both
economic
the
from
a
D-glucose
single
chiral
utilised
a scheme
via similar
and
enantiomers
has been extensively
compounds, we envisioned
compounds
compound from a
However, in many cases,
a
evaluated. the
closely
chiral
enantiomeric
enantiomer.
compound such
need
approach separate
Since D-glucose
precursor.
to
approach’
which
as will
routes.
-X
X
R’O
3 4
--)_
M -
2 -R203
OR’
t
3
I_
Y
-OR’
RG
Y
or
4 -OR3 L
-Y
D-Glucose
4
2
The general sets
of
[X-C-4-C-3-Y] tions
scheme
enantiomeric
to
derivable
synthesis
depicted
chirons from the
3
I Schrmr
via.
in
1 was
borne
out
of
the
recognition
of
two
[X-C-Z-C-3-C-4-Y ] / [X-C-4-C-3-C-Z-Y ] and [X-C-Z-C-3-Y]/
D-glucose.
enantiomeric
Scheme
I
Hence compounds
3585
it
is
possible
1 and
2 or
by proper 3 and
4
chemical (Scheme
manipula1)
from
D-
3586
glucose.
Herein
D-glucose which
we demonstrate
to the enantiomeric
incorporate
importance
of
activity
of
interest
as
two (C-4/C-2
the
chiral
naturally a
the
and C-3)
oxepane
occurring
reproductive
amenable to modifications
application
of
oxepanoisoxazolidines
medicine.
necessary
7 and 12,
chiral
centres
derivatives
oxepanes
the strategy
stems
like
of
The substitution
for a total
and a chiral
D-glucose
from
soapatanol’
the
significant in
of zoapatanol
7,
of
oxepane 13
(Scheme 2).
The
biological
which has generated pattern
synthesis
by the conversion
immense
12 and 13 is
and its
analogues.
D-Glucose 7: cdlDt
fI,_b,e,!
104.3.
,
OAc
.‘O
c 6:
b
R=
II
f
,
12
: Cdlg- 103.7.
NHAc I
,+@:R=CHO
1
6n
lo:R=CH=N<
AcO-
h -I
‘0-
13 : a NaOMe,MeOH b NaI04, H20, 25’C c NaBH4, EtOH d Ac20, pyridine e AcOH-Hz0 (3:1), 66°C f BnNHOH,benzene, 3A-mol.sieve 4 4% H2S04, CH3CN, H20, 2Y’C h cyclohexene,Pd-C, EtOH. Reagents
Scheme 2 The key reaction cycloaddition
of
employed in this
nitrones
derived
allyl-1,2:5,6-diisopropylideneglucose via
the E-benzylnitrone
63 with known3 absolute
of
synthesis
involved
the intramolecular 1,3-dipolar 3,4 . Thus, 3-0from 0-allylcarbohydrate derivatives (5) easily obtained5 from D-glucose was converted
3-0-allylglucose to the optically active oxepane derivative stereochemistry. A sequence of reactions involving deacetylation,
3587
oxidativc finally 7
cleavage
with
isolaticn
as the acetate
from 6.
yield’
The retention
was apparent
constants
of the relevant
In s separate cleavage
was converted
effected
by heating
only
isolable
product8
to
its
to
the
methylene
of
reduced
with
fulfilling
bridge
of
enantiodivergent to the optically
the isoxazolidine
yield7
mass
without -in as the
isoxasolidine
for
synthesis
according is
spectra
establishment
the
final
deprotected,
and finally
times,
step
cleaved
acetylated.
but also
enantiomers.
was
bridge
as in 11 as well
the
of
the
The resulting +I RHR, optical
the confirmation
as the completion
of 7 and 12 from D-glucose.
Finally
12 was
oxepane 136 by the reductive
to the aforementioned
of
with sodium
equal and opposite
This constituted
Thus a formal enantiodivergent
grateful
The till
from 11) and 7 not only had superimposable
GC retention
Thanks are due to hr.
for
used
116 was obtained
group.
was deferred
pure tetrasubstituted
ring.
Acknowledgement : S.D.
methylene
bridge
the methylene
converted
Fellowship.
to a5 followed
The latter,
10 which underwent cycloaddition
11 was successively
the crtteria
expedient,
wss also achieved
9.
That 11 was a bridged
sodium borohydride
and identical
the stereochemistry
Banerjee
the
1Z6 (23.8% overall
IR, mass spectra
of
76 in 20% overall
5 was deprotected
aldehyde
The oxepanoisoxazolidine
from 8).
Thus, the isoxazolidine
rotations
the
E-benzylnitrone
(55% yield
due
diacetate
and
from the appearance of a one-proton doublet at 6 2.64 and a one1 at 6 2.34 in its H NMRspectrum as well as a tripl.et at 6 26.9 in the
stereochemistry metaperiodate,
to
in benzene.
proton multiplet 1.3 C RMR spectrum synthesis.
to the oxepanoisoxazolidine
2) the common precurscr
sodium metaperiodate
situ
discernible
sodium borohydride
of 6 and 7.
(Scbae
purification,
clearly
with
of
protons
route
with
gave rise
reduction
the stereochemistry at the chiral centres during the 1 from the closely similar H RHR chemical shifts and coupling
reactions
by
sodium metaperiodate,
synthesis
of a chiral
of
of an readily
cleavage oxepane
scheme.
to the CSIR, India for the award of a Senior Research P.P.
and to RSIC,
Ghosh Lucknow,
Destidar, India,
Dr. for
R.C.
Yadev
elemental
for
NHFl, Mr.
A.
analysis.
RRFRRRNCRS ANDNOTES 1. 2. 3. 4. 5. 6.
S. Hanessian, Oxford: 1983:
The
Total
Synthesis
of
Natural
Products
:
The
Chiron
Approach;
23-26. Kocienski, P:;‘iove, C.; Witby, R. Tetrahedron 1989, 2, 3839-3848. Bhattacharjya, A.; Chattopadhyay, P.; McPhail, A.T.; McPhail, D.R. J. Chem. Soe., Chem. Commun. 1990, 1508-1509; corrigendum, ibid, 1991, 136. Collins, P.M.; Ashwood, M.S.; Wright, S.Hx Kennedy, D.J. Tetrahedron Lett. 1990, 2, 2055-2058. Smith, III, A.B.; Rivero, R.A.; Hale, K.J.; Vaccaro, H.A. J..Am.-Chem. Sot. 1991, 113, 2092-2112. Sal.ient data for 7,-U, 12 and 13 : DD.
7 : m.p. 94’-95’C; (c,
0.27,
[a],
+104.3”
(c,
0.23,
CHC13); 12 : m.p. 94’-95OC;
CHC13); 7 or 12 : HRMS,~12 : 349.1512
(KBr) : 1731,
1238 and 1060 cm-1;
1H NHR (CDC13) :6 2.04
2.04-2.44
(m, lH),
3.96-4.32
(m, 3H), 4.04 (d, J=12 Hz, lH),
[a],
-103.7’
(C18Hz306N, m/p : 349.1526);
2.58 (d, J=32 Hz, l.H), 3.56-3.72 4.64 (br.d,
(8,
3H), 2.10
(8,
IR ?H),
(m, 3H), 3.82 (d, 5112 Hz, lH), J=8 Hz, IH), 4.90 (d, 516 Hz,
and 7.36
(br.s,
(t),
72.3
(s),
170.0
(d),
1.46
(s,
3H),
3H),
3.70
(d,
lH),
4.62
(br.d,
(d),
and
1.36.7
(6);
13
23.2 169.3
2.08
The
formation
cycloaddition found
to
be
(d),
1738 2.08 (br.d,
49.3
(d),
170.1
in
these
to diols any
could insoluble
(s)
5.86
(d,
(Received in UK 23 February 1993)
(d),
27.7
128.3 [al,
(d,
4.12
(d,
J=12
136.8 CHC13);
: 61.28
lH),
(8,
4.42
(d,
(br.s, 72.3
(t),
78.3
1.11.5
(s),
127.5
(d),
128.4
(d),
129.0
+21O
(c,
1.0,
CHC~~);
1H);
13C NMR (CDC13)
71.1
J=12,8
(d),
E/E
: 6 1.96
Hz,
71.7
5H);
(m, J=4 Hz,
7.32
; ‘H NMR (CDC13)
IH),
13C NMR
(FAB)
(d), (d)
: 346
(8,
3H),
2.04
3.9-4.5
(m,
5H),
:620.6
(t),
3H),
3.56-3.84
(d),
(dd,
(2q),
20.8
(q),
(d),
78.1
(d),
73.8
(6).
viz. without
common organic
(d),
1.0,
62.5
-9
1H) and
3.46
reactions
Hz,
63.5
(t),
(III, 2H),
and 170.4
1.28.8 (c,
(d),
62.0
[aI
(t),
(d),
5~12 Hz, IH),
cm
62.1
63.1
-100.8”
and 1653
J=8 Hz,
(t),
‘l-l NMR (CDC13)
2.64
J=4 Hz,
(d),
be ascertained in
lH),
(t),
pyranoisoxazolidine
ethylacetate.
127.4
(q),
126’-127’C;
lH),
26.9
were used
not
2C.7
: 333.1577);
(br.8,
104.1
(q),
(d),
Hz,
143°-1440C;
m.p.
:
(s),
of
I-H), (q),
84.4
(t),
169.5
reduction
Hz, 26.5
and 6.16
33.7
m/e --
4.08
3H),
The intermediates their
: m.p.
Hz, IH),
(8,
(m,2H)
(s),
78.8
11
J=l;,lO,S
: 3284,
IR (KBr)
(q),
(d),
(8);
(C18H230,N,
J=lO
~520.6
73.8
(ddd,
(q),
82.3
5.0-5.4
8.
J-12
(d),
(s,
(t),
2.34
6 25.9
6~),
NMR (CDC13)
and 170.4
79.5
(M+l);
7.
72.8
(8)
‘3C
: 333.1526
HRMS, -m/z
(CDC13);
5H);
daprotection, puriffcation arising
since
the
solvents
oxidation for
out
of
material such
as
next an
to
aldehydes
and
steps. alternative
obtained chloroform,
besides
mode
of
11 was
methanol
and