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Stereospecific synthesis of (±)-fluorobotryodiplodin
oo40-4039/88 $3.00 + .OO Pergamon Press plc
Tetrahedron Letters,Vol.29,No.l9,pp 2325-2326,1988 Printed in Great Britain
-1FIC
!ZNlHESISOF (k >-SODIPIN
Yuko Nakahara, Makoto Shimizu, and Hirosuke Yashioka The Institute
of Physical and Chemical Research (RIKEN) Wako, Saitama, 351-01 Japan
Summary:Stereospecific
synthesis of (& )-fluorobotryodiplodin
which stereospecific
fluoro-olefination
employed in the crucial Botryodiplodin la, antibiotic
in
rearrangement were
steps.
isolated
from BotrUodipZodia theobrorme fat.
several groups .2 We now report the stereospecific a selective
is a mycotoxin with
and its syntheses were variously accomplished by
and antileukemic properties,’
its epimer 2b utilizing
and its epimer is described,
and [ 3,3]-sigmatropic
synthesis of a fluoro analogue lb of la and
method for the synthesis of allylated
fluoromethyl
ketones,3 whose schema are depicted as follows.
1) e-TsOH,
0
k
2)
MsCl,
6:
R1=H,
n-Bu4NF
ElnTHF,
Et3N
CH2C12
25:R'=BnOCH2.
F
O
MeOH
*
R2=H L
R2=B"OCH2
1)
F
c-16 s
4-Methylmorpholine N-oxide, cat. Os04 7~~1~20
2) cat.Pd/C,
Hp.
NaI04
-
!J
__,
HZO
AcOEt @:
,
Heat
Bn
MS
Ms+
Xylene
\
\
‘..OAc
R=Bn
!._l:R=H
6
Bn
-
E
-
!2?
‘2 Aldol reaction of the crotyloxyacetate
3 with benzyloxyacetaldehyde gave the adduct 4 in
65% yield as a mixture of syn and anti-isomers.
L&l reduction followed by acetonide formation
afforded a mixture of 5 and 6 in 76% yield in a 36 : 61 isomer ratio.’ isomers was readily attained by flash SiQ
AC
Separation of the
column chromatography, and 5 and 6 were respectively
forwarded to the synthesis of lb and 2b. The bis-mesylate 7 was prepared in 76% yield by hydrolysis of the acetonide 5 followed by mesylation. 2325
2326
The fluoro-olefinatios ether 8 in 70% yield. stereoselectivity hydroxylation
of 7 was stereospecifically
The thermal
giving
[ 3,3]-sigmatropic
9 in Q2% as a chromatographically
of 9 gave the diol
10 in 90% yield. cleavage-cyclization
yield
Acetylation
as a mixture of anomers.’
Fluoroepibotryodiplodin
and the structures
respectively.
lb and 2b could
be similarly
with a lower stereoselectivity in the present
of potential
biomedical
aspects
[ 3,3)-sigmatropic and the
synthesis
bioactive
will
offer
molecules
of the compounds lb,
and Culture,
2b and related
12 as a single
NMRspecta
15 and 18, respectively,
tool
rearrangment exercised for
with
but as the
the stereospecific
a fluoromethyl
ketone
compounds will
The
group.
be published
elesewhere.
by a grant in aid from the Ministry
of Education,
Japan, and a fund from Sankyo Co. Ltd.. and Notes Ind. J. Exp. Biol.,
Chem. Commun., 1414 (1968);
and J. R. Althaus,
Carcinogenesis,
J. Chem. Sot. Lett.,
4103 (lQ73);
T. Mukaiyama, M. Wada, and J. Hanna, Chem. Lett.,
and R. S. Mayers, J. Org. Chem., 40, 3309 (1975); K. Kojima, Tetrahedron 1840 (1985);
Lett.,
4,
152 (1966); Y. Moule and
5, 1375 (1984)
and K. Abe, Tetmhedron
P. M. McCurry, Jr.,
50,
isomer.
from 8 via the same
G. P. Arsenault
5824 (1973);
of
lb in 50%
R. Sen Gupta, R. R. Chandran, and P. V. Divekar, N. Darracq,
2.
a useful
containing
References 1.
debenzylation
rearrangement.
[ 3,3]-sigmatropic
Acknowledgement: This work was supported Science
the acetate
stereospecifically
prepared from the bis-mesylates
in the
As shown, the fluoro-olefination synthesis
1, 2-Bis
after
of lb and 2b were supported on comparison of their
those of la and 2a,z
key reactions
11 obtained
in a high
to give fluorobotryodiplodin
of lb afforded
2b was also synthesized
to give the enol crotyl also proceeded
pure stereoisomer.
The trio1
10 (78%) underwent an oxidative
sequences
conducted rearrangment
(1919);
23E
N. Rehnberg, T. Frejd,
K. Sakai,
J. Am. Chem. Sot., 1181 (1874);
96,
S. R. Wilson
S. Amemiya, K. Inoue,
and
M. J. Kurthand, and C. M. Yu, J. Org. Chem.,
and G. Magnusson, Tetrahedron
28, 3589
Lett.,
(1987) 3.
M. Shimizu, Y. Nakahara, S. Kanemoto, and H. Yoshioka,
Tetrahedron
4.
The structures
of J@p and $1~
of 5 and 8 were determined on the basis
respectively.(‘H
NMRspectra
Lett.,
were taken on a JEGL GK400 spectrometer.)
28,
1877 (1987)
values, 5: J@p = 2.14 Hz.
8: Jprp = 9.18 Hz. 5.
M. Shimizu, Y. Nakahara, and H. Yoshioka, Shimizu,
8.
E. Tanaka, and H. Yoshioka,
Fluorobotryodiprodin
lb(anomeric
1.08 (d, 3H x 12/31,
J = 7.3
(m, lH), 3.5 -4.5 J = 47.5&z), (Received
5.20 in
(m, 3H), 4.83 (s,
Japan
mixture):
Hz), 2.2
J. C%em. Sot.
ibid.,
NMR(CDCl3) 6 0.89
(br s,
lH, disappeared
(dd, 2H x 19/31,
J = 47.7,
1H) ; F NMR-231 and -228 ppm. 15 December
1987)
C&em. Commun., 867 (lQ88);
M.
138 (1987). (d, 3H x 19/31, on 90
J = 7.3
Hz),
exchange ), 2.5 -3.0
0.7 Hz), 4.89
(d, Z-l x 12/31,
Tetrahedron Letters,Vol.29,No.l9,pp 2325-2326,1988 Printed in Great Britain
-1FIC
!ZNlHESISOF (k >-SODIPIN
Yuko Nakahara, Makoto Shimizu, and Hirosuke Yashioka The Institute
of Physical and Chemical Research (RIKEN) Wako, Saitama, 351-01 Japan
Summary:Stereospecific
synthesis of (& )-fluorobotryodiplodin
which stereospecific
fluoro-olefination
employed in the crucial Botryodiplodin la, antibiotic
in
rearrangement were
steps.
isolated
from BotrUodipZodia theobrorme fat.
several groups .2 We now report the stereospecific a selective
is a mycotoxin with
and its syntheses were variously accomplished by
and antileukemic properties,’
its epimer 2b utilizing
and its epimer is described,
and [ 3,3]-sigmatropic
synthesis of a fluoro analogue lb of la and
method for the synthesis of allylated
fluoromethyl
ketones,3 whose schema are depicted as follows.
1) e-TsOH,
0
k
2)
MsCl,
6:
R1=H,
n-Bu4NF
ElnTHF,
Et3N
CH2C12
25:R'=BnOCH2.
F
O
MeOH
*
R2=H L
R2=B"OCH2
1)
F
c-16 s
4-Methylmorpholine N-oxide, cat. Os04 7~~1~20
2) cat.Pd/C,
Hp.
NaI04
-
!J
__,
HZO
AcOEt @:
,
Heat
Bn
MS
Ms+
Xylene
\
\
‘..OAc
R=Bn
!._l:R=H
6
Bn
-
E
-
!2?
‘2 Aldol reaction of the crotyloxyacetate
3 with benzyloxyacetaldehyde gave the adduct 4 in
65% yield as a mixture of syn and anti-isomers.
L&l reduction followed by acetonide formation
afforded a mixture of 5 and 6 in 76% yield in a 36 : 61 isomer ratio.’ isomers was readily attained by flash SiQ
AC
Separation of the
column chromatography, and 5 and 6 were respectively
forwarded to the synthesis of lb and 2b. The bis-mesylate 7 was prepared in 76% yield by hydrolysis of the acetonide 5 followed by mesylation. 2325
2326
The fluoro-olefinatios ether 8 in 70% yield. stereoselectivity hydroxylation
of 7 was stereospecifically
The thermal
giving
[ 3,3]-sigmatropic
9 in Q2% as a chromatographically
of 9 gave the diol
10 in 90% yield. cleavage-cyclization
yield
Acetylation
as a mixture of anomers.’
Fluoroepibotryodiplodin
and the structures
respectively.
lb and 2b could
be similarly
with a lower stereoselectivity in the present
of potential
biomedical
aspects
[ 3,3)-sigmatropic and the
synthesis
bioactive
will
offer
molecules
of the compounds lb,
and Culture,
2b and related
12 as a single
NMRspecta
15 and 18, respectively,
tool
rearrangment exercised for
with
but as the
the stereospecific
a fluoromethyl
ketone
compounds will
The
group.
be published
elesewhere.
by a grant in aid from the Ministry
of Education,
Japan, and a fund from Sankyo Co. Ltd.. and Notes Ind. J. Exp. Biol.,
Chem. Commun., 1414 (1968);
and J. R. Althaus,
Carcinogenesis,
J. Chem. Sot. Lett.,
4103 (lQ73);
T. Mukaiyama, M. Wada, and J. Hanna, Chem. Lett.,
and R. S. Mayers, J. Org. Chem., 40, 3309 (1975); K. Kojima, Tetrahedron 1840 (1985);
Lett.,
4,
152 (1966); Y. Moule and
5, 1375 (1984)
and K. Abe, Tetmhedron
P. M. McCurry, Jr.,
50,
isomer.
from 8 via the same
G. P. Arsenault
5824 (1973);
of
lb in 50%
R. Sen Gupta, R. R. Chandran, and P. V. Divekar, N. Darracq,
2.
a useful
containing
References 1.
debenzylation
rearrangement.
[ 3,3]-sigmatropic
Acknowledgement: This work was supported Science
the acetate
stereospecifically
prepared from the bis-mesylates
in the
As shown, the fluoro-olefination synthesis
1, 2-Bis
after
of lb and 2b were supported on comparison of their
those of la and 2a,z
key reactions
11 obtained
in a high
to give fluorobotryodiplodin
of lb afforded
2b was also synthesized
to give the enol crotyl also proceeded
pure stereoisomer.
The trio1
10 (78%) underwent an oxidative
sequences
conducted rearrangment
(1919);
23E
N. Rehnberg, T. Frejd,
K. Sakai,
J. Am. Chem. Sot., 1181 (1874);
96,
S. R. Wilson
S. Amemiya, K. Inoue,
and
M. J. Kurthand, and C. M. Yu, J. Org. Chem.,
and G. Magnusson, Tetrahedron
28, 3589
Lett.,
(1987) 3.
M. Shimizu, Y. Nakahara, S. Kanemoto, and H. Yoshioka,
Tetrahedron
4.
The structures
of J@p and $1~
of 5 and 8 were determined on the basis
respectively.(‘H
NMRspectra
Lett.,
were taken on a JEGL GK400 spectrometer.)
28,
1877 (1987)
values, 5: J@p = 2.14 Hz.
8: Jprp = 9.18 Hz. 5.
M. Shimizu, Y. Nakahara, and H. Yoshioka, Shimizu,
8.
E. Tanaka, and H. Yoshioka,
Fluorobotryodiprodin
lb(anomeric
1.08 (d, 3H x 12/31,
J = 7.3
(m, lH), 3.5 -4.5 J = 47.5&z), (Received
5.20 in
(m, 3H), 4.83 (s,
Japan
mixture):
Hz), 2.2
J. C%em. Sot.
ibid.,
NMR(CDCl3) 6 0.89
(br s,
lH, disappeared
(dd, 2H x 19/31,
J = 47.7,
1H) ; F NMR-231 and -228 ppm. 15 December
1987)
C&em. Commun., 867 (lQ88);
M.
138 (1987). (d, 3H x 19/31, on 90
J = 7.3
Hz),
exchange ), 2.5 -3.0
0.7 Hz), 4.89
(d, Z-l x 12/31,