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A new synthesis of (−)-anisomycin or (+)-anisomycin starting from D-tyrosine or L-tyrosine
Tetrahedron Letters,Vol.29,No.35,pp Printed in Great Britain
A NEW SYNTHESIS
OF (-)-ANISOMYCIN FROM D-TYROSINE
Samir JEGHAM
Institut
0040-4039/88 $3.00 + .OO Pergamon Press plc
4419-4422,1988
OR (+)-ANISOMYCIN
STARTING
OR L-TYROSINE
and Bhupesh
de Chimie des Substances 91198 Gif-sur-Yvette
C. DAS*
Naturelles,
Cedex,
C.N.R.S.
France.
Abstract: (R)-2-(p-methoxyphenyl)methyl-2,5-dihydrop.vrrole (-)-2 and its (S)-isomer whiral intermediates for (-)-anisomycin (-)-1 and (+)-anisomycin (+)-1, have been efficiently synthesized via an exclusively cig-olefination step starting from D-tyrosine and L-tyrosine, respectively. The diverse hav
stimulated 5 modes.
biological a great
chiral Je
These
activities1
deal of interest synthetic
(_+)-anisomycin (+)-1, elaborated 4b (2)-z.
efforts
of the antifungal in its chemical include
from the crucial
an
antibiotic synthesis
efficient
intermediate
(-)-anisomycin both
(-)-1
in the racemic4
stereoselective
synthesis
2,3 and of
(+)-2-(p-methoxyphenyl)methyl-
2,5-dihydropyrrole
(+I-2
A recent
communication6
reported
an asymmetric
synthesis
of the (S)-isomer
transformation the racemic
(+)-2 and its
into unnatural (+)-anisomycin (+)-L following the previously outlined route 4b We wish to report here a new synthesis of (R)-2-(p-methoxyphenyl)meseries.
thyl-2,5-dihydropyrrole
(-)-2
and
its
(S)-isomer 4419
(+)-2
from
D-tyrosine
and
in
L-tyrosine,
4420
anisomycin
of (-)-anisomycin
(-)-1 and (+)-
(t)-1.
It appeared reaction
a formal total synthesis
which also constitutes
respectively,
sequence
to us that outlined
an expedient
in the following
approach
to
(-)-1
from
II-tyrosine would
involve
a
scheme.
&R=CH~~H b
e
L zR=CHO
I P
Ph
f
Reactions ii.
conditions:
NaBH4-LiCl
(Boc)80,
5 equiv.),
(1:l;
C)
CH2C12,
-78"C, 98%. 94%.
e)
Na2C03,
EtOH-THF
(CF3CH20),P(0)CH2C0,Me,
-78°C.
overnight,
a)i.
(4:3),
18-crown-6,
i. MsCl, CH2C12,
f) CF3C02H,
H20-dioxane
CH2C12,
(l:l), RT, overnight,
RT, 95%.
(Me3Si)PNK,
b) (COC1)2,
DMSO,
95%; CH2C12,
THF, -78"C, 80% from 4.
Et3N, -lO"C, 20 min., 93%;
Et3N,
d) DIBAH,
ii. NaH, CH2C12,
RT,
RT, 4h, 100%.
. O-Methyl
D-tyrosine
methyl
ester
sine,' was treated with di-tert-butyl tion of the ester function
(z), readily dicarbonate
with sodium borohydride
obtained thereby
as its hydrochloride
protecting
in the presence
from D-tyro-
the amino group.
of lithium chloride8
Reducfurni-
4421
shed
the alcohol
Qxtension phonate
(4_) which
was transformed
with the anion derived at -78°C
binimize
afforded
any possible
'ly, without
exclusively lo (Z) -a,B-unsaturated of the chiral
for the olefination
(5) have the desired
hydride
lowed by intramolecular Treatment
62%.II
The
(S)-2,5-dihydropyrrole
from L-tyrosine. those previously
Both samples reported4'
Since offers noted
derivatives
(+)-1 had previously
an alternative that
D-tyrosine
route
a completely
Acknowledgement:
the alcohol
Chain
was
also
Drs.
cycliza-
(1) which after mesylation
prepared
(8).
(Boc) group to give (R)-
yield
of (-)-2 from
in the
spectral
The optical
derivative
fol-
same
manner
data which
purity12
(2) was starting
fully matched
of (-)-1 and (+)-2
of tF;ir (S)-(-)-a-methoxy(trifluorome-
e.g., 2).
been transformed6
thank
that the olefina-
of the ester group of (5)
2,5-dihydropyrrole
compound.
to this antibiotic approach
In order to avoid or
(5) was used immediate-
required
The overall
(400 MHz) analysis
been reported.
We
(t)-2
(Mosher amides,
different
has recently
Reduction
(-)-2 and (+)-2 had identical
was shown to he >95% hy 'H n.m.r. thyl)- phenylacetyl
(8).
(-)-1.
for the racemic
(6).
the tert-butyloxycarbonyl
2-(p-methoxyphenyl)methyl-2,5-dihydropyrrole ea.
Our strategy
led to the desired
acid removed
ester
the aldehyde
of the double dond for the subsequent
derivative
(DIBAH) provided
cyclization
with trifluoroacetic
centre,
step.
(Z) geometry
tion to the chiral 2,5-dihydropyrrole with diisohutylaluminium
9
(2) by Swern oxidation.
from his(2,2,2-trifluoroethyl)(methoxycarhonylmethyl)-phos-
racemization
purification,
tion product
into the aldehyde
into (+)-anisomycin
(+)-1, the present work
in its both enantiomeric
to the synthesis
of
forms.
(-)-anisomycin
It is to he starting
from
14
J.-L.
FOURREY
and
C. MARAZANO
of
this
laboratory
for
helpful discussions.
References
and Notes
a) J.E. Lynch, A.R. English, (1954);
H. Banck and H. Deligianis,
b) W.W. Frye, J.G. Mule and C. Swartzwelder,
Armstrong
and 0. Santa Maria, ibid.,
3226 (1967);
d) A. Jiimenez
Verlag,
Berlin,
Rahway,
New Jersey,
1979,
and 0. Vazquez,
pp. 1-19;
Antibiot.Ann.,
c) A.P.
e) "The Merck
820 (1955);
Grollman,
in "Antibiotics",
4, 844
J.Biol.Chem.,
T.
242,
F.E. Hahn, Ed., Springer
Index" 10th ed., M. Windholz,
Ed., Merck,
USA, 1983, p. 19.
B.A. Sohin and F.W. Tanner, Futatsuya,
824 (1955);
Antihiot.Chemotherapy,
J.Am.Chem.Soc.,
K. Ito, H. Yamamoto
76, 4053 (1954);
and K. Munakata,
b) S. Ishida, Y. Yamada,
Proc.Int.Congress
F.
IAMS lst, 3, 64 (1974).
a)
J.J. Beerehoom, K. Butler, F.C. Pennington and I.A. Solomons, J.Org.Chem., 30, 2334 (1965) ; b) K. Butler, d, ibid 2, 2136 (1968); c) J.P. Schaefer and P.J. Wheatley, Chem.
Commun., (1968).
578 (1967);
J.Org.Chem.,
2,
166 (1968);
d) C.M. Wong, Can.J.Chem.,
46, 1101
4422
4. a) S. Oida and E. Ohki, Chem.Pharm.Bull., b) D.P. Schumacher
5. a) C.M. Wong, J. Buccini Buccini,
R.S. Bhatt,
Helv.Chim.Acta,
6. A.I.
f) H. Iida, N. Yamazaki
Meyers
M.C. Rebstock, Vandenbelt, 8. Y. Hamada,
E.L. Wittle,
J.Med.Chem., M. Shibata,
9. A.J. Mancuso,
F.J. Tinney,
u,
F. Sugiura,
-Ct12Ar)), 3.70 (3H, s, Ar-Ok),
(C-5), 50.95
119.43 (C-2), (-LOOCMe,), compound
(Ar-0CH3),
51.42
129.38 (C-l’),
obtained
respectively.
b) W.
Siedel,
c) G.W. Moersch,
1252 (1987).
isolated
from column
chromatography
structures.
(-COOCH,),
(2 x C-3’),
4.76 (lH, br.s., NH), 5.21 (IH, m,
79.66 (-COOcMe,),
150.51
(C-3),
CcrlD -65" &
2.46,
CalD -89.3"
the literature6
J.Org.Chem.,
Letters,
(Received in France 24 May 1988)
2,
697 (1987).
(2 x C-2'),
158.71
The corresponding
CHC13).
(c 1.26, THF) and + 87.7"
(5
value + 9.26" for (+)-2 is diffe-
rent from that noted by us. 13. J.A. Dale, D.L. Dull and H.S. Mosher,
39.66
114.15
155.43 (C-4’),
1.8, CHC13).
showed CcrlD + 68.5” c
Curiously,
and
For exam-
1.38 (9H, s, Boc), 2.88 (2H, m,
(50.3 MHz, CDC13 6 28.47 (3 x cH3 of Boc),
as oil, showed
14. T. Shono and N. Kise, Chemistry
52,
6.20 (lH, dd, J 11.5, 8 Hz, H-3), 6.84 and 7.17
m.p. l12-114°C;
from L-tyrosine
J.Org.Chem.,
with the assigned
(400 MHz, CDC13)
(C-4), 55.39
130.38
12. (-)-2 and (+)-2 each obtained 2.40, THF),
1 (1955);
43, 2480 (1978).
3.73 (3H, s, -C02t&),
13C n.m.r.
166.25 (C-l);
z,
311 (1987).
data in agreement
'H n.m.r.
325;
d, J 8.5 Hz);
L, 1463
1069 (1986).
M.P. Hutt, T.F. Mich and J.M.
S. Kato and T. Shioiri,
H-4), 5.53 (lH, d, J = 11.5 Hz, H-2); (each 2H,
z,
59, 2951f (1963);
E.D. Nicolaides,
(see scheme) are for materials
gave spectroscopic
ple, 6 had M+' at -m/z
1363 (1978);
935 (1979).
10. H. Kogen and T. Nishi, J.Chem.Soc.,Chem.Commun., all compounds
so,
J.Chem.Soc.Perkin
J.Org.Chem.,
S.L. Huang and 0. Swern, J.Org.Chem.,
11. All reported yields
A.C. Richardson,
Pure Appl.Chem.,
J.Am.Chem.Soc.,
96, 1436 (1963);
2,
b) C.M. Wong, J. c) I. Felner and
25, 113 (1987).
Joseph and J.H. Williams,
and R. Geiger, @,
Verheyden,
and H. Paulsen,
and C. Kibayashi,
and B. Dupre, Heterocycles,
7. a) B.R. Baker, J.P. K. Sturm
R.H. Wightman
1405 (1969);
2421 (1969);
53, 754 (1970); d) J.P.H.
K.A. McLean,
_, 17
46, 3091 (1968);
ibid., _, 47
B.D. Grant, W.L. Fitch and J.G. Moffatt,
e) J.G. Buchanan,
3,
104, 6076 (1982).
and J. Te Raa, Can.J.Chem.,
I. Chang, J. Te Raa, and R. Schwenk,
K. Schenker,
(1985);
16, 2086 (1968);
and S.S. Hall, J.Am.Chem.Soc.,
2543 (1969).
A NEW SYNTHESIS
OF (-)-ANISOMYCIN FROM D-TYROSINE
Samir JEGHAM
Institut
0040-4039/88 $3.00 + .OO Pergamon Press plc
4419-4422,1988
OR (+)-ANISOMYCIN
STARTING
OR L-TYROSINE
and Bhupesh
de Chimie des Substances 91198 Gif-sur-Yvette
C. DAS*
Naturelles,
Cedex,
C.N.R.S.
France.
Abstract: (R)-2-(p-methoxyphenyl)methyl-2,5-dihydrop.vrrole (-)-2 and its (S)-isomer whiral intermediates for (-)-anisomycin (-)-1 and (+)-anisomycin (+)-1, have been efficiently synthesized via an exclusively cig-olefination step starting from D-tyrosine and L-tyrosine, respectively. The diverse hav
stimulated 5 modes.
biological a great
chiral Je
These
activities1
deal of interest synthetic
(_+)-anisomycin (+)-1, elaborated 4b (2)-z.
efforts
of the antifungal in its chemical include
from the crucial
an
antibiotic synthesis
efficient
intermediate
(-)-anisomycin both
(-)-1
in the racemic4
stereoselective
synthesis
2,3 and of
(+)-2-(p-methoxyphenyl)methyl-
2,5-dihydropyrrole
(+I-2
A recent
communication6
reported
an asymmetric
synthesis
of the (S)-isomer
transformation the racemic
(+)-2 and its
into unnatural (+)-anisomycin (+)-L following the previously outlined route 4b We wish to report here a new synthesis of (R)-2-(p-methoxyphenyl)meseries.
thyl-2,5-dihydropyrrole
(-)-2
and
its
(S)-isomer 4419
(+)-2
from
D-tyrosine
and
in
L-tyrosine,
4420
anisomycin
of (-)-anisomycin
(-)-1 and (+)-
(t)-1.
It appeared reaction
a formal total synthesis
which also constitutes
respectively,
sequence
to us that outlined
an expedient
in the following
approach
to
(-)-1
from
II-tyrosine would
involve
a
scheme.
&R=CH~~H b
e
L zR=CHO
I P
Ph
f
Reactions ii.
conditions:
NaBH4-LiCl
(Boc)80,
5 equiv.),
(1:l;
C)
CH2C12,
-78"C, 98%. 94%.
e)
Na2C03,
EtOH-THF
(CF3CH20),P(0)CH2C0,Me,
-78°C.
overnight,
a)i.
(4:3),
18-crown-6,
i. MsCl, CH2C12,
f) CF3C02H,
H20-dioxane
CH2C12,
(l:l), RT, overnight,
RT, 95%.
(Me3Si)PNK,
b) (COC1)2,
DMSO,
95%; CH2C12,
THF, -78"C, 80% from 4.
Et3N, -lO"C, 20 min., 93%;
Et3N,
d) DIBAH,
ii. NaH, CH2C12,
RT,
RT, 4h, 100%.
. O-Methyl
D-tyrosine
methyl
ester
sine,' was treated with di-tert-butyl tion of the ester function
(z), readily dicarbonate
with sodium borohydride
obtained thereby
as its hydrochloride
protecting
in the presence
from D-tyro-
the amino group.
of lithium chloride8
Reducfurni-
4421
shed
the alcohol
Qxtension phonate
(4_) which
was transformed
with the anion derived at -78°C
binimize
afforded
any possible
'ly, without
exclusively lo (Z) -a,B-unsaturated of the chiral
for the olefination
(5) have the desired
hydride
lowed by intramolecular Treatment
62%.II
The
(S)-2,5-dihydropyrrole
from L-tyrosine. those previously
Both samples reported4'
Since offers noted
derivatives
(+)-1 had previously
an alternative that
D-tyrosine
route
a completely
Acknowledgement:
the alcohol
Chain
was
also
Drs.
cycliza-
(1) which after mesylation
prepared
(8).
(Boc) group to give (R)-
yield
of (-)-2 from
in the
spectral
The optical
derivative
fol-
same
manner
data which
purity12
(2) was starting
fully matched
of (-)-1 and (+)-2
of tF;ir (S)-(-)-a-methoxy(trifluorome-
e.g., 2).
been transformed6
thank
that the olefina-
of the ester group of (5)
2,5-dihydropyrrole
compound.
to this antibiotic approach
In order to avoid or
(5) was used immediate-
required
The overall
(400 MHz) analysis
been reported.
We
(t)-2
(Mosher amides,
different
has recently
Reduction
(-)-2 and (+)-2 had identical
was shown to he >95% hy 'H n.m.r. thyl)- phenylacetyl
(8).
(-)-1.
for the racemic
(6).
the tert-butyloxycarbonyl
2-(p-methoxyphenyl)methyl-2,5-dihydropyrrole ea.
Our strategy
led to the desired
acid removed
ester
the aldehyde
of the double dond for the subsequent
derivative
(DIBAH) provided
cyclization
with trifluoroacetic
centre,
step.
(Z) geometry
tion to the chiral 2,5-dihydropyrrole with diisohutylaluminium
9
(2) by Swern oxidation.
from his(2,2,2-trifluoroethyl)(methoxycarhonylmethyl)-phos-
racemization
purification,
tion product
into the aldehyde
into (+)-anisomycin
(+)-1, the present work
in its both enantiomeric
to the synthesis
of
forms.
(-)-anisomycin
It is to he starting
from
14
J.-L.
FOURREY
and
C. MARAZANO
of
this
laboratory
for
helpful discussions.
References
and Notes
a) J.E. Lynch, A.R. English, (1954);
H. Banck and H. Deligianis,
b) W.W. Frye, J.G. Mule and C. Swartzwelder,
Armstrong
and 0. Santa Maria, ibid.,
3226 (1967);
d) A. Jiimenez
Verlag,
Berlin,
Rahway,
New Jersey,
1979,
and 0. Vazquez,
pp. 1-19;
Antibiot.Ann.,
c) A.P.
e) "The Merck
820 (1955);
Grollman,
in "Antibiotics",
4, 844
J.Biol.Chem.,
T.
242,
F.E. Hahn, Ed., Springer
Index" 10th ed., M. Windholz,
Ed., Merck,
USA, 1983, p. 19.
B.A. Sohin and F.W. Tanner, Futatsuya,
824 (1955);
Antihiot.Chemotherapy,
J.Am.Chem.Soc.,
K. Ito, H. Yamamoto
76, 4053 (1954);
and K. Munakata,
b) S. Ishida, Y. Yamada,
Proc.Int.Congress
F.
IAMS lst, 3, 64 (1974).
a)
J.J. Beerehoom, K. Butler, F.C. Pennington and I.A. Solomons, J.Org.Chem., 30, 2334 (1965) ; b) K. Butler, d, ibid 2, 2136 (1968); c) J.P. Schaefer and P.J. Wheatley, Chem.
Commun., (1968).
578 (1967);
J.Org.Chem.,
2,
166 (1968);
d) C.M. Wong, Can.J.Chem.,
46, 1101
4422
4. a) S. Oida and E. Ohki, Chem.Pharm.Bull., b) D.P. Schumacher
5. a) C.M. Wong, J. Buccini Buccini,
R.S. Bhatt,
Helv.Chim.Acta,
6. A.I.
f) H. Iida, N. Yamazaki
Meyers
M.C. Rebstock, Vandenbelt, 8. Y. Hamada,
E.L. Wittle,
J.Med.Chem., M. Shibata,
9. A.J. Mancuso,
F.J. Tinney,
u,
F. Sugiura,
-Ct12Ar)), 3.70 (3H, s, Ar-Ok),
(C-5), 50.95
119.43 (C-2), (-LOOCMe,), compound
(Ar-0CH3),
51.42
129.38 (C-l’),
obtained
respectively.
b) W.
Siedel,
c) G.W. Moersch,
1252 (1987).
isolated
from column
chromatography
structures.
(-COOCH,),
(2 x C-3’),
4.76 (lH, br.s., NH), 5.21 (IH, m,
79.66 (-COOcMe,),
150.51
(C-3),
CcrlD -65" &
2.46,
CalD -89.3"
the literature6
J.Org.Chem.,
Letters,
(Received in France 24 May 1988)
2,
697 (1987).
(2 x C-2'),
158.71
The corresponding
CHC13).
(c 1.26, THF) and + 87.7"
(5
value + 9.26" for (+)-2 is diffe-
rent from that noted by us. 13. J.A. Dale, D.L. Dull and H.S. Mosher,
39.66
114.15
155.43 (C-4’),
1.8, CHC13).
showed CcrlD + 68.5” c
Curiously,
and
For exam-
1.38 (9H, s, Boc), 2.88 (2H, m,
(50.3 MHz, CDC13 6 28.47 (3 x cH3 of Boc),
as oil, showed
14. T. Shono and N. Kise, Chemistry
52,
6.20 (lH, dd, J 11.5, 8 Hz, H-3), 6.84 and 7.17
m.p. l12-114°C;
from L-tyrosine
J.Org.Chem.,
with the assigned
(400 MHz, CDC13)
(C-4), 55.39
130.38
12. (-)-2 and (+)-2 each obtained 2.40, THF),
1 (1955);
43, 2480 (1978).
3.73 (3H, s, -C02t&),
13C n.m.r.
166.25 (C-l);
z,
311 (1987).
data in agreement
'H n.m.r.
325;
d, J 8.5 Hz);
L, 1463
1069 (1986).
M.P. Hutt, T.F. Mich and J.M.
S. Kato and T. Shioiri,
H-4), 5.53 (lH, d, J = 11.5 Hz, H-2); (each 2H,
z,
59, 2951f (1963);
E.D. Nicolaides,
(see scheme) are for materials
gave spectroscopic
ple, 6 had M+' at -m/z
1363 (1978);
935 (1979).
10. H. Kogen and T. Nishi, J.Chem.Soc.,Chem.Commun., all compounds
so,
J.Chem.Soc.Perkin
J.Org.Chem.,
S.L. Huang and 0. Swern, J.Org.Chem.,
11. All reported yields
A.C. Richardson,
Pure Appl.Chem.,
J.Am.Chem.Soc.,
96, 1436 (1963);
2,
b) C.M. Wong, J. c) I. Felner and
25, 113 (1987).
Joseph and J.H. Williams,
and R. Geiger, @,
Verheyden,
and H. Paulsen,
and C. Kibayashi,
and B. Dupre, Heterocycles,
7. a) B.R. Baker, J.P. K. Sturm
R.H. Wightman
1405 (1969);
2421 (1969);
53, 754 (1970); d) J.P.H.
K.A. McLean,
_, 17
46, 3091 (1968);
ibid., _, 47
B.D. Grant, W.L. Fitch and J.G. Moffatt,
e) J.G. Buchanan,
3,
104, 6076 (1982).
and J. Te Raa, Can.J.Chem.,
I. Chang, J. Te Raa, and R. Schwenk,
K. Schenker,
(1985);
16, 2086 (1968);
and S.S. Hall, J.Am.Chem.Soc.,
2543 (1969).