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The stereochemistry of mayumbine and structurally related oxindole alkaloids
Tetrahedron Letters in Great Britain..
No. 22,
~13.822-826,
1961. Pergamon Press
Ltd.
Printed
THE STEREOCHEMISTRY OF MAYUMBINE AND STRUCTURALLYRELATEDOXINDOLEALKALOIDS1 Ernest
Wenkert,*
Department
BBrje Wickberg
of Chemistry,
and Curtis
Iowa State
Leicht
University
Ames, Iowa (Received
5 October
A RECENT chemical noid
indole
1961;
and proton
alkaloids
in revised
magnetic
revealed
that
resonance
and akuammigine represent
forms
respectively)
of
150-H and 19a-methyl
functions.3
PMR investigation
the indole
related line,
to
oxindole
alkaloids
5 which reflects Previous
data’
mayumbine with
their
the
the gross
its four
alkaloid
base mayumbine (I)4 formosanine,
relative
and the lack
of
5
study
3-iso
of ajmalici-
derivative,
possible
tetra-
stereochemical
structure
We now wish to report
(II)
th,at of any of
spectral
ajrnalicine,
hydroalstonine (III-VI,
form 29 November 1961)
I possessing
an extension
of the
and the structurally
mitraphylline
and isomitraphyl-
stereochemistry. identity
of the PMR spectrum
the compounds III-VI
shows it
of
to be the C (19)
’ This research was supported by a grant (M-1301) from the National Institutes of Health, Public Health Service, U.S. Department of Health, Education and Welfare. 2 Present address: Department of Chemistry, Indiana University, Bloomington, Indiana. 3 E. Wenkert,, B. Wickberg and C.L. Leicht, J.Amer.Chem.Soc. g, in press 4 5
(1961).
M.M. Janoi+ R. Goutarel &, 850 (1~952).
and J. Massonneau,
C.R.Acad.Sci..Paris
J.C. Seaton, M.D. Nair, O.E. Edwards and L. Marion, 3, 1035 (1960) and references contained therein.
Fanad.J.Chem.
No.22
823
The stereochemistryof mayumbine
e
epimer of one of the four bases. The absence of a one-protondownfield 3 signal, characteristicof the equatorialC (3)-H of pseudo compounds, eliminates 19-iso-IV,while the low spin-spincouplingconstant (J H (19)H (20) = 2.6
cps) speaks against a
19,20-m
diaxial hydrogen arrangementand
hence, eliminatesboth D/E trans structures,19-iso-
and 19-iso-IV.
(VII) or 19-isoakuammigine Thus, mayumbinemust be 19-isotetrahydroalstonine (VIII). In contrastto the consistentchemicalshift (8 = 4.41 2 0.08) of 3 the C (19)-H signal in all ajmalicinoidalkaloidsinspected, mayumbine and formosanine(II) have their one-protonoctet centered fartherupfield (8 = 3.76). This A8 indicatesthat the C (19) hydrogen is orientedmore favourablyfor intramolecularshieldingby the ring E double bond in these alkaloidsthan in any of their stereoisomers, a conditionsatisfiedby the C (19)-H quasi-axialconformationin VIII. This argument and an independent one for formosanine(vide infra) support a 19-isoakuammigine(VIII)
The stereochemistry
824 structure
for
No.22
of mayumbine
mayumbine. H
Me -c”\
VII All
FMB data
be the oxindole octet
cps);
Equilibration
a5 its
to be of
configuration, As
stereochemistry
and C (19)-Me
doublet
and/or
the unstable
affecting
configuration
would be expected a consequence, depicted
at 8 = 1.29
a process
stability
has revealed
cps)l. the
this
pair
[K(form./isoform.)
=
of IX,
irrespective
to be isomerized
completely
formosanine
possesses
in X and isoformosanine
to
C (19)-H
(J = 7.0
C (7),5’6
comparable
(II)
at 6 = 1.34
and isoformosanine,
only C (3)
a compound of
X at equilibrium. migine
of
cps)
show formosanine
amyumbine [Formosaniner
C (19)~Me doublet
formosanine
alkaloids
while C (7)
(JHH = 2.9
centers
epimeric
(IX or X) of
moyumbine: of
asymmetric
to the C (19) evironment
analogue
at 6 = 3.76
(J = 6.1
of
relating
its
of to
the 19-isoakuamC (7)
epimeric
configuration.
_ COeMe
IX 6
E. Wenkert, J.H. Udelhofen c, 3763 (1959) .
X
and N.K.
Bhattacharyya,
J.Arner.Chem.Soc.
The stereochemistry
No.22 The ~MR spectra another
c
(3)
of mitraphylline
and/or
C (7)
substances
to be related
ajmalicine
(IV)
[C
(JHH
= 2.7
CPS),~
(19)-H
octet:
cpa),
III-
cpsj31.
A distinction
formosanines energy
(yide
content
configuration
of
be expected
rePresent
= 4],5
converted
depicted
ajmalicinoid
indole
at 7.32p.pmin corynantheidine
data.
phylline group
(XIV).7
C (3)
in the e 7
can
of
the
dissimilar the pseudo
substituent Hence,
isomeric
would
the ajmali-
configuration
respectively.
&3 XII olefinic
the spectra
This
too
to XI at equilibrium.
and isomitraphylline,
XI and XII
a compound of
C (7)
(J = 7.0
As in the case
are of not
quaternary
doublets 8 = 1.13
stereoformulas
in XI and its
hydrogen
alkaloids
(XIII)
8 = 4.44
8 = 1.19
XI the C (17)
(JhI, = 2.5
C (19)~Me
IV-
show these
or 3-iso-
isomitraphylline-
whereas,
w %ile
(III)
III-
cps),
~ps),~
axial
5
alkaloids,
CPS).~
equilibrium
a resultant
to be fully
mitraphylline
cps),
(II),
8 = 4.34
2.4
the mitraphyllines
[K(mit./isomit.)
stereochemistry
(Jhh=
the resulting
available
suora)
oxindole
to ajmalicine
(J = 6.0
between
XII with
of
(JHH = 1.8
(J = 6.4
8 = 1.16
be made on the basis
and isomitraphylline
mitrophylline-
6 = 4.38
8 = 1.11
(J = 6.3
pair
6 = 4.39
IV-
mitraphylline-
(II)
stereochemically
isomitraphylline-
cps),
tine
isomeric
8.25
Of maWmbine
as a singlet of
the ring
and at 7.23 upfield
alkaloids
appears
shift
in the FYdRspectra
at 8 = 7.54
E m
alkaloids
or 7.30p.pm.in indicates
that
_U,
it
all
shows up
corynantheine
the spectrum
has the stereochemistry
J.C. Seaton and L. Marion, Canad.J.Chem. references contained therein.
t 0.02,
of
and
of rhynco-
the methoxymethylene indicated 1102 (1957)
in XIII and
and
826
The stereochemistry
of mayumbine
MeO&
No.22
t
XIII 8 9 10
L.M. Jackman, Aoolications of Nuclear Maqnetic Resonance Spectroscoov in Orsanic Chemistrv pp.119-125. Pergamon Press, London (1959). The authors are most grateful to Dr. Raymond-Hamet oxindole alkaloids used in this investigation.
for a gift of the
The PMR spectra were obtained with ca. 25% deuterochloroform solutions on a Varian Model ~~60 spectrometer at 60 mc/sec with tetramethylsilane acting as internal standard. The position of major peaks was determined by the audiofrequency sideband technique, that of minor peaks by linear interpolation.
No. 22,
~13.822-826,
1961. Pergamon Press
Ltd.
Printed
THE STEREOCHEMISTRY OF MAYUMBINE AND STRUCTURALLYRELATEDOXINDOLEALKALOIDS1 Ernest
Wenkert,*
Department
BBrje Wickberg
of Chemistry,
and Curtis
Iowa State
Leicht
University
Ames, Iowa (Received
5 October
A RECENT chemical noid
indole
1961;
and proton
alkaloids
in revised
magnetic
revealed
that
resonance
and akuammigine represent
forms
respectively)
of
150-H and 19a-methyl
functions.3
PMR investigation
the indole
related line,
to
oxindole
alkaloids
5 which reflects Previous
data’
mayumbine with
their
the
the gross
its four
alkaloid
base mayumbine (I)4 formosanine,
relative
and the lack
of
5
study
3-iso
of ajmalici-
derivative,
possible
tetra-
stereochemical
structure
We now wish to report
(II)
th,at of any of
spectral
ajrnalicine,
hydroalstonine (III-VI,
form 29 November 1961)
I possessing
an extension
of the
and the structurally
mitraphylline
and isomitraphyl-
stereochemistry. identity
of the PMR spectrum
the compounds III-VI
shows it
of
to be the C (19)
’ This research was supported by a grant (M-1301) from the National Institutes of Health, Public Health Service, U.S. Department of Health, Education and Welfare. 2 Present address: Department of Chemistry, Indiana University, Bloomington, Indiana. 3 E. Wenkert,, B. Wickberg and C.L. Leicht, J.Amer.Chem.Soc. g, in press 4 5
(1961).
M.M. Janoi+ R. Goutarel &, 850 (1~952).
and J. Massonneau,
C.R.Acad.Sci..Paris
J.C. Seaton, M.D. Nair, O.E. Edwards and L. Marion, 3, 1035 (1960) and references contained therein.
Fanad.J.Chem.
No.22
823
The stereochemistryof mayumbine
e
epimer of one of the four bases. The absence of a one-protondownfield 3 signal, characteristicof the equatorialC (3)-H of pseudo compounds, eliminates 19-iso-IV,while the low spin-spincouplingconstant (J H (19)H (20) = 2.6
cps) speaks against a
19,20-m
diaxial hydrogen arrangementand
hence, eliminatesboth D/E trans structures,19-iso-
and 19-iso-IV.
(VII) or 19-isoakuammigine Thus, mayumbinemust be 19-isotetrahydroalstonine (VIII). In contrastto the consistentchemicalshift (8 = 4.41 2 0.08) of 3 the C (19)-H signal in all ajmalicinoidalkaloidsinspected, mayumbine and formosanine(II) have their one-protonoctet centered fartherupfield (8 = 3.76). This A8 indicatesthat the C (19) hydrogen is orientedmore favourablyfor intramolecularshieldingby the ring E double bond in these alkaloidsthan in any of their stereoisomers, a conditionsatisfiedby the C (19)-H quasi-axialconformationin VIII. This argument and an independent one for formosanine(vide infra) support a 19-isoakuammigine(VIII)
The stereochemistry
824 structure
for
No.22
of mayumbine
mayumbine. H
Me -c”\
VII All
FMB data
be the oxindole octet
cps);
Equilibration
a5 its
to be of
configuration, As
stereochemistry
and C (19)-Me
doublet
and/or
the unstable
affecting
configuration
would be expected a consequence, depicted
at 8 = 1.29
a process
stability
has revealed
cps)l. the
this
pair
[K(form./isoform.)
=
of IX,
irrespective
to be isomerized
completely
formosanine
possesses
in X and isoformosanine
to
C (19)-H
(J = 7.0
C (7),5’6
comparable
(II)
at 6 = 1.34
and isoformosanine,
only C (3)
a compound of
X at equilibrium. migine
of
cps)
show formosanine
amyumbine [Formosaniner
C (19)~Me doublet
formosanine
alkaloids
while C (7)
(JHH = 2.9
centers
epimeric
(IX or X) of
moyumbine: of
asymmetric
to the C (19) evironment
analogue
at 6 = 3.76
(J = 6.1
of
relating
its
of to
the 19-isoakuamC (7)
epimeric
configuration.
_ COeMe
IX 6
E. Wenkert, J.H. Udelhofen c, 3763 (1959) .
X
and N.K.
Bhattacharyya,
J.Arner.Chem.Soc.
The stereochemistry
No.22 The ~MR spectra another
c
(3)
of mitraphylline
and/or
C (7)
substances
to be related
ajmalicine
(IV)
[C
(JHH
= 2.7
CPS),~
(19)-H
octet:
cpa),
III-
cpsj31.
A distinction
formosanines energy
(yide
content
configuration
of
be expected
rePresent
= 4],5
converted
depicted
ajmalicinoid
indole
at 7.32p.pmin corynantheidine
data.
phylline group
(XIV).7
C (3)
in the e 7
can
of
the
dissimilar the pseudo
substituent Hence,
isomeric
would
the ajmali-
configuration
respectively.
&3 XII olefinic
the spectra
This
too
to XI at equilibrium.
and isomitraphylline,
XI and XII
a compound of
C (7)
(J = 7.0
As in the case
are of not
quaternary
doublets 8 = 1.13
stereoformulas
in XI and its
hydrogen
alkaloids
(XIII)
8 = 4.44
8 = 1.19
XI the C (17)
(JhI, = 2.5
C (19)~Me
IV-
show these
or 3-iso-
isomitraphylline-
whereas,
w %ile
(III)
III-
cps),
~ps),~
axial
5
alkaloids,
CPS).~
equilibrium
a resultant
to be fully
mitraphylline
cps),
(II),
8 = 4.34
2.4
the mitraphyllines
[K(mit./isomit.)
stereochemistry
(Jhh=
the resulting
available
suora)
oxindole
to ajmalicine
(J = 6.0
between
XII with
of
(JHH = 1.8
(J = 6.4
8 = 1.16
be made on the basis
and isomitraphylline
mitrophylline-
6 = 4.38
8 = 1.11
(J = 6.3
pair
6 = 4.39
IV-
mitraphylline-
(II)
stereochemically
isomitraphylline-
cps),
tine
isomeric
8.25
Of maWmbine
as a singlet of
the ring
and at 7.23 upfield
alkaloids
appears
shift
in the FYdRspectra
at 8 = 7.54
E m
alkaloids
or 7.30p.pm.in indicates
that
_U,
it
all
shows up
corynantheine
the spectrum
has the stereochemistry
J.C. Seaton and L. Marion, Canad.J.Chem. references contained therein.
t 0.02,
of
and
of rhynco-
the methoxymethylene indicated 1102 (1957)
in XIII and
and
826
The stereochemistry
of mayumbine
MeO&
No.22
t
XIII 8 9 10
L.M. Jackman, Aoolications of Nuclear Maqnetic Resonance Spectroscoov in Orsanic Chemistrv pp.119-125. Pergamon Press, London (1959). The authors are most grateful to Dr. Raymond-Hamet oxindole alkaloids used in this investigation.
for a gift of the
The PMR spectra were obtained with ca. 25% deuterochloroform solutions on a Varian Model ~~60 spectrometer at 60 mc/sec with tetramethylsilane acting as internal standard. The position of major peaks was determined by the audiofrequency sideband technique, that of minor peaks by linear interpolation.