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A convenient synthesis of lunularic acid
TetrahedronlettersNo. 16, pp 1615 - 1617, 1972.
A CONVENIENT
PergamonPress.
Printed in &eat Britain.
SYNTHESIS OF LUNULARIC ACID
Y. Arai, T. Kamikawa and T. Kubota* Faculty of Science, Osaka City University,
Sumiyoshiku,
Osaka, Japan
(Receivedin Japan 23 February1972; receivedin UK for plblioation14 March1972) Recently
lunularic acid
(lb), a new growth inhibitor from Lunularia
(L) Dum., has been isolated and characterized. was provided by the derivation
olysis of 3 would give dimethoxy
Several methods
5
However,
into lb by hydrogenolysis.
acid
(4),6 we have obtained
acid with a phenol4 seemed
of 4 and dimethyl
allene-1,3-dicarboxylate
3H, 8). 3.72
acid.
(5)' in a
3-methoxvhomophthalate
sample, in 42% yield in one step. acids.
acid from l-
3-methoxyhomophthalic
(7a), iden-
This represents
The minor product,
reaction was assigned the structure
6(CC14) l-2.2
Of the
the poor overall yield caused this route to be
synthesis of homophthalic
the Diels-Alder
of 3-
(7~) has been prepared by longer se-
sealed tube at 180° for 17 hours gave dimethyl tical with the authentic
acid in 21%
for the preparation
By applying the novel synthesis of 3-methoxyphthalic
Heating the mixture
evidence.
synthesisoflunularic
of a homophthalic
The required homophthalic
methoxycyclohexa-1,3-diene
excellent
Hydrogen-
(la), but the yield of 3 from 3-
have been investigated
the condensation
quence of reactions. rejected.
four-step
which would be converted
available,
attractive.
The synthesis of
anhydride was only 1.5% at best. 3
arylisocoumarins, methods
(2).lr2
(3), has already been reported.
lunularic acid
We wish to describe an efficient overall yield.
Final proof of the structure
of lb from hydrangenol
2, via 7,4'-dimethoxvbenzalphthalide
methoxyphthalic
1
cruciata
an
5% in yield, of
(6) on the basis of NMR
(4H, m), 3.06 (lH, m, He), 3.40, 3.56 and 3.62
(each
(lH, t, J=3 Hz, Hd), 5.62 (lH, d, J=3 Hz, Hc), 6.08 (lH, dd, J=6,
1615
1616
No. 16
%R %m (la)
(lb)
R=Me R=H
(2)
iHW= ‘6#+Me
‘6
!HCqMe
(4)
(3)
(5)
Ha tib
( 7a) (7b)
(6)
(7~)
(8a) (8b)
R=Me R=H
R’ R2=Me R’IH$=Me R’ = R’ = H
IVO.16
1617
9 Hz, Hb) and 6.36 ppm
(lH, cl, J=9 Hz, Ha).
Mild alkaline hydrolysis hydrolysis
(7b).
(acid or base) of Ja gave 3-methoxyhomophthalic
with the authentic the isocoumarin data.
of 7a gave the.half ester
sample.
5
Condensation
(Ea), mp 161-162O,
of Jc
on the condition used.
acid la in quantitative yield, mp 195-196'
acid
(7c), identical
with anisole in PPA at 90° gave
in 81% yield with the expected
When lb was condensed with anisole,the
obtained depending
More vigorous
Catalytic
yield, which afforded,
(lit. mp 192").l
keto ester
spectroscopic
(9) together with 8a was
hydrogenation
of 8a gave the
on treatment with BBr3, lb in 63%
The IR spectrum is identical with that of
the natural acid and the UV and mass spectra are in accord with the published data. Preliminary
tests for the biological
carried out using Avena straight growth, ed IAA-induced etiolated
(5 mg/l) elongation
seedlings.
activity of the synthetic At concentrations
of coleoptile
lb were
lo-30 mg/l it inhibit-
segments excised from 4 day-old
Kinetic studies, however, appear to show that the inhibition
was elicited not in a competitive manner.
Detailed
information will appear else-
where. We thank Professor W. W. Schwabe, Department London,
of Horticulture,
University
of
for the supply of the IR spectrum of lunularic acid and Professor Y.
Masuda, Department
of Biology, Osaka City University,
for biological
tests.
References 1.
I. F. M. Valio, R. S. Burdon and W. W. Schwabe, Nature, 223, 1176
2.
Y. Asahina
and J. Asano, Ber., 62, 171 (1929); 63, 429 (1930).
3.
Y. Asahina
and J. Asano, Ber., 63, 2059 (1930).
4.
G. N. Dorofeenko,
E. V. Kutznetsov
and V. E. Ryabinina,
Tetrahedron
(1969).
Letters,
711 (1969). 5.
K. Nitta, J. Imai, I. Yamamoto
and Y. Yamamoto, Agr. Biol. Chem., 21, 817
(1963). 6.
A. J. Birch and P. Hextall, Austral.
7.
E. R. H. Jones, G. H. Mansfield
J. Chem., S, 96 (1955).
and M. C. Whiting,
J. Chem. Sot., 1954, 3208.
A CONVENIENT
PergamonPress.
Printed in &eat Britain.
SYNTHESIS OF LUNULARIC ACID
Y. Arai, T. Kamikawa and T. Kubota* Faculty of Science, Osaka City University,
Sumiyoshiku,
Osaka, Japan
(Receivedin Japan 23 February1972; receivedin UK for plblioation14 March1972) Recently
lunularic acid
(lb), a new growth inhibitor from Lunularia
(L) Dum., has been isolated and characterized. was provided by the derivation
olysis of 3 would give dimethoxy
Several methods
5
However,
into lb by hydrogenolysis.
acid
(4),6 we have obtained
acid with a phenol4 seemed
of 4 and dimethyl
allene-1,3-dicarboxylate
3H, 8). 3.72
acid.
(5)' in a
3-methoxvhomophthalate
sample, in 42% yield in one step. acids.
acid from l-
3-methoxyhomophthalic
(7a), iden-
This represents
The minor product,
reaction was assigned the structure
6(CC14) l-2.2
Of the
the poor overall yield caused this route to be
synthesis of homophthalic
the Diels-Alder
of 3-
(7~) has been prepared by longer se-
sealed tube at 180° for 17 hours gave dimethyl tical with the authentic
acid in 21%
for the preparation
By applying the novel synthesis of 3-methoxyphthalic
Heating the mixture
evidence.
synthesisoflunularic
of a homophthalic
The required homophthalic
methoxycyclohexa-1,3-diene
excellent
Hydrogen-
(la), but the yield of 3 from 3-
have been investigated
the condensation
quence of reactions. rejected.
four-step
which would be converted
available,
attractive.
The synthesis of
anhydride was only 1.5% at best. 3
arylisocoumarins, methods
(2).lr2
(3), has already been reported.
lunularic acid
We wish to describe an efficient overall yield.
Final proof of the structure
of lb from hydrangenol
2, via 7,4'-dimethoxvbenzalphthalide
methoxyphthalic
1
cruciata
an
5% in yield, of
(6) on the basis of NMR
(4H, m), 3.06 (lH, m, He), 3.40, 3.56 and 3.62
(each
(lH, t, J=3 Hz, Hd), 5.62 (lH, d, J=3 Hz, Hc), 6.08 (lH, dd, J=6,
1615
1616
No. 16
%R %m (la)
(lb)
R=Me R=H
(2)
iHW= ‘6#+Me
‘6
!HCqMe
(4)
(3)
(5)
Ha tib
( 7a) (7b)
(6)
(7~)
(8a) (8b)
R=Me R=H
R’ R2=Me R’IH$=Me R’ = R’ = H
IVO.16
1617
9 Hz, Hb) and 6.36 ppm
(lH, cl, J=9 Hz, Ha).
Mild alkaline hydrolysis hydrolysis
(7b).
(acid or base) of Ja gave 3-methoxyhomophthalic
with the authentic the isocoumarin data.
of 7a gave the.half ester
sample.
5
Condensation
(Ea), mp 161-162O,
of Jc
on the condition used.
acid la in quantitative yield, mp 195-196'
acid
(7c), identical
with anisole in PPA at 90° gave
in 81% yield with the expected
When lb was condensed with anisole,the
obtained depending
More vigorous
Catalytic
yield, which afforded,
(lit. mp 192").l
keto ester
spectroscopic
(9) together with 8a was
hydrogenation
of 8a gave the
on treatment with BBr3, lb in 63%
The IR spectrum is identical with that of
the natural acid and the UV and mass spectra are in accord with the published data. Preliminary
tests for the biological
carried out using Avena straight growth, ed IAA-induced etiolated
(5 mg/l) elongation
seedlings.
activity of the synthetic At concentrations
of coleoptile
lb were
lo-30 mg/l it inhibit-
segments excised from 4 day-old
Kinetic studies, however, appear to show that the inhibition
was elicited not in a competitive manner.
Detailed
information will appear else-
where. We thank Professor W. W. Schwabe, Department London,
of Horticulture,
University
of
for the supply of the IR spectrum of lunularic acid and Professor Y.
Masuda, Department
of Biology, Osaka City University,
for biological
tests.
References 1.
I. F. M. Valio, R. S. Burdon and W. W. Schwabe, Nature, 223, 1176
2.
Y. Asahina
and J. Asano, Ber., 62, 171 (1929); 63, 429 (1930).
3.
Y. Asahina
and J. Asano, Ber., 63, 2059 (1930).
4.
G. N. Dorofeenko,
E. V. Kutznetsov
and V. E. Ryabinina,
Tetrahedron
(1969).
Letters,
711 (1969). 5.
K. Nitta, J. Imai, I. Yamamoto
and Y. Yamamoto, Agr. Biol. Chem., 21, 817
(1963). 6.
A. J. Birch and P. Hextall, Austral.
7.
E. R. H. Jones, G. H. Mansfield
J. Chem., S, 96 (1955).
and M. C. Whiting,
J. Chem. Sot., 1954, 3208.