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Amino acid synthesis II. Amidoalkylation of olefins with glyoxylic acid derivatives
Tetrahedron
Lettera
No. 43,
PP 3737 - 374G,
1975.
Pergamen Pree8.
Printed
in Great Britain.
AMIDOALXYLATION OF OLEFINS WITH
AMINO ACID SYNTHESIS II.
GLYOXYLICACID DERIVATIVES
Janina Department (Received Synthetic lysine)!
in UK 31 July
amino acids
In . the synthesis
as sweetening
agents
We would like
to report
semialdehyde glyoxylic
a sulfonic
acid
catalyst
(m.p.
97”,
afforded
afforded
to the benzamido
46%).
(8, acids
Isobutylene
reacted
3
agents
(e.g.
EDTA).
acids
and related
ester
by reacting
styrene,
the methyl ester
esters
2 (m.p.
tetramethylethylene
in boiling
benzene
of the N-benzoyl 163’C)
and
and in the presence
unsaturated
which was obtained
o-amino
in 57% yield,
193’,
51%);
methyl
1 (m.p.
esters
212,
42’);
-17 (m.p. 146, 27%) and 18 as oils. The crude acid a, was
were obtained Both the
3 and the
4-pentenoic
acid
derivatives
-9 on cyclization.
with
-10 depending trifluoride etherate
the methyl
on the
a-methoxyhippurate
reaction
conditions6
to
give
In ether
the oxazine
solution
13,
or the
and in the presence
(14%) of
oxazine -13 was obtained in 53% yield together with the In dioxane-sulfuric acid solution isobutylene afforded
a-hydroxyhippuric
acid
same experimental
and isobutylene,
or as chelating
a-hydroxyhippuric
styrene,
of two isomers.
the oily
type -2. 5,5-dimethyl-a-benzamidobutyrolactone
Under the
methionine, (Ampicillin,..),
to the S,S-diphenyl-5 (m.p. 206’C) and further cyclized 198’). By using the same procedure we have prepared the
The corresponding
benzamidolactone
yield
(e.g.
acid
5 (m.p.
the same butyrolactone
of boron
additives
(16) aspartic acid (20), aspartic acid unsaturated o-amino acid derivatives by the
u-methoxyhippurate
methyl
m.p.
to the nmr a mixture
unsaturated
15 September 1975)
and cephalosporins
ester)4
Israel
leucine
o-methyl
The diphenyl
benzamido
according
methyl of
with methyl
a-benzamidobutyrolactone crystalline
as food
penicillins
(fi,g,15) and other with methyl a-methoxyhippurate,
l,l-diphenylethylene,
(2-4,17,18). --_-
was hydrolyzed
publication
Haifa,
amide adducts?
Reacting
acids
of Technology,
for
applications
semi-synthetic
a new synthesis
2,5-dimethyl-2,4-hexadiene of
Institute
1975; accepted
(aspartylphenylalanine
of olefins
acid
Reuven Moshberg and Dov Ben-Ishai* ‘Israel
have found
of
derivatives
amidoalkylation
Altman,
of Chemistry,
conditions
(m.p.
176”,
with
45%)7
isobutylene
we have obtained
The same lactone
was obtained
in dioxane-sulphuric
acid
in 73%
solution.
from a-hydroxy-N-benzyloxycarbonylglycine’ 8 S,S-dimethyl-a-benzyloxycarbonylaminobutyrolactone (m.p. 94”, 65%).
3737
C02Me
\
15
CH -CH(OMe)2 I2 PhCONH-CH-C02Me
Lt. R=AcO; R'=H
13. R=Rl=Me
R'
R
1
H2S04
NHCOPh
Rl'
BF3 R.T.
= CH2 + MTH-C02Me
R, C
/ Me
Me \
Dioxane
11. R=MeO; R1=H
Pd-C H+
10. R=Rl=Me
9. R=Ph; R1=Me
8. R=R'=Ph H+
0
NHCOPh
16
NH2
CH-CH2-fH-C02H
9
0
R R'
H+
A PhH
A
H+
yy$Y
R*
R\
t
2. R=Rl=Ph
NHCoPh
7. R=Ph; R1=H
6. R=Ph; R'=Me
5. R=Rl=Ph
kCOPh
C = CH-CH-C02H
4. R=Ph, R=H
OH- 3. R=Ph, R1=Me
No. k3
3739
The lactone -10 was opened with n-butanol to give a mixture of butyl esters
in the presence of 8-naphthalene sulfonic
of S,y and y.6 dehydro-N-benzoylleucine.
genation of the crude mixture followed by acid hydrolysis
Catalytic
acid
hydro-
gave the amino acid in 70% yield
The two isomeric unsaturated esters were also separated and converted
(based on the lactone).
The S,y-dehydrobenzoyllecine
to the u-benzamido acids.
melted at 132’ and the y,6 isomer
melted at 134’* Vinyl acetate reacted with methyl a-methoxyhippurate in benzene solution presence of boron trifluoride 1,3-oxazine-4-carboxylic
dimethylacetal
to give the oily methyl ester of 5,6-dihydro-6-acetoxy-2-phenylThe acetoxyoxazine which is a derivative
acid (14). -
semialdehyde was converted,
on treatment with methanolic sulfuric
of N-benzoylaspartic
acid semialdehyde (15).
to 5-methoxy-u-benzamidobutyrolactone with aqueous phosphoric acid. of two stereomers.
product (m.p. 64”) and an oil.
in sulfuric-acetic aspartic
of aspartic
acid
to the methyl ester was further converted
on treatment with aqueous base followed by acidification
Both the oxazine -14 and lactone -11 were obtained as mixtures column to give a crystalline
The lactones were separated by fractional
crystallization
from
and melted at 183’ and 147’.
a-Hydroxy-N-butoxycarbonylglycine carbamate (m.p.
acid,
The latter
The oxazines 14, were separated on a florisil
ethyl acetate-hexane
and in the
(19) which was prepared from glyoxylic -
in analogy to the preparation
76”J
of the benzyl derivative5
acid mixture with l,l-dichloroethylene
acid (20, 47%).
above had satisfactory
acid and n-butyl
chloroformate.
analyses and showed characteristic
C12C = CH2+HO-CH-C02H NHC02C4H9
-19
H,SO,
with an authentic
All the new compounds described
infrared,
CH -C02H * i 2 C4H90CCNHCH -C02H
-20
was found to react
to give in one step N-butoxycarbonyl
The product which melted at 114’ was identical
sample prepared from aspartic
acid and butyl
nmr and mass spectra.
3740
No. 43
References
1. For paper I in the series see D. Ben-Ishai,I. Satati and Z. Berler,Chem. Commun., 1975, 349. 2. A.M. Altschul,Nature, 3,
643 (1974). C&EN Dec. 24 page 18 (1973).
3. Penicillinsand cephalosporins.Their Chemistryand Biology. Chapter 12.E.A.James, Editor, AcademicPress, New York (1972). R.H. Mazur. J.M. Schlatterand A.H. Goldkamp,J. Amer. Chem. Sot., 91, 2684 (1969). U. Zoller 8 D. Ben-Ishai,Tetrahedron,31, 863 (1975). H.E. Zaugg, Synthesis,49 (1970)and refs. cited. J. Fillman and N. Albertson,J. Amer. Chem. Sot., 2,
171 (1948). H.L. Goering, S.J.
Cristol and K. Dittmer,J. Amer. Chem. Sot., 70, 3312 (1948). 8. H. Faulstichand H. Trischmann,&.,x,
55 (1970).
Lettera
No. 43,
PP 3737 - 374G,
1975.
Pergamen Pree8.
Printed
in Great Britain.
AMIDOALXYLATION OF OLEFINS WITH
AMINO ACID SYNTHESIS II.
GLYOXYLICACID DERIVATIVES
Janina Department (Received Synthetic lysine)!
in UK 31 July
amino acids
In . the synthesis
as sweetening
agents
We would like
to report
semialdehyde glyoxylic
a sulfonic
acid
catalyst
(m.p.
97”,
afforded
afforded
to the benzamido
46%).
(8, acids
Isobutylene
reacted
3
agents
(e.g.
EDTA).
acids
and related
ester
by reacting
styrene,
the methyl ester
esters
2 (m.p.
tetramethylethylene
in boiling
benzene
of the N-benzoyl 163’C)
and
and in the presence
unsaturated
which was obtained
o-amino
in 57% yield,
193’,
51%);
methyl
1 (m.p.
esters
212,
42’);
-17 (m.p. 146, 27%) and 18 as oils. The crude acid a, was
were obtained Both the
3 and the
4-pentenoic
acid
derivatives
-9 on cyclization.
with
-10 depending trifluoride etherate
the methyl
on the
a-methoxyhippurate
reaction
conditions6
to
give
In ether
the oxazine
solution
13,
or the
and in the presence
(14%) of
oxazine -13 was obtained in 53% yield together with the In dioxane-sulfuric acid solution isobutylene afforded
a-hydroxyhippuric
acid
same experimental
and isobutylene,
or as chelating
a-hydroxyhippuric
styrene,
of two isomers.
the oily
type -2. 5,5-dimethyl-a-benzamidobutyrolactone
Under the
methionine, (Ampicillin,..),
to the S,S-diphenyl-5 (m.p. 206’C) and further cyclized 198’). By using the same procedure we have prepared the
The corresponding
benzamidolactone
yield
(e.g.
acid
5 (m.p.
the same butyrolactone
of boron
additives
(16) aspartic acid (20), aspartic acid unsaturated o-amino acid derivatives by the
u-methoxyhippurate
methyl
m.p.
to the nmr a mixture
unsaturated
15 September 1975)
and cephalosporins
ester)4
Israel
leucine
o-methyl
The diphenyl
benzamido
according
methyl of
with methyl
a-benzamidobutyrolactone crystalline
as food
penicillins
(fi,g,15) and other with methyl a-methoxyhippurate,
l,l-diphenylethylene,
(2-4,17,18). --_-
was hydrolyzed
publication
Haifa,
amide adducts?
Reacting
acids
of Technology,
for
applications
semi-synthetic
a new synthesis
2,5-dimethyl-2,4-hexadiene of
Institute
1975; accepted
(aspartylphenylalanine
of olefins
acid
Reuven Moshberg and Dov Ben-Ishai* ‘Israel
have found
of
derivatives
amidoalkylation
Altman,
of Chemistry,
conditions
(m.p.
176”,
with
45%)7
isobutylene
we have obtained
The same lactone
was obtained
in dioxane-sulphuric
acid
in 73%
solution.
from a-hydroxy-N-benzyloxycarbonylglycine’ 8 S,S-dimethyl-a-benzyloxycarbonylaminobutyrolactone (m.p. 94”, 65%).
3737
C02Me
\
15
CH -CH(OMe)2 I2 PhCONH-CH-C02Me
Lt. R=AcO; R'=H
13. R=Rl=Me
R'
R
1
H2S04
NHCOPh
Rl'
BF3 R.T.
= CH2 + MTH-C02Me
R, C
/ Me
Me \
Dioxane
11. R=MeO; R1=H
Pd-C H+
10. R=Rl=Me
9. R=Ph; R1=Me
8. R=R'=Ph H+
0
NHCOPh
16
NH2
CH-CH2-fH-C02H
9
0
R R'
H+
A PhH
A
H+
yy$Y
R*
R\
t
2. R=Rl=Ph
NHCoPh
7. R=Ph; R1=H
6. R=Ph; R'=Me
5. R=Rl=Ph
kCOPh
C = CH-CH-C02H
4. R=Ph, R=H
OH- 3. R=Ph, R1=Me
No. k3
3739
The lactone -10 was opened with n-butanol to give a mixture of butyl esters
in the presence of 8-naphthalene sulfonic
of S,y and y.6 dehydro-N-benzoylleucine.
genation of the crude mixture followed by acid hydrolysis
Catalytic
acid
hydro-
gave the amino acid in 70% yield
The two isomeric unsaturated esters were also separated and converted
(based on the lactone).
The S,y-dehydrobenzoyllecine
to the u-benzamido acids.
melted at 132’ and the y,6 isomer
melted at 134’* Vinyl acetate reacted with methyl a-methoxyhippurate in benzene solution presence of boron trifluoride 1,3-oxazine-4-carboxylic
dimethylacetal
to give the oily methyl ester of 5,6-dihydro-6-acetoxy-2-phenylThe acetoxyoxazine which is a derivative
acid (14). -
semialdehyde was converted,
on treatment with methanolic sulfuric
of N-benzoylaspartic
acid semialdehyde (15).
to 5-methoxy-u-benzamidobutyrolactone with aqueous phosphoric acid. of two stereomers.
product (m.p. 64”) and an oil.
in sulfuric-acetic aspartic
of aspartic
acid
to the methyl ester was further converted
on treatment with aqueous base followed by acidification
Both the oxazine -14 and lactone -11 were obtained as mixtures column to give a crystalline
The lactones were separated by fractional
crystallization
from
and melted at 183’ and 147’.
a-Hydroxy-N-butoxycarbonylglycine carbamate (m.p.
acid,
The latter
The oxazines 14, were separated on a florisil
ethyl acetate-hexane
and in the
(19) which was prepared from glyoxylic -
in analogy to the preparation
76”J
of the benzyl derivative5
acid mixture with l,l-dichloroethylene
acid (20, 47%).
above had satisfactory
acid and n-butyl
chloroformate.
analyses and showed characteristic
C12C = CH2+HO-CH-C02H NHC02C4H9
-19
H,SO,
with an authentic
All the new compounds described
infrared,
CH -C02H * i 2 C4H90CCNHCH -C02H
-20
was found to react
to give in one step N-butoxycarbonyl
The product which melted at 114’ was identical
sample prepared from aspartic
acid and butyl
nmr and mass spectra.
3740
No. 43
References
1. For paper I in the series see D. Ben-Ishai,I. Satati and Z. Berler,Chem. Commun., 1975, 349. 2. A.M. Altschul,Nature, 3,
643 (1974). C&EN Dec. 24 page 18 (1973).
3. Penicillinsand cephalosporins.Their Chemistryand Biology. Chapter 12.E.A.James, Editor, AcademicPress, New York (1972). R.H. Mazur. J.M. Schlatterand A.H. Goldkamp,J. Amer. Chem. Sot., 91, 2684 (1969). U. Zoller 8 D. Ben-Ishai,Tetrahedron,31, 863 (1975). H.E. Zaugg, Synthesis,49 (1970)and refs. cited. J. Fillman and N. Albertson,J. Amer. Chem. Sot., 2,
171 (1948). H.L. Goering, S.J.
Cristol and K. Dittmer,J. Amer. Chem. Sot., 70, 3312 (1948). 8. H. Faulstichand H. Trischmann,&.,x,
55 (1970).