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Asymmetric ring opening of cyclic acid anhydrides with lipase in organic solvents
Tetrahedron Letters,Vol.29,No.l4,pp Printed in Great Britain
ASYHHETRIC
RING OPENING WITH
LIPASE
0040-4039/88 $3.00 + .OO Pergamon Press plc
1717-1720,1988
OF CYCLIC
IN ORGANIC
ACID ANRYDRIDES
SOLVENTS
Kazuyoshi Yamamoto, Takaaki Nishioka and Jun'ichi Oda* Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan Yukio Yamamoto Department of Chemistry, College of Liberal Arts and Science, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606, Japan
A lipase (Amano P) catalyzed the asymmetric ring opening of 3-substituted glutaric anhydride with l-butanol to afford the E half esters having 60-91%ee.
Asymmetric synthesis and kinetically resolution with enzymes has been well appreciated
as an efficient
strategy to prepare optically
active comp0unds.l
Especially, asymmetric hydrolysis of meso and prochiral diesters has been extensively investigated. After the leading reference by Klibanov,2 kinetically resolution
of
lipase-mediated
several
kinds
of alcohols
esterification
has been
successfully
performed
in organic media.3 Pairs of enantiomeric
by
mono
acetates were effectively yielded by the combination of selective hydrolysis of diacetates in aqueous media and selective esterification of diols in anhydrous media.4 Simultaneously, other kinds of asymmetric synthesis and kinetically resolution were also developed in organic solvents using dehydrogenase, 5 mandelonitrile lyase6 and lipase.7 As a non-enzymatic counterpart of asymmetric hydrolysis of meso and prochiral diesters, we
have established
asymmetric
ring opening
of cyclic acid
anhydrides both in non-catalytic and catalytic modes which are based on discrimination between two enantiotopic carbonyl groups. 8 The same kind of asymmetric synthesis starting from cyclic acid anhydrides have been also reported with a chiral hydrogenation catalyst', a chiral alcohol" and a chiral boryl ester. " However, high selectivity has not been achieved in catalytic processes with readily available reagents. From this viewpoint, we wish to develop asymmetric ring opening of cyclic acid anhydrides which is catalyzed by lipase in organic solvents. Among several commercially available lipases, Amano P from Pseudomonas fluorescens (Amano
1717
1718
Pharmaceutical CO., LTD., Japan) was found to exhibit good catalytic activity for representative solvents
achiral and prochiral cyclic acid anhydrides'*
in organic
(The typical conditions, see the entry 4 and the note of Table 1).
Glutaric anhydride,
3-methylglutaric anhydride and succinic anhydride readily
reacted with 1-butanol to give the corresponding half esters whereas the formation of the diesters was not observed. Ethyl, propyl and isopropyl substituents at B-position of glutaric anhydride delayed the reaction. However, those anhydrides as well as cis-2,4_dimethylglutaric
anhydride were also converted com-
pletely to the half esters under appropriate conditions; increased enzyme quantity or prolonged
reaction time.
The reaction with 1-butanol was proved to
proceed only within 1% without the enzyme. Asymmetric ring opening of substituted glutaric anhydrides were performed with the enzyme
(Table 1). Because the specific rotations of the half esters 2
were relatively small, their configurations lows. By
the
successive
treatment
with
and ee's were determined
diborane-dimethylsulfide
as fol-
and
dilute
sulfuric acid, the half esters 2 were converted to the lactones 3 whose absolute configuration had been established.13 The enantiomeric excesses
(eels) of
the half esters 2 were determined by HPLC after converting them to the diastereomeric amides of
(S)-1-(1-naphthyl)ethylamine
(4)8d and/or by converting the
lactones 3 to the diastereomeric hydroxyamide of (S)-4.14 At first, the substrate was fixed for 3-methylglutaric anhydride (la), for which methanol, l-butanol and 2-propanol were examined as a nucleophile. Although methanol reacted as fast as 1-butanol, the stereoselectivity with methanol was somewhat lower than that with 1-butanol (entries 1 and 2 vs. 3 and 4). The reaction with 2-propanol was found to proceed very slowly (entry 6). Among several aprotic solvent examined, diisopropyl ether was most appropriate from the viewpoint of solubility and reactivity of the substrate as well as the ee of the product. Although the acid anhydrides were more soluble in toluene, the ee's of 2a(R1=CH3)
in toluene
were
inferior
(entries
1 and 3 vs. 2 and 4). The maximum
observed
when
1-butanol
and diisopropyl
to those
in diisopropyl
ether
ee of 91% of the E product
ether were
employed
was
(entry 4). The
enzyme was partly purified through ammonium sulfate fractionation and deposited on Hyflo
Super-Cell
according
to the literature.4a
product with the purified enzyme
However,
the ee of the
(entry 5) was almost same as that with the
enzyme in commercially available form. The asymmetric ring opening of 3-ethyl, 3-propyl and 3-isopropyl derivatives of glutaric anhydride was also performed under the conditions which afforded the best ee for the 3-methyl derivative la. The ee's of the products were 80%, 60% and 76%, respectively (entries 7, 8 and 9). In every case, the pro-g carbonyl group of the substrates was attacked preferentially to give the E products. In the case of cis-2,4_dimethylglutaric
anhydride, the selectivity
was low (entry 10). While the enantiotopic group differentiation of dicarboxylic acid derivatives has been attained conventionally
by hydrolysis,
the present asymmetric
1719
R’ R20H on 0 1
R’
R’ n
OLipase
R200C
-r‘, 0
COOH 2
0 3
Table 1. Asymmetric ring opening of glutaric anhydride derivatives with Amano P in organic solvents.a entry 1 2 3 4 5b 6 7 8 9 10
substituent of the substrate 3-methyl 3-methyl 3-methyl 3-methyl 3-methyl 3-methyl 3-ethyl 3-propyl 3-isopropyl cis-2,4-dimethyl
alcohol
solvent
reaction period (hr)
methanol methanol l-butanol 1-butanol l-butanol 2-propanol l-butanol 1-butanol l-butanol
toluene I-Pr20 toluene i-Pr20 T-Pr20 toluene i-Pr20 i-Pr20 I-Pr20 50% toluene 1-butanol in i-Pr20d
half ester %yield %ee config. 94 92 78 74 79 gc 67 72 85
24 6 24 6 6 24 12 48 24 48
70 87 86 91 88 80 60 76
96
8
Rl4 R R R R Z Rl5 ,15 El4 -
a Conditions: for the acid anhydride 1 (l.Ommol), were used Amano P (2OOmg), the alcohol (2.0mmol) and the solvent (10ml). The reaction mixture was stirred magnetically at 25*C for the listed period in which the reaction conversion by GLC exceeded 98% except entry 6. The reaction mixture was filtered and evaporated. The residue was dissolved in sat. NaHC03. The aqueous solution was washed with ether and made acidic with 6N HCl, and then extracted with ether. The organic solution was dried over Na2S04 and evaporated to give the half ester 2. b Partially purified Amano P (300mg) was used. c conversion determined by GLC. d 20ml.
synthesis is based on the usage of the hydrolytic enzyme for the reversed direction. If the enzyme prefers the carbonyl group of the acyclic diester on the same side in the corresponding
cyclic acid anhydride,
the diester
should be
attacked on the pro-g group and give the S half ester. In fact, dimethyl methylglutarate was hydrolyzed by Amano P in sodium phosphate buffer 37*c, 65hr) to afford
3-
(pH 7.0,
(g)-2a(R1=CH3) with 74%ee in 50% yield. Now, a pair of
enantiomeric half ester has been accessible with one kind of hydrolytic enzyme as reported with mono acetate of diols. 4 Acknowledgment: This work was supported in part by a grand in aid for scientific research on priority area, advanced molecular conversion from the Ministry of Education
of Japan
to which we are deeply
grateful.
Pharmaceutical CO., LTD. for generous supply of enzymes.
We also thank Amano
1720 References For a review, see: J. B. Jones, Tetrahedron, 42, 3351 (1986). G. Kirchner, M. P. Scollar and A. M. Klibanov, -J. Am. Chem. sot ., 107, 7072 (19851, and references cited therein. G. Langrand, M. Secchi, G. Buono, J. Baratti and C. Triantaphylides, Tetrahedron Lett.,
26, 1857
(1985); S. Koshiro, K. Sonomoto, A. Tanaka and S.
Fukui, J. Biotechnol., 2, 47 (1985); A. Belan, J. Bolte, A. Fauve, J. G. Gourcy and H. Veschambre, J. Org, Chem., 52, 256 (1987); A. Makita, T. Nihira and Y. Yamada, Tetrahedron Lett., 28, 805 (1987); A. L. Margolin, JY. Crenne and A. M. Klibanov, ibid., 28, 1607 (1987); G. Gil, E. Ferre, A. Meou,
J. LePetit
and C. Triantaphylides,
ibid.,
Stokes and A. C. Oehlschlager, ibid., 28, 2091 Zuobi and A. Boltansky, ibid., 28, 3861 (1987).
28, 1647
(1987); T. M.
(1987); A. L. Gutman,
a) G. M. R. Tombo, H. -P. SchBr, X. F. Busquests and 0. Ghisalba,
K.
Tetra-
hendon Lett., 27, 5707 (1986). b) H. Hemmerle and H. -J. Gais, ibid., 3471 (1987). J. Grunwald, B. Wirz, M. P. Scollar and A. M. Klibanov, --J. Am. Chem. Sot., 108, 6732 (1986). F. Effenberger, T. Ziegler and S. Fbrster, Angew. --Chem. Int. Ed. Engl., 26, 458 (1987). T. Kitazume,
T. Ikeya anf K. Murata,
J. Chem. ----
Sot. Chem.
Commun.,
1331
(1986). a) Y. Kawakami, J. Hiratake, Y. Yamamoto and J. Oda, ---J. Chem. Sot. Chem. Commun., 779 (1984). b) J. Hiratake, Y. Yamamoto and J. Oda, ibid., 1717 (1985). c) Y. Kawakami, J. Hiratake, Y. Yamamoto and J. Oda, Agric. Biol. Chem., 50, 693 (1986). d) J. Hiratake, M. Inagaki, Y. Yamamoto and J. Oda, J. Chem sot Perkin Trans I 1053 (1987). e) M. Inagaki, J. Hiratake, Y. _"_'1 Yamamoto and J. Oda, Bull. -Chem. Sot. Jpn., 60, 4121 (1987). K. Osakada, M. Obana, T. Ikariya, M. Saburi and S. Yoshikawa,
Tetrahedron
Lett., 22, 4297 (1981). 10
T. Rosen, M. Watanabe and C. H. Heathcock, J. Org. Chem., 49, 3657 (1984);
11
T. Rosen and H. Heathcock, --J. Am. Chem. Sot., 107, 3731 (1985). 377 (1987); M. Ohshima, M. Ohshima and T. Mukaiyama, Chem. Lett.,
N.
Miyoshi and T. Mukaiyama, ibid., 1233 (1987). 12
The acid anhydrides not commercially available were prepared according to the reference: J. N. E. Day and J. F. Thorpe, J. Chem. Sot., 1465 (1920).
13
The specific rotations of the lactons; 3a (R1=CH3, 76%ee), [CL]:'+21.1' (c 2.35 CHC13)i 3b (R1=C2H5, 73%ee), [ali
14 15
+19.3" (c 2.34, CHC13); 3c (R1=n-
+12.7" (c 1.26, CHC13); 3d (R1=i-C3H7, 76%ee), [a]~5 C3H7' 60%ee), [ali +17.0° (c 0.68, C2H50H). G. Yabuta and K. Mori, Nippon Nogei Kagaku Kaishi, 56, 1121: Chem. Abstr., 98, 1791568 (1983). L. K. P. Lam, R. A. H. F. Hui and J. B. Jones, 2 J (1986). (Received in Japan 11 December 1987)
Org. Chem.,
51, 2047
ASYHHETRIC
RING OPENING WITH
LIPASE
0040-4039/88 $3.00 + .OO Pergamon Press plc
1717-1720,1988
OF CYCLIC
IN ORGANIC
ACID ANRYDRIDES
SOLVENTS
Kazuyoshi Yamamoto, Takaaki Nishioka and Jun'ichi Oda* Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan Yukio Yamamoto Department of Chemistry, College of Liberal Arts and Science, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606, Japan
A lipase (Amano P) catalyzed the asymmetric ring opening of 3-substituted glutaric anhydride with l-butanol to afford the E half esters having 60-91%ee.
Asymmetric synthesis and kinetically resolution with enzymes has been well appreciated
as an efficient
strategy to prepare optically
active comp0unds.l
Especially, asymmetric hydrolysis of meso and prochiral diesters has been extensively investigated. After the leading reference by Klibanov,2 kinetically resolution
of
lipase-mediated
several
kinds
of alcohols
esterification
has been
successfully
performed
in organic media.3 Pairs of enantiomeric
by
mono
acetates were effectively yielded by the combination of selective hydrolysis of diacetates in aqueous media and selective esterification of diols in anhydrous media.4 Simultaneously, other kinds of asymmetric synthesis and kinetically resolution were also developed in organic solvents using dehydrogenase, 5 mandelonitrile lyase6 and lipase.7 As a non-enzymatic counterpart of asymmetric hydrolysis of meso and prochiral diesters, we
have established
asymmetric
ring opening
of cyclic acid
anhydrides both in non-catalytic and catalytic modes which are based on discrimination between two enantiotopic carbonyl groups. 8 The same kind of asymmetric synthesis starting from cyclic acid anhydrides have been also reported with a chiral hydrogenation catalyst', a chiral alcohol" and a chiral boryl ester. " However, high selectivity has not been achieved in catalytic processes with readily available reagents. From this viewpoint, we wish to develop asymmetric ring opening of cyclic acid anhydrides which is catalyzed by lipase in organic solvents. Among several commercially available lipases, Amano P from Pseudomonas fluorescens (Amano
1717
1718
Pharmaceutical CO., LTD., Japan) was found to exhibit good catalytic activity for representative solvents
achiral and prochiral cyclic acid anhydrides'*
in organic
(The typical conditions, see the entry 4 and the note of Table 1).
Glutaric anhydride,
3-methylglutaric anhydride and succinic anhydride readily
reacted with 1-butanol to give the corresponding half esters whereas the formation of the diesters was not observed. Ethyl, propyl and isopropyl substituents at B-position of glutaric anhydride delayed the reaction. However, those anhydrides as well as cis-2,4_dimethylglutaric
anhydride were also converted com-
pletely to the half esters under appropriate conditions; increased enzyme quantity or prolonged
reaction time.
The reaction with 1-butanol was proved to
proceed only within 1% without the enzyme. Asymmetric ring opening of substituted glutaric anhydrides were performed with the enzyme
(Table 1). Because the specific rotations of the half esters 2
were relatively small, their configurations lows. By
the
successive
treatment
with
and ee's were determined
diborane-dimethylsulfide
as fol-
and
dilute
sulfuric acid, the half esters 2 were converted to the lactones 3 whose absolute configuration had been established.13 The enantiomeric excesses
(eels) of
the half esters 2 were determined by HPLC after converting them to the diastereomeric amides of
(S)-1-(1-naphthyl)ethylamine
(4)8d and/or by converting the
lactones 3 to the diastereomeric hydroxyamide of (S)-4.14 At first, the substrate was fixed for 3-methylglutaric anhydride (la), for which methanol, l-butanol and 2-propanol were examined as a nucleophile. Although methanol reacted as fast as 1-butanol, the stereoselectivity with methanol was somewhat lower than that with 1-butanol (entries 1 and 2 vs. 3 and 4). The reaction with 2-propanol was found to proceed very slowly (entry 6). Among several aprotic solvent examined, diisopropyl ether was most appropriate from the viewpoint of solubility and reactivity of the substrate as well as the ee of the product. Although the acid anhydrides were more soluble in toluene, the ee's of 2a(R1=CH3)
in toluene
were
inferior
(entries
1 and 3 vs. 2 and 4). The maximum
observed
when
1-butanol
and diisopropyl
to those
in diisopropyl
ether
ee of 91% of the E product
ether were
employed
was
(entry 4). The
enzyme was partly purified through ammonium sulfate fractionation and deposited on Hyflo
Super-Cell
according
to the literature.4a
product with the purified enzyme
However,
the ee of the
(entry 5) was almost same as that with the
enzyme in commercially available form. The asymmetric ring opening of 3-ethyl, 3-propyl and 3-isopropyl derivatives of glutaric anhydride was also performed under the conditions which afforded the best ee for the 3-methyl derivative la. The ee's of the products were 80%, 60% and 76%, respectively (entries 7, 8 and 9). In every case, the pro-g carbonyl group of the substrates was attacked preferentially to give the E products. In the case of cis-2,4_dimethylglutaric
anhydride, the selectivity
was low (entry 10). While the enantiotopic group differentiation of dicarboxylic acid derivatives has been attained conventionally
by hydrolysis,
the present asymmetric
1719
R’ R20H on 0 1
R’
R’ n
OLipase
R200C
-r‘, 0
COOH 2
0 3
Table 1. Asymmetric ring opening of glutaric anhydride derivatives with Amano P in organic solvents.a entry 1 2 3 4 5b 6 7 8 9 10
substituent of the substrate 3-methyl 3-methyl 3-methyl 3-methyl 3-methyl 3-methyl 3-ethyl 3-propyl 3-isopropyl cis-2,4-dimethyl
alcohol
solvent
reaction period (hr)
methanol methanol l-butanol 1-butanol l-butanol 2-propanol l-butanol 1-butanol l-butanol
toluene I-Pr20 toluene i-Pr20 T-Pr20 toluene i-Pr20 i-Pr20 I-Pr20 50% toluene 1-butanol in i-Pr20d
half ester %yield %ee config. 94 92 78 74 79 gc 67 72 85
24 6 24 6 6 24 12 48 24 48
70 87 86 91 88 80 60 76
96
8
Rl4 R R R R Z Rl5 ,15 El4 -
a Conditions: for the acid anhydride 1 (l.Ommol), were used Amano P (2OOmg), the alcohol (2.0mmol) and the solvent (10ml). The reaction mixture was stirred magnetically at 25*C for the listed period in which the reaction conversion by GLC exceeded 98% except entry 6. The reaction mixture was filtered and evaporated. The residue was dissolved in sat. NaHC03. The aqueous solution was washed with ether and made acidic with 6N HCl, and then extracted with ether. The organic solution was dried over Na2S04 and evaporated to give the half ester 2. b Partially purified Amano P (300mg) was used. c conversion determined by GLC. d 20ml.
synthesis is based on the usage of the hydrolytic enzyme for the reversed direction. If the enzyme prefers the carbonyl group of the acyclic diester on the same side in the corresponding
cyclic acid anhydride,
the diester
should be
attacked on the pro-g group and give the S half ester. In fact, dimethyl methylglutarate was hydrolyzed by Amano P in sodium phosphate buffer 37*c, 65hr) to afford
3-
(pH 7.0,
(g)-2a(R1=CH3) with 74%ee in 50% yield. Now, a pair of
enantiomeric half ester has been accessible with one kind of hydrolytic enzyme as reported with mono acetate of diols. 4 Acknowledgment: This work was supported in part by a grand in aid for scientific research on priority area, advanced molecular conversion from the Ministry of Education
of Japan
to which we are deeply
grateful.
Pharmaceutical CO., LTD. for generous supply of enzymes.
We also thank Amano
1720 References For a review, see: J. B. Jones, Tetrahedron, 42, 3351 (1986). G. Kirchner, M. P. Scollar and A. M. Klibanov, -J. Am. Chem. sot ., 107, 7072 (19851, and references cited therein. G. Langrand, M. Secchi, G. Buono, J. Baratti and C. Triantaphylides, Tetrahedron Lett.,
26, 1857
(1985); S. Koshiro, K. Sonomoto, A. Tanaka and S.
Fukui, J. Biotechnol., 2, 47 (1985); A. Belan, J. Bolte, A. Fauve, J. G. Gourcy and H. Veschambre, J. Org, Chem., 52, 256 (1987); A. Makita, T. Nihira and Y. Yamada, Tetrahedron Lett., 28, 805 (1987); A. L. Margolin, JY. Crenne and A. M. Klibanov, ibid., 28, 1607 (1987); G. Gil, E. Ferre, A. Meou,
J. LePetit
and C. Triantaphylides,
ibid.,
Stokes and A. C. Oehlschlager, ibid., 28, 2091 Zuobi and A. Boltansky, ibid., 28, 3861 (1987).
28, 1647
(1987); T. M.
(1987); A. L. Gutman,
a) G. M. R. Tombo, H. -P. SchBr, X. F. Busquests and 0. Ghisalba,
K.
Tetra-
hendon Lett., 27, 5707 (1986). b) H. Hemmerle and H. -J. Gais, ibid., 3471 (1987). J. Grunwald, B. Wirz, M. P. Scollar and A. M. Klibanov, --J. Am. Chem. Sot., 108, 6732 (1986). F. Effenberger, T. Ziegler and S. Fbrster, Angew. --Chem. Int. Ed. Engl., 26, 458 (1987). T. Kitazume,
T. Ikeya anf K. Murata,
J. Chem. ----
Sot. Chem.
Commun.,
1331
(1986). a) Y. Kawakami, J. Hiratake, Y. Yamamoto and J. Oda, ---J. Chem. Sot. Chem. Commun., 779 (1984). b) J. Hiratake, Y. Yamamoto and J. Oda, ibid., 1717 (1985). c) Y. Kawakami, J. Hiratake, Y. Yamamoto and J. Oda, Agric. Biol. Chem., 50, 693 (1986). d) J. Hiratake, M. Inagaki, Y. Yamamoto and J. Oda, J. Chem sot Perkin Trans I 1053 (1987). e) M. Inagaki, J. Hiratake, Y. _"_'1 Yamamoto and J. Oda, Bull. -Chem. Sot. Jpn., 60, 4121 (1987). K. Osakada, M. Obana, T. Ikariya, M. Saburi and S. Yoshikawa,
Tetrahedron
Lett., 22, 4297 (1981). 10
T. Rosen, M. Watanabe and C. H. Heathcock, J. Org. Chem., 49, 3657 (1984);
11
T. Rosen and H. Heathcock, --J. Am. Chem. Sot., 107, 3731 (1985). 377 (1987); M. Ohshima, M. Ohshima and T. Mukaiyama, Chem. Lett.,
N.
Miyoshi and T. Mukaiyama, ibid., 1233 (1987). 12
The acid anhydrides not commercially available were prepared according to the reference: J. N. E. Day and J. F. Thorpe, J. Chem. Sot., 1465 (1920).
13
The specific rotations of the lactons; 3a (R1=CH3, 76%ee), [CL]:'+21.1' (c 2.35 CHC13)i 3b (R1=C2H5, 73%ee), [ali
14 15
+19.3" (c 2.34, CHC13); 3c (R1=n-
+12.7" (c 1.26, CHC13); 3d (R1=i-C3H7, 76%ee), [a]~5 C3H7' 60%ee), [ali +17.0° (c 0.68, C2H50H). G. Yabuta and K. Mori, Nippon Nogei Kagaku Kaishi, 56, 1121: Chem. Abstr., 98, 1791568 (1983). L. K. P. Lam, R. A. H. F. Hui and J. B. Jones, 2 J (1986). (Received in Japan 11 December 1987)
Org. Chem.,
51, 2047