Aline de Souza Ramos et al. / Tetrahedron: Asymmetry 20 (2009) 559–561
561
dea
Table 3
Microbial reduction of ethyl 2-methylacetoacetate
Microorganisms
Conversion
ee (2R,3S) (syn)
ee (2S,3S) (anti)
(2R,3S) (syn)/(2S,3S) (anti) ratio
Kluyveromyces marxianus
Candida sp.
Hansenula sp.
99
93
40
73
10
24
15
89
93
100
100
87
14
59
78
78
83
73
80
79
79
76
77
50
100
100
100
100
100
100
100
100
100
100
100
100
1/4.9
1/7.2
1/1.5
1.7/1
2.8/1
2.2/1
2.1/1
4/1
3.9/1
1/1.6
1/1.8
1/7.6
66
76
20
27
47
37
68
61
60
24
29
77
Pichia sp.
Saccharomyces cerevisiae 60
Saccharomyces cerevisiae 40
Saccharomyces cerevisiae 80
Rhodotorula minuta
Rhodotorula rubra
Trichoderma harzianum
Mucor ramannianus
Aspergillus níger
a
Comparison between the 2 syn isomers and the 2 anti isomers. de = syn À anti/syn + anti.
A
B
A
A
B
C
C
D
E
B
C
D
E
D
E
3
4
5
6
7
8
9
min
3
4
5
6
7
min
3
4
5
min
Ethyl 2-methylacetoacetate: A.
Ethyl acetoacetate. A. substrate; B. racemate; C.
R-enantiomer; D. R.rubra; E. K.marxianus.
BGB 176 ; isoterma75°C (10min).
Methyl acetoacetate. A. substrate; B.
racemate; C. Pichia sp.; D. M. ramannianus;
E. A.niger.
substrate; B. racemate; C. Candida
sp.; D.T.harzianun; E.R.rubra.
BGB-176 100°C (7min)
BGB 176 isoterma 70ºC
Figure 3. Typical chromatograms showing the selectivities achieved.
that good results can be obtained even with flexible substrates, so
1465; (d) Gonçalves, L. P. B.; Pinto, G. F.; Antunes, O. A. C.; Oestreicher, E. G. J.
Mol. Catal. B 1998, 4, 67; (e) Gonçalves, L. P. B.; Pinto, G. F.; Antunes, O. A. C.;
Oestreicher, E. G. Tetrahedron: Asymmetry 1996, 7, 1237; (f) Adam, W.; Lazarus,
M.; Boss, B.; Saha-Möller, CR.; Humpf, H. U.; Schreier, P. J. Org. Chem. 1997, 62,
confirming Scilimati et al. previous findings.22
Examples of chromatograms obtained are shown in Figure 3.
7841–7843; (g) Sordedrager, M. J.; van Ranjwijk, F.; Huisman, G. W.; Sheldon,
R. A. Adv. Synth. Catal. 2008, 350, 2322; (f) Perrone, M. G.; Santandrea, E.;
Scilimati, A.; Syldatk, C. Adv. Synth. Catal. 2007, 349, 1111.
0. Wong, C. H.; Whitesides, G. M. Enzymes in Synthetic Organic Chemistry; Elsevier
Science Ltd: Oxford, 1994. pp 131–194.
3
. Conclusions
1
Twelve different microorganisms were used in the reduction of
1
1. Kitayama, T. Tetrahedron: Asymmetry 1997, 22, 3765–3774.
2. Panke, S.; Wubbolts, M. G.; Schmid, A.; Withold, B. Biotechnol. Bioeng. 2000, 69,
91–100.
ethyl 2-methylacetoacetate. Diastereoisomer ratios were good and
00% anti enantioselectivity was achieved. In addition, with the
1
1
model compounds, ethyl and methyl acetoacetates very high ees
were obtained and an unexpected stereochemical reversion was
noticed changing the ester from methyl to ethyl using K. marxianus
and T. harzianum.
13. Salvi, N. A.; Chattopadhyay, S. Tetrahedron: Asymmetry 2004, 15, 3397–
400.
4. Matsumura, K.; Kawada, M.; Sugihara, Y. Japan Kokai Tokkyo Koho 1990, 2–
38235.
15. (a) Miya, K.; Kawada, M.; Sugiyama, Y. Biosci. Biotechnol. Biochem. 1996, 60, 95–
8; (b) Isihara, K.; Iwai, K.; Yamaguchi, H.; Kakajima, N.; Nakamura, K.;
3
1
1
9
Ohshima, T. Biosci. Biotechnol. Biochem. 1996, 60, 1896–1898; (c) Nakamura, K.;
Myiai, T.; Nozaki, K.; Ushio, K.; Oka, S.; Ohno, A. Tetrahedron Lett. 1986, 27,
References
3155–3156; (d) Bingfeng, P.; Jianxing, G.; Zuyi, L.; Ward, O. P. Enzym. Microb.
1
2
3
.
.
.
Mori, K. Tetrahedron 1989, 45, 3233–3298.
Technol. 1995, 17, 853–855; (e) Kuramoto, T.; Iwamoto, K.; Izumi, M.; Kirihata,
M.; Yoshizako, F. Biosci. Biotechnol. Biochem. 1999, 63, 598–601; (f) Buisson, D.;
Sanner, C.; Larcheveque, M.; Azerad, R. Tetrahedron Lett. 1987, 28, 3939–3940;
(g) Nakamura, K.; Myioshi, H.; Sugiyama, Y.; Hamada, H. Phytochemistry 1995,
40, 1419–1420.
Sheldon, R. A. Chirotechnology; Dekker: New York, 1993.
Ribeiro, J. B.; Ramos, M. C. K. V.; Aquino Neto, F. R.; Leite, S. G. F.; Antunes, O. A.
C. J. Mol. Catal. B 2003, 24–25. 121–124.
4
.
Soai, K.; Takashi, Y.; Hitoshi, H.; Oyamada, H. J. Chem. Soc., Chem. Commun.
1
985, 138–139.
16. Iwamoto, K.; Kuramoto, T.; Izumi, M.; Kirihata, M.; Dohmaru, T.; Yoshizako, F.
Biosci. Biotechnol. Biochem. 2000, 64, 194–197.
17. (a) Assuncao, J. C. C.; Machado, L. L.; Lemos, T. L. G.; Cordell, G. A.; Monte, F. J. Q.
J. Mol. Catal. B 2008, 52–53, 194–198; (b) Villa, R.; Molinari, J. Nat. Prod. 2008,
71, 693–696.
18. (a) Pereira, R. S. Quim. Nova 1995, 18, 452–459; (b) Molinari, F.; Gandolfi, R.;
Villa, R.; Occhiato, E. G. Tetrahedron: Asymmetry 1999, 10, 3515–3520; (c)
Nakamura, K.; Higaki, M.; Ushio, K.; Oka, S.; Ohno, A. Tetrahedron Lett. 1985, 26,
4213–4216.
19. Shieh, W.; Gopalan, A. S.; Sih, C. J. J. Am. Chem. Soc. 1985, 107, 2993–2994.
20. Speichner, A.; Roeser, H.; Heisel, R. J. Mol. Catal. B 2003, 22, 71–77.
21. Ribeiro, J. B.; Sousa, L. M. A.; Soares, M. V.; Ramos, M. C. K. V.; de Aquino Neto, F.
R.; Fraga, C. A. M.; Leite, S. G. F.; Cordeiro, Y.; Antunes, O. A. C. Tetrahedron:
Asymmetry 2006, 17, 984.
5
6
.
.
Noyori, R. Angew. Chem., Int. Ed. 2002, 41, 2008–2022.
Alessandrini, S.; Bartoli, G.; Bellucci, M. C.; Dalpozzo, R.; Malavolta, M.;
Marcantoni, E.; Sambri, L. J. Org. Chem. 1999, 64, 1986.
(a) Evans, D. A.; Morrissey, M. M.; Dorow, R. L. J. Am. Chem. Soc. 1985, 107,
4
7
.
.
346–4348; (b) Ribeiro, L. P.; Antunes, O. A. C.; Bergter, L.; Costa, P. R. R.
Tetrahedron: Asymmetry 1994, 5, 1873–1874.
8
(a) Lacerda, P. S. B.; Ribeiro, J. B.; Leite, S. G. F.; Coelho, R. B.; Lima, E. L. S.;
Antunes, O. A. C. Biochem. Eng. J. 2006, 28, 3, 299–302; (b) Ribeiro, J. B.; Ramos,
M. C. K. V.; Aquino Neto, F. R.; Leite, S. G. F.; Antunes, O. A. C. Catal. Commun.
2
005, 6, 131–133; (c) De Wildeman, S. M. A.; Sonke, T.; Shoemaker, H. E.; May,
O. Acc. Chem. Res. 2007, 40, 1260.
(a) Gonçalves, L. P. B.; Antunes, O. A. C.; Oestreicher, E. G. Org. Process Res. Dev.
9
.
2
006, 10, 673–677; (b) Gonçalves, L. P. B.; Antunes, O. A. C.; Pinto, G. F.;
Oestreicher, E. G. J. Fluorine Chem. 2003, 124, 219; (c) Gonçalves, L. P. B.; Pinto,
G. F.; Antunes, O. A. C.; Oestreicher, E. G. Tetrahedron: Asymmetry 2000, 11,
22. Perrone, M. G.; Santandrea, E.; Scilimati, A.; Tortorella, V.; Capitelli, F.;
Bertolasi, V. Tetrahedron: Asymmetry 2004, 15, 3501.