1446 Bull. Chem. Soc. Jpn., 76, No. 7 (2003)
Lipase Reaction at Very Low Temperatures
V. Sunjic, Helv. Chim. Acta, 81, 85 (1998).
ˇ
´
rate: 1.0 mL/min. retention time = 30 min for (R)-2a and 43 min.
for (S)-2; 2: Daicel Chiralcel OD-H, hexane/i-PrOH (20:1), flow
rate: 0.5 mL/min; retention time = 43 min for (R)-2 and 49
min for (S)-2]. Details (E value, ee, and calculated conversion)
are summarized in Table 4.
´ ´
Review: E. Ljubovic, M. Majeric-Elenkov, A. Avdagic,
9
ˇ
´
and V. Sunjic, Food Technol. Biotechnol., 37, 215 (1999).
10 a) R. S. Phillips, Trends. Biotechnol., 14, 13 (1996). b) C.
Heiss, M. Laivenieks, J. G. Zeikus, and R. S. Phillips, J. Am.
Chem. Soc., 123, 345 (2001). The linear temperature effect on
enantioselectivity (ln E and 1=T) is not attributable to the confor-
mational change of enzyme, but meaning that the rigid transition
state for enantio-discrimination is preserved under the tempera-
tures examined.
(S)-2-Hydroxymethyl-1,4-benzodioxane ((S)-2):24 IR (neat)
1
3253 cmꢁ1; H NMR (CDCl3) ꢀ 2.03 (t, 1H), 3.89 (dd, J ¼ 4:8,
2.6 Hz, 2H), 4.05–4.16 (m, 1H), 4.21–4.33 (m, 2H), 6.80–6.92 (m,
26
4H); ½ꢁꢆD 28.4 (c 1.1, EtOH, 77% ee).
(S)-2-Acetoxymethyl-1,4-benzodioxane ((S)-2a): IR (neat)
1
1743 cmꢁ1; H NMR (CDCl3) ꢀ 2.11 (s, 3H), 4.06 (dd, J ¼ 4:8,
11 B. Galunsky, S. Ignatova, and V. Kasche, Biochim. Bio-
phys. Acta, 1343, 130 (1997): temperature dependence of enan-
tioselectivity for ꢁ-chymotrypsin.
2.6 Hz, 1H), 4.21–4.33 (m, 2H), 4.30–4.45 (m, 2H), 6.80–6.92 (m,
4H).
Lipase-Catalyzed Resolution of 2-Phenylpropanol ((Æ)-
4).2;22 Freshly distilled vinyl acetate (32 mg, 0.37 mmol) was
added to a cooled mixture of (ꢃ)-4 (50 mg, 0.37 mmol), lipase (6
mg in the reaction at 30 ꢂC, 45 mg at 0 ꢂC, 100 mg at ꢁ20 ꢂC, and
12 T. Sakai, Y. Miki, M. Tsuboi, H. Takeuchi, T. Ema, K.
Uneyama, and M. Utaka, J. Org. Chem., 65, 2740 (2000).
13 Here we used Toyonite type 200 without organic bridges
on the surface: a new type of spherical porous ceramics support
having 155 ꢃ 5 mm average diameter and 60 nm average sized
pores (Y. Yamashita, M. Kamori, H. Takenaka, and J. Takahashi,
Jpn. Kokai Tokkyo Koho, JP 09313179 (1997); U. S. Patent
6004786). Toyonite 200 was supplied by Toyo Denka Kogyo
Co. Ltd., Kochi, Japan. For the lipase-catalyzed reactions, we
attached the appropriate organic bridges and lipases on Toyonite
by ourselves as shown in experimental section. Commercially
available Toyonite 200M is the one that 3-(2-methylpropenoyl-
oxy)propylsilanetrioxyl groups are attached on Toyonite 200. Li-
pase PS-immobilized Toyonite 200M is also available from Ama-
no Pharmaceutical Co., Ltd. or Wako Pure Chemical Industries,
Ltd. as Lipase PS-C “Amano”b. See also Ref. 12.
ꢂ
150 mg at ꢁ30 C), and i-Pr2O (3 mL). Progress of the reaction
was monitored by TLC analysis (SiO2, hexane/EtOAc (4:1)), and
the reaction was stopped by filtration with suction at a suitable
conversion. The product mixture was purified by silica-gel col-
umn chromatography (SiO2 4 g, 1:1 ꢅ 11 cm, hexane/EtOAc
(50:1)) to yield (S)-4a and (R)-4. Then, a mixture of (S)-4a and
KOH (0.1 mL, 0.25 M) in MeOH (0.1 mL) was stirred at room
temperature for 12 h and treated in the usual manner to give (S)-4.
Optical purities (% ee) of (S)-4 and (R)-4 thus obtained were
determined by HPLC analyses with a chiral column (Daicel Chi-
ralcel OB-H, hexane/i-PrOH (50:1), flow rate 0.5 mL/min, detec-
tor 254 nm; (S)-4: retention time (rt) = 27.7 min; (R)-4: 30.3 min.)
Data for HPLC analyses in Table 3: for entry 1: E ¼ 2:1: (S)-4:
26% ee; (R)-4: 23% ee; E ¼ 3:4: (S)-4: 43% ee; (R)-4: 33% ee; for
entry 2: E ¼ 2:4: (S)-4: 29% ee; (R)-4: 27% ee; E ¼ 5:4: (S)-4:
50% ee; (R)-4: 41% ee.
14 M. Kamori, T. Hori, Y. Yamashita, Y. Hirose, and Y.
Naoshima, J. Mol. Catal. B: Enzym., 9, 269 (2000).
15 K. Kato, Y. Gong, T. Saito, and H. Kimoto, J. Biosci.
Bioeng., 90, 332 (2000).
16 M. Suzuki, C. Nagasawa, and T. Sugai, Tetrahedron, 57,
4841 (2001).
The authors are grateful to Amano Pharmaceutical Co. Ltd.
and Toyo Denka Kogyo Co. Ltd. for providing us with lipase
PS and the support Toyonite, respectively. We also thank the
SC-NMR laboratory for 1H and 13C NMR analyses. This work
was partially supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology.
17 For a current example: a) J. M. Palomo, G. F.-Lorente, C.
Mateo, M. Fuentes, R. F.-Lafuente, and J. M. Guisan, Tetrahe-
dron: Asymmetry, 13, 1337 (2002). b) M. Terreni, C. Mateo, A.
Bastida, P. Dalmases, L. Hugust, and J. M. Guisan, Enzyme Mi-
crob. Technol., 28, 389 (2001).
18 M. Yamatani and T. Yamasaki, (Shin-Etsu Chemical) Jpn.
Tokkyo Koho, JP 06005077 (1994).
19 J. Williams, Acc. Chem. Res., 26, 593 (1993). See also
Ref. 12.
20 M. Bradford, Anal. Biochem., 72, 248 (1976).
21 A. N. E. Weissfloch and R. J. Kazlauskas, J. Org. Chem.,
60, 6959 (1995).
22 5a: F. Iu and G. Liu, Macromolecules, 34, 1302 (2001); 5b:
C. W. Lee and R. H. Grubbs, J. Org. Chem., 66, 7155 (2001); 5c:
S. Warwel, G. Steinke, and M. R. Klass, Biotechnol. Tech., 10,
283 (1996); 5d: M. Hilker and S. Schulz, J. Chem. Ecol., 20, 1075
(1994); 5f: E. Hata, T. Yamada, and T. Mukaiyama, Bull. Chem.
Soc. Jpn., 68, 3629 (1995); 5g : T. Ikeda, S. Yue, and C. R.
Hutchinson, J. Org. Chem., 50, 5193 (1985).
23 6a: M. Yamatani and T. Yamasaki, (Shin-Etsu Chemical),
Jpn. Tokkyo Koho, JP 06005077 (1994); 6b: M. Yonekura, M.
Noda, and H. Yamanaka, Jpn. Tokkyo Koho, JP 09085891
(1997); 6c: M. Kawashima, I. Komura, and J. Yamauchi, Jpn.
Tokkyo Koho, JP 01050888 (1989).
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´
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8
r.t
ˇ
´
´
½ꢁꢆD 34.3 (c 0.7, EtOH); >99% ee.