T. Miyazawa et al. / Tetrahedron Letters 48 (2007) 8334–8337
8337
COCH2CH3), 6.92 (1H, d, J = 2.5 Hz, H-2), 6.98 (1H,
dd, J = 8.5 and 2.5 Hz, H-6), 7.33 (1H, d, J = 8.5 Hz,
H-5).
where CAL-B is known to be an excellent enantioselec-
tive biocatalyst.11 In contrast, this lipase has no measur-
able activity on reactions with tertiary alcohols or
secondary alcohols bearing two large or bulky groups.
Such a salient substituent size limitation has been
explained by the existence in the lipase’s alcohol binding
site of the stereospecificity pocket,12 which practically
can accept a substituent shorter than n-propyl.
7. Boehringer Mannheim Chirazyme L-2, which had a
specific activity of 3.2 U/mg lyo. with tributyrin at 25 °C.
8. Typical experimental procedure: A solution of 4-ethyl-1,3-
di-O-propanoylresorcinol (1a) (0.05 mmol) and 2-propa-
nol (0.15 mmol) in anhydrous diisopropyl ether (240 ll)
was stirred with a lipase preparation (25 mg) at 45 °C (in a
thermostated incubator). After a certain period of time,
the reaction mixture was filtered through a glass filter and
evaporated to dryness under reduced pressure. The
residual oil was dissolved in DMSO-d6 and subjected to
1H NMR (500 MHz) analysis for the quantification of the
reaction products. The proton signals in the aromatic
region were mainly employed for the purpose. The whole
content of the reaction mixture was used up for one
analysis, and several discrete reaction mixtures were used
at different reaction times.
In conclusion, CAL-B has sufficient activity and high
regioselectivity in the deacylation of peracylated pheno-
lic hydroxyls. In the CAL-B-catalyzed reactions, second-
ary alcohols can act as better nucleophiles than primary
alcohols.
References and notes
9. The authentic samples of isomeric monoesters of each
dihydroxybenzene were prepared by enzymatic methods.
For example, both the monopropanoates of 4-ethylresor-
cinol (4a) were prepared as follows: 4-Ethyl-3-O-propa-
noylresorcinol (2a) was prepared as the main product of
the lipase-catalyzed deacylation of 4-ethyl-1,3-di-O-prop-
anoylresorcinol (1a) (0.5 mmol) as described in Ref. 8 and
purified by preparative TLC on silica gel using toluene–
ethyl acetate (9:1, v/v) as a developing solvent. On the
other hand, the isomer of 2a, that is, 4-ethyl-1-O-propa-
noylresorcinol (3a), was prepared as the main product of
the lipase-catalyzed direct acylation of 4-ethylresorcinol
(4a) (1.5 mmol) with vinyl propanoate in diisopropyl ether
at 45 °C and purified in the same manner as above. The
structure of these isomeric monoesters was unambigu-
ously determined by 1H NMR (500 MHz), 13C NMR, and
2D NMR. Thus, for example, cross-peaks of the proton of
1-OH with the carbons at C-1, C-2, and C-6 appeared in
1. For reviews, see: (a) Faber, K. Biotransformations in
Organic Chemistry, 5th ed.; Springer: Berlin, 2004; pp 94–
123, 344–367; (b) Gais, H. J.; Theil, F. In Enzyme
Catalysis in Organic Synthesis; Drauz, K., Waldmann,
H., Eds.; Wiley-VHC: Weinheim, 2002; pp 335–578.
2. (a) Parmar, V. S.; Prasad, A. K.; Sharma, N. K.; Singh, S.
K.; Pati, H. N.; Gupta, S. Tetrahedron 1992, 48, 6495–
6498; (b) Parmar, V. S.; Prasad, A. K.; Sharma, N. K.;
Vardhan, A.; Pati, H. N.; Sharma, S. K.; Bisht, K. S. J.
Chem. Soc., Chem. Commun. 1993, 27–29; (c) Bisht, K. S.;
Tyagi, O. D.; Prasad, A. K.; Sharma, N. K.; Gupta, S.;
Parmar, V. S. Bioorg. Med. Chem. 1994, 2, 1015–1020; (d)
Parmar, V. S.; Kumar, A.; Bisht, K. S.; Mukherjee, S.;
Prasad, A. K.; Sharma, S. K.; Wengel, J.; Olsen, C. E.
Tetrahedron 1997, 53, 2163–2176.
3. They have also reported on the lipase-catalyzed chemo-
and regioselective deacylation of peracetylated enolic
forms of polyphenolic benzyl phenyl ketones: Parmar, V.
S.; Pati, H. N.; Azim, A.; Kumar, R.; Himanshu; Bisht, K.
S.; Prasad, A. K.; Errington, W. Bioorg. Med. Chem. 1998,
6, 109–118.
4. (a) Natoli, M.; Nicolosi, G.; Piattelli, M. Tetrahedron Lett.
1990, 31, 7371–7374; (b) Natoli, M.; Nicolosi, G.; Piattelli,
M. J. Org. Chem. 1992, 57, 5776–5778.
1
the HMBC spectrum of 2a. Selected data for 2a: oil; H
NMR (500 MHz, DMSO-d6): d 1.05 (3H, t, J = 7.5 Hz,
ArCH2CH3), 1.14 (3H, t, J = 7.5 Hz, COCH2CH3), 2.34
(2H, q, J = 7.5 Hz, ArCH2CH3), 2.59 (2H, q, J = 7.5 Hz,
COCH2CH3), 6.43 (1H, d, J = 2.5 Hz, H-2), 6.61 (1H, dd,
J = 8.5 and 2.5 Hz, H-6), 7.06 (1H, d, J = 8.5 Hz, H-5),
9.45 (1H, s, OH). For compound 3a: oil; 1H NMR
(DMSO-d6): d 1.11 (3H, t, J = 7.5 Hz, COCH2CH3), 1.12
(3H, t, J = 7.5 Hz, ArCH2CH3), 2.51 (2H, q, J = 7.5 Hz,
COCH2CH3), 2.55 (2H, q, J = 7.5 Hz, ArCH2CH3),
6.46 (1H, dd, J = 8.5 and 2.5 Hz, H-6), 6.52 (1H, d,
J = 2.5 Hz, H-2), 7.05 (1H, d, J = 8.5 Hz, H-5), 9.55
(1H, s, OH).
5. Rubio, E.; Fernandez-Mayorales, A.; Klibanov, A. M. J.
Am. Chem. Soc. 1991, 113, 695–696.
6. The substrates were prepared through the acylation of the
parent dihydroxybenzenes with propanoyl chloride
(3 mol equiv) in dry pyridine at ambient temperature
and purified by column chromatography on silica gel
using toluene–ethyl acetate as an eluent. Selected data for
1a: oil; 1H NMR (500 MHz, DMSO-d6): d 1.11 (3H,
t, J = 7.5 Hz, ArCH2CH3), 1.12 (3H, t, J = 7.5 Hz,
COCH2CH3), 1.16 (3H, t, J = 7.5 Hz, COCH2CH3),
2.47 (2H, q, J= 7.5 Hz, ArCH2CH3), 2.58 (2H, q,
J = 7.5 Hz, COCH2CH3), 2.63 (2H, q, J = 7.5 Hz,
10. The reaction time for the PCL-catalyzed deacylation of
peracetylated flavonoids was 24 h: see, Ref. 4.
11. For a review on the application of CAL-B in organic
synthesis, see: Anderson, E. M.; Larsson, K. M.; Kirk, O.
Biocatal. Biotrans. 1998, 16, 181–204.
¨
12. Orrenius, C.; Hæffner, F.; Rotticci, D.; Ohrner, N.; Norin,
T.; Hult, K. Biocatal. Biotrans. 1998, 16, 1–15.