Enzymatic desymmetrization of meso-1α,4α-dihydroxy-cis-decalins

Article abstract of DOI:10.1016/j.tetasy.2004.10.004

The stereoselective acetylation of meso-decalindiols 1 and 2 by vinyl acetate in the presence of Candida antarctica lipase gave monoester (1R,4S,4aR,8aS)-5 and (1R,4S,4aR,8aS)-6 in high enantiomeric excess (ee ≥98%). The hydrolysis of the corresponding meso-diacetates 3 and 4 in the presence of porcine liver esterase in phosphate buffer provided the opposite enantiomers.

Full text of DOI:10.1016/j.tetasy.2004.10.004

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3587–3590
Enzymatic desymmetrization of meso-1a,4a-dihydroxy-cis-decalins
*
Robert Ch eˆ nevert, Gabriel Courchesne and Fr e´ d e´ ric Jacques
D e´ partement de Chimie, CREFSIP, Facult e´ des Sciences et de G e´ nie, Universit e´ Laval, Qu e´ bec, Canada G1K7P4
Received 18 August 2004; accepted 7 October 2004
Abstract—The stereoselective acetylation of meso-decalindiols 1 and 2 by vinyl acetate in the presence of Candida antarctica lipase
gave monoester (1R,4S,4aR,8aS)-5 and (1R,4S,4aR,8aS)-6 in high enantiomeric excess (ee P98%). The hydrolysis of the corre-
sponding meso-diacetates 3 and 4 in the presence of porcine liver esterase in phosphate buffer provided the opposite enantiomers.
ꢀ
2004 Elsevier Ltd. All rights reserved.
1
. Introduction
OH
OH
OH
OH
H
H
a
The decalin ring system is an important structural fea-
ture often encountered in many natural products espe-
H
H
1
–5
cially in terpenoid compounds. Decalins exist in two
stereoisomeric configurations; cis-decalin in which the
substituents are on the same side of the ring junction,
and trans-decalin in which they are on the opposite sides.
The trans junction is more common but the cis junction is
found in a significant number of natural products. Given
the importance of the cis-decalin ring systems, the devel-
opment of their synthesis has been the subject of consid-
1
2
b
b
OAc
OAc
H
H
6
–20
H
H
erable interest.
Herein we report the enzymatic
desymmetrization of meso-1a,4a-dihydroxy-cis-decalins.
OAc
OAc
3
4
2 2
Scheme 1. Reagents and conditions: (a) H , Pd/C, EtOAc; (b) Ac O,
pyridine.
2
. Results and discussion
.1. Substrate preparation
Diol 1 was prepared in three steps from cis-1,3-butadiene
2
diols 1 and 2 were subjected to the enzyme-catalyzed
esterification by treatment with Pseudomonas cepacia
lipase (PCL) in vinyl acetate (solvent and acyl donor)
to give optically active esters (1R,4S,4aR,8aS)-5 and
2
1
and p-benzoquinone according to a known procedure.
Hydrogenation of 1 in ethyl acetate over palladium on
carbon gave the saturated diol 2 (Scheme 1). Corre-
sponding diacetates 3 and 4 were prepared by the acetyl-
ation of 1 and 2 with acetic anhydride in pyridine.
(1R,4S,4aR,8aS)-6 in high yield (85%) and high enantio-
2
2
meric excess (P98%) along with traces of the corre-
sponding achiral diesters 3 and 4 (Scheme 2). Only one
enantiomer of monoacetate 5 or 6 was detected by chiral
GC but the reaction was slow (ꢀ3days). The use of
Candida antarctica lipase B (CAL-B) as catalyst at
2
.2. Enzymatic desymmetrizations
4
0ꢁC gave the same yields and enantiomeric excesses
Initially, a wide range of lipases and esterases were
screened for activity with the meso-substrates 1–4. First,
in a shorter reaction time (1day).
In general, the esterification (transesterification) of
meso-diols and the hydrolysis of the corresponding
meso-diesters are complementary and give the opposite
enantiomers. Unexpectedly, many enzymes including
*
Corresponding author. Tel.: +1 418 656 3283; fax: +1 418 656
916; e-mail: robert.chenevert@chm.ulaval.ca
7
0
957-4166/$ - see front matter ꢀ 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.10.004

3588
R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 15 (2004) 3587–3590
OH
OAc
OAc
OAc
OAc
OR
OH
H
H
H
H
H
H
H
a
b
a
a
+
+
H
1
H
5
H
3
H
OH
OH
OH
OAc
OAc
OH
6 R = H
5
8
7
R = Ms
OAc
H
H
H
c
OH
H
OH
H
H
H
H
H
OH
OH
OAc
2
6
4
+
H
Scheme 2. Reagents and conditions: (a) Pseudomonas cepacia lipase,
vinyl acetate, rt or Candida antarctica lipase B, vinyl acetate, 40ꢁC.
(1S)-10
(1R)-9
Scheme 4. Reagents and conditions: (a) (i) H
2
, Pd/C, EtOAc; (ii)
PCL and CAL-B showed no or very little hydrolytic
activity in the presence of diesters 3 and 4. Hydrolysis
of diesters 3 and 4 by pig liver esterase (PLE) in a phos-
phate buffer provided enantiomerically pure (ee P98%)
monoesters (1S,4R,4aS,8aR)-5 and (1S,4R,4aS,8aR)-6
(60–70% yield) and the corresponding achiral diols 1
and 2 (30–40% yield) indicating that monoacetates were
also substrates (Scheme 3).
MsCl, Et N, CH Cl ; (b) LiAlH , THF; (c) H , Pd/C, EtOAc.
4
3
2
2
2
on a Bomem MB-100 spectrometer. Optical rotations
were measured using a JASCO DIP-360 digital polari-
meter (c as gram of compound per 100mL). Flash column
chromatography was carried out using 40–63lm (230–
400 mesh) silica gel. Lipase PS from P. cepacia was a gift
from Amano International Enzyme Co. C. antarctica
lipase B (chirazyme L-2) was obtained from Boehringer
Mannheim and pig liver esterase from Sigma Chem.
Co. The enantiomeric excesses (ee) were determined by
GC analysis on a Chiraldex B-DM (b-cyclodextrin
dimethyl) capillary column (30m · 0.25mm) using
racemic compounds as references.
OAc
OH
OH
H
H
H
a
a
+
+
H
3
H
5
H
1
OAc
OAc
OAc
OH
OH
OH
H
H
H
3
.2. (1R,4S,4aR,8aS)-Decahydronaphthalene-1,4-diol 2
A solution of meso-diol 1 (417mg, 2.48mmol) in ethyl
acetate (10mL) was stirred at rt with 10% Pd-on-carbon
(125mg) under hydrogen (40psi) for 4h. The catalyst
was removed by filtration on Celite and the solvent
H
H
H
OAc
OAc
OH
4
6
2
Scheme 3. Reagents and conditions: (a) pig liver esterase, phosphate
buffer, pH7.
evaporated to give 2 (417mg, quantitative yield) as a
2
2
white solid: mp 93–94ꢁC; lit. mp 93–94ꢁC; IR (KBr)
À1
1
3
456, 2945, 1726, 1448, 1027, 949cm
;
H NMR
The absolute configurations of monoesters 5 and 6 were
determined by chemical correlation with compounds 9
and 10 of known absolute configurations (Scheme 4).
Hydrogenation of 5 in the presence of 10% Pd/C gave
the saturated compound 6, which was then treated with
mesyl chloride in pyridine to yield 7. Treatment of 7
(
(
2
400MHz, CDCl ): d 1.40 (m, 14H), 2.79 (s, 2H), 3.59
3
13
m, 2H); C NMR (100MHz, CDCl ): d 24.9, 26.0,
3
7.4, 39.2, 72.6.
3
.3. Preparation of diacetates 3 and 4: general procedure
with LiAlH reduced the acetyl and mesylate groups
4
2
3
To a stirred solution of diol 1 or 2 (3.8mmol) in pyridine
(5mL) was added acetic anhydride (3equiv) and the
solution stirred overnight at rt. The solvent was co-evap-
orated with hexanes and CH Cl . The crude product
to give 8. Hydrogenation of 8 in the presence of 10%
22
Pd/C gave the saturated compounds 9, ½aŠ ¼ À35:3 (c
D
2
4
25
D
0
(
lit.
.22, EtOH); lit. ½aŠ ¼ À34:5 (c 1.1, EtOH) for the
2
2
2
2
1R)-enantiomer, and 10, ½aŠ ¼ þ24:0 (c 1.25, CHCl );
D
3
25
21
D
was purified by flash chromatography (hexanes/EtOAc,
6
½aŠ ¼ À22:0 (c 1.0, CHCl ) for the (1S)-
3
:1) to give diester 3 or 4 (87–90%).
enantiomer.
3.3.1. (1R,4S,4aR,8aS)-4-(Acetyloxy)-1,2,3,4,4a,5,8,8a-
octahydronaphthalen-1-yl acetate 3. White solid: mp
3. Experimental
2
1
5
6–57ꢁC; lit. mp 56–57ꢁC; IR (KBr) 3449, 2933,
À1
1
3
.1. General
1735, 1234, 1025cm ; H NMR (400MHz, CDCl ): d
3
1
.52 (m, 2H), 1.80 (m, 14H), 4.93 (m, 2H), 5.52
1
3
NMR spectra were recorded on a Varian Inova AS400
spectrometer (400MHz). Infrared spectra were recorded
(s, 2H); C NMR (100MHz, CDCl ): d 21.5, 25.0,
3
27.4, 35.0, 73.6, 125.4, 170.7.

R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 15 (2004) 3587–3590
3589
3.3.2. (1R,4S,4aR,8aS)-4-(Acetyloxy)-decahydronaphth-
alen-1-yl acetate 4. Colorless oil; IR (NaCl) 3449,
tate (10mL) was stirred at rt with 10% Pd-on-carbon
(160mg) under hydrogen (40psi) for 4h. The catalyst
was then removed by filtration on Celite and the solvent
evaporated. The crude product was purified by flash
À1
1
2
933, 1735, 1375, 1234, 1025cm
;
H
NMR
(
4
400MHz, CDCl ): d 1.50 (m, 14H), 1.92 (m, 6H),
3
1
3
.79 (m, 2H); C NMR (100MHz, CDCl ): d 21.2,
chromatography (hexanes/EtOAc, 3:1) to give 6
3
22
D
2
calcd for C H NO (M+NH ) : 272.1862. Found:
5.2, 26.1, 29.2, 39.0, 72.5, 170.3; HRMS (CI, NH )
(519mg, 87%) as a colorless oil: ½aŠ ¼ À26:5 (c 2.1,
3
+
CHCl ).
3
1
4
26
4
4
2
72.1865.
3
.6.2.
(1R,4S,4aR,8aS)-4-[(Methylsulfonyl)oxy]-deca-
hydronaphthalen-1-yl acetate 7. To a stirred solution
3.4. Enzymatic acylation of diols 1 and 2: general
procedure
of 6 (243mg, 1.14mmol) and triethylamine (796lL,
5
.70mmol) in anhydrous CH Cl (20mL) under a dry
2 2
To a stirred solution of diol 1 or 2 (0.63mmol) in vinyl
acetate (5mL) was added the lipase (50mg, PCL at rt or
CAL-B at 40ꢁC). The reaction course was monitored by
TLC and when the substrate had disappeared (ꢀ3days
with PLC, ꢀ1day with CAL-B), the mixture was filtered
and the solvent evaporated. The crude product was puri-
fied by flash chromatography (CH Cl /acetone, 98:2) to
atmosphere at 0ꢁC was added dropwise a solution of
mesyl chloride (352lL, 4.56mmol) in CH Cl (3mL).
The mixture was stirred overnight at rt, diluted with
ethyl acetate (25mL), then washed with 3M HCl
2
2
(
(
2 · 20mL), saturated NaHCO3 (25mL), brine
2 · 20mL), dried over MgSO , and evaporated. The
4
2
2
crude product was purified by flash chromatography
(hexanes/EtOAc, 1:1) to yield 7 (301mg, 91%) as a
give 5 or 6 (85%) as colorless oils.
22
colorless oil: ½aŠ ¼ À17:2 (c 2.1, CHCl ); IR (NaCl)
D
017, 2869, 1730, 1448, 1372, 1254, 1029, 930cm ; H
3
À1
1
3
.4.1. (1R,4S,4aR,8aS)-4-Hydroxy-1,2,3,4,4a,8,8a-octa-
3
22
hydronaphthalen-1-yl acetate 5. ½aŠ ¼ þ44:7 (c 2.1,
D
CHCl ); IR (NaCl) 3371, 3020, 2917, 1732, 1435, 1375,
NMR (400MHz, CDCl ): d 1.28 (m, 2H), 1.55 (m,
10H), 1.88 (m, 2H), 1.98 (s, 3H), 2.94(s, 3H), 4. 71 (m,
1H), 4.85 (m, 1H); C NMR (100MHz, CDCl ): d
21.8, 23.8, 27.7, 28.4, 38.1, 38.9, 73.5, 83.2, 170.5;
HRMS (CI, NH ) calcd for C H O S (M+NH ) :
308.1532. Found: 308.1536.
3
3
À1
1
1
3
1
248, 1038cm ; H NMR (400MHz, CDCl ): d 1.44
3
3
(
(
m, 2H), 1.70 (m, 2H), 1.87 (s, 3H), 2.01 (m, 6H), 2.41
s, 1H), 3.74(m, 1H), 4. 86 (m, 1H), 5.60 (m, 2H);
1
3
+
C
3
13 22
5
4
NMR (100MHz, CDCl ): d 21.5, 24.3, 25.8, 26.7, 28.2,
3
3
4.8, 36.7, 72.1, 74.3, 126.0, 126.9, 170.9; HRMS (CI,
NH ) calcd for C H O (M+H) : 211.1334. Found:
+
3
12 18
3
3.6.3. (1R,8aS)-1,2,3,5,6,7,8,8a-Octahydronaphthalen-1-
ol 8. To a solution of 7 (103mg, 0.35mmol) in anhy-
2
11.1338.
drous THF (4mL) was added dropwise a solution of
LiAlH (1M in THF, 1,79mL, 1.79mmol) and the mix-
4
ture was stirred at rt under dry atmosphere for 4h. The
mixture was cooled to 0ꢁC and carefully quenched by
dropwise addition of water (100lL), followed by a
3
1
3
.4.2. (1R,4S,4aR,8aS)-4-Hydroxydecahydronaphthalen-
22
-yl acetate 6. ½aŠ ¼ À26:5 (c 4.0, CHCl ); IR (NaCl)
D
448, 2864, 1734, 1447, 1376, 1251, 1024cm ; H NMR
3
À1 1
(
(
(
400MHz, CDCl ): d 1.32 (m, 2H), 1.60 (m, 13H), 2.03
3
13
s, 3H), 3.80 (m, 1H), 4.91 (m, 1H);
C NMR
0
.15M NaOH solution (100lL). The white inorganic
precipitate was filtered off and washed with ethyl ether.
The combined filtrates were dried (MgSO ) and evapo-
100MHz, CDCl ): d 22.0, 24.1, 25.1, 27.0, 38.1, 40.6,
3
72.7, 74.7, 170.8; + HRMS (CI, NH3) calcd for
C H O (M+NH ) : 230.1756. Found: 230.1760.
4
1
2
20
3
4
rated. The crude product was purified by flash chroma-
tography (hexanes/EtOAc, 2:1) to give 8 (47mg, 88%) as
3.5. Enzymatic hydrolysis of diesters 3 and 4: general
procedure
22
2
3
a colorless oil: ½aŠ ¼ þ22:0 (c 1.0, CHCl ); IR (NaCl)
D
361, 2927, 2851, 1457, 1374, 1258, 1043, 947cm ; H
3
À1
1
3
NMR (400MHz, CDCl ): d 1.15–2.17 (m, 14H), 3.86
(
3
In a typical experiment, a suspension of ester 3 or 4
(
13
m, 1H), 5.29 (m, 1H); C NMR (100MHz, CDCl3)
0.40mmol) was hydrolyzed with PLE (10mg) in a phos-
22.1, 26.4, 28.1, 28.2, 28.7, 35.7, 43.0, 69.4, 118.4, 139.1.
phate buffer (5mL, pH7) at 38ꢁC. The reaction was
monitored by TLC, and terminated when the substrate
had disappeared (ꢀ48h). The mixture was extracted
with CH Cl (3 · 25mL), and the combined organic
3.6.4. Reduction of olefin 8. A solution of 8 (40mg,
0,26mmol) in diethyl ether (10mL) was stirred at rt with
10% Pd-on-carbon (50mg) under hydrogen (55psi) for
2h. The catalyst was removed by filtration on Celite
2
2
phases dried over MgSO and evaporated. The crude
4
product was purified by flash chromatography (hex-
anes/EtOAc, 3:1) to give monoesters 5 and 6 (57–63%)
as colorless oils and diols 1 and 2 (25–35%). Monoester
and the solvent evaporated. The crude product was puri-
fied by flash chromatography (hexanes/Et O, 3:1) to give
2
2
D
2
9
(11mg, 27%) and 10 (25mg, 62%) as white solids.
5
: ½aŠ ¼ À44:7 (c 1.3, CHCl ), ee P98%, spectral data
3
2
D
2
as above. Monoester 6: ½aŠ ¼ þ26:5 (c 1.2, CHCl ), ee
3
P98%, spectral data as above.
3.6.5. (1R,4aS,8aS)-Decahydronaphthalen-1-ol 9. Mp
24
2
D
2
7
2–73ꢁC; ½aŠ ¼ À35:3 (c 0.22, EtOH); lit.
25
3.6. Determination of absolute configuration by chemical
correlation
½aŠ ¼ À34:5 (c 1.1, EtOH); IR (KBr) 3374, 2924,
D
2841, 1445, 1319, 1057, 1011, 942cm
À1
1
;
H NMR
(
400MHz, CDCl ): d 0.92–1.85 (m, 17H), 3.75 (m,
3
13
3
2
.6.1. Reduction of 5 to 6. A solution of 5 (459mg,
.18mmol; from CAL-B or PCL acylation) in ethyl ace-
1H); C NMR (100MHz, CDCl ): d 20.0, 26.4, 26.8,
3
29.7, 33.7, 33.9, 34.4, 35.6, 47.2, 70.7.

3590
R. Ch eˆ nevert et al. / Tetrahedron: Asymmetry 15 (2004) 3587–3590
3
6
.6.6. (1R,4aR,8aS)-Decahydronaphthalen-1-ol 10. Mp
25
9. Anderson, J. C.; Blake, A. J.; Graham, J. P.; Wilson, C.
Org. Biomol. Chem. 2003, 1, 2877–2885.
0. Fleming, F. F.; Zhang, Z. Y.; Wang, Q. Z.; Steward, O.
W. J. Org. Chem. 2003, 68, 7646–7650.
2
2
21
D
7–69ꢁC; ½aŠ ¼ þ24:0 (c 1.25, CHCl ); lit. ½aŠ ¼
D
3
1
À22:0 (c 1.0, CHCl ); IR (KBr) 3318, 2926, 2856,
3
À1
1
448, 1089, 1061, 1030, 938cm ; H NMR (400MHz,
1
1
3
11. Jung, M. E.; Piizzi, G. J. Org. Chem. 2003, 68, 2572–
582.
2. Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103,
945–2963.
3. Guay, B.; Deslongchamps, P. J. Org. Chem. 2003, 68,
140–6148.
4. Abd Rahman, N.; Landais, Y. Curr. Org. Chem. 2002, 6,
369–1395.
CDCl ): d 1.06–1.84(m, 17H), 3.60 (m, 1H);
NMR (100MHz, CDCl ): d 19.1, 21.8, 24.5, 24.6, 26.5,
2
C
3
2
3
1
1
1
9.6, 32.0, 36.0, 43.1, 73.8.
2
6
Acknowledgements
1
The authors would like to thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support. G.C. was the holder of a NSERC
postgraduate scholarship.
1
1
5. Singh, V.; Iyer, S. Chem. Commun. 2001, 2578–2579.
6. Tsai, Y. F.; Peddinti, R. K.; Liao, C. C. Chem. Commun.
2000, 475–476.
17. Melekhov, A.; Forgione, P.; Legoupry, S.; Fallis, A. G.
Org. Lett. 2000, 2, 2793–2796.
1
8. Tokoroyama, T. Synthesis 2000, 611–633.
19. Liu, H. J.; Yip, J. Synlett 2000, 1119–1122.
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