An efficient Amano PS-catalyzed chemo-, regio- and enantioselective hydrolysis of (±)-2,3-di-O-acetyl-2-C-methyl-d-erythrono-1,4-lactone: a facile preparation of bioactive natural products (-)-saccharinic acid lactone and potassium (2R,3R)-2,3,4-trihydrox

Article abstract of DOI:10.1016/j.tetasy.2006.02.025

Saccharinic acid lactone (-)-1a is a suitable building block for the synthesis of many bioactive natural products. Amano PS-induced chemo-, regio- and enantioselective hydrolysis of diacetyl lactone (±)-3 has been carried out to obtain (-)-1a in 46% yield

Full text of DOI:10.1016/j.tetasy.2006.02.025

Tetrahedron: Asymmetry 17 (2006) 927–932
An efficient Amano PS-catalyzed chemo-, regio- and
enantioselective hydrolysis of ( )-2,3-di-O-acetyl-2-C-methyl-D-
erythrono-1,4-lactone: a facile preparation of bioactive natural
products (ꢀ)-saccharinic acid lactone and potassium (2R,3R)-
2,3,4-trihydroxy-2-methylbutanoateI
Sanjib Gogoi and Narshinha P. Argade*
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
Received 20 January 2006; accepted 22 February 2006
Available online 12 April 2006
Abstract—Saccharinic acid lactone (ꢀ)-1a is a suitable building block for the synthesis of many bioactive natural products. Amano PS-
induced chemo-, regio- and enantioselective hydrolysis of diacetyl lactone ( )-3 has been carried out to obtain (ꢀ)-1a in 46% yield with
99% ee and diacetyl lactone (+)-3 in 49% yield with 99% ee. The Amano PS-catalyzed enantioselective acylation of ( )-1a with vinyl
acetate as an acyl donor was relatively less efficient and furnished (ꢀ)-7 in 31% yield with 99% ee and (+)-1a in 63% yield. The conversion
of (ꢀ)-1a to leaf-closing substance 2a and an attempted approach to naturally occurring compounds 1b and 2b have been also described.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
aldol reaction.8 Biotransformations are often more effi-
cient9 and in continuation of our earlier studies10 on the
enzymatic resolution of important chiral intermediates, we
herein report an efficient enzyme-catalyzed hydrolysis of
lactone ( )-3 and our studies on the synthesis of natural
products (ꢀ)-1b and (ꢀ)-2b (Schemes 1–3).
In recent years, a number of natural products have been iso-
lated, which contain the saccharinic acid lactone [(2R,3R)-
2,3-dihydroxy-2-methyl-c-butyrolactone, (ꢀ)-1a] unit (Fig. 1).
Very recently, Ogawa et al. have isolated a new sugar
lactone derivative, 3-O-caffeoyl-2-C-methyl-D-erythrono-
1,4-lactone (ꢀ)-1b from the leaves of Bidens pilosa.1 The
natural products such as potassium 2,3,4-trihydroxy-2-
methylbutanoate 2a and potassium aeshynomate 2b have
been isolated as the leaf-closing and leaf-opening substances
from Leucaena leucocephalam2 and Aeshynomene indica L.,3
respectively. The saccharinic acid lactone (ꢀ)-1a is itself a
bioactive natural product isolated from Astragalus lusitani-
cus L.4 and Cicer arietinum L.5 Natural lactone (ꢀ)-1a was
thought to be a plant growth regulator involved in feedback
inhibition in the biosynthesis of valine.6 To date, three syn-
theses of enantiomerically pure erythro-saccaharinic acid
lactone (ꢀ)-1a are known from D-mannitol,6 D-erythrose7
and using the chiral tin(II) Lewis acid mediated asymmetric
2. Results and discussion
In our focused efforts to convert cyclic anhydrides to bioac-
tive natural and unnatural products,11 starting from citra-
conic anhydride, we synthesized lactone ( )-1a in five
steps with 29% overall yield.12 In our hands, the asymmetric
dihydroxylation of 3-methyl-2(5H)-furanone was unsuc-
cessful and we prepared a systematic plan to study the
enzyme-catalyzed enantioselective hydrolysis of diacetyl
lactone ( )-3 and the enzyme-catalyzed enantioselective
acylation of dihydroxy lactone ( )-1a. Lactone ( )-1a, on
treatment with Ac2O in the presence of pyridine, gave diace-
tyl lactone ( )-3 in 90% yield (Scheme 1). The enzyme
Amano PS did not recognize substrate ( )-3 at 25 ꢁC, while
we observed 26%, 30% and 33% hydrolysis of ( )-3 to (ꢀ)-
1a at 30, 35 and 40 ꢁC, respectively, in 36 h time. The Amano
PS-catalyzed biphasic chemo-, regio- and enantioselective
q NCL Communication No. 6692.
Corresponding author. Tel.: +91 20 25902333; fax: +91 20
*
25893153; e-mail: np.argade@ncl.res.in
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.02.025

928
S. Gogoi, N. P. Argade / Tetrahedron: Asymmetry 17 (2006) 927–932
comparison with literature data.6,7 The 1H NMR spectrum
O
O
CH3
OH
OH
CH3
OH
of a diastereomeric mixture of Mosher’s esters13 obtained
from dihydroxy lactone ( )-1a and (R)-Mosher’s acid
showed a very clean resolution of the signals for the meth-
oxy and methylene group protons on the lactone moiety.
The 1H NMR spectrum of Mosher’s esters of lactones
(+)-1a and (ꢀ)-1a revealed that both of them possess
>99% ee. Next, we performed the Amano PS-catalyzed acyl-
ation of dihydroxy lactone ( )-1a using vinyl acetate as an
acyl donor at 45 ꢁC and obtained the monoacetyl lactone
(ꢀ)-7 in 31% yield and dihydroxy lactone (+)-1a in 63%
yield (Scheme 2). The present enzyme-catalyzed acylation
was also highly regio- and enantioselective and, as expected,
exclusively furnished the secondary alcohol, acylated prod-
uct, (ꢀ)-7. This monoacetyl lactone (ꢀ)-7 on methanoly-
sis in the presence of K2CO3 as a catalyst furnished the
dihydroxy lactone (ꢀ)-1a in 91% yield with 99% ee. The
dihydroxy lactone (ꢀ)-1a on treatment with aqueous
KOH at room temperature gave the enantiomerically
pure naturally occurring leaf-closing compound, potassium
(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate 2a in quanti-
tative yield.12,14 This plant-specific leaf-movement factor
2a could be useful as a herbicide.15
O
O
O
OH
OH
O
H
H
(-)-saccharinic acid lactone 1a
(-)-3-O-caffeoyl-2-C-methyl-
erythrono-1,4-lactone 1b
D-
(Plant growth regulator)5
OH
OH
H3C
+K-OOC
OH
OH
OH
CH3
COO-K+
OH
O
N
H
OH
potassium (2R,3R)-4-trihydroxy
2-methylbutanoate 2a
(Leaf closing)1
-
potassium aeshynomate 2b
(Leaf opening)2
Figure 1. Naturally occurring bioactive a,b-dihydroxylactones/carboxylic
acids.
hydrolysis of the diacetyl lactone ( )-3 at 45 ꢁC directly
We then planned to synthesize natural products (ꢀ)-1b and
(ꢀ)-2b from enantiomerically pure lactone (ꢀ)-1a. Lactone
(ꢀ)-1a, on treatment with 3,4-dimethoxycinnamic acid 9 in
the presence of DCC and a catalytic amount of DMAP at
room temperature, exclusively furnished the desired ester
(ꢀ)-10 in 85% yield (Scheme 3). Unfortunately, BBr3-in-
duced demethylation at ꢀ78 ꢁC furnished the dehydrated
product 11. Herein the tertiary hydroxyl group was elimi-
nated, forming the a,b-unsaturated lactone 11 in preference
to the deprotection of the two methyl ether units. However,
the synthesis of unnatural (+)-1b using TBDMS protection
of phenolic hydroxy groups is well known in the litera-
ture.16 Lactone (ꢀ)-1a on reaction with 2,2-dimethoxypro-
pane gave the protected lactone (ꢀ)-8 in 91% yield. In our
hands, all our attempts to ring open the lactone (ꢀ)-8 with
1
furnished nearly a 1:1 mixture (by H NMR) of the dihy-
droxy lactone (ꢀ)-1a with the recognition of secondary
(R)-acetate in the presence of c-lactone and tertiary acetate
and the unrecognized diacetyl lactone (+)-3 in 36 h reaction
time. The above formed mixture of (ꢀ)-1a and (+)-3 was
easily separated using silica gel column chromatography
to obtain (ꢀ)-1a in 46% yield and (+)-3 in 49% yield. Here-
in, we propose10b that the enzyme first recognizes the sec-
ondary acetate group to form the unisolable intermediate
vicinal hydroxyacetate, which on in situ intramolecular
hydroxy catalyzed further hydrolysis, furnished (ꢀ)-1a.
Diacetyl lactone (+)-3 in base catalyzed methanolysis gave
(+)-1a in 92% yield. The stereochemical assignments of
lactones (+)-1a and (ꢀ)-1a were done on the basis of
O
O
O
CH3
OH
OH
O
CH3
OAc
OAc
CH3
CH3
ii
R
R
OAc
OAc
i
OH
OH
O
O
O
+
O
H
H
H
H
( )-1a
(+)-3 (49%, 99% ee)
(-)-1a (46%, 99% ee)
( )-3 (90%)
iv
iii
iv
O
O
O
O
CH3
CH3
OH
CH3
OH
O
CH3
OH OMe
OMe
OH
iv
S
S
OMe
O
O
O
O
R
R
O
O
R
OH
CF3
CF3
CF3
Ph
H
Ph
H
H
O
H
Ph
O
O
(+)-1a (92%, 99% ee)
4 (99%)
5
(99%)
6 (99%)
Scheme 1. Reagents, conditions and yields: (i) Ac2O, pyridine, rt, 12 h (90%); (ii) Amano PS, petroleum ether/benzene (2:1), sodium phosphate buffer
(0.1 M, pH 7.0), 45 ꢁC, 36 h, (+)-3 (49%) and (ꢀ)-1a (46%); (iii) K2CO3, CH3OH, 0 ꢁC to rt, 3 h (92%); (iv) (R)-Mosher’s acid, DCC, DMAP, CH2Cl2,
0 ꢁC to rt, 8 h (99%).

S. Gogoi, N. P. Argade / Tetrahedron: Asymmetry 17 (2006) 927–932
929
O
O
O
CH3
OH
OH
CH3
OH
OAc
CH3
OH
OH
i
O
O
O
+
H
H
H
(+)-1a (63%)
( )-1a
(-)-7 (31%)
ii
O
O
CH3
CH3
H3C
+K-OOC
OH
OH
O
OH
OH
iii
iv
O
O
OH
O
H
H
(-)-8 (91%)
potassium (2R,3R)-4-trihydroxy-
2-methylbutanoate 2a
(-)-1a (91%, 99% ee)
Scheme 2. Reagents, conditions and yields: (i) Amano PS, vinyl acetate, n-hexane/benzene (2:1), 45 ꢁC, 96 h, (+)-1a (63%) and (ꢀ)-7 (31%); (ii) K2CO3,
CH3OH, 0 ꢁC to rt, 3 h (91%); (iii) (CH3)2C(OCH3)2, p-TSA, rt, 10 h (91%); (iv) aq KOH (1 equiv), rt, 10 min (ꢁ100%).
OMe
O
O
O
CH3
OH
CH3
OH
OH
CH3
O
OMe
O
O
ii
i
O
O
O
OMe
OMe
OMe
OMe
+
O
H
H
11 (64%)
(-)-10 (85%)
9
(-)-1a
COOH
Scheme 3. Reagents, conditions and yields: (i) DCC, DMAP, CH2Cl2, rt, 10 h (85%); (ii) BBr3, CH2Cl2, ꢀ78 ꢁC, 0.5 h (64%).
sodium azide17 via the nucleophilic attack of the azide
anion on a methylene carbon met with failure and hence
we were unable to design naturally occurring 2b.
butyric acid liberated (estimation by GC) from glyceryl
tributyrate per minute per milligram of enzyme powder.18
Column chromatographic separations were done on ACME
silica gel (60–120 mesh). Commercially available acetic
anhydride, DCC, DMAP, vinyl acetate, 3,4-dimethoxycin-
namic acid, boron tribromide, 2,2-dimethoxypropane and
(R)-Mosher’s acid were used.
3. Conclusion
In summary, we have demonstrated an efficient practical
chemo-, regio- and enantioselective Amano PS-catalyzed
hydrolysis of diacetyl lactone ( )-3 to obtain the enantio-
merically pure lactones (+)-1a and (ꢀ)-1a in 45% yield
(99% ee) (two steps) and 46% yield (99% ee), respectively.
We feel that the present highly efficient and selective enzy-
matic resolution of saccharinic acid lactone is noteworthy
and these enantiomerically pure lactones will serve as
potential building blocks for the synthesis of several natu-
ral and unnatural bioactive products.
4.2. ( )-2,3-Di-O-acetyl-2-C-methyl-D-erythrono-1,4-
lactone, 3
To a stirred solution of dihydroxy lactone ( )-1a (400 mg,
3.03 mmol) in pyridine (5 mL) were added acetic anhydride
(0.9 mL, 9.09 mmol) and a catalytic amount of DMAP
(10 mg). The reaction mixture was stirred at room temper-
ature for 5 h and then concentrated in vacuo and diluted
with water (15 mL). The aqueous layer was extracted with
ethyl acetate (15 mL · 5) and the combined organic layer
washed with 5% CuSO4 solution, water, brine and dried
over Na2SO4. Concentration of the organic layer in vacuo
followed by silica gel column chromatographic purification
of the residue using a mixture of ethyl acetate and petro-
leum ether (1:9) as an eluant gave diacetyl lactone ( )-3:
589 mg (90% yield); colourless solid; mp 86–87 ꢁC; 1H
NMR (CDCl3, 200 MHz) d 1.65 (s, 3H), 2.06 (s, 3H),
2.11 (s, 3H), 4.29 (dd, J = 10 and 4 Hz, 1H), 4.57 (dd,
J = 10 and 6 Hz, 1H), 5.33 (dd, J = 6 and 4 Hz, 1H); 13C
NMR (CDCl3, 50 MHz) d 20.0, 20.1, 21.3, 69.8, 71.5,
4. Experimental
4.1. General
Stereochemical assignments are based on the optical rota-
tion of known compounds. Melting points are uncorrected.
Amano PS-1400 U from Amano Pharmaceuticals, Japan
was used. The activity of the lipase powder used is expressed
in terms of units, 1 unit corresponding to micromoles of

930
S. Gogoi, N. P. Argade / Tetrahedron: Asymmetry 17 (2006) 927–932
74.7, 169.2, 169.3, 172.9; IR (CHCl3) mmax 1794, 1760, 1751,
1219, 1109 cmꢀ1. Anal. Calcd for C9H12O6: C, 50.00; H,
5.59. Found: C, 50.08; H, 5.65.
4.5.1. (ꢀ)-(3R,4R)-Acetic acid 4-hydroxy-4-methyl-5-oxo-
20
tetrahydrofuran-3-yl ester, 7. Colourless oil; ½aꢂD ¼ ꢀ44:0
(c 0.2, CHCl3); 1H NMR (CDCl3, 200 MHz) d 1.52 (s,
3H), 2.13 (s, 3H), 3.41 (br s, 1H), 4.29 (dd, J = 10 and
2 Hz, 1H), 4.47 (dd, J = 12 and 4 Hz, 1H), 5.16 (dd, J = 4
and 2 Hz, 1H); 13C NMR (CDCl3, 50 MHz) d 20.6, 21.7,
69.6, 72.3, 74.4, 170.1, 177.0; IR (CHCl3) mmax 3460, 1788,
1744, 1232, 1215 cmꢀ1. Anal. Calcd for C7H10O5: C,
48.28; H, 5.79. Found: C, 48.35; H, 5.69.
4.3. Amano PS-catalyzed hydrolysis of diacetyl lactone ( )-3
A solution of diacetyl lactone ( )-3 (400 mg, 1.85 mmol) in
petroleum ether/benzene (2:1) mixture (12 mL) was added
to a suspension of Amano PS lipase (40 mg) in aqueous
sodium phosphate (0.01 M, 4 mL) at pH 7.0. The reaction
mixture was stirred at 45 ꢁC for 36 h. The reaction mixture
was filtered through Celite and the aqueous layer extracted
with ethyl acetate (15 mL · 5). The combined organic layer
was washed with water, brine and dried over Na2SO4. Con-
centration of the organic layer in vacuo followed by silica
gel column chromatographic separation using a mixture
of ethyl acetate and petroleum ether (2:8) mixture as an
eluant gave diacetyl lactone (+)-3 (196 mg, 49%) and dihy-
droxy lactone (ꢀ)-1a (112 mg, 46%).
4.5.2. (+)-(3S,4S)-3,4-Dihydroxy-3-methyldihydrofuran-2-
20
one, 1a. Colourless thick oil; ½aꢂD ¼ þ35:0 (c 0.40, H2O).
Analytical and spectral data obtained were identical with
( )-1a.12
4.6. (ꢀ)-(3R,4R)-3,4-Dihydroxy-3-methyldihydrofuran-2-
one, 1a
To a stirred solution of acetyl lactone (ꢀ)-7 (80 mg,
0.45 mmol) in dry methanol (6 mL) was added anhydrous
K2CO3 (5 mg) at 0 ꢁC. The reaction mixture was allowed
to warm to room temperature and stirred for 3 h. Metha-
nol was removed in vacuo at room temperature and water
(7 mL) was added to the reaction mixture, then acidified to
pH 2 using 2 M HCl and extracted with ethyl acetate
(10 mL · 4). The combined organic layer was washed with
water, brine and dried over Na2SO4. Concentration of the
organic layer in vacuo followed by silica gel column chro-
matographic purification of the residue using a mixture of
ethyl acetate and petroleum ether (2.5:7.5) as an eluant
4.3.1. (ꢀ)-(3R,4R)-3,4-Dihydroxy-3-methyldihydrofuran-2-
20
one, 1a. Colourless thick oil; ½aꢂD ¼ ꢀ58:6 (c 0.50,
H2O). Analytical and spectral data obtained were identical
with ( )-1a.12
4.3.2. (+)-(2S,3S)-2,3-Di-O-acetyl-2-C-methyl-D-erythrono-
20
1,4-lactone, 3. Colourless solid; ½aꢂD ¼ þ8:96 (c 1.6,
CHCl3). Analytical and spectral data obtained were identi-
cal with ( )-3.
4.4. (+)-(3S,4S)-3,4-Dihydroxy-3-methyldihydrofuran-2-
one, 1a
gave (ꢀ)-1a: 55 mg (91% yield); colourless thick oil;
obtained were identical with ( )-1a.12
20
½aꢂD ¼ ꢀ58:5 (c 0.50, H2O). Analytical and spectral data
To a stirred solution of diacetyl lactone (+)-3 (60 mg,
0.28 mmol) in dry methanol (3 mL) was added anhydrous
K2CO3 (10 mg, 0.07 mmol) at 0 ꢁC. The reaction mixture
was allowed to warm to room temperature and stirred
for 3 h. Methanol was removed in vacuo at room temper-
ature and water (10 mL) was added to the reaction mixture,
then acidified to pH 2 using 2 M HCl and extracted with
ethyl acetate (15 mL · 4). The combined organic layer
was washed with water, brine and dried over Na2SO4. Con-
centration of the organic layer in vacuo, followed by silica
gel column chromatographic purification of the residue
using a mixture of ethyl acetate and petroleum ether (2:8)
4.7. (ꢀ)-(2R,3R)-2,3-O-Isopropylidene-2-C-methyl-D-
erythrono-1,4-lactone, 8
To a stirred solution of lactone (ꢀ)-1a (50 mg, 0.38 mmol)
in 2,2-dimethoxypropane (5 mL) was added p-toluenesulf-
onic acid monohydrate (4 mg, 0.02 mmol). The reaction
mixture was stirred at room temperature for 10 h and then
concentrated in vacuo. The residue was chromatographed
over silica gel using a mixture of ethyl acetate and petro-
leum ether (0.5:9.5) as an eluant to give lactone (ꢀ)-8:
20
59 mg (91% yield); colourless thick oil; ½aꢂD ¼ ꢀ82:2
as an eluant gave (+)-1a: 34 mg (92% yield); colourless
(c 2.0, acetone); 1H NMR (CDCl3, 200 MHz) d 1.42
(s, 3H), 1.47 (s, 3H), 1.57 (s, 3H), 4.32 (dd, J = 10 and
4 Hz, 1H), 4.44 (d, J = 10 Hz, 1H), 4.49 (d, J = 4 Hz,
1H); 13C NMR (CDCl3, 50 MHz) d 18.4, 26.6, 26.9, 68.9,
80.3, 81.4, 113.0, 176.7; IR (CHCl3) mmax 1788, 1379,
1105 cmꢀ1. Anal. Calcd for C8H12O4: C, 55.81; H, 7.02.
Found: C, 55.72; H, 6.97.
20
thick oil; ½aꢂD ¼ þ58:5 (c 0.50, H2O). Analytical and spec-
tral data obtained were identical with ( )-1a.12
4.5. Amano PS-catalyzed acylation of ( )-1a
A solution of dihydroxy lactone ( )-1a (200 mg, 1.52 mmol)
in n-hexane/benzene (2:1) (12 mL) was added to Amano PS
lipase (40 mg) and vinyl acetate (0.8 mL, 7.6 mmol). The
reaction mixture was stirred at 45 ꢁC for 96 h and then
allowed to cool to room temperature. The enzyme was fil-
tered off, washed with ethyl acetate and the organic layer
concentrated in vacuo. The residue was chromatographed
over silica gel using a mixture of ethyl acetate and petroleum
ether (2.5:7.5) as an eluant to give acetyl lactone (ꢀ)-7
(82 mg, 31%) and dihydroxy lactone (+)-1a (126 mg, 63%),
respectively.
4.8. (ꢀ)-(3R,4R)-b-(3,4-Dimethoxyphenyl)acrylic acid 4-
hydroxy-4-methyl-5-oxotetrahydrofuran-3-yl ester, 10
To a stirred solution of acid 9 (158 mg, 0.76 mmol), dihy-
droxy lactone (ꢀ)-1a (100 mg, 0.76 mmol) and DMAP
(cat.) in dry CH2Cl2 (7 mL) was added a solution of
DCC (156 mg, 0.76 mmol) in dry CH2Cl2 (5 mL) at 0 ꢁC.
The reaction mixture was allowed to warm to room tem-
perature and stirred for 10 h. The formed urea was filtered

S. Gogoi, N. P. Argade / Tetrahedron: Asymmetry 17 (2006) 927–932
931
off and the organic layer concentrated in vacuo. Silica
gel column chromatographic purification of the residue
using ethyl acetate and petroleum ether (2:8) as an eluant
(CDCl3, 200 MHz) d 1.60 (s, 3H), 2.82 (br s, 1H),
3.57 (s, 3H), 4.27 (dd, J = 12 and 2 Hz, 1H), 4.51 (dd,
J = 12 and 4 Hz, 1H), 5.41 (d, J = 4 Hz, 1H), 7.41–7.57
(m, 5H).
yielded ester (ꢀ)-10: 208 mg (85% yield); yellow crystal-
20
line solid; mp 123–124 ꢁC; ½aꢂD ¼ ꢀ70:0 (c 0.4, CHCl3);
1H NMR (CDCl3, 200 MHz) d 1.58 (s, 3H), 3.32 (br s,
1H), 3.90 (s, 6H), 4.38 (dd, J = 12 and 2 Hz, 1H), 4.54
(dd, J = 10 and 4 Hz, 1H), 5.30 (d, J = 4 Hz, 1H), 6.33
(d, J = 16 Hz, 1H), 6.85 (d, J = 8 Hz, 1H), 7.04–7.13 (m,
2H), 7.69 (d, J = 16 Hz, 1H); 13C NMR (CDCl3,
50 MHz) d 21.9, 55.8, 55.9, 69.9, 72.6, 74.5, 109.6, 111.0,
113.7, 123.1, 126.8, 147.0, 149.2, 151.6, 166.1, 177.0; IR
(CHCl3) mmax 3477, 1786, 1719, 1632, 1599, 1512, 1263,
1215, 1140 cmꢀ1. Anal. Calcd for C16H18O7: C, 59.62; H,
5.63. Found: C, 59.58; H, 5.68.
4.10.3. MTPA-ester of (+)-(3S,4S)-3,4-dihydroxy-3-methyl-
dihydrofuran-2-one, 5. Colourless thick oil; 1H NMR
(CDCl3, 200 MHz) d 1.57 (s, 3H), 2.57 (br s, 1H), 3.53
(s, 3H), 4.40 (dd, J = 12 and 2 Hz, 1H), 4.56 (dd,
J = 12 and 4 Hz, 1H), 5.41 (d, J = 4 Hz, 1H), 7.41–7.57
(m, 5H).
Acknowledgements
S.G. thanks CSIR, New Delhi, for the award of a research
fellowship. We thank Amano Pharmaceuticals Co., Japan
for a generous gift of enzyme Amano PS.
4.9. 3-(3,4-Dimethoxyphenyl)acrylic acid 4-methyl-5-oxo-
2,5-dihydrofuran-3-yl ester, 11
To a stirred solution of lactone 10 (100 mg, 0.31 mmol) in
CH2Cl2 (5 mL) was added a 1.0 M solution of boron tri-
bromide (2.20 mL, 2.18 mmol) in CH2Cl2 at ꢀ78 ꢁC in a
drop wise fashion under an argon atmosphere. The reac-
tion mixture was stirred at ꢀ78 ꢁC temperature for
30 min. The reaction was then slowly quenched with water
and extracted with ethyl acetate (15 mL · 3) and the com-
bined organic layer washed with brine and dried over
Na2SO4. Concentration of the organic layer in vacuo fol-
lowed by silica gel column chromatographic purification
of the residue using ethyl acetate and petroleum ether
(0.5:9.5) as an eluant gave 11: 60 mg (64% yield); yellow
crystalline solid; mp 115–116 ꢁC; 1H NMR (CDCl3,
200 MHz) d 2.22 (s, 3H), 3.89 (s, 3H), 3.92 (s, 3H), 5.30
(s, 2H), 6.60 (d, J = 16 Hz, 1H), 6.87 (d, J = 8 Hz, 1H),
7.00–7.11 (m, 2H), 7.62 (d, J = 16 Hz, 1H); IR (CHCl3)
mmax 1779, 1733, 1640, 1602, 1260 cmꢀ1. Anal. Calcd for
C16H16O6: C, 63.15; H, 5.30. Found: C, 63.04; H, 5.36.
References
1. Ogawa, K.; Sashida, Y. Phytochemistry 1992, 31, 3657.
2. Ueda, M.; Sohtome, Y.; Ueda, K.; Yamamura, S. Tetra-
hedron Lett. 2001, 42, 3109.
3. Ueda, M.; Hiraoka, T.; Niwa, M.; Yamamura, S. Tetra-
hedron Lett. 1999, 40, 6777, and references cited therein.
4. Teresa, J. d. P.; Aubanell, J. C. H.; Feliciano, A. S.; Corral,
J. M. M. d. Tetrahedron Lett. 1980, 21, 1359.
5. Ford, C. W. Phytochemistry 1981, 20, 2019.
6. Kis, K.; Wungsintaweekul, J.; Eisenreich, W.; Zenk, M. H.;
Bacher, A. J. Org. Chem. 2000, 65, 587.
7. Yoshimura, J.; Hara, K.; Yamaura, M. Carbohydr. Res. 1982,
101, 343.
8. (a) Kobayashi, S.; Horibe, M.; Saito, Y. Tetrahedron 1994,
50, 9629; (b) Mukaiyama, T.; Shiina, I.; Izumi, J.; Kobayashi,
S. Heterocycles 1993, 35, 719.
9. (a) Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 2001, 1475;
(b) Davis, B. G.; Boyer, V. Nat. Prod. Rep. 2001, 18, 618; (c)
Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 2000, 611; (d)
Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 1; (e)
Schmid, R. D.; Verger, R. Angew. Chem., Int. Ed. 1998, 37,
1608; (f) Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 1998,
157; (g) Theil, F. Chem. Rev. 1995, 95, 2203; (h) Mori, K.
Synlett 1995, 1097; (i) Hanson, J. R. In An Introduction to
Biotransformations in Organic Chemistry; Mann, J., Ed.;
W.H. Freeman: New York, 1995; (j) Faber, K. Biotransfor-
mations in Organic Chemistry; Springer: Heidelberg, 1995; (k)
Sheldon, R. In Chirotechnology: Industrial Synthesis of
Optically Active Compounds; Marcel Dekker: New York,
1993; (l) Csuk, R.; Gla¨nzer, B. I. Chem. Rev. 1991, 91, 49; (m)
Servi, S. Synthesis 1990, 1.
10. (a) Desai, S. B.; Argade, N. P.; Ganesh, K. N. J. Org. Chem.
1996, 61, 6730; (b) Desai, S. B.; Argade, N. P.; Ganesh, K. N.
J. Org. Chem. 1999, 64, 8105; (c) Easwar, S.; Desai, S. B.;
Argade, N. P.; Ganesh, K. N. Tetrahedron: Asymmetry 2002,
13, 1367; (d) Easwar, S.; Argade, N. P. Tetrahedron:
Asymmetry 2003, 14, 333.
11. (a) Haval, K.; Argade, N. P. Tetrahedron 2006, 62, 937; (b)
Haval, K.; Argade, N. P. Tetrahedron 2006, 62, 3557; (c)
Gogoi, S.; Argade, N. P. Tetrahedron 2006, 62, 2715; (d)
Gogoi, S.; Argade, N. P. Tetrahedron 2006, 62, 2999; (e)
Easwar, S.; Argade, N. P. Synthesis 2006, 831, and references
cited therein.
4.10. General procedure for MTPA-ester preparation
To a solution of (R)-Mosher’s acid (27 mg, 0.11 mmol),
dihydroxy alcohol ( )-1a or (+)-1a or (ꢀ)-1a (15 mg,
0.11 mmol) and DMAP (cat.) in dry CH2Cl2 (3 mL) was
added a solution of DCC (24 mg, 0.11 mmol) in dry
CH2Cl2 (2 mL) at 0 ꢁC. The reaction mixture was allowed
to warm to room temperature and stirred for 8 h. The
formed urea was filtered off and the organic layer concen-
trated in vacuo. Silica gel column chromatographic purifi-
cation of the residue using ethyl acetate and petroleum
ether mixture (1:9) gave the MTPA-ester in quantitative
yield.
4.10.1. MTPA-ester of ( )-3,4-dihydroxy-3-methyldihydro-
furan-2-one, 6. Colourless thick oil; 1H NMR (CDCl3,
200 MHz) d 1.57 (s, 3H), 1.59 (s, 3H), 2.70 (br s, 1H), 2.96
(br s, 1H), 3.53 (s, 3H), 3.57 (s, 3H), 4.27 (dd, J = 12 and
2 Hz, 1H), 4.40 (dd, J = 12 and 2 Hz, 1H), 4.50 (dd,
J = 12 and 4 Hz, 1H), 4.56 (dd, J = 12 and 4 Hz, 1H),
5.41 (d, J = 4 Hz, 2H), 7.38–7.56 (m, 10H).
4.10.2. MTPA-ester of (ꢀ)-(3R,4R)-3,4-dihydroxy-3-methyl-
dihydrofuran-2-one, 4. Colourless thick oil; 1H NMR
12. Gogoi, S.; Argade, N. P. Tetrahedron 2004, 60, 9093.

932
S. Gogoi, N. P. Argade / Tetrahedron: Asymmetry 17 (2006) 927–932
13. (a) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543; (b) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc.
1973, 95, 512.
16. Marco, J. A.; Carda, M.; Gonzalez, F.; Rodriguez, S.;
Murga, J.; Falomir, E. An. Quim. 1995, 91, 103; Chem. Abstr.
1996, 125, 196189.
14. The leaf-closing compound 2a is unstable around neutral or
basic pH, and gradually decomposes to lactate.
17. Musich, A. J.; Rapoport, H. J. Am. Chem. Soc. 1978, 100,
4865.
15. Ueda, M.; Sohtome, Y.; Ueda, K.; Yamamura, S. Tetra-
hedron Lett. 2001, 42, 3109, and references cited therein.
18. Dupuis, C.; Corre, C.; Boyaval, P. Appl. Environ. Microbiol.
1993, 59, 4004.