First enantioselective syntheses of (2R,3R)- and (2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde

Article abstract of DOI:10.1016/S0957-4166(00)00234-2

An enantioselective and regioselective total synthesis approach to chiral 1,4-benzodioxane lignans (2R,3R)- and (2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde is reported. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00234-2

Tetrahedron: Asymmetry 11 (2000) 2801±2807
First enantioselective syntheses of (2R,3R)- and (2S,3S)-3-
(4-hydroxy-3-methoxyphenyl)-2-hydroxymethyl-
1,4-benzodioxan-6-carbaldehyde
Wenxin Gu,a Xiaochuan Chen,a Xinfu Pan,a,* Albert S. C. Chanb
and Teng-Kuei Yangc
aDepartment of Chemistry, National Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, PR China
bUnion Laboratory of Asymmetry Synthesis and Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hong Kong, Hong Kong
cDepartment of Chemistry, National Chung-Hsing University, Taichang, Taiwan
Received 24 May 2000; accepted 12 June 2000
Abstract
An enantioselective and regioselective total synthesis approach to chiral 1,4-benzodioxane lignans
(2R,3R)- and (2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde
is reported. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The 1,4-benzodioxane framework has often been found in biologically active lignans. Silybin1
and americanin A2 are antihepatotoxic, and haedoxan A3 has insecticidal activity. Silybin has
been used as a folk medicine in Jammu aur Kashmir and Europe.1 This type of natural product,
which has shown a variety of bioactivities, is of synthetic interest. Recently, several ecient
syntheses of natural 1,4-benzodioxane lignans have been reported.4 Recently, we reported the
total synthesis of (þ)-sinaiticin, a natural ¯avonolignan.5 An unsolved problem in this area has
been the asymmetric synthesis of chiral 1,4-benzodioxane lignans.6
We now report the ®rst enantioselective and regioselective synthetic approach to the 3-aryl-1,4-
benzodioxane moiety, the important structure of natural 1,4-benzodioxane lignans.1 In this
* Corresponding author. E-mail: panxf@lzu.edu.cn
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00234-2

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approach the important key intermediate for the synthesis of silybin7 (2R,3R)- and (2S,3S)-3-(4-
hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde is synthesized.
2. Results and discussion
As shown in Scheme 1, ferulic acid 2 was converted to a benzyl ether 3 in 94% yield by
esteri®cation with acidic methanol followed by treatment with benzyl chloride. Reduction of 3
Scheme 1. Reagents and conditions: (i) MeOH, H2SO4, 90ꢀC, 16 h; (ii) BnCl, DMF, K2CO3, 160ꢀC, 3 h (i and ii 94%);
(iii) LAH, THF, ^10ꢀC, 1 h (88%); (iv) AD-mix-a, MeSO2NH2, t-BuOH, H2O, 0ꢀC, 20 h (94%); (v) N-tosylimidazole,
NaH, THF, rt, 2 h (71%); (vi) DE (83%); (vii) Pd/C (5%), H2, EtOAc, rt, 6 h (90%); (viii) K2CO3, MeOH, rt, 1 h
(98%); (ix) AD-mix-b, MeSO2NH2, t-BuOH, H2O, 0ꢀC, 20 h (90%)

W. Gu et al. / Tetrahedron: Asymmetry 11 (2000) 2801±2807
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gave the corresponding unsaturated alcohol 4 in 88% yield. Asymmetric dihydroxylation of 4 by AD-
mix-a a€orded (1S,2S)-5 in 92% e.e. and 94% yield.8 (1S,2S)-5 was treated with N-tosylimidazole9 in
dry THF giving oxirane (1S,2S)-6 in 71% yield. Mitsunobu reaction10 between (1S,2S)-6 and
4-benzyloxy-3-hydroxybenzaldehyde11 gave a characterized ether (1R,2S)-7 in 83% yield. In this
reaction the absolute con®guration of the C1-position was converted completely by a SN2-type
nucleophilic displacement of 4-benzyloxy-3-hydroxybenzaldehyde. Two benzyl groups of
(1R,2S)-7 were removed by hydrogenolysis under an atmospheric pressure of hydrogen in the
presence of 5% palladized charcoal in ethyl acetate to a€ord (1R,2S)-8 in 90% yield as well as the
epoxide moiety remaining intact.12 (1R,2S)-8 underwent cyclization with potassium carbonate to
a€ord (2R,3R)-1 in 98% yield. In this reaction an intramolecular nucleophilic attack at the
C2-position of oxirane by the phenol hydroxyl as its potassium salt led to a complete inversion of
the absolute con®guration of the C2-position and the formation of 1,4-benzodioxane.13 In the 1H
NMR spectrum of (2R,3R)-1 H-3 resonated a doublet signal at ꢀ 5.10 with a coupling
constant (J=8 Hz) indicating a typical of trans-isomer and threo con®guration. 13C NMR spectrum
showed ꢀ 61.5, 77.5, 79.5 indicating a six-membered 2-hydroxymethyl-3-aryl-1,4-benzodioxane
skeleton.14 Similarly, asymmetric dihydroxylation of 4 by AD-mix-b a€orded (1R,2R)-5 in 91%
e.e. and 90% yield.8 (1R,2R)-5 was treated in the same four steps to a€ord (2S,3S)-1 in good
yield.
Advantages of the synthetic approach include: (i) 2-aryl- and 3-aryl-1,4-benzodioxane lignans
can be synthesized regioselectively when 3-benzyloxy-4-hydroxybenzaldehyde and 4-benzyloxy-3-
hydroxybenzaldehyde was used, respectively; and (ii) SN2-type nucleophilic displacement on the
two stereogenic carbons led to the complete conversion of their absolute con®gurations, so that
the absolute con®guration of 1,4-benzodioxane can be assigned since the trans-isomers are the
only products.
3. Experimental
3.1. General
1
The H NMR and 13C NMR data were recorded with Bruker AM-80 or AM-400 MHz
spectrometers. The chemical shifts are reported in ppm relative to TMS. Optical rotations were
determined on a JASCO J-20C polarimeter with 0.2 dm tube. Mass spectra were recorded on a
ZAB-HS mass spectrometer. Microanalyses were performed on a MOD-1106 elemental analyser.
Chiral analysis was performed on Varian Dynamax SD-300 using Chiralcel column CDMPC
(150Â4.6 mm D) with hexane/isopropyl alcohol as eluant. Flash column chromatography was
generally performed on silica gel (200±300 mesh) eluting with petroleum ether:EtOAc and TLC
inspections on silica gel GF254 plates with petroleum ether:EtOAc, if not noted especially below.
3.2. 4-Benzyloxy-3-methoxycinnamyl alcohol 4
At ^10ꢀC, to a suspension of LiAlH4 (1.7 g, 45 mmol) in dry diethyl ether (100 mL), compound
7 (8.9 g, 30 mmol) in dry THF (100 mL) was added dropwise. The mixture was stirred at this
temperature for 1 h. Then the reaction was quenched with ice-water, extracted with ether and the
combined organic layer was washed with brine, then dried with Na2SO4. The solvent was distilled

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W. Gu et al. / Tetrahedron: Asymmetry 11 (2000) 2801±2807
o€ under reduced pressure, the residue was ¯ash chromatographed using petroleum ether and
ethyl acetate (5:1, v/v) as eluent. A white solid 4 (7.1 g) was obtained in 88% yield. M.p. 89±90ꢀC.
1H NMR (CDCl3, 400 MHz): ꢀ 3.90 (s, 3H), 4.30 (d, 2H, J=5.3 Hz), 5.16 (s, 2H), 6.26 (dt, 1H,
J=5.8, 15.8 Hz), 6.55 (d, 1H, J=16.0 Hz), 6.81±7.44 (m, 8H). MS (EI): 270, 179, 151, 119, 91
(Found: C, 75.60; H, 6.73. C17H18O3 requires: C, 75.53; H, 6.71%).
3.3. (1S,2S)-1-(4-Benzyloxy-3-methoxyphenyl)-2,3-dihydroxypropanol (1S,2S)-5
To a stirred solution of t-BuOH (50 mL) and H2O (50 mL) was added AD-mix-a (14 g),
MeSO2NH2 (950 mg), and the mixture was stirred at room temperature until both phases were
clear, and then cooled to 0ꢀC. Compound 4 (2.7 g, 0.1 mol) was added at once, and the mixture
was stirred vigorously at 0ꢀC until TLC revealed the absence of 4. The reaction was quenched at
0ꢀC by addition of Na2SO3 (15 g), then warmed to room temperature and stirred for 0.5 h. The
reaction mixture was extracted with CH2Cl2 (3Â100 mL) and dried (Na2SO4), then the CH2Cl2
was distilled o€. The residue was ¯ash chromatographed using petroleum ether and ethyl acetate
(1:1, v/v) as eluent. A white powder (1S,2S)-5 (2.9 g) was obtained in 94% yield. Enantiomeric
purity: 92% e.e. (Chiralcel column CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1
mL/min, 25ꢀC, retention times 26.6 min). M.p. 155±156ꢀC. ‰ꢁŠ2D5=^76 (c 1.50, MeOH). 1H NMR
(400 MHz, d6-acetone): ꢀ 3.39 and 3.47 (2dd, 2H, J=3.0, 9.7 Hz), 3.80 (m, 1H), 3.86 (s, 3H), 4.64
(d, 1H, J=6.5 Hz), 5.13 (s, 2H), 6.78±7.44 (m, 8H). MS (EI): 304, 286, 243, 153, 91. (Found: C,
66.98; H, 6.64. C17H20O5 requires: C, 67.09; H, 6.62%).
3.4. (1R,2R)-1-(4-Benzyloxy-3-methoxyphenyl)-2,3-dihydroxypropanol (1R,2R)-5
By a procedure similar to the preparation for (1S,2S)-5, the reaction of 4 (2.7 g, 0.1 mmol),
AD-mix-b (14 g), MeSO2NH2 (950 mg), t-BuOH (50 mL) and H2O (50 mL) gave (1R,2R)-5 (2.7
g) in 90% yield. (1R,2R)-5: A white powder. Enantiomeric purity: 91% e.e. (Chiralcel column
CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min, 25ꢀC, retention times 30.4
min). M.p. 139±140ꢀC. ‰ꢁŠD25=+74 (c 1.50, MeOH) (Found: C, 67.05; H, 6.63. C17H20O5 requires:
C, 67.09; H, 6.62%). Other spectra data were the same as those of (1S,2S)-5.
3.5. (1S,2S)-2,3-Expoxy-1-(4-benzyloxy-3-methoxyphenyl)propanol (1S,2S)-6
Sodium hydride (50% oil dispersion) (270 mg, 5.6 mmol) was placed in a dry ¯ask equipped
with a magnetic stirrer and drying tube, and washed free of oil with pentane. Dry THF (10 mL)
was added followed by (1S,2S)-5 (850 mg, 2.8 mmol), and the mixture was stirred for 1 h at room
temperature. N-Tosylimidazole (650 mg, 2.9 mmol) was then added and the suspension stirred for
a further 3 h. The reaction mixture was then poured with stirring into ice-water, extracted with
diethyl ether and the combined organic layer was washed with brine, then dried with Na2SO4.
The solvent was distilled o€ under reduced pressure, the residue was ¯ash chromatographed using
petroleum ether and ethyl acetate (4:1, v/v) as eluent to a€ord (1S,2S)-6 (570 mg, 71%) as a col-
orless oil. Enantiomeric purity: 92% e.e. (Chiralcel column CDMPC, 150Â4.6 mm D, n-hexane:
isopropyl alcohol, 50:1, 1 mL/min, 25ꢀC, retention times 15.7 min). ‰ꢁŠD20=^52 (c 1.00, CHCl3).
1H NMR (400 MHz, CDCl3): ꢀ 2.77 and 2.81 (2dd, 2H, J=3.1, 8.8 Hz), 3.19 (m, 1H), 3.89 (s,
3H), 4.37 (d, 1H, J=6.3 Hz), 5.14 (s, 2H), 6.82±7.43 (m, 8H). MS (EI): 286, 268, 256, 243, 177, 91
(Found: C, 71.28; H, 6.32. C17H18O4 requires: C, 71.31; H, 6.34%).

W. Gu et al. / Tetrahedron: Asymmetry 11 (2000) 2801±2807
2805
3.6. (1R,2R)-2,3-Expoxy-1-(4-benzyloxy-3-methoxyphenyl)propanol (1R,2R)-6
By a procedure similar to the preparation of (1S,2S)-6, the reaction of (1R,2R)-5 (850 mg, 2.8
mmol) with N-tosylimidazole (650 mg, 2.9 mmol) gave (1R,2R)-6 (550 mg) as a colorless oil in
68% yield. (1R,2R)-6: Enantiomeric purity: 91% e.e. (Chiralcel column CDMPC, 150Â4.6 mm
D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min, 25ꢀC, retention times 21.3 min). ‰ꢁŠD20=+52
(c 1.00, CHCl3) (Found: C, 71.25; H, 6.30. C17H18O4 requires: C, 71.31; H, 6.34%). Other
spectral data are the same as those of (1S,2S)-6.
3.7. (1R,2S)-4-Benzyloxy-3-[2,3-epoxy-1-(4-benzyloxy-3-methoxyphenyl)propoxy]benzaldehyde
(1R,2S)-7
A solution of PPh3 (520 mg, 2.0 mmol) and (1S,2S)-6 (500 mg, 1.8 mmol) in dry THF (10 mL)
was added dropwise to a solution of 4-benzyloxy-3-hydroxybenzaldehyde11 (450 mg, 2.0 mmol)
and DEAD (350 mg, 2.0 mmol) at room temperature under nitrogen. After stirring of the mixture
overnight at room temperature, it was evaporated in vacuum. The residue was ¯ash chromato-
graphed using petroleum ether and ethyl acetate (2:1, v/v) as eluent. A white solid (1R,2S)-7 (720
mg) was obtained in 83% yield. Enantiomeric purity: 92% e.e. (Chiralcel column CDMPC,
150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min, 25ꢀC, retention times 20.6 min).
M.p. 76±78ꢀC. ‰ꢁŠD20=+10 (c 1.00, CHCl3). 1H NMR (400 MHz, d6-acetone): ꢀ 2.76 and 2.79 (2dd,
2H, J=2.7, 5.5 Hz), 3.38 (m, 1H), 3.76 (s, 3H), 5.08 (s, 2H), 5.31 (s, 2H), 5.42 (d, 1H, J=4.0 Hz),
7.00±7.72 (m, 16H), 9.77 (s, 1H). MS (EI): 496, 466, 375, 347, 269, 227, 91 (Found: C, 74.91; H,
5.66. C31H28O6 requires: C, 74.98; H, 5.68%).
3.8. (1S,2R)-4-Benzyloxy-3-[2,3-epoxy-1-(4-benzyloxy-3-methoxyphenyl)propoxy]benzaldehyde
(1S,2R)-7
By a procedure similar to the preparation of (1R,2S)-7, Mitsunobu reaction of (1R,2R)-6 gave
(1S,2R)-7 (700 mg) in 81% yield. (1S, 2R)-7: A white powder. Enantiomeric purity: 91% e.e.
(Chiralcel column CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min, 25ꢀC,
retention times 26.0 min). M.p. 90±92ꢀC. ‰ꢁŠD20=^12 (c 1.00, CHCl3) (Found: C, 74.94; H, 5.66.
C31H28O6 requires: C, 74.98; H, 5.68%). Other spectral data were the same as those of (1R,2S)-7.
3.9. (1R,2S)-4-Hydroxy-3-[2,3-epoxy-1-(4-hydroxy-3-methoxyphenyl)propoxy]benzaldehyde
(1R,2S)-8
A solution of (1R,2S)-7 (500 mg, 1.0 mmol) in ethyl acetate (10 mL) was hydrogenated over
5% Pd±C (50 mg) under an H2 atmosphere. The reaction mixture was ®ltered and the ®ltrate was
concentrated. The residue was ¯ash chromatographed using petroleum ether and ethyl acetate
(1:2, v/v) as eluent. A white solid (1R,2S)-8 (280 mg, 90%) was obtained. Enantiomeric purity:
92% e.e. (Chiralcel column CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min,
25
ꢀ
ꢀ
1
25 C, retention times 28.4 min). M.p. 135±136 C. ‰ꢁŠD =+8.3 (c 1.00, MeOH). H NMR (d6-
acetone, 400 Hz): ꢀ 2.83 and 2.86 (2dd, 2H, J=2.5, 12.2 Hz), 3.41 (m, 1H), 3.82 (s, 3H), 5.34
(d, 1H, J=4.0 Hz), 6.80±7.43 (m, 6H), 9.70 (s, 1H). MS (EI): 316, 179, 151, 137, 123, 93. IR
(KBr/cm^1): 3506, 3286, 3010, 2844, 1707, 1596, 1514, 1271, 1237 (Found: C, 64.61; H, 5.11.
C17H16O6 requires: C, 64.55; H, 5.10%).

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W. Gu et al. / Tetrahedron: Asymmetry 11 (2000) 2801±2807
3.10. (1S,2R)-4-Hydroxy-3-[2,3-epoxy-1-(4-hydroxy-3-methoxyphenyl)propoxy]benzaldehyde
(1S,2R)-8
By a procedure similar to the preparation of (1R,2S)-8, debenzylation of (1S,2R)-7 (500 g, 1.0
mmol) gave (1S,2R)-8 (270 mg) in 85% yield. (1S,2R)-8: A white powder. Enantiomeric purity:
91% e.e. (Chiralcel column CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min,
25ꢀC, retention times 32.0 min). M.p. 157±159ꢀC. ‰ꢁŠ2D5=^7.6 (c 1.00, MeOH) (Found: C, 64.58;
H, 5.09. C17H16O6 requires: C, 64.55; H, 5.10%). Other spectral data were the same as those of
(1R,2S)-8.
3.11. (2R,3R)-3-(4-Hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde
(2R,3R)-1
A mixture of (1R,2S)-8 (100 mg, 0.3 mmol) and anhydrous K2CO3 (140 mg, 1.0 mmol) in
MeOH (5 mL) was stirred at room temperature for 30 min. The solvent was evaporated and 2N
HCl (2 mL) was added, then the mixture was extracted with EtOAc. The combined organic was
washed with brine and dried with Na2SO4. The solvent was removed under reduced pressure. The
residue was ¯ash chromatographed using petroleum ether and ethyl acetate (1:2, v/v) as eluent to
a€ord (2R,3R)-1 (98 mg, 98%) as a white solid. Enantiomeric purity: 92% e.e. (Chiralcel column
CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min, 25ꢀC, retention times 34.3
min). M.p. 112±113ꢀC. ‰ꢁŠD25=+13 (c 0.9, CHCl3). 1H NMR (d6-acetone, 400 Hz): ꢀ 3.51 and 3.78
(2dd, 2H, J=12.5, 4.0 Hz), 3.76 (s, 3H), 4.15 (m, 1H), 5.10 (d, 1H, J=8.0 Hz), 6.71±7.47 (m, 6H),
9.86 (s, 1H). 13C NMR (d6-acetone, 100 Hz): 55.8, 61.5, 77.5, 79.5, 112.9±133.0, 191.2. MS
(FAB): 317 (M+1). IR (KBr/cm^1): 3444, 3351, 2937, 2856, 1739, 1606, 1598, 1270, 1246 (Found:
C, 64.52; H, 5.08. C17H16O6 requires: C, 64.55; H, 5.10%).
3.12. (2S,3S)-3-(4-Hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde
(2S,3S)-1
By a procedure similar to the preparation of (2R,3R)-1, cyclization of (1S,2R)-8 (100 mg, 0.3
mmol) gave (2S,3S)-1 (90 mg) in 90% yield. (2S,3S)-1: A white powder. Enantiomeric purity:
91% e.e. (Chiralcel column CDMPC, 150Â4.6 mm D, n-hexane:isopropyl alcohol, 50:1, 1 mL/min,
25ꢀC, retention times 42.9 min). M.p. 137±139ꢀC. ‰ꢁŠD20=^12 (c 1.0, CHCl3) (Found: C, 64.59; H,
5.09. C17H16O6 requires: C, 64.55; H, 5.10%). Other spectral data were the same as those of
(2R,3R)-1.
Acknowledgements
Support from the National Natural Science Foundation of China (No. 29972015) is gratefully
acknowledged.
References
1. (a) Hansel, R.; Shulz, J.; Pelter, A. J. Chem. Soc., Chem. Commun. 1972, 195±196; (b) Chem. Commun. 1975, 108,
1482±1501; (c) Wagner, H.; Horhammer, L.; Munster, R. Arzneimittel-Forsch. 1968, 18, 688; (d) Wanger, H.;

W. Gu et al. / Tetrahedron: Asymmetry 11 (2000) 2801±2807
2807
Diesel, P.; Seitz, M. Arzneimittel-Forsch. 1974, 24, 466±471; (e) Bandopadhyay, M.; Pardeshi, N. P.; Seshadri,
T. R. Indian J. Chem. 1972, 10, 808; (f) Abraham, D. J.; Takagi, S.; Rosenstein, R. D.; Shiono, R. Tetrahedron
Lett. 970, 2675.
2. Woo, W. S.; Kang, S. S.; Wanger, H.; Chari, V. M. Tetrahedron Lett. 1978, 3239±3242.
3. Taniguchi, E.; Imamura, K.; Ishibashi, F.; Matsui, T.; Nishio, A. Agric. Biol. Chem. 1989, 53, 631±649.
4. Merlini, L.; Zanarotti, A.; Pelter, A.; Rochefort, M. P.; Hansel, R. J. Chem. Soc., Perkin Trans. 1 1980, 775.
5. She, X. G.; Jing, X. B.; Pan, X. F.; Chan, A. C.; Yang T. K. Tetrahedron Lett. 1999, 40, 4567±4570.
6. (a) Ward, R. S. Nat. Prod. Rep. 1997, 14, 43; (b) Ward, R. S. Nat. Prod. Rep. 1999, 16, 75±96.
7. Tanaka, H.; Shibata, M.; Ohira, K.; Ito, K. Chem. Pharm. Bull. 1985, 33, 1419±1423.
8. Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K. S.; Kwong, H. L.;
Morikawa, K.; Wang, Z. M.; Xu, D.; Zhang, X. L. J. Org. Chem. 1992, 57, 2768±2771.
9. Hicks, D. R.; Fraser-Reid, B. Synthesis 1974, 203.
10. Mitsunobu, O. Synthesis 1981, 1±26.
11. Kessar, S. V.; Guputa, Y. P.; Mohammad, T.; Goyal, M.; Sawal, K. K. J. Chem. Soc., Chem. Commun. 1983, 400±
401.
12. Taniguchi, E.; Yamauchi, S.; Nagata, S.; Ohnishi, T. Biosci. Biotech. Biochem. 1992, 56, 630±635.
13. Ganesh, T.; Krupadanam, G. L. D. Synth. Commun. 1998, 28, 3121±3131.
14. Fukiyama, Y.; Hasegawa, T.; Toda, M.; Kodama, M. Chem. Pharm. Bull. 1992, 40, 252.