Synthesis and structural pattern recognition of 5-(2′-alkoxycarbonyl- substituted phenoxy)furfural derivatives

Article abstract of DOI:10.1248/cpb.57.550

The ethyl 5-(2′-alkoxycarbonyl-substituted phenoxy)furan-2- carboxylates (1C-13C) showed good antiplatelet aggregation,¹⁾ anti-allergic²⁾ and anti-inflammatory activities.²⁾ A series of 5-(2′-alkoxycarbonyl-substituted phenoxy)furfurals (1F-13F) were prepared for comparing the above activities. The objectives of this research are the synthesis and structural pattern recognition of compounds 1F-13F. The Silica Gel 60 column chromatography method was employed to separate and purify pure compounds 1F-13F by three solvent systems. For the structure elucidation of compounds 1F-13F, four spectroscopic methods were used: electron impact mass (EI-MS), UV-VIS, IR and NMR spectrometers. With the help of spectrometers, investigations can be performed on spectroscopic data. A simple methodology for recognizing structural patterns was carried out with the aid of statistical analysis designed to establish the classification model of the structural skeleton in this research. It was found that compounds 1C-13C and 1F-13F have similar chemical profiles and are clustered into one group. The pattern plots revealed valuable information and showed good correlation between compounds 1C-13C and 1F-13F. These findings correlate directly with the resulting spectroscopic data. These results with those obtained by EI-MS and NMR patterns give insight into a reliable pattern recognition for determining both 1C-13C and 1F-13F skeletons.

Full text of DOI:10.1248/cpb.57.550

550
Chem. Pharm. Bull. 57(6) 550—556 (2009)
Vol. 57, No. 6
ꢀ
Synthesis and Structural Pattern Recognition of 5-(2 -Alkoxycarbonyl-
substituted phenoxy)furfural Derivatives
Chia-Lin CHANG
Research Institute of Biotechnology, HungKuang University; No. 34, Chungchie Rd., Shalu Township, Taichung Hsien
43302, Taiwan (R.O.C.). Received October 3, 2008; accepted March 22, 2009; published online March 27, 2009
The ethyl 5-(2ꢀ-alkoxycarbonyl-substituted phenoxy)furan-2-carboxylates (1C—13C) showed good anti-
platelet aggregation,1) anti-allergic2) and anti-inflammatory activities.2) A series of 5-(2ꢀ-alkoxycarbonyl-substi-
tuted phenoxy)furfurals (1F—13F) were prepared for comparing the above activities. The objectives of this re-
search are the synthesis and structural pattern recognition of compounds 1F—13F. The Silica Gel 60 column
chromatography method was employed to separate and purify pure compounds 1F—13F by three solvent sys-
tems. For the structure elucidation of compounds 1F—13F, four spectroscopic methods were used: electron im-
pact mass (EI-MS), UV–VIS, IR and NMR spectrometers. With the help of spectrometers, investigations can be
performed on spectroscopic data. A simple methodology for recognizing structural patterns was carried out with
the aid of statistical analysis designed to establish the classification model of the structural skeleton in this re-
search. It was found that compounds 1C—13C and 1F—13F have similar chemical profiles and are clustered into
one group. The pattern plots revealed valuable information and showed good correlation between compounds
1C—13C and 1F—13F. These findings correlate directly with the resulting spectroscopic data. These results with
those obtained by EI-MS and NMR patterns give insight into a reliable pattern recognition for determining both
1C—13C and 1F—13F skeletons.
Key words 5-(2ꢀ-alkoxycarbonyl-substituted phenoxy)furfural; structural pattern; 1H-NMR; 13C-NMR; MS
Some active medicines with anti-platelet aggregation, anti- using spectroscopic data of electron impact (EI)-MS and
allergy, and anti-inflammation properties are used on clinic at NMR.12—17) Structural pattern recognition could help re-
present. The research and development of these medicines searchers in interpretation and prediction of chemical struc-
aims to treat human diseases effectively. Anti-agglutinate tures. An unknown spectrum will be identified by the struc-
medicines of blood platelet include ketanserin,3) milrinone4) tural pattern, and both the research and structure elucidation
and ticlopidine.5) Ketanserin produced a decrease in risto- will be easy. In my previous research of compounds 1C—
cetin-induced platelet aggregation, fibrinogen and prolonga- 13C on novel anti-platelet aggregation,1) anti-allergic2) and
tion of the bleeding time.3) Milrinone (0.9 mM) inhibited anti-inflammatory agents,2) a series of compounds 1F—13F,
thrombin-induced platelet aggregation. This inhibitory effect which are targeted as bioisosteres of the above compounds,
was mainly mediated by suppressing calcium release from were synthesized. In this study, these analogues 1F—13F
the dense tubular system.4) Ticlopidine with an active reduc- with another substituent on the 2ꢀ-alkoxycarbonylphenoxy
tion in platelet aggregation was detected in response to group were synthesized, separated, purified and identified.
adenosine diphosphate.5) Anti-allergy medicines include an- Then their structural pattern plots were also established by
tazoline,6) brompheniramine7) and chlorpheniramine.8) Be- EI-MS and NMR data for the prediction of their skeleton
cause allergic conjunctivitis is one of the most frequent aller- types. There have been no reports on the synthesis and struc-
gic diseases of the anterior eye segment, the benefit of using tural pattern recognition of compounds 1F—13F; therefore,
antazoline eye drops was clearly outweighed.6) Brompheni- this study is an innovative application of a method. Finally,
ramine has been used in the treatment of allergic rhinitis and the synthesis and structural pattern recognition of com-
other disorders during the past 40 years. In particular, a sin- pounds 1F—13F are necessary for drug discoveries.
gle dose of brompheniramine produces prompt, long-lasting
peripheral H1-blockade in children.7) Histamine H1 antago-
Experimental
Solvents and Chemicals Deionized water was obtained from the Ultra-
nist chlorpheniramine blocks the ragweed-induced nasal con-
pure Water System (Putity-UV, Suntex Instruments Corporation, Ltd.,
gestion.8) Anti-inflammation medicines include diclofenac,9)
Taipei, Taiwan, R.O.C.). Methyl salicylate (1A), 5-nitrofurfural, cesium fluo-
ketoprofen10) and tolmetin.11) However, the effect of indo-
ride (CsF) and 60% sodium hydride (NaH) were purchased from Lancaster
methacin on prenatal ductal constriction is well known, and
widely prescribed non-steroidal anti-inflammatory drugs
such as diclofenac can have an adverse effect and are best
avoided in the third trimester of pregnancy.9) Ketoprofen is
effective and safe in treating acute painful conditions for one
week.10) Tolmetin is safe and effective treatment for arthritic
rheumatic fever patients without carditis, and can be used
particularly in patients who cannot tolerate aspirin.11) There-
fore, the research of the above medicinal effects is necessary
for drug discoveries.
(Lancashire, U.K.). Potassium bromide (KBr) and 2-hydroxy-6-methoxyben-
zoic acid were purchased from Sigma-Aldrich (Shanghai, China). Methyl io-
dide (CH3I), sodium hydrogen carbonate (NaHCO3), N,N-dimethylfor-
mamide (DMF), dimethyl sulfoxide (DMSO), chloroform-d1 (CDCl3) with
tetramethylsilane (TMS) for NMR spectroscopy and 80% NaH were pur-
chased from Merck (Darmstadt, Germany). Ethyl acetate, n-hexane, chloro-
form and methanol were purchased from Mallinckrodt Baker (Phillipsburg,
U.S.A.). Potassium hydroxide (KOH) and anhydrous magnesium sulfate
were purchased from Shimakyu’s Pure Chemical Corporation (Osaka,
Japan). Benzene was purchased from Uni-Onward Corporation (Taipei, Tai-
wan, R.O.C.). The 2-hydroxy-6-methylbenzoic acid ethyl ester (5A) was
purchased from TCI (Tokyo, Japan). All the starting materials except 2-hy-
A lot of structural pattern recognition has been established droxy-6-methoxybenzoic acid methyl ester (9A), substituted salicylic acid
e-mail: clchang@sunrise.hk.edu.tw © 2009 Pharmaceutical Society of Japan

June 2009
551
methyl esters (2A—4A, 6A—8A and 10A—13A) (structures 1A—13A see
Fig. 2) and ethyl 5-nitro-2-furoate, were synthesized as described in ref. 2.
added dropwise. The reaction solution was stirred at room temperature for
23 h and the reaction mixture was then poured into ice water. The oily prod-
Synthesis of 2-Hydroxy-6-methoxybenzoic Acid Methyl Ester (9A) uct was extracted with chloroform. The chloroform extract was washed with
A solution of 26.90 g (0.16 mol) of 2-hydroxy-6-methoxybenzoic acid, 5% KOH and water, and was dried over anhydrous magnesium sulfate. The
34.46 g (0.24 mol) of CsF and 34.06 g (0.24 mol) of CH3I in DMF (250 ml) chloroform was concentrated by rotary evaporation and the residue was sub-
was mixed and stirred at room temperature for 24 h. The reaction mixture jected to column chromatography with different solvent systems (see Re-
was filtered. The filtrate was extracted with ethyl acetate and then washed sults) to obtain pure compounds 1F—13F (synthetic scheme see Fig. 2).20)
with 5% NaHCO3. The ethyl acetate layer was dried over anhydrous magne-
Chromatography and Equipments The TLC experiment was per-
sium sulfate. The ethyl acetate was removed by rotary evaporation and the formed on aluminium sheets (20 by 20 cm2; Art. 5554; Merck, Darmstadt,
residue was then subjected to column chromatography with mobile phase Germany) precoated with silica gel 60 F254. The TLC plates (2 by 5 cm2)
consisting of a mixture of ethyl acetate–n-hexane (1 : 8, v/v) to obtain pure
were developed in 10-ml solvent systems. The optimal solvent systems of
the TLC plates were applied to the column chromatography method further.
compound 9A (synthetic scheme see Fig. 1).2,18)
Synthesis of Ethyl 5-(2ꢀ-Methoxycarbonyl-3ꢀ-methoxyphenoxy)furan- Column chromatography separations were achieved employing Silica Gel 60
2-carboxylate (9C) In comparison with compounds 1F—13F, compound (Kieselgel 60, 70—230 mesh; Merck, Darmstadt, Germany). A column was
9C was synthesized. To a vigorously stirred solution of 9.11 g (0.05 mol) of
9A, DMSO (50 ml) and 1.50 g (0.05 mol) of 80% NaH, a solution of 7.59 g
prepared by slurry packing the Silica Gel 60 sorbent in the optimal solvent
system of the TLC plate. The residues were eluted using the optimal mobile
(0.041 mol) of ethyl 5-nitro-2-furoate and DMSO (50 ml) was added drop- phase composition of the TLC plate by a series of chromatography proce-
wise. The reaction solution was stirred at 84—86 °C for 24 h and the reac- dures. Each chromatographic experiment was completed until pure com-
tion mixture was then poured into ice water. The oily product was extracted pounds 9A, 9C and 1F—13F were obtained.
with chloroform. The chloroform extract was washed with 5% KOH and
The melting point (mp) of the compounds were determined on a MP-
water, and was dried over anhydrous magnesium sulfate. The chloroform 500D micro-melting point apparatus (Yanaco Company, Kyoto, Japan). The
was concentrated by rotary evaporation and the residue was subjected to col- IR spectra were obtained in KBr discs on a Nicolet Impact-400 FT-IR spec-
umn chromatography with mobile phase consisting of a mixture of ethyl ac- trophotometer (Labequip Ltd., Ontario, Canada) in the 400—4000 cmꢁ1 re-
etate–n-hexane (1 : 4, v/v) to obtain pure compound 9C.2,19)
gion. 1H- and 13C-NMR spectra were obtained at 200 MHz and 50 MHz
Synthesis of 5-(2ꢀ-Alkoxycarbonyl-substituted phenoxy)furfural De- using a Bruker DPX-200 FT-NMR spectrometer (Bruker BioSpin GmbH,
rivatives (1F—13F) A facile synthetic route is that 5-nitrofurfural reacted Rheinstetten, Germany) respectively. Chemical shifts are given on the d ppm
with corresponding salicylates. To a vigorously stirred solution of 0.12 mol
of compounds 1A—13A, DMSO (150 ml) and 4.8 g (0.12 mol) of 60% NaH,
a solution of 14.11 g (0.10 mol) of 5-nitrofurfural and DMSO (90 ml) was
scale downfield from TMS as an internal standard. The UV–vis spectra of
the compounds (MeOH solution) were taken on a UV–visible-light record-
ing spectrophotometer (UV-160A; Shimadzu Corporation, Kyoto, Japan).
The EI-MS spectra were taken on a Hewlett-Packard benchtop model 5995
GC-MS (Hewlett-Packard, Palo Alto, CA, U.S.A.) under a 70 eV ionisation
potential. A HP-20, 25 mꢂ0.32 mm (i.d.) capillary column was used for
GC-MS. The column temperature was programmed from 110 to 300 °C at a
rate of 5 °C/min. Helium was used as the carrier gas at a flow-rate of
1 ml/min. Elemental analyses (C and H) were performed on a Perkin-Elmer
2400 Series II CHNS/O Analyzer (Perkin-Elmer Corporation, Boston, MA,
U.S.A.).
Identification and Pattern Recognition Analysis of 5-(2ꢀ-Alkoxycar-
bonyl-substituted phenoxy)furfural Derivatives (1F—13F) Compounds
9A, 9C and 1F—13F were elucidated and identified by the spectral data (EI-
Fig. 1. Synthetic Scheme of the 2-Hydroxy-6-methoxybenzoic Acid
Methyl Ester (9A)
1
MS, UV, IR, H- and 13C-NMR). For comparison of the EI-MS and NMR
patterns, an Excel worksheet was constructed with the codification of com-
pounds 1C—13C (structure see Fig. 3) and 1F—13F with their respective
EI-MS and NMR data. In the worksheet, fragmented and molecular ions,
and chemical shifts of carbon and hydrogen were placed in their correspon-
ding columns. The simple Excel worksheet analysis method can be suitable
for any size of data set by a minimum of human input. Upon construction of
the worksheet, the next step involves representing it on the EI-MS and NMR
pattern plots.
Fig. 2. Chemical Structures of the Substituted Salicylic Acid Methyl Es-
ters (1A—13A) and Synthetic Scheme of the 5-(2ꢀ-Alkoxycarbonyl-substi-
tuted phenoxy)furfural Derivatives (1F—13F)
Fig. 3. Chemical Structures of the Ethyl 5-(2ꢀ-Alkoxycarbonyl-substituted
phenoxy)furan-2-carboxylates (1C—13C)

552
Vol. 57, No. 6
Results
C14H12O5: C, 64.61; H, 4.65. Found: C, 64.55; H, 4.73.
ꢀ ꢀ
5-(2 -Methoxycarbonyl-5 -methylphenoxy)furfural (3F)
Analysis and Identification of 2-Hydroxy-6-methoxy-
benzoic Acid Methyl Ester (9A) Column chromatography Column chromatography with chloroform; yield 3.16 g
with mobile phase consisting of a mixture of ethyl acetate– (10.1%). Brown solid; mp 60.5—61.5 °C. EI-MS m/z (rela-
n-hexane (1 : 8, v/v); yield 24.50 g (84.1%). White solid; tive intensity %): 260 [M]ꢃ (41.0), 134 (100). UV lmax
mp 46.5—47.5 °C. EI-MS m/z (relative intensity %): 182 (MeOH) nm (log e): 301 (4.79), 231 (4.55), 208 (4.55). IR
1
1
[M]ꢃ (29.9), 107 (100). H-NMR (CDCl3) d: 3.84 (3H, s, (KBr) cmꢁ1: 1723 (CꢄO), 1670 (CHO). H-NMR (CDCl3)
COOCH3), 3.93 (3H, s, OCH3-6), 6.39 (1H, d, Jꢄ8.3 Hz, H- d: 2.38 (3H, s, CH3-5ꢀ), 3.77 (3H, s, COOCH3), 5.40 (1H, d,
3), 6.57 (1H, d, Jꢄ8.3 Hz, H-5), 7.31 (1H, t, Jꢄ8.3 Hz, H-4), Jꢄ3.8 Hz, H-4), 7.00 (1H, s, H-6ꢀ), 7.13 (1H, d, Jꢄ8.0 Hz,
11.48 (1H, s, OH). 13C-NMR (CDCl3) d: 52.4 (COOCH3), H-4ꢀ), 7.18 (1H, d, Jꢄ3.8 Hz, H-3), 7.87 (1H, d, Jꢄ8.0 Hz,
56.1 (OCH3-6), 102.2 (C-1), 103.0 (C-5), 110.1 (C-3), 135.1 H-3ꢀ), 9.34 (1H, s, CHO). 13C-NMR (CDCl3) d: 21.4 (CH3-
(C-4), 160.8 (C-2), 163.5 (C-6), 171.6 (CO). Anal. Calcd for 5ꢀ), 52.2 (COOCH3), 88.9 (C-4), 119.9 (C-2ꢀ), 122.2 (C-6ꢀ),
C9H10O4: C, 59.34; H, 5.53. Found: C, 59.26; H, 5.62.
125.4 (C-3), 127.2 (C-4ꢀ), 132.3 (C-3ꢀ), 144.7 (C-2), 145.6
ꢀ
Analysis and Identification of Ethyl 5-(2 -Methoxycar- (C-5ꢀ), 152.7 (C-1ꢀ), 163.3 (C-5), 164.8 (COOCH3), 175.5
ꢀ
bonyl-3 -methoxyphenoxy)furan-2-carboxylate (9C) (CHO). Anal. Calcd for C14H12O5: C, 64.61; H, 4.65. Found:
Column chromatography with mobile phase consisting of a C, 64.68; H, 4.70.
ꢀ ꢀ
5-(2 -Methoxycarbonyl-4 -methylphenoxy)furfural (4F)
mixture of ethyl acetate–n-hexane (1 : 4, v/v); yield 4.10 g
(25.6%). Yellow liquid. EI-MS m/z (relative intensity %): Column chromatography with chloroform; yield 4.36 g
320 [M]ꢃ (67.2), 150 (100). UV lmax (MeOH) nm (log e): (14.0%). Brown liquid. EI-MS m/z (relative intensity %): 260
1
273 (4.36), 206 (4.34). IR (KBr) cmꢁ1: 1721 (CꢄO). H- [M]ꢃ (27.5), 134 (100). UV lmax (MeOH) nm (log e): 311
NMR (CDCl3) d: 1.32 (3H, t, Jꢄ7.1 Hz, COOCH2CH3), 3.83 (3.99), 238 (4.16), 211 (4.60). IR (KBr) cmꢁ1: 1729 (CꢄO),
(3H, s, COOCH3), 3.85 (3H, s, OCH3-3ꢀ), 4.30 (2H, q, 1677 (CHO). 1H-NMR (CDCl3) d: 2.37 (3H, s, CH3-4ꢀ), 3.78
Jꢄ7.1 Hz, COOCH2CH3), 5.56 (1H, d, Jꢄ3.6 Hz, H-4), 6.64 (3H, s, COOCH3), 5.36 (1H, d, Jꢄ3.7 Hz, H-4), 7.10 (1H, d,
(1H, d, Jꢄ8.4 Hz, H-6ꢀ), 6.74 (1H, d, Jꢄ8.4 Hz, H-4ꢀ), 7.10 Jꢄ8.3 Hz, H-6ꢀ), 7.16 (1H, d, Jꢄ3.7 Hz, H-3), 7.35 (1H, dd,
(1H, d, Jꢄ3.6 Hz, H-3), 7.30 (1H, t, Jꢄ8.4 Hz, H-5ꢀ). 13C- Jꢄ8.3, 2.3 Hz, H-5ꢀ), 7.76 (1H, d, Jꢄ2.3 Hz, H-3ꢀ), 9.33
NMR (CDCl3) d: 14.3 (COOCH2CH3), 52.6 (COOCH3), (1H, s, CHO). 13C-NMR (CDCl3) d: 20.6 (CH3-4ꢀ), 52.3
56.2 (OCH3-3ꢀ), 60.8 (COOCH2CH3), 90.8 (C-4), 107.7 (C- (COOCH3), 88.5 (C-4), 121.6 (C-6ꢀ), 122.6 (C-2ꢀ), 125.4 (C-
4ꢀ), 110.0 (C-6ꢀ), 115.2 (C-2ꢀ), 120.3 (C-3), 131.4 (C-5ꢀ), 3), 132.6 (C-3ꢀ), 134.7 (C-5ꢀ), 136.4 (C-4ꢀ), 144.7 (C-2),
136.6 (C-2), 152.8 (COOCH2CH3), 157.7 (C-1ꢀ), 158.2 (C- 150.4 (C-1ꢀ), 163.6 (C-5), 165.0 (COOCH3), 175.5 (CHO).
3ꢀ), 158.9 (C-5), 165.1 (COOCH3). Anal. Calcd for Anal. Calcd for C14H12O5: C, 64.61; H, 4.65. Found: C,
C16H16O7: C, 60.00; H, 5.04. Found: C, 60.06; H, 4.97.
64.69; H, 4.59.
Analysis and Identification of 5-(2ꢀ-Alkoxycarbonyl-
5-(2ꢀ-Ethoxycarbonyl-3ꢀ-methylphenoxy)furfural (5F)
substituted phenoxy)furfural Derivatives (1F—13F). 5- Column chromatography with chloroform; yield 6.23 g
(2ꢀ-Methoxycarbonylphenoxy)furfural (1F) Column (18.9%). Yellow liquid. EI-MS m/z (relative intensity %):
chromatography with chloroform; yield 3.84 g (13.0%). 274 [M]ꢃ (30.6), 112 (100). UV lmax (MeOH) nm (log e):
Brown liquid. EI-MS m/z (relative intensity %): 246 [M]ꢃ 301 (4.39), 210 (4.58). IR (KBr) cmꢁ1: 1736 (CꢄO), 1677
(19.0), 126 (100). UV lmax (MeOH) nm (log e): 302 (4.60), (CHO). 1H-NMR (CDCl3) d: 1.23 (3H, t, Jꢄ7.1 Hz,
1
209 (4.36). IR (KBr) cmꢁ1: 1729 (CꢄO), 1675 (CHO). H- COOCH2CH3), 2.36 (3H, s, CH3-3ꢀ), 4.29 (2H, q, Jꢄ7.1 Hz,
NMR (CDCl3) d: 3.82 (3H, s, COOCH3), 5.44 (1H, d, COOCH2CH3), 5.48 (1H, d, Jꢄ3.7 Hz, H-4), 6.99 (1H, d,
Jꢄ3.7 Hz, H-4), 7.20 (1H, d, Jꢄ3.7 Hz, H-3), 7.25 (1H, d, Jꢄ7.9 Hz, H-6ꢀ), 7.10 (1H, d, Jꢄ7.9 Hz, H-4ꢀ), 7.17 (1H, d,
Jꢄ1.1 Hz, H-6ꢀ), 7.35 (1H, ddd, Jꢄ7.7, 1.1 Hz, H-4ꢀ), 7.58 Jꢄ3.7 Hz, H-3), 7.30 (1H, t, Jꢄ7.9 Hz, H-5ꢀ), 9.35 (1H, s,
(1H, ddd, Jꢄ7.7, 1.8 Hz, H-5ꢀ), 7.99 (1H, dd, Jꢄ7.7, 1.8 Hz, CHO). 13C-NMR (CDCl3) d: 14.0 (COOCH2CH3), 19.5
H-3ꢀ), 9.37 (1H, s, CHO). 13C-NMR (CDCl3) d: 52.4 (CH3-3ꢀ), 61.5 (COOCH2CH3), 89.6 (C-4), 117.1 (C-6ꢀ),
(COOCH3), 89.0 (C-4), 121.6 (C-3), 123.0 (C-2ꢀ), 125.3 (C- 125.0 (C-3), 126.2 (C-2ꢀ), 128.0 (C-4ꢀ), 130.8 (C-5ꢀ), 138.4
6ꢀ), 126.3 (C-4ꢀ), 132.3 (C-3ꢀ), 134.1 (C-5ꢀ), 144.8 (C-2), (C-3ꢀ), 144.8 (C-2), 150.9 (C-1ꢀ), 162.8 (C-5), 166.0
152.7 (C-1ꢀ), 163.1 (C-5), 164.8 (COOCH3), 175.6 (CHO). (COOCH2CH3), 175.6 (CHO). Anal. Calcd for C15H14O5: C,
Anal. Calcd for C13H10O5: C, 63.42; H, 4.09. Found: C, 65.69; H, 5.15. Found: C, 65.73; H, 5.09.
63.35; H, 4.14.
5-(2ꢀ-Methoxycarbonyl-6ꢀ-methoxyphenoxy)furfural
5-(2ꢀ-Methoxycarbonyl-6ꢀ-methylphenoxy)furfural (2F) (6F) Column chromatography with mobile phase consist-
Column chromatography with chloroform; yield 3.71 g ing of a mixture of ethyl acetate–n-hexane (1 : 2, v/v); yield
(11.9%). Brown liquid. EI-MS m/z (relative intensity %): 260 1.03 g (3.1%). Green solid; mp 79—80 °C. EI-MS m/z (rela-
[M]ꢃ (39.2), 134 (100). UV lmax (MeOH) nm (log e): 302 tive intensity %): 276 [M]ꢃ (14.2), 150 (100). UV lmax
(4.58). IR (KBr) cmꢁ1: 1736 (CꢄO), 1670 (CHO). 1H-NMR (MeOH) nm (log e): 305 (4.65), 209 (4.60). IR (KBr) cmꢁ1:
(CDCl3) d: 2.27 (3H, s, CH3-6ꢀ), 3.77 (3H, s, COOCH3), 1736 (CꢄO), 1670 (CHO). 1H-NMR (CDCl3) d: 3.81 (3H, s,
5.23 (1H, d, Jꢄ3.8 Hz, H-4), 7.18 (1H, d, Jꢄ3.8 Hz, H-3), COOCH3), 3.83 (3H, s, OCH3-6ꢀ), 5.35 (1H, d, Jꢄ3.8 Hz, H-
7.29 (1H, t, Jꢄ7.6 Hz, H-4ꢀ), 7.48 (1H, dd, Jꢄ7.6, 1.7 Hz, H- 4), 7.19 (1H, d, Jꢄ3.8 Hz, H-3), 7.20 (1H, dd, Jꢄ8.0, 1.7 Hz,
5ꢀ), 7.83 (1H, dd, Jꢄ7.6, 1.7 Hz, H-3ꢀ), 9.34 (1H, s, CHO). H-5ꢀ), 7.32 (1H, t, Jꢄ8.0 Hz, H-4ꢀ), 7.53 (1H, dd, Jꢄ8.0,
13C-NMR (CDCl3) d: 15.9 (CH3-6ꢀ), 52.4 (COOCH3), 87.0 1.7 Hz, H-3ꢀ), 9.33 (1H, s, CHO). 13C-NMR (CDCl3) d: 52.5
(C-4), 123.7 (C-3), 126.5 (C-4ꢀ), 126.5 (C-6ꢀ), 130.0 (C-3ꢀ), (COOCH3), 56.4 (OCH3-6ꢀ), 87.3 (C-4), 116.9 (C-5ꢀ), 122.9
132.1 (C-2ꢀ), 136.0 (C-5ꢀ), 144.5 (C-2), 150.3 (C-1ꢀ), 163.6 (C-3ꢀ), 125.0 (C-2ꢀ), 127.0 (C-3), 127.0 (C-4ꢀ), 141.1 (C-1ꢀ),
(C-5), 165.0 (COOCH3), 175.3 (CHO). Anal. Calcd for 144.3 (C-2), 152.1 (C-6ꢀ), 163.7 (C-5), 164.8 (COOCH3),

June 2009
553
175.3 (CHO). Anal. Calcd for C14H12O6: C, 60.87; H, 4.38. 175.7 (CHO). Anal. Calcd for C13H9ClO5: C, 55.63; H, 3.23.
Found: C, 60.79; H, 4.34. Found: C, 55.71; H, 3.28.
ꢀ
ꢀ
ꢀ ꢀ
5-(2 -Methoxycarbonyl-4 -chlorophenoxy)furfural
5-(2 -Methoxycarbonyl-5 -methoxyphenoxy)furfural
(7F) Column chromatography with chloroform; yield (11F) Column chromatography with chloroform; yield
1.37 g (4.1%). Green solid; mp 99—100 °C. EI-MS m/z (rel- 1.88 g (5.6%). Brown liquid. EI-MS m/z (relative intensity
ative intensity %): 276 [M]ꢃ (41.6), 63 (100). UV lmax %): 282 [M]ꢃꢃ2 (2.9), 280 [M]ꢃ (8.7), 126 (100). UV lmax
(MeOH) nm (log e): 301 (4.64), 254 (4.50), 209 (4.51). IR (MeOH) nm (log e): 301 (4.71), 208 (4.61). IR (KBr) cmꢁ1:
1
(KBr) cmꢁ1: 1723 (CꢄO), 1670 (CHO). H-NMR (CDCl3) 1729 (CꢄO), 1675 (CHO). 1H-NMR (CDCl3) d: 3.81 (3H, s,
d: 3.75 (3H, s, COOCH3), 3.83 (3H, s, OCH3-5ꢀ), 5.42 (1H, COOCH3), 5.48 (1H, d, Jꢄ3.7 Hz, H-4), 7.15—7.20 (2H, m,
d, Jꢄ3.7 Hz, H-4), 6.70 (1H, d, Jꢄ2.5 Hz, H-6ꢀ), 6.83 (1H, H-3, 6ꢀ), 7.52 (1H, dd, Jꢄ8.7, 2.7 Hz, H-5ꢀ), 7.95 (1H, d,
dd, Jꢄ8.8, 2.5 Hz, H-4ꢀ), 7.18 (1H, d, Jꢄ3.7 Hz, H-3), 7.97 Jꢄ2.7 Hz, H-3ꢀ), 9.36 (1H, s, CHO). 13C-NMR (CDCl3) d:
(1H, d, Jꢄ8.8 Hz, H-3ꢀ), 9.34 (1H, s, CHO). 13C-NMR 52.7 (COOCH3), 89.3 (C-4), 123.0 (C-6ꢀ), 124.3 (C-2ꢀ),
(CDCl3) d: 52.1 (COOCH3), 55.8 (OCH3-5ꢀ), 88.9 (C-4), 125.2 (C-3), 131.8 (C-4ꢀ), 132.1 (C-3ꢀ), 134.0 (C-5ꢀ), 144.9
107.5 (C-6ꢀ), 111.8 (C-4ꢀ), 114.9 (C-2ꢀ), 125.2 (C-3), 134.0 (C-2), 151.2 (C-1ꢀ), 162.4 (C-5), 163.6 (COOCH3), 175.6
(C-3ꢀ), 144.7 (C-2), 154.3 (C-1ꢀ), 163.1 (C-5ꢀ), 164.2 (C-5), (CHO). Anal. Calcd for C13H9ClO5: C, 55.63; H, 3.23.
164.4 (COOCH3), 175.6 (CHO). Anal. Calcd for C14H12O6: Found: C, 55.59; H, 3.31.
ꢀ ꢀ
5-(2 -Methoxycarbonyl-4 -bromophenoxy)furfural
C, 60.87; H, 4.38. Found: C, 60.96; H, 4.33.
ꢀ
ꢀ
5-(2 -Methoxycarbonyl-4 -methoxyphenoxy)furfural (12F) Column chromatography with mobile phase consist-
(8F) Column chromatography with chloroform; yield ing of a mixture of chloroform–benzene (1 : 1, v/v); yield
6.48 g (19.5%). Brown solid; mp 50.5—51.5 °C. EI-MS m/z 4.72 g (12.1%). Yellow liquid. EI-MS m/z (relative intensity
(relative intensity %): 276 [M]ꢃ (21.1), 150 (100). UV lmax %): 326 [M]ꢃꢃ2 (10.5), 324 [M]ꢃ (10.5), 126 (100). UV
(MeOH) nm (log e): 306 (4.16), 209 (4.18). IR (KBr) cmꢁ1: lmax (MeOH) nm (log e): 300 (4.89), 212 (4.78). IR (KBr)
1
1729 (CꢄO), 1664 (CHO). 1H-NMR (CDCl3) d: 3.78 (3H, s, cmꢁ1: 1737 (CꢄO), 1667 (CHO). H-NMR (CDCl3) d: 3.81
COOCH3), 3.83 (3H, s, OCH3-4ꢀ), 5.31 (1H, d, Jꢄ3.8 Hz, H- (3H, s, COOCH3), 5.48 (1H, d, Jꢄ3.7 Hz, H-4), 7.10 (1H, d,
4), 7.07 (1H, dd, Jꢄ9.0, 3.0 Hz, H-5ꢀ), 7.14—7.18 (2H, m, Jꢄ8.7 Hz, H-6ꢀ), 7.19 (1H, d, Jꢄ3.7 Hz, H-3), 7.66 (1H, dd,
H-3, 6ꢀ), 7.45 (1H, d, Jꢄ3.0 Hz, H-3ꢀ), 9.32 (1H, s, CHO). Jꢄ8.7, 2.6 Hz, H-5ꢀ), 8.09 (1H, d, Jꢄ2.6 Hz, H-3ꢀ), 9.36
13C-NMR (CDCl3) d: 52.5 (COOCH3), 55.9 (OCH3-4ꢀ), 88.0 (1H, s, CHO). 13C-NMR (CDCl3) d: 52.7 (COOCH3), 89.4
(C-4), 116.1 (C-3ꢀ), 120.1 (C-5ꢀ), 123.3 (C-6ꢀ), 123.7 (C-2ꢀ), (C-4), 119.2 (C-4ꢀ), 123.2 (C-6ꢀ), 124.5 (C-2ꢀ), 125.2 (C-3),
125.8 (C-3), 144.5 (C-2), 146.0 (C-1ꢀ), 157.4 (C-4ꢀ), 164.1 135.1 (C-3ꢀ), 137.0 (C-5ꢀ), 145.0 (C-2), 151.8 (C-1ꢀ), 162.3
(C-5), 164.7 (COOCH3), 175.4 (CHO). Anal. Calcd for (C-5), 163.5 (COOCH3), 175.6 (CHO). Anal. Calcd for
C14H12O6: C, 60.87; H, 4.38. Found: C, 60.80; H, 4.29.
C13H9BrO5: C, 48.03; H, 2.79. Found: C, 48.09; H, 2.85.
5-(2ꢀ-Methoxycarbonyl-3ꢀ-methoxyphenoxy)furfural
5-(2ꢀ-Methoxycarbonyl-4ꢀ-iodophenoxy)furfural (13F)
(9F) Column chromatography with mobile phase consist- Column chromatography with mobile phase consisting of a
ing of a mixture of ethyl acetate–n-hexane (1 : 2, v/v); yield mixture of chloroform–benzene (1 : 1, v/v); yield 5.45 g
7.82 g (23.6%). Yellow liquid. EI-MS m/z (relative intensity (12.2%). Brown solid; mp 59.5—60.5 °C. EI-MS m/z (rela-
%): 276 [M]ꢃ (6.7), 55 (100). UV lmax (MeOH) nm (log e): tive intensity %): 372 [M]ꢃ (15.3), 126 (100). UV lmax
298 (4.79), 209 (4.61). IR (KBr) cmꢁ1: 1737 (CꢄO), 1675 (MeOH) nm (log e): 305 (4.44), 218 (4.41). IR (KBr) cmꢁ1:
1
(CHO). H-NMR (CDCl3) d: 3.83 (3H, s, COOCH3), 3.84 1729 (CꢄO), 1659 (CHO). 1H-NMR (CDCl3) d: 3.81 (3H, s,
(3H, s, OCH3-3ꢀ), 5.59 (1H, d, Jꢄ3.8 Hz, H-4), 6.73 (1H, d, COOCH3), 5.52 (1H, d, Jꢄ3.7 Hz, H-4), 6.96 (1H, d,
Jꢄ8.4 Hz, H-6ꢀ), 6.80 (1H, d, Jꢄ8.4 Hz, H-4ꢀ), 7.18 (1H, d, Jꢄ8.6 Hz, H-6ꢀ), 7.19 (1H, d, Jꢄ3.7 Hz, H-3), 7.84 (1H, dd,
Jꢄ3.8 Hz, H-3), 7.35 (1H, t, Jꢄ8.4 Hz, H-5ꢀ), 9.37 (1H, s, Jꢄ8.6, 2.3 Hz, H-5ꢀ), 8.27 (1H, d, Jꢄ2.3 Hz, H-3ꢀ), 9.38
CHO). 13C-NMR (CDCl3) d: 52.7 (COOCH3), 56.3 (OCH3-
3ꢀ), 90.7 (C-4), 108.6 (C-4ꢀ), 111.1 (C-6ꢀ), 115.9 (C-2ꢀ),
124.8 (C-3), 131.7 (C-5ꢀ), 145.0 (C-2), 151.8 (C-1ꢀ), 157.9
(C-3ꢀ), 161.9 (C-5), 164.8 (COOCH3), 175.9 (CHO). Anal.
Calcd for C14H12O6: C, 60.87; H, 4.38. Found: C, 60.90; H,
4.43.
5-(2ꢀ-Methoxycarbonyl-5ꢀ-chlorophenoxy)furfural
(10F) Column chromatography with mobile phase consist-
ing of a mixture of chloroform–benzene (1 : 1, v/v); yield
1.07 g (3.2%). Green solid; mp 79.5—80.5 °C. EI-MS m/z
(relative intensity %): 282 [M]ꢃꢃ2 (3.5), 280 [M]ꢃ (10.5),
126 (100). UV lmax (MeOH) nm (log e): 302 (4.53), 235
(4.37), 206 (4.44). IR (KBr) cmꢁ1: 1721 (CꢄO), 1667
1
(CHO). H-NMR (CDCl3) d: 3.80 (3H, s, COOCH3), 5.54
(1H, d, Jꢄ3.8 Hz, H-4), 7.19 (1H, s, H-6ꢀ), 7.21 (1H, d,
Jꢄ3.8 Hz, H-3), 7.31 (1H, dd, Jꢄ8.5, 2.0 Hz, H-4ꢀ), 7.93
(1H, d, Jꢄ8.5 Hz, H-3ꢀ), 9.38 (1H, s, CHO). 13C-NMR
(CDCl3) d: 52.6 (COOCH3), 89.9 (C-4), 121.3 (C-2ꢀ), 121.8
(C-6ꢀ), 125.0 (C-3), 126.6 (C-4ꢀ), 133.4 (C-3ꢀ), 139.8 (C-5ꢀ),
145.1 (C-2), 153.3 (C-1ꢀ), 161.9 (C-5), 164.0 (COOCH3),
Fig. 4. Plot of Compounds 1C—13C and 1F—13F for Fragmented and
Molecular Ions Generated as an Excel Worksheet Method
Each point represents fragmented and molecular ions of 1C—13C versus 1F—13F.

554
Vol. 57, No. 6
zoic acid/CH3I/CsFꢄ1/1.5/1.5 dissolved in DMF at room
temperature for 24 h.18) According to the nucleophilic substi-
tution reaction as shown in Fig. 2, a mixture of 5-nitrofur-
fural and various phenoxides in DMSO was reacted at room
temperature for 23 h to yield compounds 1F—13F.20)
Three solvent systems, chloroform, ethyl acetate–n-hexane
and chloroform–benzene, were applied to column chro-
matography for the separation of compounds 1F—13F. This
gentle and expeditious chromatography technique suits well
solid and viscous samples. The yield and mp of compounds
1F—13F were from 3.1—23.6% and 50.5—100.0 °C, re-
spectively. Some compounds (1F, 2F, 4F, 5F, 9F, 11F, 12F)
were liquid and some compounds (3F, 6F—8F, 10F, 13F)
were solid. After investigating mass spectra of compounds
1F—13F, the base peaks (relative intensityꢄ100%): 126 m/z
for 1F and 10F—13F; 134 m/z for 2F—4F; 112 m/z for 5F;
150 m/z for 6F and 8F; 63 m/z for 7F and 55 m/z for 9F. EI-
1
MS, UV, IR, H- and 13C-NMR spectral analyses confirmed
Fig. 5. Plot of Compounds 1C—13C and 1F—13F for Chemical Shifts of
the chemical structures of compounds 1F—13F. For in-
stance, compound 1F was determined as C13H10O5 according
to its EI-MS spectrum [m/z (relative intensity %): 246 (Mꢃ,
Carbon Generated as an Excel Worksheet Method
Each point represents chemical shifts of carbons of 1C—13C versus 1F—13F.
1
19.0)]. Its H-NMR spectrum showed two doublet signals,
one singlet signal and four sets of signals with spin coupling
system. The one doublet signal at d 5.44 (1H, d, Jꢄ3.7 Hz)
was assigned to be H-4, while the other at d 7.20 (1H, d,
Jꢄ3.7 Hz) was assigned to be H-3. The singlet signal at d
9.37 (1H, s) was assigned to be the aldehyde group. The first
set of spin coupling systems was observed at d 7.25 (1H, d,
Jꢄ1.1 Hz), the second set at d 7.35 (1H, ddd, Jꢄ7.7, 1.1 Hz),
the third set at d 7.58 (1H, ddd, Jꢄ7.7, 1.8 Hz) and the fourth
set at d 7.99 (1H, dd, Jꢄ7.7, 1.8 Hz), attributed to the H-6ꢀ,
H-4ꢀ, H-5ꢀ and H-3ꢀ of the 2ꢀ-methoxycarbonylphenoxy
group, respectively. Furthermore, the structural assignment
was also confirmed by 2D-NMR (heteronuclear multiple
quantum coherence (HMQC) and heteronuclear multiple
bond coherence (HMBC) correlations in Fig. 7) spectra. Ac-
1
cording to the EI-MS, UV, IR, H- and 13C-NMR data, com-
pound 1F was elucidated to be 5-(2ꢀ-methoxycarbonylphe-
noxy)furfural.
Fig. 6. Plot of Compounds 1C—13C and 1F—13F for Chemical Shifts of
Carbon versus Hydrogen Generated as an Excel Worksheet Method
Figure 4 shows a map of fragmented and molecular ions
obtained by measuring EI-MS spectra for compounds 1C—
13C and 1F—13F. Each point on the map represents the
Each point represents chemical shifts of carbon versus hydrogen of both 1C—13C
and 1F—13F.
(1H, s, CHO). 13C-NMR (CDCl3) d: 52.7 (COOCH3), 89.5 fragmented and molecular ion of 1C—13C versus 1F—13F.
(C-4), 89.5 (C-4ꢀ), 123.3 (C-6ꢀ), 124.7 (C-2ꢀ), 125.1 (C-3), The data give an rꢄ0.985 and show good performance for
141.0 (C-3ꢀ), 142.9 (C-5ꢀ), 145.0 (C-2), 152.6 (C-1ꢀ), 162.1 both 1C—13C and 1F—13F. There is an equation of
(C-5), 163.4 (COOCH3), 175.6 (CHO). Anal. Calcd for yꢄ0.831xꢃ10.303. Only two points of 11C versus 11F and
C13H9IO5: C, 41.96; H, 2.44. Found: C, 41.89; H, 2.37.
12C versus 12F are clearly well separated from all the other
Pattern Recognition Analysis of 5-(2ꢀ-Alkoxycarbonyl- points as a result of the halogen group. To analyze the frag-
substituted phenoxy)furfural Derivatives (1F—13F) by mented ions of compounds 1C—13C and 1F—13F, “active
EI-MS and NMR Compounds 1C—13C and 1F—13F structure” is shown in Fig. 8. Figure 5 shows a chemical shift
were pure, so the data could be easily interpreted. After con- map obtained by measuring 13C-NMR spectra for compounds
structing the EI-MS and NMR worksheet with all com- 1C—13C and 1F—13F. Each point on the map represents
pounds 1C—13C and 1F—13F, the results obtained are de- the chemical shift of the carbon (C-2, 3, 4, 5, 1ꢀ, 2ꢀ, 3ꢀ, 4ꢀ,
scribed in Figs. 4—6, which allowed each of these com- 5ꢀ, 6ꢀ) for 1C—13C versus 1F—13F. The data give an
pounds to be classified according to the EI-MS and NMR rꢄ0.997 and also show good performance for both 1C—13C
pattern plots and their equations.
and 1F—13F. There is an equation of yꢄ0.995xꢃ0.926.
Only these C-2 points are clearly well separated from all the
other points as a result of both COOC2H5 and CHO groups.
Discussion
As shown in Fig. 1, the esterification of 2-hydroxy-6- Figure 6 shows a chemical shift map obtained by measuring
methoxybenzoic acid with CH3I in the presence of CsF was 1H- and 13C-NMR spectra for both 1C—13C and 1F—13F.
optimized at the reaction ratio of 2-hydroxy-6-methoxyben- Each point on the map represents the chemical shift of the

June 2009
555
Fig. 9. The M–A Plot of the Chemical Shifts of the Carbons for Both
1C—13C and 1F—13F Uses M as the y-Axis and A as the x-Axis
Fig. 7. HMQC and HMBC Correlations of Compound 1F
carbon versus hydrogen (C-3 vs. H-3; C-4 vs. H-4; C-3ꢀ vs.
H-3ꢀ; C-4ꢀ vs. H-4ꢀ; C-5ꢀ vs. H-5ꢀ; C-6ꢀ vs. H-6ꢀ) for both
1C—13C and 1F—13F. The data give an rꢄ0.868 and also
show good performance for the carbon versus hydrogen
of both 1C—13C and 1F—13F. There is an equation of
yꢄ0.052xꢃ0.830. These results above indicate that it is
unlikely that compounds 1C—13C and 1F—13F belong to
more than one skeleton. In addition, these equations may be
applied to analysis of new synthesized derivatives in ad-
vance. To research the probable structure skeleton of a syn-
thesized compound, it is only necessary to add fragmented
and molecular ions, and chemical shifts to the Excel work-
sheet and to the equation of the pattern plot on a case-by-
case basis. The simple Excel worksheet analysis method will
allow the combination of data from EI-MS and NMR spec-
trometers at different fragmented and molecular ions, and
chemical shifts, respectively.
M–A plots were employed to visualize differences in
chemical shifts of the carbon (C-2, 3, 4, 5, 1ꢀ, 2ꢀ, 3ꢀ, 4ꢀ, 5ꢀ,
6ꢀ) between both 1C—13C and 1F—13F. Mꢄlog(chemical
shift of the carbon in 1F—13F/chemical shift of the carbon
in 1C—13C) represents a log ratio of the chemical shift of
the carbon for both 1F—13F and 1C—13C. Aꢄ[log(chemi-
cal shift of the carbon in 1F—13F)ꢃlog(chemical shift of
the carbon in 1C—13C)]/2 is the average logarithmic chemi-
cal shift of the carbon. M and A were calculated for each car-
bon (C-2, 3, 4, 5, 1ꢀ, 2ꢀ, 3ꢀ, 4ꢀ, 5ꢀ, 6ꢀ) in both 1C—13C and
1F—13F. The general assumption is that both 1F—13F and
1C—13C will not show any change in most of the chemical
shifts of the carbon. Therefore, the majority of these points
on the y-axis (M) would be located at zero. In this M–A plot
(Fig. 9), the result fills the bill. The objective of the above
analysis processes was to determine a correct skeleton of
these synthesized compounds from the EI-MS and NMR pat-
terns. The construction of this Excel worksheet will be a sim-
ple method, superior to special statistical software, for
achieving EI-MS and NMR pattern recognition.
Conclusion
A series of derivatives 1F—13F had been synthesized and
their structural pattern recognition had been studied by com-
parison with compounds 1C—13C. Compounds 1F—13F
were purified by column chromatography. The exact struc-
Fig. 8. Proposed EI-MS Fragmentation Patterns of Compounds 1C—13C
and 1F—13F
1
tures were elucidated and identified by EI-MS, UV, IR, H-,
13C-NMR and 2D-NMR (HMQC and HMBC) spectrometers.
Pattern recognition analysis was studied and discussed in

556
Vol. 57, No. 6
2) Chang C. L., Wu C. S., Wang S. W., Wang J. P., Chin. Pharm. J., 54,
95—113 (2002).
3) Borawski J., Rydzewski A., Pawlak K., Azzadin A., Buczko W., Mys-
liwiec M., Thromb. Res., 90, 171—180 (1998).
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depth. According to the EI-MS pattern recognition analysis,
the halogen substitute was much more changed than the
methoxy and methyl substitutes. Among 13C-NMR pattern
recognition analysis, chemical shifts of C-2 showed greater
differences because of the difference between COOC2H5 and
CHO groups. However, chemical shifts of 13C-NMR versus
1H-NMR showed no obvious differences in the pattern recog-
nition analysis. The M–A plot also shows good performance.
The simple Excel worksheet analysis method requires no
prior knowledge of the data and the results are statistically
valid. The spectroscopic data mining technique thus offers
high-throughput screening for pattern recognition analysis
and structural skeleton identification. It is possible to deter-
mine the correct skeleton of synthetic structures in future
structural elucidation studies. Mass and NMR spectral data
are essential to identify the compounds 1C—13C and 1F—
13F. If these data work as an index of the biological activi-
ties, it is very useful to avoid some of complicated proce-
dures. For the preliminary tests of the biological activities,
compound 1F also showed anti-platelet aggregation, anti-al-
lergic and anti-inflammatory activities. The study of anti-
platelet aggregation, anti-allergic and anti-inflammatory ac-
tivities of compounds 2F—13F is still in progress. The struc-
12) Praisler M., Dirinck I., Van Bocxlaer J., De Leenheer A., Massart D.
L., Talanta, 53, 177—193 (2000).
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Anal., 44, 1163—1167 (2007).
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Sci., 30, 3233—3239 (2007).
17) Aursand M., Standal I. B., Axelson D. E., J. Agric. Food Chem., 55,
be reported in future.
38—47 (2007).
Acknowledgements The author wishes to express his gratitude to Dr.
Chin-Sheng Wu for the scientific support. This work was financially sup-
ported by the China Medical University, Taichung, Taiwan, R.O.C.
18) Sato T., Otera J., Nozaki H., J. Org. Chem., 57, 2166—2169 (1992).
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