Synthesis of a piceatannol analog: Replacement of hydroxy group with amide functionality

Article abstract of DOI:10.1081/SCC-120030700

Polyhydroxylated stilbene analogs of piceatannol are shown to possess protein-tyrosine kinase (PTK) inbibitory activity. We have developed a novel approach to introduce an amide moiety into the structure of piceatannol. The amido substituted stilbene deri

Full text of DOI:10.1081/SCC-120030700

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Synthesis of a Piceatannol Analog: Replacement of
Hydroxy Group with Amide Functionality
T. K. Venkatachalam a , H. Huang a , G. Yu a & F. M. Uckun b c d
a Department of Chemistry, Parker Hughes Institute, St. Paul, Minnesota, USA
b Department of Cancer Biology, Parker Hughes Institute, 2699 Patton Road, St. Paul,
Minnesota, 55113, USA
c Virology, Parker Hughes Institute, St. Paul, Minnesota, USA
d Drug Discovery Program, Parker Hughes Cancer Center, 2848 Patton Road, St. Paul,
Minnesota, USA
Published online: 21 Aug 2006.
To cite this article: T. K. Venkatachalam , H. Huang , G. Yu & F. M. Uckun (2004) Synthesis of a Piceatannol Analog:
Replacement of Hydroxy Group with Amide Functionality, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:8, 1489-1497, DOI: 10.1081/SCC-120030700
To link to this article: http://dx.doi.org/10.1081/SCC-120030700
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 8, pp. 1489–1497, 2004
Synthesis of a Piceatannol Analog:
Replacement of Hydroxy Group
with Amide Functionality
T. K. Venkatachalam,1 H. Huang,1 G. Yu,1 and
F. M. Uckun2,3,4,
*
2
1Department of Chemistry, Cancer Biology, and
3Virology, Parker Hughes Institute, St. Paul, Minnesota, USA
4Drug Discovery Program, Parker Hughes Cancer Center, St. Paul,
Minnesota, USA
ABSTRACT
Polyhydroxylated stilbene analogs of piceatannol are shown to possess
protein-tyrosine kinase (PTK) inhibitory activity. We have developed
a novel approach to introduce an amide moiety into the structure of
piceatannol. The amido substituted stilbene derivative was synthesized
in 10 steps with an overall yield of 30%.
Key Words: Protein-tyrosine kinase; Piceatannol; Stilbene derivatives;
Amido group.
*
Correspondence: F. M. Uckun, Parker Hughes Cancer Center, 2848 Patton Road,
St. Paul, MN 55113, USA; Fax: (651) 796-5493; E-mail: fatih_uckun@ih.org.
1489
DOI: 10.1081/SCC-120030700
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Venkatachalam et al.
INTRODUCTION
Protein-tyrosine kinases (PTKs) mediate important signaling events associ-
ated with cellular activation, differentiation, and mitogenesis. Highly potent and
selective PTK inhibitors may serve as active drug substances with immunosup-
pressive, anti-inflammatory and anti-cancer activities.[1–4] Piceatannol analogs
exhibit potent PTK inhibiting activity.[5–8] Although several syntheses of pice-
atannol and its analogs are known, these routes are found to proceed in moderate
to low yields. In addition, instability of the phenolic stilbene derivative towards
oxidation forming quinones made isolation of the product difficult.[9] This
communication reports the synthesis of an amido-substituted stilbene
derivative.
RESULTS AND DISCUSSION
Synthesis of an amido-substituted piceatannol was initiated following the
synthetic (Sch. 1). 3,5-Dihydroxy benzoic acid (1) was converted into its ben-
zyl ester (2) using benzyl bromide. The crystalline benzyl ester was reduced to
the alcohol (3) with LAH. Conversion of the alcohol into its bromo derivative
was achieved using phosphorus tribromide in anhydrous dichloromethane.
The bromo derivative (4) thus obtained was treated with triethyl phosphite
in the presence of tetrabutyl ammonium iodide to furnish the required phos-
phate ester (5). Compound (7) was obtained by condensing 5-formyl salicylic
acid (6) with benzyl bromide in presence of anhydrous potassium carbonate
in dimethylformamide. Condensation of compound (5) with compound (7)
was accomplished in dimethylformamide in presence of potassium tertiary
butoxide at room temperature to afford protected stilbene derivative (8).
Compound (10) was prepared from p-amino benzoic acid (9) and EDC in
t-BuOH. Compounds (8) and (10) were mixed together in presence of EDC
in methylene chloride and refluxed for 18 hr. Usual workup gave compound
(11) as a solid, which upon treatment with trifluroacetic acid for 1 hr at low
temperature yielded the partially protected stilbene derivative (12). Finally,
reaction of compound (12) with N-dimethyl aniline in dichloromethane at
room temperature followed by anhydrous aluminum chloride treatment
furnished the required stilbene analog (13) with an over all yield of 30%.
CONCLUSION
We have developed an efficient method for the introduction of an amido
group into piceatannol. It is hoped that due to increased interest on PTK inhibi-
tory activity shown by stilbene derivatives, the above synthetic methodology

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Synthesis of Piceatannol Analog
1491
Scheme 1. Synthesis of piceatannol analog.
may be beneficial. It is envisioned that the amido-substituted piceatannol will
be useful with properties of tyrosine kinase inhibiting immunoconjugates
targeted against specific surface receptors on cancer cells.[10–12]
EXPERIMENTAL
All chemicals were purchased from Aldrich (Milwaukee, WI) and were
used without further purification. Unless otherwise noted, each reaction vessel

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Venkatachalam et al.
was secured with a rubber septa, and the reaction was performed under nitro-
gen atmosphere. 1H, 13C NMR were obtained on a Varian Mercury 300 instru-
ment at ambient temperature in either CDCl3 or DMSO-d6. Chemical shifts
are reported as d values in parts per million downfield from tetramethylsilane
(d ¼ 0.0 ppm) as an internal standard in the case of CDCl3 or from the residual
1
dimethylsufloxide signal (d ¼ 2.49 ppm for H NMR or d ¼ 39.7 ppm for
13C NMR). 31P NMR were obtained using either of the above solvent and a
capillary containing 0.1% phosphoric acid in water served as internal stan-
dard. Splitting patterns are designated as follows: s, singlet; d, doublet; t,
triplet; m, multiplet; br, broad peak. FT-IR spectra were recorded on a Nicolet
Protege 460 spectrometer. Mass spectra were performed either on a Hewlett
Packard HP GC System 6890 Series or MALDI-TOF spectrometer (Model
G2025A LD-TOF). Melting points were determined using a Melt John’s
apparatus and are uncorrected. Analytical thin-layer chromatography was
done on Whatman silica 60 aluminum coated plates. Flash column chromato-
graphy was carried out with 230–400 mesh silica gel obtained from J. T. Baker
Company.
Benzyl 3,5-dibenzyloxybenzoate (2). A mixture of 3,5-dihydroxyl-
benzoic acid (1) (3.08 g, 20 mmol), benzyl bromide (1.25 equiv., 8.9 mL,
75 mmol), and anhydrous potassium carbonate (16.6 g, 120 mmol) in anhy-
drous DMF (30 mL) was stirred and heated at 1008C under N2 for 18 hr.
After cooling, 150 mL of ethyl acetate was added and the inorganic salt was
removed by filtration. The filtrate was successively washed with 10%
NaOH (40 mL), H2O (50 mL) and finally dried over anhydrous MgSO4. The
solvent was removed under vacuum, leaving a yellow residue. Recrystalliza-
tion from Et2O–ethanol gave analytically pure product: yield 6.87 g (81%);
Single spot in TLC (hexane/ethylacetate: 3 : 1); mp 50–528C; IR (KBr)
1
3090, 3066, 3030, 2920, 2871, 1711, 1599 cm21; H NMR (CDCl3) d 5.06
(s, 4H), 5.34 (s, 2H), 6.80 (s, 1H), 7.32 (m, 17H); 13C NMR (CDCl3)
d 165.9, 159.6, 127.5, 108.5, 107.1, 70.3, 66.9, GC/MS: 424 (Mþ), single
peak, purity .98% by gas chromatography. Anal. calcd. for C28H24O4: C:
79.22; H: 5.70; found; C: 79.33; H: 5.69.
3,5-Dibenzyloxybenzyl alcohol (3). The protected ester (2) (6.87 g,
16.2 mmol) in 60 mL anhydrous ether was added to a cold suspension of
LiAlH4 (1.23 g, 32.4 mmol) in anhydrous ether (100 mL) over a period of
40 min. The mixture was stirred at room temperature for 4 hr. The excess
LiAlH4 was decomposed by the treatment with methanol (2 mL), H2O
(4 mL), and 10% NaOH (5 mL). The inorganic salt was removed by filtration.
The filtrate was dried over anhydrous MgSO4. The solvent was evaporated by
rotavap. Recrystallization from ethanol/water mixture gave the product as
needle: yield 4.56 g (88%); mp 75–768C (lit.,[7] m.p. 858C); IR (KBr) 3288,
3032, 2859, 1596, 1451, 1291, 1168 cm21; 1H NMR (CDCl3) d 4.63 (s, 2H),

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Synthesis of Piceatannol Analog
1493
5.04 (s, 4H), 6.55 (s, 1H), 6.62 (d, J ¼ 2.4 Hz, 2H), 7.36 (m, 10H); [lit.,[7]
1H NMR (CDCl3), 200 MHz] d 4.63 (s, 2H), 5.03 (s, 4H), 6.56 (t, 1H), 6.63
(d, J ¼ 2.0 Hz, 2H), 7.40 (m, 10H); 13C NMR (CDCl3) d 159.9, 143.3,
136.7, 128.5, 127.9, 127.4, 105.7, 101.2, 70.1, 65.3; GC/MS: 320 (Mþ); single
peak, purity .99% by gas chromatography. Anal. calcd. for C21H20O3: C:
78.73; H: 6.29; found: C: 78.92; H: 6.28.
3,5-Dibenzyloxybenzyl bromide (4). Phosphorous tribromide (2.4 mL,
2.9 mmol) was added to a solution of benzyloxybenzyl alcohol (3) (4.13 g,
12.9 mmol) in anhydrous CH2Cl2 (50 mL) at 08C under N2 and the reaction
mixture was stirred for 2 hr at 08C followed by 3 hr at room temperature.
The mixture was poured into ice/water (200 mL) and the product was
extracted with ether (6 ꢀ 50 mL). The combined ether layers were dried
over anhydrous MgSO4. Evaporation of the solvent gave the crude product
as a yellow residue. Subsequent recrystallization from ethanol gave an analyti-
cally pure product: yield 2.2 g (42%); m.p. 77–798C; IR (KBr) 3068, 3032,
1
2930, 2873, 1598, 1450, 1168 cm21; H NMR (CDCl3) d 4.42 (s, 2H), 5.03
(s, 4H), 6.55 (s, 1H), 6.64 (d, J ¼ 2.4 Hz, 2H), 7.35 (m, 10H); [lit.,[7] 1
H
NMR (CDCl3)] d 4.41 (s, 2H), 5.02 (s, 4H), 6.55 (t, J ¼ 2.0 Hz, 1H), 6.63
(d, J ¼ 2.0 Hz, 2H), 7.40 (m, 10H); 13C NMR (CDCl3) d 159.9, 139.6,
136.5, 128.5, 127.9, 127.5, 108.1, 102.1, 70.1, 33.6; GC/MS: 384 (M þ 1)þ,
303 (M-HBr), 91 (Bn), single peak, purity .99% by gas chromatography.
Anal. calcd. for C21H19O2Br: C: 65.81; H: 5.00; found: C: 66.03; H: 5.06.
Diethyl[2,4-dibenzyloxybenzyl]phosphonate (5). Freshly distilled
triethyl phosphite (1.4 mL, 1.5 mmol) was added to the benzyl bromide (4)
(2.0 g. 5.2 mmol) in presence of catalytic amount (40 mg) of tetrabutylammo-
nium iodide, and the reaction mixture was heated at 110–1308C for 18 hr.
Excess triethyl phosphite was removed by vacuum distillation (0.2 mmHg),
and the resultant mixture was heated at 508C for 3 hr to obtain a yellowish
syrup: yield 2.11 g (92%); IR (KBr) 3278, 3028, 2858, 1946, 1870, 1737,
1
1691, 1588, 1153 cm21; H NMR (CDCl3) d 1.22 (t, J ¼ 6.9 Hz, 6H), 3.2
(d, J ¼ 21.6 Hz, 2H), 3.97 (q, J ¼ 6.9 Hz, 4H), 5.02 (s, 4H), 6.52 (m, 3H),
7.31 (m, 10H); [lit.,[7] 1H NMR (CDCl3)] d 1.22 (t, J ¼ 7.4 Hz, 6H), 3.10
(d, J ¼ 21.6 Hz, 2H), 3.95 (q, J ¼ 7.4 Hz, 4H), 5.05 (s, 4H), 6.54
(t, J ¼ 2.1 Hz, 1H), 6.57 (d, J ¼ 2.1 Hz, 2H), 7.38 (m, 10H)); 13C NMR
(CDCl3) d 159.7, 159.6, 136.6, 133.6, 133.5, 128.4, 127.8, 127.3, 108.9,
108.8, 100.8, 100.7, 69.9, 62.2, 62.1, 34.9, 33.1, 16.5, 16.4; 31P NMR
(CDCl3) coupling with six protons gave septet peaks, decoupling with proton
showed single peak (3.17 ppm); GC/MS: 440 (Mþ), 349 (M-Bn), 91 (Bn);
single peak, purity .99% by gas chromatography. Anal. calcd. for
C25H29O5P: C: 68.17; H: 6.64; found: C: 67.29; H: 6.80.
Benzyl 5-formyl-2-(benzyloxy) benzoate (7). To a well-stirred mixture
of 5-formyl salicylic acid (6) (1.66 g, 10 mmol) in anhydrous DMF (15 mL),

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Venkatachalam et al.
anhydrous potassium carbonate (5.53 g, 40 mmol), was added benzyl bromide
(3 mL, 1.25 equiv., 25 mmol) under N2. The resulting mixture was heated at
1108C for 20 hr. After cooling to 08C, the mixture was poured into EtOAc
(50 mL), and the precipitated inorganic salt was filtered. The organic layer
was washed with 1 N KOH (15 mL), H2O (15 mL) and dried over MgSO4.
The solvent was removed under vacuum. The residue was recrystallized
from chloroform–hexane to yield a pale yellow solid: yield 2.94 g (85%);
mp 90–928C (lit.,[8] m.p. 80–858C); IR (KBr) 3058, 3026, 2972, 2848,
2746, 1700, 1690, 1600, 1500, 1290 cm21; 1H NMR (CDCl3) d 5.27 (s, 2H),
5.37 (s, 2H), 7.13 (d, J ¼ 8.7 Hz, 1H), 7.33 (m, 10H), 7.97 (m, 1H), 8.36
(d, J ¼ 2.1 Hz, 1H); (lit.,[8] 1H NMR (CDCl3) d 5.26 (s, 2H), 5.36 (s, 2H),
7.14 (d, J ¼ 8.7 Hz, 1H), 7.35 (m, 10H), 7.97 (dd, J ¼ 8.67, 2.22 Hz, 1H),
8.34 (d, J ¼ 2.18 Hz, 1H), 9.89 (s, 1H)); 13C NMR (CDCl3) d 189.8, 162.4,
135.5, 135.3, 134.6, 134.2, 129.2, 128.6, 128.5, 128.3, 128.2, 128.1, 126.9,
113.6, 70.9, 67.2; MS: 346 (M)þ, 255 (M-Bn), 149 (M-2Bn), 91(Bn); single
peak, purity .98% by gas chromatography. Anal. calcd. for C22H18O4: C:
76.29; H: 5.24; found: C: 75.84; H: 5.33.
(E)-1(30-Carboxy-40-benzyloxy)phenyl-2-(300,500-dibenzyloxy)phenyl
ethene (8). To phosphonate (5) (2.11 g, 4.8 mmol) in anhydrous DMF
(20 mL) at 08C under N2 was added potassium t-butoxide (0.81 g,
7.2 mmol). The resulting yellow solution was stirred for 25 min, and then
the aldehyde (7) (1.66 g, 4.8 mmol) in anhydrous DMF (5 mL) was added.
The mixture was allowed to stir at room temperature for 4 hr. After this period,
10 N NaOH (5.0 mL) was added to the mixture and the contents were stirred
for an additional hour. Finally, the reaction mixture was diluted with H2O
(100 mL) and acidified with 6 N HCl, extracted with CH2Cl2 (3 ꢀ 100 mL)
and the organic layer was dried over anhydrous MgSO4. Removal of solvent
under vacuum resulted in a yellow liquid as crude product. Further purification
was done using flash chromatography (hexanes–EtOAc: 5 : 1). Pooling of
appropriate fractions, evaporation of the solvent, and further recrystallization
from CH2Cl2–hexanes provided pure product: yield 1.3 g (50%); pale yellow
solid; m.p. 156–1588C; (lit.,[8] 200,500 compound: m.p. 139–1408C); IR (KBr)
3278, 3028, 2858, 1946, 1870, 1737, 1691, 1588, 1153 cm21 1H NMR
;
(CDCl3) d 5.07 (s, 4H), 5.31 (s, 2H), 6.57 (s, 1H), 6.75 (d, J ¼ 1.8 Hz, 2H),
7.01 (s, 2H), 7.26 (m, 15H), 7.62 (d, J ¼ 7.2 Hz, 1H), 8.35 (s, 1H); (lit.,[8]
200,500 compound); 13C NMR (CDCl3) d 160.0, 138.8, 136.7, 132.7, 131.5,
129.1, 128.5, 127.9, 127.8, 127.4, 126.8, 113.4, 105.7, 101.8, 72.5, 70.1;
MALDI-TOF MS: 543 (M þ 1): purity .90%. Anal. calcd. for C36H30O5:
C: 79.68; H: 5.57; found: C: 78.63; H: 5.50. t-Butyl-4-aminobenzoate (10)
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (3.815 g,
19.9 mmol) dissolved in dry t-butyl alcohol (60 mL, dried over anhydrous
MgSO4) was added to 4-amino benzoic acid (9) (2.5 g, 18.2 mmol) in

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1495
t-butyl alcohol (60 mL). The reaction mixture was refluxed for 18 hr. The reac-
tion mixture was cooled to 08C and water (100 mL) was added. The resultant
mixture was extracted with ether (4 ꢀ 100 mL) and the organic layer was sep-
arated from the aqueous layer. The organic layer was dried over anhydrous
magnesium sulfate and filtered. The filtrate was evaporated under vacuum
to furnish a yellow solid as crude product. Additional purification was done
by recrystallization from ethanol, which gave analytically pure product:
yield 2.1 g (60%); m.p. 106–1088C; IR (KBr) 3416, 3355, 3232, 2981,
1
1691, 1598 cm21; H NMR (CDCl3) d 1.57 (m, 9H), 6.61 (m, 2H), 7.79
(m, 2H); 13C NMR (CDCl3) d 165.8, 150.2, 131.2, 121.6, 113.6, 79.9, 28.4;
GC/MS: 193 (M)þ, 137 (M 2 tBu), 120 (M 2 tBu–NH2) single peak, purity
.98% by gas chromatography. Anal. calcd. for C11H15O2N: C: 68.37; H:
7.82; N: 7.61; found: C: 67.88; H: 7.87; N: 7.16.
(E)-1-[30-Benzamide(400-t-butyl)benzoate)-40-benzyloxy]phenyl-2-
(3000,5000-dibenzyloxy)phenyl ethene (11). A stirred mixture of trans-1(30-car-
boxy-40-benzyloxy)phenyl-2-(300,500-dibenzyloxy)phenyl ethene (8) (1.084 g,
2 mmol), t-butyl-4-aminobenzoate (10) (0.386 g, 2 mmol), and 1-(3-dimethy-
laminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (0.422 g, 2.2 mmol)
in CHCl3 was refluxed for 18 hr. After cooling to 08C, H2O (100 mL) was
added, and the mixture was extracted with CHCl3 (3 ꢀ 50 mL). The organic
layer was separated from the aqueous layer and dried over anhydrous mag-
nesium sulfate. Filtration and evaporation of the solvent under vacuum gave
crude product. The crude material was recrystallized from ether to furnish
compound (11): yield 0.8 g (56%); TLC single spot (hexane/ethylacetate:
3 : 1); m.p. 168–1708C; IR (KBr) 3327, 3032, 2974, 2931, 1701, 1668, 1597,
1
1294, 1151 cm21; H NMR (CDCl3) d 1.59 (m, 9H), 5.09 (s, 4H), 5.25
(s, 2H), 6.57 (s, 1H), 6.77 (d, J ¼ 2.1 Hz, 2H), 7.36 (m, 22H), 7.82
(d, J ¼ 8.4 Hz, 1H), 8.49 (d, J ¼ 2.4 Hz, 1H), 10.16 (s, 1H, NH); 13C NMR
(CDCl3) d 165.3, 159.9, 141.9, 139.1, 136.7, 131.4, 131.2, 130.5, 130.3,
129.3, 129.2, 128.7, 128.4, 127.9, 127.4, 118.7, 112.9, 105.7, 101.7, 80.7,
72.2, 70.1, 28.4, 28.3; MALDI (TOF)/MS: 717 (M)þ. Anal. calcd. for
C47H46O6N: C: 78.64; H: 6.04; N: 1.95; found: C: 77.90; H: 5.94; N: 1.94.
(E)-1-[30-Benzamide(400-carboxy)-40-benzyloxy]phenyl-2-(3000,5000-diben-
zyloxy)phenyl ethene (12). Freshly distilled trifluoroacetic acid (1 mL)
precooled in an ice bath was added to trans-1-[30-benzamide(400-t-butyl)-
benzoate)-40-benzyloxy]phenyl-2-(3000,5000-dibenzyloxy)phenyl ethene (11)
(0.717 g, 0.1 mmol) at 08C, and the mixture was allowed to stir for 1 hr. The
product was collected by filtration: yield 0.59 g (90%); m.p. .2008C; IR
(KBr) 3335, 3064, 3033, 2879, 2674, 2546, 1784, 1686, 1593, 1163 cm21
;
1H NMR (DMSO-d6) d 5.13 (s, 4H), 5.27 (s, 2H), 6.59 (s, 1H), 6.91 (s, 2H),
7.43 (m, 24H), 10.56 (s, 1H, NH); 13C NMR (DMSO-d6) d 166.9, 159.7,
142.9, 139.3, 137.1, 136.5, 130.4, 129.9, 128.5, 128.2, 127.9, 127.8, 125.4,

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Venkatachalam et al.
118.7, 105.5, 69.4; MALDI(TOF)/MS: 661 (M þ 1)þ; purity .98%. Anal.
calcd. for C43H38O6N: C: 78.05; H: 5.33; N: 2.12; found: C: 77.77; H: 5.49;
N: 2.24.
(E)-1-[30-Benzamide(400-carboxy)-40-hydroxy]phenyl-2-(3000,5000-dihydroxy)
phenyl ethene (13). Freshly distilled N,N0-dimethylaniline (0.94 mL,
7.4 mmol, 8 equiv.) was added to a solution of benzyl protected stilbene
(12) (0.204 g, 0.31 mmol) in anhydrous CH2Cl2 (10 mL) at room temperature
under N2. After 10 min, anhydrous AlCl3 (0.53 g, 4 mmol) was added.
The reaction was allowed to stir for 4 hr at room temperature. Subsequently
the reaction mixture was cooled to 08C, and was treated with H2O (5 mL)
and 1 M HCl (10 mL). The resulting mixture was extracted with EtOAc
(6 ꢀ 10 mL). The ethyl acetate layer was separated from the aqueous layer
and dried over anhydrous magnesium sulfate. Filtration and evaporation of
the solvent gave a residue. This residue was further purified using preparative
thin layer chromatography technique using 3 : 1 CHCl3–MeOH to give (13) as
dark brown solid. Single band in PTLC: yield: 36 mg (30%); IR (KBr) 3448,
1
2983, 2254, 2127, 1658, 1250, 1050 cm21; H NMR (DMSO-d6) d 6.01
(s, 1H), 6.31–6.30 (m, 2H), 6.37 (m, 1H), 6.50 (m, 1H), 6.83 (m, 1H),
7.29–7.27 (m, 1H) 7.72–7.70 (m, 2H), 7.85–7.80 (m, 3H), 9.08 (bs, 1H).
GC/MS: 391 (Mþ). HPLC Rt: 2.3 min, % purity: 85%. Anal. calcd. for
C22H17O6N: C: 67.51; H: 4.38; N: 3.58; found: C: 52.06; H: 3.92; N: 2.85ꢁ
(ꢁanalysis low due to contamination of SiO2 in the sample since the com-
pound is extremely polar).
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Received in the USA November 2, 2003

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