Selective reduction of ortho-Acylatedβ-enaminones of homoveratryamine and their cyclization to 1,2,3,4-tetrahydroisoquinolines withβ-enaminone moiety

Article abstract of DOI:10.1080/00397911.2011.589020

Enaminones are very stable compounds and can be prepared from cheap and easily available starting materials. Therefore they are excellent starting materials in organic synthesis. The selective reduction of ortho-acylated- enaminones under mild conditions,

Full text of DOI:10.1080/00397911.2011.589020

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Selective Reduction of ortho-Acylated
β-Enaminones of Homoveratryamine
and Their Cyclization to 1,2,3,4-
Tetrahydroisoquinolines with β-
Enaminone Moiety
Stoyanka Nikolova a , Ekaterina Kochovska a & Iliyan Ivanov a
a Department of Organic Chemistry, University of Plovdiv, Bulgaria,
Plovdiv, Bulgaria
Accepted author version posted online: 20 Jan 2012.Published
online: 02 Nov 2012.
To cite this article: Stoyanka Nikolova , Ekaterina Kochovska & Iliyan Ivanov (2013) Selective
Reduction of ortho-Acylated β-Enaminones of Homoveratryamine and Their Cyclization to
1,2,3,4-Tetrahydroisoquinolines with β-Enaminone Moiety, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:3, 326-336, DOI:
10.1080/00397911.2011.589020
To link to this article: http://dx.doi.org/10.1080/00397911.2011.589020
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Synthetic Communications1, 43: 326–336, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.589020
SELECTIVE REDUCTION OF ORTHO-ACYLATED
b-ENAMINONES OF HOMOVERATRYAMINE
AND THEIR CYCLIZATION TO
1,2,3,4-TETRAHYDROISOQUINOLINES WITH
b-ENAMINONE MOIETY
Stoyanka Nikolova, Ekaterina Kochovska, and Iliyan Ivanov
Department of Organic Chemistry, University of Plovdiv, Bulgaria, Plovdiv,
Bulgaria
GRAPHICAL ABSTRACT
Abstract Enaminones are very stable compounds and can be prepared from cheap and easily
available starting materials. Therefore they are excellent starting materials in organic syn-
thesis. The selective reduction of ortho-acylated b-enaminones under mild conditions, keep-
ing the enaminone moiety intact, is reported. The appropriated conditions for cyclization of
newly obtained hydroxienamides were found. Novel 1-substituted 1,2,3,4-tetrahydroisoqui-
nolines with potential anticonvulsic activity were synthesized.
Keywords Cyclization; b-enaminones; reduction; tetrahydroisoquinolines
Received May 4, 2011.
Address correspondence to Iliyan Ivanov, Department of Organic Chemistry, University of
Plovdiv, 24, Tsar Assen St., 4000, Plovdiv, Bulgaria. E-mail: ivanov@uni-plovdiv.bg
326

TETRAHYDROISOQUINOLINES
327
INTRODUCTION
The reactions of enaminones have received considerable attention in recent
years because of their versatility and potential utility as synthetic intermediates,
particularly in heterocyclic chemistry.[1] The enaminone system N-C C-C O con-
sists of three functional groups and shows interesting and sometimes complicated
reactivity with five possible reaction sites. The synthesis and reactivity of
enaminones represent an active area of investigation in organic chemistry.[2]
Enaminones have been studied extensively for their properties and as precursors
of several interesting classes of compounds.[3] The special value of these com-
pounds is a result of their use as valuable intermediate for the synthesis of inter-
esting compounds.[4] Functionalized 1,2,3,4-tetrahydro-b-carbolines[5] and
1,2,3,4-tetrahydroisoquinolines[6] can be synthesized via the Pictet–Spengler reac-
tion starting from b-enaminones containing (hetero)arylethyl substituents tethered
to the nitrogen.
=
=
Enaminones also have been shown to possess anticonvulsant activity in vivo
animal models of seizures. The cellular mechanism by which these compounds
produce their anticonvulsant effects is not yet known. This study examined the
effects of enaminones on excitatory synaptic transmission. Based on their anticon-
vulsant activity, enaminones have been classified into three classes (1, 2, and 3),
with class 1 being the most potent in these tests.[7] E139, E121, and E118 (see
Figure 1), all class 1 anticonvulsants, have shown promise in preventing seizures
in mouse and rat models of epilepsy, while others (e.g., E169) are inactive as
anticonvulsants.[7,8]
Thus, the unique enaminone pharmacophore presents an excellent opportunity
to develop anticonvulsant compounds that are devoid of neurotoxicity and yet pos-
sess wider margins of safety than conventional antiepileptic drugs such as valproate,
carbamazepine, and phenytoin.[9] This compounds are known also to possess anti-
malarial, anti-inflamatory, and cardiovascular effects.[7–9]
RESULTS AND DISCUSSION
Despite their wide range of pharmacological activity and synthetic applica-
tions, the synthesis of enaminones has received little attention.[10] Recently, consider-
able attention has been focused on the development of new synthetic methods for the
Figure 1. Biologically active b-enaminones.

328
S. NIKOLOVA, E. KOCHOVSKA, AND I. IVANOV
construction of nitrogen-containing heterocyclic systems, such as indoles, quinolines,
and isoquinolines, particularly under nonacidic conditions.[11] Palmieri and Cimar-
elli[12] described chemistry of the preparation of b-enamino ketones and b-enamino
esters and their use as useful starting materials in reductive procedures for the prep-
aration of biologically active natural products. Nitrogen-containing heterocycles as
recognized pharmacophores have received great attention in drug discovery and lead
optimization.[13] Traditional cycloadditions and cyclizations of nitrogen radicals or
nitrogen-containing carbon radicals are the new approaches to N-heterocycles.[14,15]
In our previous reports we showed regioselective acylation in aromatic ring
of N-phenethylenaminones, keeping the enaminone moiety intact.[16] We reported
also the synthesis of new enaminones of secondary amines, as 1,2,3,4-tetrahydro-
isoquinoline and 1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline with cyclic
diketones.[17] Here we describe our investigations about application of acylated
enaminones for the synthesis of some 1-substituted 1,2,3,4-tetrahydroisoquinolines.
Our synthetic approach was delineated through the retrosynthetic analysis
depicted in Scheme 1, which identified the key steps as well as the main starting
material. We anticipated that 5 could be constructed by reduction of acylated
enaminones 3 with following cyclization.
Starting b-enaminones 3 were obtained by Friedel–Crafts-type acylations from
b-enaminones 1 and acetic, benzoic, or phenylacetic acids in polyphosphoric acid
(PPA) (Scheme 2).[16] The next step in our synthesis was the reduction of acylated
enaminones with following cyclization to the isoquinoline ring system (see Table 1).
Recently, numerous methodologies for the chemo- and stereoselective
reduction of enaminones to the c-amino alcohols were reported, including Na=
i-PrOH,[18] CeCl3=LiBH4,[19] LAH, or LiAlH4-Cu or H2=PtO2,[20] and NaBH4=
AcOH at 10 ꢀC.[21] Palmieri and Cimarelli[12,22] described the chemistry of the prep-
aration of b-enamino ketones and b-enamino esters and their use as useful starting
materials in reductive procedures for the preparation of biologically active natural
products. The authors founded that both cyclic N-acylenaminones or acyclic ones
can be reduced regioselectively under mild conditions with sodium borohydride in
methanol to the corresponding hydroxyenamides.[22] We applied the same protocol
for the reduction of 3 to the corresponding hydroxyenamides 4 and have found that
reduction kept the enaminone moiety and gave easily obtained corresponding hydro-
xyenamides with 85–90% yields.
All of our trials for the cyclization of hydroxienamides to the corresponding
1-substituted 1,2,3,4-tetrahydroisoquinolines in the presence of polyposphoric or
Scheme 1. Retrosynthetic route for the synthesis of 1,2,3,4-tetrahydroisoquinolines.

TETRAHYDROISOQUINOLINES
329
Scheme 2. Synthesis of 1,2,3,4-tetrahydroisoquinolines with b-enaminone moiety.
toluene-p-sulfonic acid were unsuccessful. Finally, we carried out the cyclization
reaction of hydroxienamides in a triflouracetic acid (TFA) milieu for 2 h reflux
and obtained products 5 with 90% yield.
In conclusion, compounds containing the enaminone system are very stable
and have a long shelf life in room conditions. At the same, time they can be easily
prepared starting from cheap and easily available reagents; therefore, they can be
considered excellent starting materials for organic synthesis. In this article, we
describe selective reduction of acylated enaminones under mild conditions, keeping
the enaminone moiety intact, and cyclization in boiling CF3COOH of newly
Table 1. Synthesis of 1,2,3,4-tetrahydroisoquinolines with b-enaminone moiety
Product
R
R1
Mp ꢀC
Yield (%)
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
H
CH3
CH3
Oil
88
88
87
86
85
89
92
90
91
90
CH3
H
189–191
Oil
84–86
C6H5
C6H5
CH3
CH3
H
CH2C6H5
CH3
CH3
121–122
72–74
CH3
H
238–240
185–187
234–236
80–84
C6H5
C6H5
CH2C6H5
CH3
CH3

330
S. NIKOLOVA, E. KOCHOVSKA, AND I. IVANOV
obtained hydroxyenamides to give corresponding 1-substituted 1,2,3,4-tetrahydro-
isoquinolines 5.
EXPERIMENTAL
Reagents and chemicals were purchased from commercial sources
[Sigma-Aldrich S.A. and Riedel-de Hae¨n] and used as received. Melting points were
determined on a Boetius hot-stage apparatus and are uncorrected. Spectra were
recorded on a Bruker Avance DRX250 spectrometer. 1H NMR and 13C NMR spec-
tra were taken in CDCl3 (unless otherwise specified) at 250 MHz and 62.5 MHz
respectively. Chemical shifts were given in part per million (ppm) relative and were
referenced to tetramethylsilane (TMS, d ¼ 0.00 ppm) as an internal standard, and
coupling constants are indicated in hertz. All the NMR spectra were taken at rt
(ac. 295 K). Elemental analyses were performed with a Vario EL III. Thin-layer
chromatography (TLC) was carried out on precoated 0.2-mm Fluka silica gel 60
plates, using diethyl ether–n-hexane 1:1 as chromatographic system. Merck silica
gel 60 (0.063–0.2 mm) was used for column chromatographic separation.
Polyphosphoric acid was obtained from 85% phosphoric acid and P2O5 (1:1 w=w).
Acylation of Enaminones 3a–e
PPA (7 g) was added to a solution of homoveratrylamine (5 mmol) and the
corresponding carboxylic acid 2 (7 mmol) in dichloromethane (10 mL). The reaction
mixture was stirred for 2 h at 80 ꢀC and then poured on crushed ice. The solution was
carefully alkalized with 25% ammonia and then extracted with CH2Cl2 (3 ꢁ 20 ml),
and combined extracts were dried (Na2SO4). The products, after evaporation of
the solvent, were purified by column chromatography on silica gel. Compounds
3a–d are all known compounds.[16]
3-[2-(2-Phenylacetyl-4,5-dimethoxyphenyl)-ethylamino]-5,5-dimethyl-
1
cyclohex-2-enone (3e). Yield 75%, mp 80–84 ꢀC; H NMR: 1.04 (s, 6H), 2.12 (s,
2H), 2.16 (s, 2H), 2.95 (t, 2H, J ¼ 6.3), 3.34 (dd, 2H, J ¼ 6.03, 11.16), 3.92 (s, 3H),
3.95 (s, 3H), 4.25 (s, 2H), 5.09 (s, 1H), 6.09 (t, 1H, NH, J ¼ 5.47), 6.75 (s,
1H),7.25 (s, 1H), 7.27–7.38 (m, 5H); 13C NMR: 201.5, 181.6, 163.0, 152.1, 147.0,
134.3, 134.0, 129.8, 129.3, 128.8, 127.1, 113.7, 112.2, 94.9, 56.2, 56.1, 50.2, 48.5,
44.9, 43.3, 31.6, 28.2, 22.6, 19.4. Anal. calcd. for C26H31NO4: C, 74.08; H, 7.41;
N, 3.32. Found: C, 73.82; H, 7.635; N, 3.241.
Reduction of Acylated Enaminones 4a–e
NaBH4 (2 mmol, 0.1 g) was added portionwise to a solution of 1 mmol of the
corresponding acylated enaminone 3 in 15 mL methanol. The solution was stirred
30 min at room temperature, and then the solvent was removed under vacuum.
Water (30 mL) was added to the residue, and the solution was extracted with CH2Cl2
(3 ꢁ 20 mL). Then the combined extracts were dried (Na2SO4). The products, after
evaporation of the solvent, were obtained with more than 85% yields.

TETRAHYDROISOQUINOLINES
331
3-f2-[2-(1-Hydroxy-ethyl)-4,5-dimethoxy-phenyl]-ethylaminog-cyclohex-
1
2-enone (4a). H NMR: 1.60 (d, 3H, J ¼ 6.36), 1.91 (dd, 2H, J ¼ 6.37, 12.74), 2.26
(t, 4H, J ¼ 6.42), 2.96 (dq, 2H, J ¼ 6.5, 13.5, 13.6), 3.31 (dq, 2H, J ¼ 6.3, 6.5, 12.7),
3.877 (s, 3H), 3.884 (s, 3H), 4.03 (dt, 1H, J ¼ 5.37, 9.98), 4.72 (s, 1H), 5.07 (t, 1H,
J ¼ 6.25, NH), 5.09 (dd, 1H, J ¼ 4.6, 11.0), 6.65 (s, 1H), 7.01 (s, 1H); 13C NMR:
197.4, 171.7, 148.4, 147.9, 135.3, 128.2, 112.8, 109.2, 65.9, 56.0, 55.95, 44.2, 36.2,
30.2, 26.4, 24.2, 21.9. Anal. calcd. for C18H25NO4: C, 67.69; H, 7.89; N, 4.39. Found:
C, 67.38; H, 7.994; N, 4.412.
3-f2-[2-(1-Hydroxy-ethyl)-4,5-dimethoxy-phenyl]-ethylaminog-5,5-
dimethyl-cyclohex-2-enone (4b). 1H NMR: 0.978 (s, 3H), 0.984 (s, 3H), 1.54 (d,
3H, J ¼ 6.39), 2.07 (s, 4H), 2.81–3.04 (m, 2H), 3.17–3.67 (m, 2H), 3.86 (s, 3H), 3.88
(s, 3H), 5.07 (dt, 2H, J ¼ 3.75, 10.25), 5.296 (s, 1H), 6.08 (br s, 1H, NH), 6.63 (s, 1H),
7.00 (s, 1H); 13C NMR: 196.8, 163.8, 148.3, 147.9, 135.5, 128.2, 112.8, 109.3, 94.6,
65.96, 55.96, 55.88, 50.1, 44.36, 32.6, 28.3, 24.2, 23.0, 14.1. Anal. calcd. for
C20H29NO4: C, 69.14; H, 8.41; N, 4.03. Found: C, 69.32; H, 8.232; N, 3.973.
3-f2-[2-(Hydroxy-phenyl-methyl)-4,5-dimethoxy-phenyl]-ethylaminog-
cyclohex-2-enone (4c). 1H NMR (DMSO): 1.76 (t, 1H, J ¼ 6), 2.08 (t, 2H, J ¼ 5.75),
2.27 (t, 2H, J ¼ 5.5), 2.50 (td, 1H, J ¼ 2.0, 3.6), 2.74 (dt, 2H, J ¼ 7.5, 12.5), 3.03 (dd, 2H,
J ¼ 7.3, 13.3), 3.67 (s, 6H), 5.69 (s, 1H), 5.82 (br s, 1H), 5.93 (br s, 1H, NH), 6.76 (s, 1H),
7.00 (s, 1H), 7.12 (s, 1H), 7.2 (dt, 1H, J ¼ 4.51, 9.26), 7.28 (d, 3H, J ¼ 4.13); 13C NMR:
195.5, 165.2, 147.9, 147.3, 145.2, 135.4, 128.8, 128.3, 127.0, 126.9, 113.8, 111.6, 94.98,
71.4, 55.8, 55.0, 43.8, 36.6, 30.3, 28.8, 21.9. Anal. calcd. for C23H27NO4: C, 72.42; H,
7.13; N, 3.67. Found: C, 72.11; H, 6.991; N, 3.781.
3-f2-[2-(Hydroxy-phenyl-methyl)-4,5-dimethoxy-phenyl]-ethylaminog-
5,5-dimethyl-cyclohex-2-enone (4d). 1H NMR: 0.976 (s, 6H), 2.04 (s, 4H),
2.77–3.00 (m, 2H), 3.22 (dt, 2H, J ¼ 5.60, 11.24), 3.73 (s, 3H), 3.86 (s, 3H), 5.06 (s,
1H), 5.97 (s, 1H), 6.00 (br s, 1H, NH), 6.67 (s, 1H), 6.75 (s, 1H), 7.28–7.31 (m,
1H), 7.33–7.35 (m,4H); 13C NMR: 198.8, 163.9, 148.6, 147.6, 134.3, 129.2, 128.4,
127.3, 126.5, 112.9, 112.0, 106.6, 94.7, 72.8, 56.0, 55.8, 50.0, 44.3, 32.6, 30.4, 28.3,
28.2. Anal. calcd. for C25H31NO4: C, 73.32; H, 7.63; N, 3.42. Found: C, 73.00; H,
7.233; N, 3.474.
3-(2-(1-Hydroxy-2-phenylethyl)-4,5-dimethoxyphenethylamino)-5,5-
dimethylcyclohex-2-enone (4e). 1H NMR: 0.997 (d, 6H, J ¼ 2.34), 2.05 (s, 2H),
2.09 (s, 2H), 2.71–2.91 (m, 2H), 3.08 (dt, 2H, J ¼ 5.61, 13.43, 13.64) overlapped with
3.09 (s, 1H, OH), 3.17–3.29 (m, 2H), 3.86 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 5.04
(dd, 1H, J ¼ 5.78, 7.73), 5.09 (s, 1H), 5.36 (t, 1H, NH, J ¼ 6.03), 6.59 (s, 1H, Ar), 7.02
(s, 1H, Ar), 7.15–7.19 (m, 2H, Ar), 7.24–7.34 (m, 3H, Ar); 13C NMR: 196.8, 163.0,
148.4, 147.9, 137.9, 133.6, 129.5, 128.6, 128.3, 126.7, 112.5, 109.8, 106.0, 71.8, 55.95,
55.9, 50.1, 45.2, 44.1, 43.2, 32.6, 30.1, 28.22, 28.19. Anal. calcd. for C26H33NO4: C,
73.73; H, 7.85; N, 3.31. Found: C, 73.87; H, 7.594; N, 3.174.
Synthesis of 1-Substituted Isoquinolines 5a–e
Trifluoracetic acid (2 ml) was added to 1 mmol of the corresponding hydroxy-
enamides 4. The solution was refluxed 2 h, and then the solution was washed with

332
S. NIKOLOVA, E. KOCHOVSKA, AND I. IVANOV
water, 25% ammonia, and once again with water. Extract was dried with Na2SO4,
and filtered on a short column with silica gel. The products, after evaporation of
the solvent, were obtained with more than 90% yield.
3-(6,7-Dimethoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)-cyclohex-
2-enone (5a). 1H NMR: 1.50 (d, 3H, J ¼ 6.7), 1.95–2.12 (m, 2H), 2.33 (dd, 2H,
J ¼ 5.4, 7.4), 2.56 (dd, 2H, J ¼ 5.3, 9.4), 2.78 (dt, 1H, J ¼ 4.3, 9.2), 2.92 (ddd, 1H,
J ¼ 5.1, 9.9, 14.8), 3.20 (s, 1H), 3.45 (dt, 1H, J ¼ 3.5, 9.3), 3.86 (s, 3H), 3.87
(s, 3H), 4.90 (q, 1H, J ¼ 6.6), 5.45 (s, 1H), 6.60 (d, 2H, J ¼ 9.6); 13C NMR: 196.8,
164.4, 148.0, 147.9, 129.7, 125.5, 111.2, 109.6, 98.8, 56.1, 55.9, 52.97, 40.9, 35.2,
27.1, 22.2. Anal. calcd. for C18H23NO3: C, 71.73; H, 7.69; N, 4.65. Found: C,
72.02; H, 7.451; N, 4.553.
3-(6,7-Dimethoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)-5,5-
dimethyl-cyclohex-2-enone (5b). 1H NMR: 1.08 (s, 3H), 1.13 (s, 3H), 2.19 (d,
3H, J ¼ 6.7), 2.19 (d, 2H, J ¼ 3.8), 2.37 (dd, 2H, J ¼ 15.8, 20.8), 2.77 (dt, 1H,
J ¼ 4.3, 15.9), 2.91 (ddd, 1H, J ¼ 5.2, 9.9, 15.4), 3.43 (dt, 1H, J ¼ 4.3, 9.5), 3.86 (s,
3H), overlapped with 3.78 (dt, 1H, J ¼ 4.5, 14), 3.87 (s, 3H), 4.87 (q, 1H, J ¼ 6.7),
5.37 (s, 1H), 6.60 (d, 2H, J ¼ 12.3); 13C NMR: 196.4, 162.1, 147.96, 147.8, 129.8,
125.6, 111.2, 109.5, 97.7, 56.0, 55.9, 52.8, 49.3, 40.9, 40.7, 32.8, 29.9, 27.5. Anal.
calcd. for C20H27NO3: C, 72.92; H, 8.26; N, 4.25. Found: C, 73.28; H, 8.438; N,
4.095.
3-(6,7-Dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-cyclohex-
2-enone (5c). 1H NMR: 2.04 (ddd, 2H, J ¼ 4.3, 6.4, 8.1), 2.30–2.35 (m, 2H), 2.64
(ddd, 2H, J ¼ 2.5, 6.2, 8.9), 2.71 (t, 1H, J ¼ 6.5), 2.88 (dt, 1H, J ¼ 6.1, 15.8), 3.56
(t, 2H, J ¼ 6.3), 3.87 (s, 6H), 5.48 (s, 1H), 5.95 (s, 1H), 6.69 (s, 1H), 6.73 (s, 1H),
7.11–7.15 (m, 2H), 7.24–7.31 (m, 3H); 13C NMR: 197.1, 164.2, 148.6, 147.6, 140.9,
128.5, 127.7, 127.5, 127.1, 126.8, 111.3, 111.1, 99.6, 60.2, 56.1, 55.9, 42.7, 35.7,
27.1, 22.3. Anal. calcd. for C23H25NO3: C, 76.01; H, 6.93; N, 3.85. Found: C,
75.83; H, 7.153; N, 3.951.
3-(6,7-Dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-5,5-
dimethyl-cyclohex-2-enone (5d). 1H NMR: 1.10 (s, 3H), 1.11 (s, 3H), 2.21 (d,
2H, J ¼ 2.3), 2.46 (q, 2H, J ¼ 15, 16), 2.67 (dt, 1H, J ¼ 6.6, 16.1), 2.87 (dt, 1H,
J ¼ 5.9, 15.7), 3.55 (t, 2H, J ¼ 6.3), 3.88 (s, 3H), 3.89 (s, 3H), 5.49 (s, 1H), 5.94 (s,
1H), 6.69 (s, 1H), 6.75 (s, 1H), 7.13 (dd, 2H, J ¼ 1.9, 7.7), 7.25–7.34 (m, 3H); 13C
NMR: 196.7, 162.8, 148.7, 147.6, 140.9, 128.5, 127.7, 127.5, 127.2, 126.8, 111.3,
111.1, 98.3, 60.2, 56.2, 55.95, 49.3, 43.0, 41.0, 33.0, 29.8, 27.5, 27.1. Anal. calcd.
for C25H29NO3: C, 76.70; H, 7.47; N, 3.58. Found: C, 76.87; H, 7.692; N, 3.568.
3-(1-Benzyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-5,5-
dimethyl-cyclohex-2-enone (5e). 1H NMR: 0.96 (s, 3H), 1.00 (s, 3H), 2.09–2.21
(m, 4H), 2.80 (t, 1H, J ¼ 4.98), 3.04 (dd, 2H, J ¼ 6.60, 12.91), 3.13–3.26 (m, 1H),
3.78–3.83 (m, 2H), 3.89 (s, 3H), 3.95 (s, 3H), 5.43 (s, 1H), 6.66 (s, 1H), 7.10–7.15
(m, 3H), 7.28–7.31 (m, 4H); 13C NMR: 196.8, 149.2, 148.3, 147.2, 137.6, 137.3,
129.7, 128.7, 126.9, 125.2, 124.8, 112.9, 111.2, 98.0, 59.3, 56.1, 55.9, 49.3, 44.1,
43.8, 40.9, 32.7, 32.6, 28.2, 27.3, 8.3. Anal. calcd. for C26H31NO3: C, 77.01; H,
7.71; N, 3.45. Found: C, 76.83; H, 7.680; N 3.402.

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ACKNOWLEDGMENTS
We acknowledge financial support from the National Fund for Scientific
Research DO-02-195 and the Fund for Scientific Research of Plovdiv University.
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