Synthesis of chalcones derived from (+)- and (-)-usnic acids

Article abstract of DOI:10.1007/s11172-011-0370-x

A number of chalcones with the (+)- and (-)-usnic acid moieties were synthesized by the following sequence: the reaction of these acids with phenylhydrazine, reduction of the C(1)=O group with sodium borohydride, O-methylation of the intermediate compounds with diazomethane, and subsequent condensation with substituted benzaldehydes at the acetyl group.

Full text of DOI:10.1007/s11172-011-0370-x

Russian Chemical Bulletin, International Edition, Vol. 60, No. 11, pp. 2406—2411, November, 2011
2406
Synthesis of chalcones derived from (+)ꢀ and (–)ꢀusnic acids*
D. N. Sokolov, O. A. Luzina, M. P. Polovinka, N. F. Salakhutdinov, and G. A. Tolstikov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 8850. Eꢀmail: dsokolov@nioch.nsc.ru
A number of chalcones with the (+)ꢀ and (–)ꢀusnic acid moieties were synthesized by the
following sequence: the reaction of these acids with phenylhydrazine, reduction of the C(1)=O
group with sodium borohydride, Oꢀmethylation of the intermediate compounds with diꢀ
azomethane, and subsequent condensation with substituted benzaldehydes at the acetyl group.
Key words: usnic acid, Claisen—Schmidt condensation, flavonoids, diazomethane,
chalcones.
Chalcone (1,3ꢀdiphenylpropꢀ2ꢀenꢀ1ꢀone) derivatives is
struction of chalcones. At the same time, no data on the
transformation of usnic acid to the corresponding chalꢀ
cones are currently known.
a wide group of naturally occurring openꢀchain flavonoids.
They possess antibacterial, antifungal, anticancer, antiinꢀ
flammatory activities, and a number of other valuable bioꢀ
logical properties.1 Chalcones are commonly obtained by
condensation of benzaldehydes and acetophenones.2,3
Introduction of a fragment with the native biological
activity into the chalcone structure can lead to its enꢀ
hancement and/or preparation of compounds with new
biological properties. The secondary metabolite of the liꢀ
chen series, usnic acid (1), possessing antiviral, antibiotic,
analgesic,4 antituberculosis,5 and insecticide activity,
seems a promising compound.6 Some lichen species are
selective producents of levoꢀ and dextrorotating enantioꢀ
mers of usnic acid with high optical purity, that broadens
synthetic potential and further application of the products
of its chemical modification.
We have attempted to involve acid 1 into condensation
with a number of benzaldehydes under conditions comꢀ
monly used for the preparation of chalcones. However,
the use of H2SO4 or K2CO3 as catalysts did not lead to the
expected products, whereas application of strong alkali
(KOH) caused destruction of the starting acid. Destrucꢀ
tion of compound (+)ꢀ1 upon the action of an alkali is
described in the work,7 which showed that the initial cleavꢀ
age occurs in the ring C. It seems that for the baseꢀcataꢀ
lyzed conversion of compound (+)ꢀ1 to be successful, an
introduction of protecting groups to the corresponding
positions of the molecule is required.
We carried out chemical modifications of usnic acid
(1) directed on the increase in its stability in basic mediꢀ
um. The reaction with phenylhydrazine led to pyrazole
derivative (+)ꢀ2 (Scheme 1). Unfortunately, attempted
The structure of usnic acid (1) contains an acetoꢀ
phenone fragment, which seems promising for the conꢀ
Scheme 1
Reaction conditions: i. PhNHNH2; ii. Boc2O, DMAP.
* Dedicated to Academician of the Russian Academy of Sciences O. M. Nefedov on the occasion of his 80th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2359—2364, November, 2011.
1066ꢀ5285/11/6011ꢀ2406 © 2011 Springer Science+Business Media, Inc.

Usnic acidꢀderived chalcones
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011 2407
involvement of this compound into the baseꢀcatalyzed
condensation with benzaldehyde led to the destruction of
the substrate, whereas under conditions of acid catalysis,
the starting reactants remained unchanged.
into transformation: it underwent ringꢀexpansion, and its
carbonyl group C(1)=O reacted with CH2N2 to give an
oxirane ring. The reaction of compound (+)ꢀ2 with diazoꢀ
methane was carried out with a large excess of the latter,
since a decrease in the ratio of the reactant and the subꢀ
strate even to 10 : 1 led to the incomplete conversion of
the substrate. Note that even the use of a large excess of
diazomethane leaves the phenol hydroxyl at the C(7) atom
unmethylated. Taking into account the literature data,10
this phenomenon can be presumably accounted for by
the presence of the closely positioned carbonyl group
C(13)=O, whose oxygen atom forms a strong hydrogen
bond with the proton of the OH group at the atom C(7).
Since the phenol hydroxyl at the atom C(9) in compound
(+)ꢀ2 is also involved into the hydrogen bonding11 and yet
is methylated in the reaction course, we can suggest that,
apparently, the transformation of ring C occurs initially,
which destroys the hydrogen bond between the hydrogen
of the phenol hydroxyl at the atom C(9) and the oxygen
atom of the carbonyl group C(1)=O, and then this phenol
hydroxyl undergoes unimpeded methylation. This is also
confirmed by the data in the work,11 in which the authors
were intended to methylate the phenol hydroxy groups of
usnic acid upon treatment with diazomethane, but did not
isolate the target products, possibly, for the reason that
both OH groups are involved into the hydrogen bonding.12
Based on the reaction mechanism of diazomethane
with cyclic carbonyl compounds, we can suggest that exꢀ
pansion of ring C in compound (+)ꢀ2 takes place initially,
then the oxirane ring is formed from the carbonyl group
C(1)=O, which is followed by the methylation of the phenol
hydroxyl. Thus, three different sequential reactions take
place upon the action of diazomethane on compound (+)ꢀ2,
which is quite unusual, and earlier13 has not been menꢀ
tioned in the literature. In addition, the process is stereoꢀ
selective and gives only one stereoisomer of compound
(+)ꢀ4 (the NMR spectra contain a single set of signals).
The condensation of compound (+)ꢀ4 with benzaldeꢀ
hydes in methanol in the presence of aqueous KOH leads
to chalcones (+)ꢀ5a,b in 21 and 31% yields, respectively,
and a complete conversion of the substrate (see Scheme 2).
Possibly, the presence of the labile exocyclic oxirane fragꢀ
ment is the reason for the low yields and considerable
resinification in this reaction.
To increase resistance of compound (+)ꢀ2 to the basic
medium, we attempted selection of protecting groups for
the phenol hydroxyls. These attempts showed that the reꢀ
actants and reaction conditions tried for the protection of
the phenol hydroxy groups in compound (+)ꢀ2 (MeI,
Me2SO4, DHP) turned out to be inefficient: either the
yields of the products were low, or the reaction did not
take place at all. Usnic acid is known8,9 to react with
carboxylic anhydrides with the formation of esters at both
phenol hydroxy groups. We carried out the reaction of
compound (+)ꢀ2 with Boc2O, which is generally used for
the introduction of the tertꢀbutoxycarbonyl groups, which
are stable in basic medium. The reaction resulted in the
product (+)ꢀ3 with the Bocꢀprotected hydroxy groups in
nearly quantitative yield (see Scheme 1). However, it
turned out that compound (+)ꢀ3 cannot be involved into
condensation with benzaldehyde.
Another widely used approach to the protection of
phenol hydroxy groups consists in their methylation with
diazomethane. The reaction of compound (+)ꢀ2 with diꢀ
azomethane led to the product (+)ꢀ4 bearing a methylated
phenol hydroxyl at position 9 in 55% yield (Scheme 2). In
this case, ring C in compound (+)ꢀ2 was also involved
Scheme 2
Earlier,14 we have shown that the pyrazole derivative
(+)ꢀ2 is regioselectively reduced at the carbonyl group
C(1)=O upon the action of NaBH4 to give compound
(+)ꢀ6 in 94% yield. Treatment of the latter with diꢀ
azomethane leads to the product (+)ꢀ7 monomethylated
at the phenol hydroxyl at the atom C(9) in 80% yield
(Scheme 3). Thus, we consider compound 7 to be more
promising substrate for the synthesis of chalcones as comꢀ
pared to the unstable derivatives 4.
The condensation of compound (+)ꢀ7 with benzaldeꢀ
hydes in methanol (70 °C, 2.5—3 h) in the presence of
R = H (a), Cl (b)

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011
Sokolov et al.
Scheme 3
8
a
b
c
R1 R2
R3 R4
Yield (%)
8
d
e
f
R1
H
F
R2
H
H
R3
OMe
H
R4
H
H
Yield (%)
8
g
h
i
R1
H
H
R2
NO2
OMe
OMe
R3
H
OMe
OMe
R4
H
OMe
H
Yield (%)
H
H
H
H
H
H
H
F
H
H
H
77
77
61
70
46
68
40
58
60
Cl
OMe
H
H
H
H
20
acid ((–)ꢀ1) ([α]D –458 (c 0.1, CHCl3)), from the lichen
Cladonia Stellaris according to the known procedure.15 Comꢀ
pound (+)ꢀ2 was synthesized according to the described proceꢀ
dure.16 Sodium borohydride was purchased from EvroKhimꢀ
Proekt Ltd. Merck silica gel (63—200μ) was used for column
chromatography. Thinꢀlayer chromatography was performed on
Sorbfil plates (UVꢀ254).
aqueous KOH led to the expected chalcones (+)ꢀ8a—i
(see Scheme 3).
The highest yields were observed in the reactions
with unsubstituted benzaldehyde ((+)ꢀ8a) and with benzꢀ
aldehydes containing methoxy groups at the paraꢀ and
orthoꢀpositions ((+)ꢀ8d,f). An increase in the number of
methoxy substituents in benzaldehyde leads to a decrease
in the yields of chalcones ((+)ꢀ8h,i), the same is true if
a fluorine atom is present at the orthoꢀposition of benzꢀ
aldehyde ((+)ꢀ8e). Benzaldehyde with a strong acceptor,
nitro group at the metaꢀposition, reacts with compound
(+)ꢀ7 at room temperature, but the yield of chalcone
(+)ꢀ8g has proved the lowest in the series of interest. In
the case of 4ꢀdimethylaminobenzaldehyde bearing a strong
electronꢀdonating substituent, the aldehyde is predoꢀ
minantly involved into the Cannizzaro reaction. The simꢀ
ilar approach was used for the preparation of chalcones
(–)ꢀ8a—i based on the acid (–)ꢀ1.
The atom numeration in compounds (see Schemes 1—3) is
given for the assignment of signals in the NMR spectra and
sometimes differ from the atom numeration in the nomenclature
names. Spectral characteristics are given only for compounds
(+)ꢀ7 and (+)ꢀ8a—i, derived from (+)ꢀ1. For their enantiomers,
derived from (–)ꢀ1, nomenclature names and values of specific
rotation are only given.
(S)ꢀ8ꢀAcetylꢀ5,7ꢀdi(tertꢀbutoxycarbonyloxy)ꢀ3,4a,6ꢀtrimethylꢀ
1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ4ꢀone
((+)ꢀ3). Triethylamine (1 mL), a small crystal of DMAP, and
Boc2O (6 mmol) were added to a solution of compound (+)ꢀ2
(1 mmol) in diethyl ether (5 mL), the mixture was stirred at
room temperature until the substrate was completely converted
(TLC monitoring). The reaction mixture was washed with water,
dried with MgSO4, the solvent was evaporated, and the residue
was subjected to chromatography on a silica gel column (eluent
CHCl3). The yield was 95%, m.p. 93—95 °C, [α]D30 +211 (c 0.2,
In conclusion, we have developed a fourꢀstep synthesis
of chalcones based on (+)ꢀ and (–)ꢀusnic acids. Nine
pares of enantiomeric chalcones ((+)ꢀ and (–)ꢀ8a—i) with
different substituents in ring D have been synthesized.
1
CHCl3). H NMR, δ: 1.48, 1.53 (both s, 18 H, H(24), H(24´),
H(24″), H(25), H(25´), H(25″)); 1.83 (s, 3 H, H(15)); 2.04 (s, 3
H, H(10)); 2.48 (s, 3 H, H(12)); 2.53 (s, 3 H, H(14)); 6.14 (s, 1
H, H(4)); 7.39 (s, 1 H, H(19)); 7.43—7.54 (m, 4 H, H(17),
H(17´), H(18), H(18´)). 13C NMR, δ: 9.42 (C(15)); 12.80
(C(12)); 27.47, 27.59 (C(24), C(24´), C(24″), C(25), C(25´),
C(25″)); 29.30 (C(10)); 31.73 (C(14)); 60.58 (C(9b)); 83.96,
84.11 (C(22), C(23)); 89.30 (C(4)); 110.81 (C(9a)); 115.69
(C(6)); 119.30 (C(8)); 122.49 (C(2)); 123.57 (C(17), C(17´));
128.12 (C(19)); 129.41 (C(18), C(18´)); 138.06 (C(16)); 145.30
(C(11)); 146.60 (C(3)); 147.87 (C(5a)); 148.19 (C(7)); 150.79,
150.67 (C(20), C(21)); 154.16 (C(9)); 171.22 (C(4a)); 190.39
(C(1)); 195.07 (C(13)). HRMS, found: m/z 616.2410 [M]+.
C34H36N2O9. Calculated: M = 616.2415.
Experimental
1
H and 13C NMR spectra were recorded on a Bruker AVꢀ400
spectrometer (400.13 and 100.61 MHz, respectively) for soluꢀ
tions of compounds in CDCl3. Residual signals of the solvent
were used as references (δH 7.24, δC 76.90). Mass spectra (70 eV)
were recorded on a DFS Thermo Scientific high resolution mass
spectrometer. Melting points were measured on a Kofler heating
stage. Specific rotation is given in (deg mL) (g dm)–1, concenꢀ
tration of solutions, in g (100 mL)–1
(+)ꢀUsnic acid ((+)ꢀ1) ([α]D +478 (c 0.1, CHCl3)) was
isolated from the lichens mixture of the Usnea family, (–)ꢀusnic
.
20

Usnic acidꢀderived chalcones
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011 2409
[benzofuro[3´,2´:5,6]cyclohepta[1,2ꢀc]pyrazoleꢀ5,2´ꢀoxirane]
Reactions of compounds (+)ꢀ2 and (+)ꢀ6 with diazomethane
(general procedure). A solution of diazomethane (prepared from
NꢀmethylꢀNꢀnitrosourea (2 g)) was carefully added to a solution
of compound (+)ꢀ2 or (+)ꢀ6 (1 mmol) in chloroform (5 mL)
with stirring, and the reaction mixture was kept at room temperꢀ
ature until evolution of the gas ceased, then the solvent was
evaporated, and the residue was subjected to chromatography on
a silica gel column (60—200μ, eluent chloroform) to obtain comꢀ
pounds (+)ꢀ4 and (+)ꢀ7, respectively.
(5aS)ꢀ9ꢀAcetylꢀ8ꢀhydroxyꢀ6ꢀmethoxyꢀ3,5a,7ꢀtrimethylꢀ1ꢀ
phenylꢀ4,5aꢀdihydroꢀ1Hꢀspiro[benzofuro[3´,2´:5,6]cycloheptaꢀ
[1,2ꢀc]pyrazoleꢀ5,2´ꢀoxirane] ((+)ꢀ4). The yield was 55%, m.p.
112—114 °C. 1H NMR, δ: 1.73 (s, 3 H, H(15)); 2.11 (s, 3 H,
H(10)); 2.14 (dd, 1 H, H(21)α, 2J = 4.7 Hz, J21,1a = 2.0 Hz); 2.24
(s, 3 H, H(12)); 2.39 (d, 1 H, H(4)β, 2J = 17.0 Hz); 2.44 (d, 1 H,
H(12)β, 2J = 4.7 Hz); 2.61 (s, 3 H, H(14)); 3.66 (dd, 1 H, H(1a)α,
2J = 17.0 Hz, J1a,21 = 2.0 Hz); 3.93 (s, 3 H, OCH3); 6.10 (s, 1 H,
H(4)); 7.34—7.38 (m, 1 H, H(19)); 7.42—7.50 (m, 4 H, H(17),
H(17´), H(18), H(18´)); 13.30 (s, 1 H, C(7)OH). 13C NMR, δ:
9.66 (C(10)); 11.57 (C(12)); 17.95 (C(15)); 30.17 (C(1a)); 31.44
(C(14)); 50.84 (C(21)); 52.07 (C(9b)); 58.15 (C(1)); 61.63
(C(20)); 91.95 (C(4)); 102.86 (C(6)); 111.30 (C(9a)); 111.35
(C(3)); 112.75 (C(8)); 125.19 (C(17), C(17´)); 127.43 (C(19));
129.06 (C(18), C(18´)); 133.33 (C(2)); 139.37 (C(16)); 147.90
(C(11)); 156.49 (C(5a)); 163.13 (C(9)); 163.61 (C(7)); 163.78
(C(9a)); 201.62 (C(13)). HRMS, found: m/z 458.1835 [M]+.
C27H26N2O5. Calculated: M = 458.1836.
(4S,4aR)ꢀ8ꢀAcetylꢀ4,7ꢀdihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtriꢀ
methylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazole
((+)ꢀ7). The yield was 80%, m.p. 78—79 °C, [α]D20 +218 (c 0.3,
CHCl3). 1H NMR, δ: 1.48 (s, 3 H, H(15)); 2.13 (s, 3 H, H(10));
2.44 (s, 3 H, H(12)); 2.67 (s, 3 H, H(14)); 3.94 (s, 3 H, OCH3);
3.97 (s, 1 H, C(1)OH); 5.40 (s, 1 H, H(1)); 5.96 (s, 1 H, H(4));
7.30—7.51 (m, 5 H, H arom.); 13.26 (s, 1 H, C(7)OH).
13C NMR, δ: 8.94 (C(10)); 12.49 (C(12)); 17.77 (C(15)); 31.30
(C(14)); 52.00 (C(9b)); 61.49 (C(20)); 74.21 (C(1)); 89.93 (C(4));
103.92 (C(6)); 111.96 (C(2)); 112.05 (C(9a)); 114.77 (C(8));
122.66 (C(17), C(17´)); 126.55 (C(19)); 128.83 (C(18), C(18´));
136.01 (C(16)); 138.86 (C(3)); 147.52 (C(11)); 157.63 (C(5a));
159.36 (C(9)); 162.86 (C(7)); 166.71 (C(4a)); 201.59 (C(13)).
HRMS, found: m/z 432.1678 [M]+. C25H24N2O5. Calculated:
M = 432.16797.
30
((+)ꢀ5a). The yield was 21%, m.p. 125—127 °C, [α]D +130
1
(c 0.2, CHCl3). H NMR, δ: 1.76 (s, 3 H, H(15)); 2.15 (s, 3 H,
H(10)); 2.19 (dd, 1 H, H(21)α, 2J = 4.7 Hz, J21,1a = 2.0 Hz); 2.25
(s, 3 H, H(12)); 2.38 (d, 1 H, H(4)β, 2J = 17.0 Hz); 2.46 (d, 1 H,
H(12)β, 2J = 4.7 Hz); 3.68 (dd, 1 H, H(1a)α, 2J = 17.0 Hz, J1a,21
=
= 2.0 Hz); 3.95 (s, 3 H, OCH3); 6.19 (s, 1 H, H(4)); 7.28—7.59
(m, 10 H, H(17), H(17´), H(18), H(18´), H(19), H(24), H(24´),
H(25), H(25´), H(26)); 7.85 (d, 1 H, H(14), J = 15.5 Hz); 7.93
(d, 1 H, H(22), J = 15.5 Hz); 13.90 (s, 1 H, C(7)OH). 13C NMR,
δ: 9.53 (C(10)); 11.33 (C(12)); 17.69 (C(15)); 29.88 (C(1a));
50.57 (C(21)); 51.69 (C(9b)); 57.92 (C(1)); 61.41 (C(20)); 91.72
(C(4)); 102.94 (C(6)); 111.14 (C(3)); 111.16 (C(9a)); 112.77
(C(8)); 124.73 (C(17), C(17´)); 124.99 (C(14)); 127.09 (C(19));
128.20 (C(24), C(24´)); 128.47 (C(25), C(25´)); 128.65 (C(18),
C(18´)); 130.20 (C(26)); 132.90 (C(2)); 134.55 (C(23));
139.02 (C(16)); 143.96 (C(22)); 147.67 (C(11)); 155.59 (C(5a));
162.98 (C(9)); 163.21 (C(9a)); 164.55 (C(7)); 190.80 (C(13)).
HRMS, found: m/z 546.2150 [M]+. C34H30N2O5. Calculated:
M = 546.2141.
(5aS)ꢀ8ꢀHydroxyꢀ6ꢀmethoxyꢀ3,5a,7ꢀtrimethylꢀ9ꢀ[1ꢀoxoꢀ3ꢀ
(4ꢀchlorophenyl)propꢀ2(E)ꢀenꢀ1ꢀyl]ꢀ1ꢀphenylꢀ4,5aꢀdihydroꢀ1Hꢀ
spiro[benzofuro[3´,2´:5,6]cyclohepta[1,2ꢀc]pyrazoleꢀ5,2´ꢀoxꢀ
30
irane] ((+)ꢀ5b). The yield was 31%, m.p. 110—113 °C, [α]D
+147 (c 0.2, CHCl3). 1H NMR, δ: 1.76 (s, 3 H, H(15)); 2.14 (s, 3 H,
H(10)); 2.19 (dd, 1 H, H(21)α, 2J = 4.7 Hz, J21,1a = 2.0 Hz); 2.25
(s, 3 H, H(12)); 2.41 (d, 1 H, H(4)β, 2J = 17.0 Hz); 2.46 (d, 1 H,
H(12)β, 2J = 4.7 Hz); 3.68 (dd, 1 H, H(1a)α, 2J = 17.0 Hz,
J1a,21 = 2.0 Hz); 3.95 (s, 3 H, OCH3); 6.15 (s, 1 H, H(4));
7.22—7.52 (m, 9 H, H(17), H(17´), H(18), H(18´), H(19),
H(24), H(24´), H(25), H(25´)); 7.77 (d, 1 H, H(14), J = 15.6 Hz);
7.87 (d, 1 H, H(22), J = 15.6 Hz); 13.82 (s, 1 H, C(7)OH).
13C NMR, δ: 9.83 (C(10)); 11.60 (C(12)); 17.97 (C(15)); 30.15
(C(1a)); 50.86 (C(21)); 52.00 (C(9b)); 58.21 (C(1)); 61.72
(C(20)); 92.05 (C(4)); 103.17 (C(6)); 111.47 (C(3)); 111.52
(C(9a)); 113.13 (C(8)); 125.07 (C(17), C(17´)); 125.77 (C(14));
127.52 (C(19)); 128.99 (C(18), C(18´)); 129.06 (C(25), C(25´));
129.60 (C(24), C(24´)); 133.16 (C(2)); 133.35 (C(23)); 136.35
(C(26)); 139.27 (C(16)); 142.67 (C(22)); 147.99 (C(11)); 155.85
(C(5a)); 163.41 (C(9)); 163.50 (C(9a)); 164.85 (C(7)); 190.82
(C(13)). HRMS, found: m/z 580.1765 [M]+. C34H29ClN2O5.
Calculated: M = 580.1760.
(4R,4aS)ꢀ8ꢀAcetylꢀ4,7ꢀdihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtriꢀ
methylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazole
((–)ꢀ7). M.p. 80 °C, [α]D20 –203 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
phenylpropꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8a). The yield was 77%, m.p.
120—122 °C, [α]D +38 (c 0.2, CHCl3). 1H NMR, δ: 1.52
20
Reactions of compounds (+)ꢀ4 and (+)ꢀ7 with substituted benzꢀ
aldehydes (general procedure). A 50% aqueous KOH (2 mL) was
added to a solution of compound (+)ꢀ4 or (+)ꢀ7 (1 mmol) and
the corresponding substituted benzaldehyde (4 mmol) in MeOH
(16 mL). The mixture was heated for 2.5—3 h at 70 °C (in the
case of 3ꢀnitrobenzaldehyde, at 20 °C). The substrate conversion
was monitored by TLC, using the hexane—diethyl ether (7 : 3)
mixture as an eluent. The reaction mixture was poured into cold
water (100 mL), acidified with 10% aq. AcOH to pH ~5, extractꢀ
ed with CH2Cl2 (3×30 mL). The combined extract was dried
with calcined MgSO4, the solvent was evaporated, and the resiꢀ
due was subjected to chromatography on a silica gel column
(60—200μ), using the CH2Cl2—MeOH (to 0.5%) mixture as an
eluent to obtain compounds (+)ꢀ5a,b and (+)ꢀ8a—i.
(s, 3 H, H(15)); 2.18 (s, 3 H, H(10)); 2.46 (s, 3 H, H(12)); 3.97
(s, 3 H, OCH3); 4.04 (s, 1 H, C(1)OH); 5.44 (s, 1 H, H(1)); 6.01
(s, 1 H, H(4)); 7.31—7.63 (m, 10 H, H arom.); 7.93 (s, 2 H,
H(14), H(21)); 13.91 (s, 1 H, C(7)OH). 13C NMR, δ: 9.44
(C(10)); 12.83 (C(12)); 18.13 (C(15)); 52.25 (C(9b)); 61.86
(C(20)); 74.49 (C(1)); 90.20 (C(4)); 104.63 (C(6)); 112.40 (C(2));
112.72 (C(9a)); 115.16 (C(8)); 123.14 (C(17), C(17´)); 124.82
(C(14)); 126.89 (C(19)); 128.73 (C(18), C(18´)); 128.92 (C(23),
C(27)); 129.21 (C(24), C(26)); 130.72 (C(25)); 134.71 (C(22));
136.32 (C(16)); 139.24 (C(3)); 145.30 (C(21)); 147.89 (C(11));
157.32 (C(5a)); 159.75 (C(9)); 164.48 (C(7)); 167.01 (C(4a));
191.26 (C(13)). HRMS, found: m/z 520.1995 [M]+. C32H28N2O5.
Calculated: M = 520.1993.
(5aS)ꢀ8ꢀHydroxyꢀ6ꢀmethoxyꢀ3,5a,7ꢀtrimethylꢀ9ꢀ(1ꢀoxoꢀ3ꢀ
phenylpropꢀ2(E)ꢀenꢀ1ꢀyl)ꢀ1ꢀphenylꢀ4,5aꢀdihydroꢀ1Hꢀspiroꢀ
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ

2410
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011
Sokolov et al.
phenylpropꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8a). M.p. 121—122 °C, [α]D20 –41
(c 0.2, CHCl3).
147.86 (C(11)); 157.16 (C(5a)); 159.44 (C(9)); 161.85 (C(25));
164.46 (C(7)); 167.09 (C(4a)); 191.04 (C(13)). HRMS, found:
m/z 550.2099 [M]+. C33H30N2O6. Calculated: M = 550.2098.
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8d). M.p. 105—106 °C,
[α]D19 –57 (c 0.4, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(4ꢀfluorophenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8b). The yield was 77%,
m.p. 103—105 °C, [α]D20 +57 (c 0.2, CHCl3). 1H NMR, δ: 1.51
(s, 3 H, H(15)); 2.16 (s, 3 H, H(10)); 2.46 (s, 3 H, H(12)); 3.96
(s, 3 H, OCH3); 4.03 (s, 1 H, C(1)OH); 5.43 (s, 1 H, H(1)); 5.99
(s, 1 H, H(4)); 7.09 (m, 2 H, H(24)); 7.28—7.55 (m, 5 H,
H arom.); 7.61 (m, 2 H, H(23)); 7.83 (d, 1 H, H(14), J =15.5 Hz);
7.90 (d, 1 H, H(21), J = 15.5 Hz); 14.05 (s, 1 H, C(7)OH).
13C NMR, δ: 9.42 (C(10)); 12.81 (C(12)); 18.12 (C(15)); 52.25
(C(9b)); 61.88 (C(20)); 74.52 (C(1)); 90.24 (C(4)); 104.57 (C(6));
112.47 (C(2)); 112.78 (C(9a)); 115.25 (C(8)); 116.15 (d, C(24),
C(26), JC,F = 21.9 Hz); 123.18 (C(17), C(17´)); 124.51 (C(14));
126.94 (C(19)); 129.22 (C(18), C(18´)); 130.67 (d, C(23), C(27),
JC,F = 8.2 Hz); 130.98 (d, C(22), JC,F = 3.3 Hz); 136.27 (C(16));
139.24 (C(3)); 143.95 (C(21)); 147.90 (C(11)); 157.27 (C(5a));
159.80 (C(9)); 164.11 (d, C(25), JC,F = 250.7 Hz); 164.49 (C(7));
166.96 (C(4a)); 191.05 (C(13)). HRMS, found: m/z 538.1899
[M]+. C32H27FN2O5. Calculated: M = 538.1890.
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(2ꢀfluorophenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8e). The yield was 46%,
27
m.p. 93—96 °C, [α]D +96 (c 0.2, CHCl3). 1H NMR, δ: 1.52
(s, 3 H, H(15)); 2.16 (s, 3 H, H(10)); 2.47 (s, 3 H, H(12)); 3.97
(s, 3 H, OCH3); 4.04 (d, 1 H, C(1)OH, J = 1.3 Hz); 5.44 (s, 1 H,
H(1)); 5.99 (s, 1 H, H(4)); 7.08 (m, 1 H, H(24)); 7.13 (m, 1 H,
H(26)); 7.31—7.50 (m, 6 H, H arom.); 7.61 (m, 1 H, H(25));
7.99 (d, 1 H, H(14), J = 15.6 Hz); 8.06 (d, 1 H, H(21), J = 15.6 Hz);
13.85 (s, 1 H, C(7)OH). 13C NMR, δ: 9.39 (C(10)); 12.80 (C(12));
18.08 (C(15)); 52.23 (C(9b)); 61.83 (C(20)); 74.43 (C(1)); 90.17
(C(4)); 104.57 (C(6)); 112.40 (C(2)); 112.69 (C(9a)); 115.17
(C(8)); 116.22 (d, C(24), JC,F = 21.9 Hz); 122.87 (d, C(22),
JC,F = 11.6 Hz); 123.05 (C(17), C(17´)); 124.45 (d, C(14),
JC,F = 3.6 Hz); 126.84 (C(19)); 127.30 (d, C(26), JC,F = 7.3 Hz);
129.18 (C(18), C(18´)); 129.86 (d, C(27), JC,F = 2.9 Hz); 132.02
(d, C(25), JC,F = 8.6 Hz); 136.29 (C(16)); 137.70 (d, C(21),
JC,F = 2.0 Hz); 139.23 (C(3)); 147.85 (C(11)); 157.33 (C(5a));
159.85 (C(9)); 160 (d, C(23), JC,F = 255.4 Hz); 164.48 (C(7));
166.96 (C(4a)); 191.16 (C(13)). HRMS, found: m/z 538.1902
[M]+. C33H30N2O6. Calculated: M = 538.1899.
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(4ꢀfluorophenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8b). M.p. 102—103 °C,
[α]D27 –75 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(4ꢀchlorophenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8c). The yield was 61%,
m.p. 111—114 °C, [α]D20 +57 (c 0.2, CHCl3). 1H NMR, δ: 1.53
(s, 3 H, H(15)); 2.18 (s, 3 H, H(10)); 2.47 (s, 3 H, H(12)); 3.98
(s, 3 H, OCH3); 4.04 (s, 1 H, C(1)OH); 5.45 (s, 1 H, H(1)); 6.00
(s, 1 H, H(4)); 7.27—7.58 (m, 9 H, H arom.); 7.85 (d, 1 H,
H(14), J = 15.4 Hz); 7.90 (d, 1 H, H(21), J = 15.4 Hz); 13.87
(s, 1 H, C(7)OH). 13C NMR, δ: 9.42 (C(10)); 12.81 (C(12)); 18.12
(C(15)); 52.24 (C(9b)); 61.86 (C(20)); 74.47 (C(1)); 90.24 (C(4));
104.55 (C(6)); 112.37 (C(2)); 112.78 (C(9a)); 115.20 (C(8));
123.14 (C(17), C(17´)); 125.24 (C(14)); 126.95 (C(19)); 129.20
(C(18), C(18´)); 129.23 (C(24), C(26)); 129.81 (C(23), C(27));
133.18 (C(22)); 136.24 (C(16)); 136.63 (C(25)); 139.19 (C(3));
143.71 (C(21)); 147.88 (C(11)); 157.27 (C(5a)); 159.87 (C(9));
164.49 (C(7)); 166.93 (C(4a)); 190.96 (C(13)). HRMS, found:
m/z 554.1603 [M]+. C32H27ClN2O5. Calculated: M = 554.1587.
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(4ꢀchlorophenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8c). M.p. 112—113 °C,
[α]D27 –68 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8d). The yield was 70%,
m.p. 105—107 °C, [α]D20 +23 (c 0.2, CHCl3). 1H NMR, δ: 1.50
(s, 3 H, H(15)); 2.14 (s, 3 H, H(10)); 2.45 (s, 3 H, H(12)); 3.81,
3.94 (both s, 3 H each, OCH3); 4.05 (s, 1 H, C(1)OH); 5.42
(s, 1 H, H(1)); 5.97 (s, 1 H, H(4)); 6.89 (d, 2 H, H(23), J = 8.65 Hz);
7.29—7.58 (m, 7 H, H arom.); 7.77 (d, 1 H, H(14), J = 15.5 Hz);
7.87 (d, 1 H, H(21), J = 15.5 Hz); 14.06 (s, 1 H, C(7)OH).
13C NMR, δ: 9.40 (C(10)); 12.83 (C(12)); 18.14 (C(15)); 52.20
(C(9b)); 55.31 (C(28)); 61.82 (C(20)); 74.43 (C(1)); 90.07 (C(4));
104.62 (C(6)); 112.38 (C(2)); 112.65 (C(9a)); 114.38 (C(24),
C(26)); 115.01 (C(8)); 122.28 (C(14)); 123.11 (C(17), C(17´));
126.85 (C(19)); 127.42 (C(22)); 129.23 (C(18), C(18´)); 130.63
(C(23), C(27)); 136.35 (C(16)); 139.26 (C(3)); 145.28 (C(21));
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(2ꢀfluorophenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8e). M.p. 94—96 °C,
[α]D20 –109 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(2ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8f). The yield was 68%,
20
1
m.p. 99—103 °C, [α]D +81 (c 0.2, CHCl3). H NMR, δ: 1.52
(s, 3 H, H(15)); 2.17 (s, 3 H, H(10)); 2.47 (s, 3 H, H(12)); 3.89
(s, 3 H, OCH3); 3.97 (s, 3 H, OCH3); 4.06 (d, 1 H, C(1)OH,
J = 1.3 Hz); 5.45 (s, 1 H, H(1)); 5.99 (s, 1 H, H(4)); 6.92 (d, 1 H,
H(26), J = 8.3 Hz); 6.98 (m, 1 H, H(24)); 7.31—7.60 (m, 6 H, H
arom.); 7.63 (m, 1 H, H(23)); 8.04 (d, 1 H, H(14), J = 15.7 Hz);
8.28 (d, 1 H, H(21), J = 15.7 Hz); 14.07 (s, 1 H, C(7)OH).
13C NMR, δ: 9.42 (C(10)); 12.83 (C(12)); 18.12 (C(15)); 52.27
(C(9b)); 55.39 (C(28)); 61.82 (C(20)); 74.51 (C(1)); 89.99 (C(4));
104.74 (C(6)); 111.13 (C(24)); 112.41 (C(2)); 112.63 (C(9a));
115.02 (C(8)); 120.70 (C(26)); 123.02 (C(17), C(17´)); 123.76
(C(22)); 125.21 (C(14)); 126.84 (C(19)); 129.14 (C(18), C(18´));
129.25 (C(25)); 132.08 (C(27)); 136.37 (C(16)); 139.25 (C(3));
140.72 (C(21)); 147.89 (C(11)); 157.31 (C(5a)); 158.87 (C(23));
159.53 (C(9)); 164.50 (C(7)); 167.15 (C(4a)); 191.67 (C(13)).
HRMS, found: m/z 550.2091 [M]+. C33H30N2O6. Calculated:
M = 550.2098.
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(2ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8f). M.p. 100—103 °C,
[α]D20 –73 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(3ꢀnitrophenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8g). The yield was 40%,
m.p. 95—98 °C, [α]D +85 (c 0.2, CHCl3). 1H NMR, δ: 1.52
27
(s, 3 H, H(15)); 2.17 (s, 3 H, H(10)); 2.45 (s, 3 H, H(12)); 3.97

Usnic acidꢀderived chalcones
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011 2411
(s, 3 H, OCH3); 4.01 (s, 1 H, C(1)OH); 5.44 (s, 1 H, H(1)); 6.09
(s, 1 H, H(4)); 7.07—7.63 (m, 9 H, H arom.); 7.86 (d, 1 H,
H(14), J = 15.6 Hz); 8.06 (d, 1 H, H(21), J = 15.6 Hz); 13.62
(s, 1 H, C(7)OH). 13C NMR, δ: 9.07 (C(10)); 12.48 (C(12)); 17.75
(C(15)); 52.00 (C(9b)); 61.57 (C(20)); 74.15 (C(1)); 90.26 (C(4));
104.16 (C(6)); 112.06 (C(2)); 112.53 (C(9a)); 115.12 (C(8));
122.55 (C(23)); 122.65 (C(17), C(17´)); 124.30 (C(25)); 126.62
(C(19)); 127.66 (C(14)); 128.94 (C(18), C(18´)); 129.65 (C(26));
134.01 (C(27)); 135.76 (C(22)); 136.24 (C(16)); 138.81 (C(3));
141.14 (C(21)); 147.52 (C(11)); 148.31 (C(24)); 157.08 (C(5a));
159.96 (C(9)); 164.10 (C(7)); 166.32 (C(4a)); 190.33 (C(13)).
HRMS, found: m/z 565.1848 [M]+. C32H27N3O7. Calculated:
M = 565.1844.
(d, 1 H, H(21), J = 15.7 Hz); 14.05 (s, 1 H, C(7)OH). 13C NMR, δ:
9.37 (C(10)); 12.79 (C(12)); 18.08 (C(15)); 52.30 (C(9b)); 55.45,
55.88 (C(28), C(29)); 61.79 (C(20)); 74.47 (C(1)); 89.79 (C(4));
104.60 (C(6)); 110.03, 111.02 (C(23), C(26)); 112.37, 112.69
(C(2), C(9a)); 115.00 (C(8)); 122.83 (C(27)); 122.98 (C(17),
C(17´)); 123.49 (C(14)); 126.87 (C(19)); 127.75 (C(22)); 129.08
(C(18), C(18´)); 136.21 (C(16)); 139.18 (C(3)); 145.07 (C(21));
147.90 (C(25)); 149.01 (C(24)); 151.58 (C(11)); 157.17 (C(5a));
159.52 (C(9)); 164.49 (C(7)); 167.00 (C(4a)); 190.93 (C(13)).
HRMS, found: m/z 580.2190 [M]+. C34H32N2O7. Calculated:
M = 580.2204.
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(3,4ꢀdimethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8i). M.p. 115—118 °C,
[α]D27 –24 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
27
(3ꢀnitrophenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8g). M.p. 95—97 °C, [α]D
–79 (c 0.2, CHCl3).
References
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(3,4,5ꢀtrimethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8h). The yield
1. D. Batovska, I. Todorova, Curr. Clin. Pharm., 2010, 5, 1.
2. S. Vogel, S. Ohmayer, G. Brunner, J. Heilmann, Bioorg.
Med. Chem., 2008, 16, 4286.
20
was 58%, m.p. 119—121 °C, [α]D +23 (c 0.2, CHCl3).
1H NMR, δ: 1.49 (s, 3 H, H(15)); 2.12 (s, 3 H, H(10)); 2.44 (s, 3 H,
H(12)); 3.83 (s, 6 H, 2 OCH3); 3.87, 3.95 (both s, 3 H each,
OCH3); 3.96 (s, 1 H, C(1)OH); 5.40 (s, 1 H, H(1)); 5.86 (s, 1 H,
H(4)); 6.82 (s, 2 H, H(23), H(27)); 7.28—7.50 (m, 5 H, H arom.);
7.74 (d, 1 H, H(14), J = 15.3 Hz); 7.91 (d, 1 H, H(21), J = 15.3 Hz);
13.90 (s, 1 H, C(7)OH). 13C NMR, δ: 9.34 (C(10)); 12.81 (C(12));
18.04 (C(15)); 52.35 (C(9b)); 55.76 (C(28), C(28´)); 60.88
(C(29)); 61.80 (C(20)); 74.49 (C(1)); 89.73 (C(4)); 104.55 (C(6));
105.62 (C(23), C(27)); 112.35 (C(2)); 112.75 (C(9a)); 115.07
(C(8)); 122.89 (C(17), C(17´)); 124.44 (C(14)); 126.95 (C(19));
129.03 (C(18), C(18´)); 130.24 (C(22)); 136.09 (C(16)); 139.13
(C(3)); 40.52 (C(25)); 144.71 (C(21)); 147.92 (C(11)); 153.24
(C(24), C(26)); 157.17 (C(5a)); 159.71 (C(9)); 164.49 (C(7));
166.85 (C(4a)); 190.89 (C(13)). HRMS, found: m/z 610.2303
[M]+. C35H34N2O8. Calculated: M = 610.2310.
(E)ꢀ1ꢀ[(4R,4aS)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ
3ꢀ(3,4,5ꢀtrimethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((–)ꢀ8h). M.p.
118—121 °C, [α]D20 –29 (c 0.2, CHCl3).
(E)ꢀ1ꢀ[(4S,4aR)ꢀ4,7ꢀDihydroxyꢀ5ꢀmethoxyꢀ3,4a,6ꢀtrimethꢀ
ylꢀ1ꢀphenylꢀ4,4aꢀdihydroꢀ1Hꢀbenzofuro[3,2ꢀf]indazolꢀ8ꢀyl]ꢀ3ꢀ
(3,4ꢀdimethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone ((+)ꢀ8i). The yield was
60%, m.p. 115—117 °C, [α]D +19 (c 0.3, CHCl3). 1H NMR, δ:
1.52 (s, 3 H, H(15)); 2.17 (s, 3 H, H(10)); 2.47 (s, 3 H, H(12));
3.83, 3.87 (both s, 6 H, 2 OCH3); 3.98 (s, 3 H, OCH3); 4.04
(s, 1 H, C(1)OH); 5.46 (s, 1 H, H(1)); 5.94 (s, 1 H, H(4)); 6.89
(d, 1 H, H(26), J = 8.4 Hz); 7.16 (s, 1 H, H(23)); 7.22 (d, 1 H,
H(27), J = 8.4 Hz); 7.34 (m, 1 H, H(19)); 7.49 (m, 4 H, H(17),
H(17´), H(18), H(18´)); 7.86 (d, 1 H, H(14), J = 15.7 Hz); 7.90
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Received May 10, 2011;
in revised form August 30, 2011