Synthesis of pyrroloquinolines as indole analogues of flavonols

Article abstract of DOI:10.1021/jo010915b

7-Acetyl-4,6-dimethoxy-3-phenylindole 10 was converted into a range of 7-indolyl chalcones 13 by reaction with aryl aldehydes under basic conditions. Oxidation of the chalcones 13 with alkaline hydrogen peroxide gave the isolable epoxides 14, which were cyclized with further base treatment into the indole flavonols, or 5-hydroxy-6-oxopyrroloquinolines 15. The related compounds 25 and 26, examples of indole flavanones and flavones, respectively, were also synthesized. UV spectroscopic comparisons between flavonoids and indole flavonoids are discussed.

Full text of DOI:10.1021/jo010915b

2464
J . Org. Chem. 2002, 67, 2464-2473
Syn th esis of P yr r oloqu in olin es a s In d ole An a logu es of F la von ols
David StC. Black,* Naresh Kumar, and Peter S. R. Mitchell
School of Chemistry, The University of New South Wales, UNSW Sydney, NSW 2052, Australia
d.black@unsw.edu.au
Received September 10, 2001
7-Acetyl-4,6-dimethoxy-3-phenylindole 10 was converted into a range of 7-indolyl chalcones 13 by
reaction with aryl aldehydes under basic conditions. Oxidation of the chalcones 13 with alkaline
hydrogen peroxide gave the isolable epoxides 14, which were cyclized with further base treatment
into the indole flavonols, or 5-hydroxy-6-oxopyrroloquinolines 15. The related compounds 25 and
26, examples of indole flavanones and flavones, respectively, were also synthesized. UV spectroscopic
comparisons between flavonoids and indole flavonoids are discussed.
In tr od u ction
Pyrrolo[3,2,1-ij]quinoline systems, such as that shown
by the reduced structure 1, have been found in nature
and their synthesis and reactions have been reviewed.1
Compounds of this class, and especially the hexahydro-
pyrroloquinolines 1, show a wide range of biological
activity.2,3
Pyrroloquinolines also exist in a variety of oxidized
forms, especially the 4- and 6-oxo-pyrroloquinolines 2 and
3, respectively.1 Some 4-oxopyrroloquinolines 2 have been
found to induce the reversible inhibition of fertility in
male rats.4-6 The reduced compound lycorine acts against
tumor cells and inhibits protein and DNA synthesis.4 As
yet there appears to be no report of any naturally
occurring 6-oxopyrroloquinoline. Synthetic 6-oxopyrrolo-
quinolines 3 utilize one of two general approaches,
involving either the construction of a pyrrole ring on to
a quinoline by a standard indole synthesis,7-14 or the
construction of a new six-membered ring between N1 and
C7 of an indole.1,15-22
Synthesis of both natural and unnatural flavonoids
have been widely studied because of their extensive
biological properties.23-32 Incorporation of the indole
nucleus within the flavonoid structure leads to 6-oxopyr-
roloquinolines, which could be derived from indoles. A
similar comparison of flavanones and 2-aryl-1,2,3,4-
tetrahydro-4-quinolones has been considered previ-
ously.33,34 This synthetic prospect has been made acces-
sible by the development of electron-rich 4,6-dimeth-
oxyindoles which are activated at C7, thus providing a
wide extension of the chemistry that can occur at that
position, including the possibility of cyclization between
C7 and N1.35-37 In particular traditional flavonoid syn-
thetic routes can be employed with such systems.
(1) Black, D. StC.; Kumar, N. Org. Prep. Proc. Int. 1990, 23, 67-
92.
(2) Patchter, I. J . U. S. Pat. U.S. 3,299,078, 1967; Chem. Abstr. 1968,
68, 21919a.
(3) Kappe, C. O.; Kappe, T. J . Heterocycl. Chem. 1989, 26, 1555-
1560.
(4) Ghosal, S.; Saini, K. S.; Razdan, S. Phytochemistry 1985, 24,
2141-2156.
(5) Ghosal, S.; Rao, P. H.; J aisural, D. K.; Kumar, Y.; Frahm, A. W.
Phytochemistry 1981, 20, 2003-2007.
(6) Chattopadhyay, S.; Chattopadhyay, U.; Mathur, P. P.; Saini, K.
S.; Ghosal, S. Planta Med. 1983, 49, 252-254.
(7) Yudin, L. G.; Budylin, V. A.; Kost, A. N. Khim. Geterotsikl.
Soedin. 1967, 704-707; Chem. Abstr. 68, 114351z, 1967.
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Chem. 1974, 11, 387-393.
(9) Stanton, J . L.; Ackerman, M. H. J . Med. Chem. 1983, 26, 986-
989.
(10) Reisch, J .; Salehi-Artimani, R. A. Montash. Chem. 1985, 116,
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1990, 121, 147-155.
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586.
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16, 949-951.
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1976, 30, 50-52.
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315, 901-912.
(22) Black, D. StC.; Ivory, A. J .; Keller, P. A. Synthesis 1988, 322-
323.
(23) Geissman, T. A. The Chemistry of Flavonoid Compounds;
Pergamon Press: Oxford, 1962.
(24) Harborne, J . B.; Mabry, T. J .; Mabry, H. The Flavonoids;
Chapman & Hall: London, 1975.
(25) Dean, F. M. Naturally Occurring Oxygen Ring Compounds;
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1989, 42, 1523-1525.
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J . Nat. Prod. 1994, 57, 42-51.
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Phytochemistry 1990, 29, 1103-1105.
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7601-7608.
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10.1021/jo010915b CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/22/2002

Synthesis of Pyrroloquinolines
Sch em e 1
J . Org. Chem., Vol. 67, No. 8, 2002 2465
Sch em e 3
Sch em e 2
7-acetylindole 10 in 65% yield, the 2-acetylindole 11 in
20% yield, and the 2,7-diacetylindole 12 in 8% yield
(Scheme 3).
Condensation of the 7-acetylindole 10 with a variety
of substituted benzaldehydes gave a range of new indol-
7-yl chalcones 13a -d , in yields of 58-95%. A similar
reaction with cinnamaldehyde gave the corresponding
diene analogue 13e (Scheme 4). The 2-acetylindole 11 and
2,7-diacetylindole 12 were also readily condensed with
benzaldehyde to produce the same products, 8 and 9, that
were obtained from the Friedel-Crafts acylation with
cinnamoyl chloride, but this time in almost quantitative
Resu lts a n d Discu ssion
1
yield (Scheme 3). The H NMR spectra of the cinnamoyl
Most flavonoid syntheses use the requisite chalcone
either as an immediate precursor or as an unisolated
intermediate en route to the cyclic flavonoids.23-25
It was therefore essential to obtain the indole ana-
logues of the chalcones, namely the 7-cinnamoylin-
doles. Such materials would provide a new synthetic
approach to the construction of 6-oxopyrroloquinolines
3 and also extend the chemistry of electron-rich indole
systems.
The 7-cinnamoylindole 5 has been prepared from 4,6-
dimethoxy-2,3-phenylindole 4 by direct Friedel-Crafts
acylation using cinnamoyl chloride and stannic chloride
in benzene (Scheme 1).38,39 Acetylation has been previ-
ously carried out on the 2,3-diphenylindole 4 either via
a modified Vilsmeier-Haack acetylation in 88% yield or
a Friedel-Crafts acylation in 50% yield.38 Acylation of
4,6-dimethoxy-3-phenylindole 737 with cinnamoyl chloride
and stannic chloride in toluene did not yield the desired
7-cinnamoylindole but instead gave the 2-cinnamoylin-
dole 8 and the 2,7-bis-(cinnamoyl)indole 9 in 10% yield
each (Scheme 2). The alternative aldol approach was
therefore investigated. Acetylation of indole 7 utilizing
N,N-dimethylacetamide and phosphoryl chloride gave the
compounds showed a characteristic set of AB doublets
ranging between 7.74 and 8.04 ppm for the olefinic
protons H3 and H2; the coupling constant was 16 Hz and
indicative of trans geometry.
F la von ols. The two most common methods for the
cyclization of the indole chalcones are the Rasoda reac-
tion, the base-catalyzed cyclization of chalcone dibro-
mides and bromohydrins,40,41 and the Algar-Flynn-
Oyamada reaction, the alkaline hydrogen peroxide
oxidation of the chalcone.42-45 Numerous other methods
exist and new ones continue to appear in the literature.46
The Rasoda method was not attempted since indole 4 is
susceptible to bromination at C2, so the latter was
chosen. The Algar-Flynn-Oyamada reaction is thought
to proceed via an epoxide intermediate, though this has
been the subject of debate for some time.42,44 Oyamada
initially proposed that the reaction proceeded via the
flavanone, which was then oxidized at a later stage to
the flavonol, in a fashion similar to the von Kostanecki
synthesis of flavonol.43 Algar and Flynn believed that
either an epoxide or a glycol was formed initially, and
this then underwent intramolecular cyclization to give
(40) Donnelly, J . A.; Fox, M. J .; Sharma, T. C. Tetrahedron 1979,
35, 1987-1991.
(41) Marathey, M. G. J . Org. Chem. 1955, 20, 563-571.
(42) Cummins, B.; Donnelly, D. M. X.; Eades, J . F.; Fletcher, H.;
O’Cinneide, F.; Philbin, E. M.; Swirski, J .; Wheeler, T. S.; Wilson, R.
K. Tetrahedron 1963, 19, 499-512.
(43) Oyamada, T. Bull. Chem. Soc. J pn. 1935, 10, 182-186.
(44) Dean, F. M.; Podimuang, V. J . Chem. Soc. 1965, 3978-3987.
(45) Geissman, T. A.; Fukushima, D. K. J . Am. Chem. Soc. 1948,
70, 1686-1689.
(46) Chawla, H. M.; Sharma, S. K. Tetrahedron 1990, 46, 1611-
1624.
(35) Black, D. StC.; Bowyer, M. C.; Bowyer, P. K.; Ivory, A. J .; Kim,
M.; Kumar, N.; McConnell, D. B.; Popiolek, M. Aust. J . Chem. 1994,
47, 1741-1750.
(36) Black, D. StC.; Craig, D. C.; Kumar, N.; Wong, L. C. H. J . Chem.
Soc., Chem. Commun. 1985, 1172-1173.
(37) Black, D. StC. J . Proc. R. Soc. New South Wales 1990, 123,
1-13.
(38) Black, D. StC.; Deb-Das, R. B.; Kumar, N. Aust. J . Chem. 1992,
45, 1051-1056.
(39) Black, D. StC.; Deb-Das, R. B.; Kumar, N. Aust. J . Chem. 1992,
45, 611-621.

2466 J . Org. Chem., Vol. 67, No. 8, 2002
Black et al.
Sch em e 4
the flavonol.42 Further investigations of the reaction by
Geissman and Fukushima45 revealed that the type of
product depended on the chalcone substrate. Certain
chalcones gave the flavonol, while others gave aurones,
otherwise known as benzal-coumarones, and in some
cases a mixture of both flavonol and aurone was obtained.
The product was found to be somewhat dependent on the
type and position of substituents on the 2-hydroxy
chalcone.42,45 These results gave more concrete evidence
for the existence of an epoxide intermediate, with fla-
vonols forming from attack upon the â-carbon of the
epoxide and aurones resulting from attack upon the
R-carbon of the epoxide. Interestingly, no trace of a
chalcone epoxide was ever isolated from these re-
actions.45 However, if the 2′-hydroxy group of chalcone
was replaced with a methoxy group, then the same
conditions readily yielded only the epoxide of the chal-
cone.47 More recently dimethyldioxirane has been used
to prepare a series of chalcone epoxides from a range of
chalcones.48,49 The C2 position of indole 7 was likely to
be susceptible to oxidation by both peracids and dimeth-
yldioxirane.50,51
Reaction of the chalcones 13a -d in aqueous tetrahy-
drofuran with saturated sodium hydroxide and 30%
hydrogen peroxide solution gave the corresponding ep-
oxides 14a -d in yields ranging from 54 to 94% (Scheme
4). Similarly, chalcone 5 yielded the epoxide 16, and the
2-cinnamoyl indole 8 gave the epoxide 17. Once isolated,
these epoxides were surprisingly stable, as were those
chalcone epoxides made by Patonay, Toth, and Adam.48
The 1H NMR spectra of these compounds showed a
downfield shift for the signals of H3 and H2, which
ranged between 3.32 and 4.5 ppm, with a coupling
constant of 2 Hz indicative of a trans-disubstituted
epoxide. However, the indol-7-yl chalcone epoxide 14a
underwent a facile ring-opening reaction in acidic metha-
nol to yield the methoxy alcohol 18.
Patonay, Toth, and Adam used a variety of bases such
as tetrabutylammonium hydroxide, triethylamine, and
(dimethylamino)pyridine to cyclize their epoxides to give
benzyl coumaranones and dihydroflavonols.48 The cy-
clization of these epoxides in base to give dihydroflavonols
provided good evidence that the Algar-Flynn-Oyamada
reaction does indeed proceed via the unisolated epoxide
to give dihydroflavonols and flavonols.
The indole epoxides 14a -d were cyclized with potas-
sium hydroxide in aqueous tetrahydrofuran yielding the
bright yellow indole flavonols or 6-oxopyrroloquinolines
15a -d in yields ranging from 54 to 82% (Scheme 4). In
contrast, the 2,3-diphenylindole-7-cinnamoyl epoxide 16
failed to give either the expected 6-oxopyrroloquinoline
product 19 or the isomeric aurone analogue 20 (Scheme
5). It is assumed that in this case the steric hindrance
resulting from the buttressing of the adjacent phenyl
groups prevents cyclization. Because of the steric inter-
ference, this example more than any other offered
encouragement for cyclization to be forced to proceed via
attack at the R-carbon rather than the â-carbon of the
epoxide to yield an aurone. However, this did not occur,
and consequently it is noteworthy that this general
cyclization reaction exclusively produces the flavonol
analogue rather than the aurone analogue, especially
(47) Bezuidenhoudt, B. C. B.; Brandt, E. V.; Roux, D. G. J . Chem.
Soc., Perkin Trans 1. 1981, 263-269.
(48) Patonay, T.; Toth, G.; Adam, W. Tetrahedron Lett. 1993, 34,
5055-5058.
(49) Baumstark, A. L.; Harden, D. B. J . Org. Chem. 1993, 58, 7615-
7618.
(50) Bourlot, A. S.; Desarbre, E.; Me´rour, J . Y. Synthesis 1994, 411-
416.
(51) Adam, W.; Ahrweiler, M.; Sauter, M.; Schmiedeskamp, B.
Tetrahedron Lett. 1993, 34, 5247-5250.

Synthesis of Pyrroloquinolines
Sch em e 5
J . Org. Chem., Vol. 67, No. 8, 2002 2467
probable that the hydroxyl group is strongly hydrogen
bonded to the adjacent carbonyl group, which appears
at around 1610 cm-1 in the IR spectra and is in most
1
cases too broad to be seen in either the H NMR or IR
spectra. The IR spectra of these compounds revealed a
very small absorption consistent with a hydroxyl group
of this nature. However, mass spectroscopy confirmed the
correct mass for these compounds and supported the
presence of the hydroxyl group.
The existence of the hydroxyl group at C5 was further
proven by the derivatization of the indole flavonol 15a
through acetylation with acetic anhydride to give the
unstable acetate 24, which although characterized by 1H
and 13C NMR spectroscopy and mass spectroscopy was
found to be susceptible to hydrolytic degradation over
time (Scheme 7). Like the true flavonols, the indole
flavonols display a bright orange phosphorescence under
long wave UV radiation. Acetylation of the hydroxyl
group at C5 cancels the contribution of the hydroxyl
group, altering the bright blue phosphorescence to a
brilliant blue. The acetylated indole flavonols thus dis-
play a phosphorescence similar to that found for the
indole flavones. A similar effect is observed in flavonols
when the equivalent hydroxyl group is acetylated.52
F la va n on es. Flavanones, the 2,3-dihydro derivatives
of flavones, form the central intermediates from which
most, if not all, other natural flavonoids originate.23 They
often occur with the corresponding flavones, but generally
in heartwoods, barks, roots, and to a lesser extent leaves
and petals, thus demonstrating the tendency for the
oxidation state of flavonoids to increase in the upper
extremities of a plant.24,25 Flavanones are isomeric with
chalcones, and the two species readily undergo inter-
conversion, with acid favoring ring closure and base
favoring chalcones.24,25 Most methods for the synthesis
of flavanones utilize either the cyclization of a chalc-
one53-55 or the hydrogenation of a flavone.56,57 Analogous
to these conversions, the base-catalyzed isomerization of
2-amino chalcones gives the corresponding tetrahydro-
4-quinolones.58
since the same substitution pattern of methoxy groups
on the simple chalcones favors aurone formation.42,45 It
would appear that in this case, attack at the â-carbon of
the epoxide is exclusively favored over attack at the
R-position. This outcome is not surprising when it is
considered that each of the possible products contains
three fused rings. However, the favored six-six-five-
membered ring flavone-analogue product would be sub-
stantially less strained than the alternative six-five-
five-membered ring aurone-analogue product. Further-
more, the indole-2-cinnamoyl epoxide 17 failed to produce
an indole pyrrolone 21 and instead yielded a mixture of
decomposition products (Scheme 5).
A more detailed mechanism for the cyclization of 14
to 15 presumably involves deprotonation of the indole
nitrogen of compound 14 followed by attack of the
nitrogen anion on the epoxide ring to give the anion of
the indole dihydroflavonol 22 (Scheme 6). The cyclization
then proceeds beyond the indole dihydroflavonol, possibly
via an enolized diketone 23 right through to the indole
flavonol 15. It is assumed that the dihydroflavonol 22
forms during the reaction but then undergoes oxidation
in the air to give the flavonol 15. The dependence of the
reaction on oxygen was demonstrated by experiments
showing that substantially shorter times were required
for reaction completion when air was bubbled through
the reaction mixture.
Indole chalcones readily undergo intermolecular Michael
addition,38,39,59-61 and intramolecular addition of the
indole anion should yield the indole flavanones. When
the two representative indole chalcones 13a and 13b
were further treated with sodium hydride in tetrahydro-
furan under reflux, the indole flavanones 25a and 25b
were formed respectively in moderate yield (Scheme 8).
These compounds 25a and 25b displayed a pale blue
phosphorescence under UV light, as do the simple fla-
vanones. The benzylidene compound 27 was further
prepared by base-catalyzed reaction of compound 25a
with benzaldehyde (Scheme 9). Similar benzylidene
It is interesting to note that the same conditions
required for the Algar-Flynn-Oyamada reaction when
applied to the indole chalcones 13 result only in epoxi-
dation and not cyclization. It is presumed that the NH
of the indole epoxide is less acidic than the OH of the
chalcone epoxides and therefore requires either a stron-
ger base or a longer reaction time to produce the anion.
Closer examination of the epoxidation reaction mixtures,
in which the reaction had been allowed to proceed for an
extended period, showed traces of the indole flavonol
product. This observation also supports the proposed
mechanism of the Algar-Flynn-Oyamada reaction.
There were significant aspects of the spectral data that
were characteristic for these compounds 15, most notably
(52) Mabry, T. J .; Markham, K. R.; Thomas, M. B. The Systematic
Identification of Flavonoids; Springer-Verlag: New York, 1970.
(53) von Kostanecki, St.; Lampe, V.; Tambor, J . Ber. Dtsch. Chem.
Ges. 1904, 37, 2803-2806.
(54) von Kostanecki, St.; Lampe, V.; Tambor, J . Ber. Dtsch. Chem.
Ges. 1904, 37, 1402-1404.
(55) Reichel, L.; Mu¨ller, K. Ber. Dtsch. Chem. Ges. 1941, 74, 1741-
1
the absence of an indole NH peak in both H NMR and
1742.
IR spectra, confirming that cyclization had indeed oc-
curred at this position. The epoxide proton and carbon
resonances were absent from both 1H and 13C NMR
spectra and a new proton peak at ∼6.60 ppm was
identified as the new H8 of the pyrroloquinoline. It was
difficult to assign unequivocally a signal for the hydroxyl
(56) Geissman, T. A.; Clinton, R. D. J . Am. Chem. Soc. 1946, 68,
697-700.
(57) Geissman, T. A.; Lischner, H. J . Am. Chem. Soc. 1952, 74,
3001-3004.
(58) Mannich, C.; Dannehl, M. Ber. Dtsch. Chem. Ges. 1938, 71,
1899-1901.
(59) Kohler, E. P. J . Am. Chem. Soc. 1916, 38, 889-900.
(60) Davey, W.; Tivey, D. J . J . Chem. Soc. 1958, 2276-2282.
(61) Ono, N.; Kamimura, A.; Kaji, A. Synthesis 1984, 226-227.
1
proton at C5 in either the H NMR or IR spectra. It is

2468 J . Org. Chem., Vol. 67, No. 8, 2002
Black et al.
Sch em e 6
Sch em e 7
for H4 and H5: compound 25b showed an ABX pattern,
but the accidental equivalence of the 5-protons in com-
pound 25a led to a simple AB system.
F la von es. Flavones, particularly those substituted
with methoxy groups, are widespead among plants.24
Their biochemical role is unclear, but it has been sug-
gested to be that of a natural fungicide.64 They can be
synthesized by cyclization of dibromo chalcones65,66 or
â-diketones,67,68 or by the oxidation of flavanones with
selenium dioxide23 or their dehydrogenation using pal-
ladium in n-octadecanol.70 Previous synthesis of 6-oxo-
pyrroloquinolines was effected by the acid-catalyzed
cyclization of indole â-diketones.22 However, given the
availability of the indole flavanones 25a and 25b, dicy-
anodichloroquinone (DDQ) was used to oxidize them to
the indole flavones 26a and 26b although in yields of only
16-25% (Scheme 8). These compounds showed less
complex 1H NMR spectra, with H5 appearing as a singlet
in the region 6.40-6.60 ppm. Under UV light, these
compounds displayed a brilliant blue phosphorescence,
similar to that displayed by the flavones, but more
intense than that displayed by the flavanones and their
indole analogues.
Sch em e 8
Com p a r ison of UV Sp ectr a of P yr r oloqu in olin es
a n d Th eir Rela ted F la von oid s. The UV spectrum of
the unsubstituted indole nucleus contains a peak at 216
nm (assigned as â-bands) and a wide absorption between
260 and 290 nm (assigned as 260 nm for the F-bands and
287 nm for the R-bands).71 That of 4,6-dimethoxy-3-
phenylindole 7 shows similar absorptions which display
(62) Sathyanarayana, S.; Krishnamurty, H. G. Ind. J . Chem. 1988,
Sch em e 9
27B, 889-901.
(63) Srikanth, N.; Kon, O.-L.; Ng, S.-C.; Sim, K.-Y. J . Chem. Res.
1997, 202-203.
(64) Ben-Aziz, A. Science 1967, 155, 1026-1027.
(65) Emilewicz, T.; von Kostanecki, St. Ber. Dtsch. Chem. Ges. 1898,
31, 696-705.
(66) Donnelly, J . A.; Doran, H. J . Tetrahedron Lett. 1974, 47, 4083-
4084.
(67) Spatz, S. M.; Koral, M. J . Org. Chem. 1959, 24, 1381-1382.
(68) Mahal, H. S.; Rai, H. S.; Venkataraman, K. J . Chem. Soc. 1935,
58, 866-868.
(69) Massicot, J . C. R. Compt. Rend. Acad. Sci. Paris 1955, 240, 94-
96.
compounds have been made from flavanones and chro-
mones through either acid- or base initiated-condensa-
(70) Geissman, T. A.; Clinton, R. D. J . Am. Chem. Soc. 1946, 68,
700-706.
(71) Remers, W. A. in The Chemistry of Heterocyclic Compounds,
Indoles; Houlihan, W. J ., Ed.; J ohn Wiley and Sons: New York, 1972;
Part 1.
1
tions with benzaldehydes.62,63 The H NMR spectra for
compounds 25 showed characteristic splitting patterns

Synthesis of Pyrroloquinolines
J . Org. Chem., Vol. 67, No. 8, 2002 2469
F igu r e 1. Comparison of UV spectra of 4′,6′-dimethoxy-2′-
hydroxy chalcone with its indole chalcone analogue 13a .
F igu r e 3. Comparison of UV spectra of 5,7-dimethoxy-2-
phenylflavone with its indole flavone analogue 26a .
F igu r e 2. Comparison of UV spectra of 5,7-dimethoxy-2-
phenylflavanone with its indole flavanone analogue 25a .
F igu r e 4. Comparison of UV spectra of 5,7-dimethoxy-2-
phenylflavonol with its indole flavonol analogue 15a .
a slight bathochromic shift in all bands. The addition of
further conjugation provided by the acetyl group in-
creases the shift of these bands in the spectrum of
compound 10.71 The UV spectra of flavonoids show two
distinct band regions corresponding to the cinnamoyl
component (Band I, 300-380 nm) and the phenolic
component (Band II, 240-280 nm).23,24,72
Ch a lcon es. Polyhydroxy chalcones absorb strongly in
Band I and less strongly in the Band II region, with
further hydroxy or methoxy substitution resulting in a
bathochromic shift in the relevant band of the affected
chromophore.
The UV spectrum of the indole chalcone 13a possesses
little similarity with that of the phenol analogue 4′,6′-
dimethoxy-2′-hydroxy chalcone, extending further into
the visible region and containing many more absorp-
tion maxima. The maximum at 397 nm, most probably
due to the cinnamoyl chromophore and related to Band
I, has experienced a bathochromic shift of some 57 nm
from that of the parent chalcone, possibly because of the
increase in conjugation arising from the indole nucleus
(Figure 1).
F la va n on es. Flavanones do not show the conjugation
between the B ring and the carbonyl group so absorb at
comparatively shorter wavelengths. The major absor-
bance appears for Band II in the 270-290 nm region and
Band I generally appears as a low intensity inflection
between 320 and 330 nm. The spectrum of the indole
flavanone 25a contained two strong maxima at 258 and
353 nm, unlike that of its flavanone analogue (Figure 2),
and showed more in common with the spectrum of the
7-acetyl indole 10.
F la von es a n d F la von ols. Flavones and flavonols
generally exhibit high-intensity Band II maxima between
240 and 270 nm and Band I maxima between 320 and
380 nm. The position of Band I becomes important in
distinguishing between flavones and flavonols. Band I
appears for flavones between 304 and 350 nm and for
flavonols between 352 and 385 nm, the bathochromic
shift being attributed to the effect of the hydroxyl group
at position-3.23,24 The spectrum of the indole flavone
26a contained a maximum at 340 nm assigned as the
Band I equivalent and bathochromically shifted by ap-
proximately 34 nm from that of the simple flavone
analogue (Figure 3). The spectrum of the indole flavonol
15a , showed the greatest similarity with that of its
flavonoid analogue. Apart from a maximum at 243 nm
attributed to the indole nucleus, there were two maxima
at 317 and 356 nm of similar shape and position to Band
I of the simple flavonol, the spectrum of which gave
maxima at 261 nm for Band II and at 349 nm for Band
I. At the base of the Band I equivalent, an inflection
extended further into the visible region, as a consequence
of other conjugation within the pyrroloquinoline ring
(Figure 4).
Clearly there are certain similarities between the
indole flavonoid analogues or pyrroloquinolines and the
flavonoids themselves. These similarities are attributed
to the presence of the cinnamyol component common to
both species and evident as long as the conjugation
associated with this component remains intact. These
comparisons are dependent upon the cinnamoyl compo-
nent being part of a ring system, and the similarity
increases with the increase in the oxidation state of this
moiety. This is most noticeable in the comparison of the
indole flavonols with the simple flavonols.
(72) Black, D. StC.; Craig, D. C.; Kumar, N.; Ivory, A. J . J . Chem.
Soc., Chem. Commun. 1989, 111-112.

2470 J . Org. Chem., Vol. 67, No. 8, 2002
Black et al.
under an atmosphere of N2. The reaction mixture was quenched
with ice-water, made strongly basic with 5 M sodium hydrox-
ide and stirred for a further 8 h. The resultant precipitate was
filtered, washed with water, and dried. The crude product was
purified via flash column chromatography (4:1 of dichlo-
romethane/petroleum ether) and afforded three products.
(i) 1-(4,6-Dim eth oxy-3-p h en ylin d ol-7-yl)eth a n on e (10).
Colorless prisms (1.88 g, 65%) mp 179-181 °C (from dichlo-
Con clu sion s
The replacement of phenols by suitably activated
indoles enables the adaptation of flavonoid syntheses to
generate a new range of pyrroloquinolines, which serve
as indole analogues of flavonoids. While similar synthetic
approaches can be used, there are some significant
differences in the regiochemistry involved and also in the
stability of some intermediates. A consideration of UV
spectra also highlights similarities and differences in the
two systems.
1
romethane/petroleum ether). H NMR (CDCl3) δ 2.74 (s, 3H),
3.93 (s, 3H), 4.03 (s, 3H), 6.25 (s, 1H), 7.15 (d, J 2.6 Hz, 1H),
7.29-7.65 (m, 5H), 11.12 (br s, 1H); 13C NMR (CDCl3) 33.21,
55.17, 56.14, 87.20, 104.77, 110.37, 118.37, 121.71, 125.79,
127.60, 129.48, 135.77, 139.05, 159.57, 161.00, 198.63; IR 3340
(m), 1620 (m); UV 225 (18000), 250 (22100), 259 (16000), 329
Exp er im en ta l Section
(11500), 351 (9700); MS 295 (M+, 100). Anal. Calcd for C18H17
-
1
Gen er a l In for m a tion . H NMR spectra were recorded at
NO3 (295): C, 73.2; H, 5.8; N, 4.7. Found: C, 73.0; H, 5.9; N,
4.7.
300 MHz or at 500 MHz and refer to deuteriochloroform
solutions with chloroform (7.26 ppm) as an internal standard.
Signals due to exchangeable protons (NH) were identified by
exchange with deuterium oxide. 13C NMR spectra were re-
corded at 125.77 MHz and refer to deuteriochloroform solutions
with chloroform (77.0 ppm) as an internal standard. Low
resolution mass spectra were obtained at 70 eV and 8000 V
accelerating potential at 210 °C ion source temperature.
Infrared spectra refer to paraffin mulls or KBr disks of solids.
Ultraviolet spectra refer to solutions in absolute methanol.
Microanalyses were performed by Dr. H. P. Pham of the
UNSW Microanalytical Unit. Flash column chromatography
was carried out using Merck silica gel 7736 60H, while thin-
layer chromatography was performed on 3 mm plates using
(ii) 1-(4,6-Dim eth oxy-3-p h en ylin d ol-2-yl)eth a n on e (11).
Colorless prisms (0.58 g, 20%) mp 202-204 °C (from dichlo-
romethane/petroleum ether). 1H NMR (CDCl3) δ, 2.01 (s, 3H),
3.61 (s, 3H), 3.88 (s, 3H), 6.12 (d, J 2.0 Hz, 1H), 6.44 (d, J 2.0
Hz, 1H), 7.40-7.44 (m, 5H), 9.23 (br s, 1H); 13C NMR (CDCl3)
δ 27.96, 55.18, 56.60, 85.66, 93.02, 113.80, 115.00, 125.40,
127.46, 130.55, 131.09, 136.78, 137.90, 157.00, 161.03, 190.39;
IR 3320 (m), 1630 (m); UV 257 (20300), 332 (19500); MS 295
(M+, 100). Anal. Calcd for C18H17NO3 (295): C, 73.2; H, 5.8;
N, 4.7. Found: C, 72.9; H, 6.0; N, 4.7.
(iii) 1-(2-Acetyl-4,6-d im eth oxy-3-p h en ylin d ol-7-yl)eth a -
n on e (12). Colorless prisms (0.26 g, 8%) mp 216-218 °C (from
dichloromethane/petroleum ether). 1H NMR (CDCl3) δ 1.92 (s,
3H), 2.62 (s, 3H), 3.64 (s, 3H), 3.96 (s, 3H), 6.07 (s, 1H), 7.36
(m, 5H), 11.29 (br s, 1H); 13C NMR (CDCl3) δ 28.14, 33.07,
55.29, 56.15, 87.52, 104.35, 113.43, 124.08, 127.37, 127.45,
130.41, 131.90, 135.45, 137.88, 161.41, 163.46, 189.91, 197.64;
IR 3430 (m), 1655 (m); UV 210 (21380), 241 (19750), 305
Merck silica gel 7730 60GF254
.
Syn t h esis of In d ole Ch a lcon es via F r ied el-Cr a ft s
Acetyla tion . A solution of stannic chloride (1.13 g, 4.33 mmol)
in anhydrous toluene (5 mL) was added dropwise with stirring
into a solution of 4,6-dimethoxy-3-phenylindole 7 (0.88 g, 3.5
mmol) and cinnamoyl chloride (0.64 g, 3.8 mmol) in anhydrous
toluene (25 mL) at 0 °C. The mixture was brought to room
temperature and allowed to stir for 30 h. Ice-water was added,
and the mixture was stirred at room temperature for 1 h,
producing an insoluble precipitate. When made strongly
alkaline with 10% sodium hydroxide solution, this formed an
orange solution, which was extracted with dichloromethane
and dried and the solvent reduced. The resultant orange solid
was then purified via column chromatography (ethyl acetate/
petroleum ether 30:70), and afforded two products.
(i) 1-(4,6-Dim eth oxy-3-p h en ylin d ol-2-yl)-3-p h en ylp r op -
2-en -1-on e (8). Orange prisms (0.13 g, 10%), mp 244-245 °C
(dichloromethane/petroleum ether). 1H NMR (CDCl3) δ 3.63
(s, 3H), 3.87 (s, 3H), 6.12 (d, J 1.5 Hz, 1H), 6.48 (d, J 1.5 Hz,
1H), 6.63 (d, J 15.9 Hz, 1H), 7.05-7.53 (m, 10H), 7.64 (d, J
15.4 Hz, 1H), 9.58 (br s, 1H); 13C NMR (CDCl3) δ 55.18, 55.58,
85.75, 93.08, 113.75, 124.0, 125.48, 127.34, 127.42, 128.15,
128.63, 129.87, 131.41, 132.30, 135.08, 135.86, 138.50, 140.74,
157.02, 161.17, 181.31; IR 3280 (br m), 1620 (m); UV 232
(18000), 279 (12000), 330 (11000), 407 (17000); MS 383 (M+,
100). Anal. Calcd for C25H21NO3 (383): C, 78.3; H, 5.8; N, 3.6.
Found: C, 78.3; H, 5.5; N, 3.7.
(ii) 1-(4,6-Dim et h oxy-(7-(3-p h en ylp r op -2-en -1-on e-3-
p h en ylin d ol-2-yl))-3-p h en yl-p r op -2-en -1-on e (9). Yellow
powder (0.17 g, 10%), mp 217-219 °C (dichloromethane/
petroleum ether). 1H NMR (CDCl3) δ 3.75 (s, 3H), 4.07 (s, 3H),
6.17 (s, 1H), 6.57 (d, J 15.9 Hz, 1H), 7.04-7.63 (m, 15H), 7.63
(d, J 15.4 Hz, 1H), 7.80 (d, J 15.4 Hz, 1H), 7.93 (d, J 15.4 Hz,
1H), 11.54 (br s, 1H); 13C NMR (CDCl3) δ 55.39, 56.66, 88.12,
105.13, 113.67, 123.97, 127.50, 128.04, 128.12, 128.55, 128.77,
129.63, 131.30, 132.24, 135.05, 135.51, 135.89, 138.87, 140.95,
141.0, 161.60, 163.17, 181.23, 188.77; IR 3400 (m), 1640 (m);
UV 222 (18200), 321 (14000), 370 (22200); MS 515 (M+, 14).
Anal. Calcd for C34H27NO4 (515): C, 79.5; H, 5.3; N, 2.7.
Found: C, 79.9; H, 5.5; N, 2.7.
(14100), 344 (24750); MS 337 (M+, 100). Anal. Calcd for C20H19
-
NO4 (337): C, 71.2; H, 5.7; N, 4.2. Found: C, 71.1; H, 5.9; N,
4.1.
Gen er a l Meth od for Ald ol Con d en sa tion of Acetyla ted
In d oles w ith Ar om a tic Ald eh yd es. 1-(4,6-Dim eth oxy-3-
p h en ylin d ol-7-yl)-3-p h en yl-2-p r op en -1-on e (13a ). Acetyl
indole 10 (0.83 g, 2.82 mmol) was added to a suspension of
sodium amide (0.65 g, 16.6 mmol) in anhydrous tetrahydro-
furan (30 mL). The mixture was allowed to stir for 5 min,
benzaldehyde (2 mL, 19.8 mmol) was added dropwise to the
resulting suspension, and the mixture was stirred for a further
30min. Ice-water was then added, followed by ammonium
chloride solution. The resulting yellow precipitate was filtered,
washed with water and petroleum ether, dried, and recrystal-
lized (dichloromethane/petroleum ether) to afford the indole
1
chalcone as a yellow powder (1.0 g, 92%), mp 169-171 °C. H
NMR (CDCl3) δ 3.93 (s, 3H), 4.14 (s, 3H), 6.28 (s, 1H), 7.14 (d,
J 2.0 Hz, 1H), 7.26-7.67 (m, 10H), 7.78 (d J 15.4 Hz, 1H),
8.04 (d J 15.9 Hz, 1H), 11.16 (br s, 1H); 13C NMR (CDCl3) δ
55.26, 56.82, 87.96, 105.48, 110.74, 118.61, 121.87, 125.83,
127.61, 128.15, 128.47, 128.76, 129.47, 129.55, 135.7, 135.99,
139.58, 140.6, 159.82, 160.77, 189.45; IR 3480 (w), 1630 (m),
1590 (s), 1570 (s); UV 228 (30000), 280 (20000), 300 (17400),
343 (11300), 397 (10500); MS 383 (M+, 27). Anal. Calcd for
C
25H21NO3 (383): C, 78.3; H, 5.5; N, 3.7. Found: C, 78.0; H,
5.8; N, 3.6.
1-(4,6-Dim et h oxy-3-p h en ylin d ol-7-yl)-3-(3,4-d im et h -
oxyp h en yl)-p r op -2-en -1-on e (13b). This compound was
prepared as described for the indole chalcone 13a from indole
10 (0.348 g, 1.18 mmol), sodium amide (0.40 g, 11.6 mmol),
and veratraldehyde (0.23 g, 1.42 mmol) in anhydrous tetrahy-
drofuran (20 mL), except that the suspension was heated to
50 °C for 20 min. The indole chalcone 13b was collected and
recrystallized (dichloromethane/petroleum ether) as a yellow
powder (0.491 g, 94%), mp 218-220 °C. 1H NMR (CDCl3) δ
3.93 (s, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 4.07, (s, 3H), 6.98 (s,
1H), 7.18 (d, J 2.1 Hz, 1H), 6.89-7.61 (m, 8H), 7.74 (d, J 15.3
Hz, 1H), 7.93 (d, J 15.4 Hz, 1H), 11.15 (br s, 1H); 13C NMR
(CDCl3) δ 55.29, 55.88, 55.99, 56.95, 88.20, 105.75, 110.38,
111.19, 116.6, 121.92, 122.27, 125.85, 126.53, 127.63, 129.09,
Acetyla tion of 4,6-Dim eth oxy-3-p h en ylin d ole (7). Phos-
phoryl chloride (10.52 g, 68.6 mmol) was added slowly to a
stirred ice-cold solution of indole 7 (2.48 g, 9.8 mmol) in dry
N,N-dimethylacetamide (10 mL). The solution was allowed to
warm to room temperature and then heated to 55 °C for 22 h

Synthesis of Pyrroloquinolines
J . Org. Chem., Vol. 67, No. 8, 2002 2471
129.49, 139.63, 140.87, 149.12, 150.68, 159.68, 160.00, 160.59,
160.60, 193.59; IR 3360 (m), 1630 (m); UV 228 (6310), 266
(4170), 353 (4060), 396 (3380); MS 443 (M+, 20). Anal. Calcd
for C27H25NO5 (443): C, 73.1; H, 5.7; N, 3.2. Found: C, 73.0;
H, 6.0; N, 3.0.
pound was prepared as described for the indole chalcone 13a
from indole 12 (0.26 g, 0.5 mmol), sodium amide (0.08 g, 2.0
mmol), and benzaldehyde (0.5 mL, 4.95 mmol) in anhydrous
tetrahydrofuran (20 mL). This gave the indole chalcone 9
which was collected and recrystallized (dichloromethane/
petroleum ether) as a yellow powder (0.26 g, 99%) and shown
to be identical with an authentic sample (see above).
1-(4,6-Dim et h oxy-3-p h en ylin d ol-7-yl)-3-(4-m et h oxy-
p h en yl)-p r op -2-en -1-on e (13c). This compound was pre-
pared as described for the indole chalcone 13b from indole 10
(0.22 g, 0.73 mmol), sodium amide (0.28 g, 7.2 mmol), and
anisaldehyde (1 mL, 19.8 mmol) in anhydrous tetrahydrofuran
(25 mL). The indole chalcone 13c was collected and recrystal-
lized (dichloromethane/petroleum ether) as a yellow powder
(0.29 g, 95%), mp 204-206 °C. 1H NMR (CDCl3) δ 3.86 (s, 3H),
3.92 (s, 3H), 4.07 (s, 3H), 6.28 (s, 1H), 6.93 (d, J 8.7 Hz, 2H),
7.58 (d, J 8.7 Hz, 2H), 7.14 (d, J 2.6 Hz, 1H), 7.24-7.62 (m,
5H), 7.74 (d, J 15.4 Hz, 1H), 7.93 (d, J 15.9 Hz, 1H), 11.15 (br
s, 1H); 13C NMR (CDCl3) δ 55.23, 55.31, 56.90, 88.12, 105.82,
110.79, 114.24, 118.53, 121.81, 125.78, 126.16, 127.58, 128.72,
129.44, 129.77, 135.75, 139.58, 140.63, 159.58, 160.58, 160.93,
189.50; IR 3320 (br m), 1620 (m); UV 235 (9930), 273 (9250),
340 (10800), 397 (8980); MS 413 (M+, 71). Anal. Calcd for
Gen er a l Meth od for Ep oxid a tion of In d ole Ch a lcon es.
1-(4,6-D im e t h o x y -3-p h e n y lin d o l-7-y l)-3-p h e n y l-2,3-
ep oxyp r op a n -1-on e (14a ). Indole chalcone 13a (0.69 g, 1.8
mmol) was dissolved in aqueous tetrahydrofuran (30 mL) to
which saturated sodium hydroxide solution (10 mL) was added
and the mixture allowed to stir at room temperature for 5 min.
Hydrogen peroxide solution (15 mL, 30%) was added dropwise
and the mixture allowed to stir for a further 6-8h. Water was
added, and the resulting pale yellow precipitate was filtered,
washed, and dried. After flash chromatography (dichlo-
romethane) and recrystallization (dichloromethane/petroleum
ether), the indole chalcone epoxide 14a (0.59 g, 82%) was
obtained as a pale yellow powder mp 217-219 °C. 1H NMR
(CDCl3) δ 3.60 (s, 3H), 3.90 (s, 3H), 4.0 (d, J 2.0 Hz, 1H), 4.49
(d, J 2.0 Hz, 1H), 6.15 (s, 1H), 7.13 (d, J 2.6 Hz, 1H), 7.26-
7.59 (m, 10H), 10.9 (br s, 1H); 13C NMR (CDCl3) δ 55.39, 56.23,
59.06, 65.26, 87.96, 103.16, 110.63, 118.85, 122.03, 125.83,
126.05, 127.72, 128.55, 129.52, 135.48, 137.02, 138.77, 160.74,
161.57, 192.09; IR 3400 (br m), 1630 (s); UV 255 (32320), 337
C
26H36NO4 (413): C, 75.5; H, 5.6; N, 3.4. Found: C, 75.7; H,
5.9; N, 3.3.
1-(4,6-Dim e t h oxy-3-p h e n ylin d ol-7-yl))-3-(4-ch lor o-
p h en yl)-p r op -2-en -1-on e (13d ). This compound was pre-
pared as described for the indole chalcone 13a from indole 10
(0.34 g, 1.16 mmol), sodium amide (0.32 g, 8.1 mmol), and
p-chlorobenzaldehyde (0.2 g, 1.4 mmol) in anhydrous tetrahy-
drofuran (30 mL), and the mixture was stirred at room
temperature for 45 min. The indole chalcone 13d was collected
and recrystallized (dichloromethane/petroleum ether) as a
yellow powder (0.28 g, 58%), mp 213-215 °C. 1H NMR (CDCl3)
δ 3.94 (s, 3H), 4.07 (s, 3H), 6.28 (s, 1H), 7.14 (d, J 2.6 Hz, 1H),
7.29-7.62 (m, 9H), 7.70 (d, J 15.9 Hz, 1H), 8.99 (d, J 15.4 Hz,
1H), 11.14 (br s, 1H); 13C NMR (CDCl3) δ 55.29, 56.85, 87.88,
105.6, 110.76, 118.69, 121.9, 125.89, 127.64, 128.99, 129.04,
129.28, 129.47, 134.54, 135.29, 135.64, 139.12, 139.55, 160.01,
160.82, 189.13; IR 3400 (br m), 1640 (m); UV 230 (26100), 284
(19500), 297 (18700), 307 (17700); HRMS calcd for C25H20NO3-
Cl 417.1132, found 417.1100 (35Cl).
(28120), 358 (1250); MS 399 (M+, 34). Anal. Calcd for C25H21
-
NO4 (399): C, 75.5; H, 5.6; N, 3.5. Found: C, 75.2; H, 5.3; N,
3.5.
1-(4,6-Dim et h oxy-3-p h en ylin d ol-7-yl)-3-(3,4-d im et h -
oxyp h en yl)-2,3-ep oxyp r op en -1-on e (14b). This compound
was prepared as described for the indole chalcone epoxide 14a
from indole chalcone 13b (0.12 g, 0.27 mmol), saturated sodium
hydroxide solution (5 mL), and hydrogen peroxide solution (15
mL, 30%) in anhydrous tetrahydrofuran (20 mL). After flash
column chromatography (dichloromethane) and recrystalliza-
tion (dichloromethane/petroleum ether), the indole chalcone
epoxide 14b was obtained as a pale yellow powder (0.11 g,
86%), mp 218-220 °C. 1H NMR (CDCl3) δ 3.66 (s, 6H), 3.90
(s, 3H), 3.91 (s, 3H), 3.96 (d, J 2.1 Hz, 1H), 4.49 (d, J 2.1 Hz,
1H), 6.17 (s, 1H), 6.90 (d, J 2.1 Hz, 1H), 6.88-7.59 (m, 9H),
10.89 (br s, 1H); 13C NMR (CDCl3) δ 55.34, 55.96, 56.31, 59.09,
59.09, 65.13, 86.99, 103.46, 108.23, 110.68, 111.03, 118.8,
121.98, 125.99, 127.64, 129.47, 135.43, 138.82, 149.26, 149.34,
1-(4,6-Dim et h oxy-3-p h en ylin d ol-7-yl)-3-p h en ylp en t a -
2,4-d ien -1-on e (13e). This compound was prepared as de-
scribed for the indole chalcone 13a from indole 10 (0.29 g, 0.98
mmol), sodium amide (0.10 g, 2.45 mmol) and cinnamaldehyde
(0.2 mL, 2.45 mmol) in anhydrous tetrahydrofuran (30 mL),
and the mixture was stirred at room temperature for 1 h. The
indole chalcone 13e after chromatography (dichloromethane)
was collected and recrystallized (dichloromethane/petroleum
ether) as a yellow crystalline powder (0.34 g, 85%), mp 226-
160.66, 161.47, 192.09; MS 459 (M+, 47). Anal. Calcd for C26H25
-
NO6‚1/2H2O (468): C, 69.3; H, 5.5; N, 3.0. Found: C, 69.4; H,
5.5; N, 2.8.
(1-(4,6-Dim et h oxy-3-p h en ylin d ol-7-yl)-3-(4-m et h oxy-
p h en yl)-2,3-ep oxyp r op a n -1-on e (14c). This compound was
prepared as described for the indole chalcone epoxide 14a from
indole chalcone 13c (0.249 g, 0.60 mmol), saturated sodium
hydroxide solution (5 mL), and hydrogen peroxide solution (10
mL, 30%) in anhydrous tetrahydrofuran (20 mL). After flash
column chromatography (dichloromethane) and recrystalliza-
tion (dichloromethane/petroleum ether), the indole chalcone
epoxide 14c (0.14 g, 54%) was obtained as a pale yellow powder
1
228 °C. H NMR (CDCl3) δ 3.93 (s, 3H), 4.06 (s, 3H), 6.27 (s,
1H), 7.00 (s, 1H), 7.03-7.61 (m, 14H), 11.15 (br s, 1H); 13C
NMR (CDCl3) δ 55.32, 56.82, 88.03, 105.57, 110.80, 118.64,
121.91, 125.87, 127.09, 127.65, 128.01, 128.71, 128.79, 129.52,
132.00, 135.79, 136.69, 139.64. 139.75, 141.29, 159.77, 160.69,
189.42; IR 3310 (br m), 1610 (w); UV 235 (14000), 278 (9700),
345 (16000); HRMS calcd for C27H22NO3 409.1678, found
409.1621.
1
mp 223-225 °C. H NMR (CDCl3) δ 3.65 (s, 3H), 3.84 (s,3H),
1-(4,6-Dim et h oxy-2,3-d ip h en ylin d ol-7-yl)-3-p h en yl-2-
p r op en -1-on e (5).38 This compound was prepared as described
for the indole chalcone 13a from indole 6 (0.03 g, 0.10 mmol),
sodium amide (0.04 g, 1.0 mmol), and benzaldehyde (0.1 mL,
0.10 mmol) in anhydrous tetrahydrofuran (15 mL). Chalcone
5 was collected and recrystallized (dichloromethane/petroleum
ether) (0.04 g, 90%), mp 195-197 °C, and shown to be identical
with an authentic sample.38
1-(4,6-Dim et h oxy-3-p h en ylin d ol-2-yl)-3-p h en yl-2-p r o-
p en -1-on e (8). This compound was prepared as described for
the indole chalcone 13a from indole 11 (0.41 g, 1.4 mmol),
sodium amide (0.22 g, 5.5 mmol), and benzaldehyde (0.5 mL,
5 mmol) in anhydrous tetrahydrofuran (20 mL). The indole
chalcone 8 was collected and recrystallized (dichloromethane/
petroleum ether) as a yellow powder (0.52 g, 97%) and shown
to be identical with an authentic sample (see above).
1-(4,6-D im e t h o x y -(7-(3-p h e n y l)-2-p r o p e n -1-o n e -3-
p h en ylin d ol-2-yl))-3-p h en yl-2-p r op en -1-on e (9). This com-
3.90 (s, 3H), 3.94 (d J 2.0 Hz, 1H), 4.51 (d J 2.0 Hz, 1H), 6.16
(s, 1H), 6.93 (d, J 8.7 Hz, 2H), 7.57 (d, J 8.7 Hz, 2H), 7.13 (d,
J 2.1 Hz, 1H), 7.28-7.40 (m, 5H), 10.89 (br s, 1H); 13C NMR
(CDCl3) δ 55.31, 55.32, 56.28, 58.95, 65.02, 86.99, 103.46,
110.60, 113.94, 118.77, 121.98, 125.976, 127.21, 127.64, 128.9,
129.47, 135.46, 138.72, 159.9, 160.61, 161.47, 192.28; IR 3320
(br m), 1630 (m); UV 223 (28670), 255 (29410), 335 (13250),
352 (12180); MS 429 (M+, 27). Anal. Calcd for C26H23NO5
(429): C, 72.7; H, 5.4; N, 3.3. Found: C, 72.5; H, 5.7; N, 3.1.
1-(4,6-D im e t h o x y -3-p h e n y lin d o l-7-y l)-3-(4-c h lo r o -
p h en yl)-2,3-ep oxyp r op a n -1-on e (14d ). This compound was
prepared as described for the indole chalcone epoxide 14a from
indole chalcone 13d (0.11 g, 0.27 mmol), saturated sodium
hydroxide solution (5 mL), and hydrogen peroxide solution (10
mL, 30%) in anhydrous tetrahydrofuran (20 mL). After flash
column chromatography (dichloromethane) and recrystalliza-
tion (dichloromethane/petroleum ether), the indole chalcone
epoxide 14d was obtained as a pale yellow powder (0.08 g,

2472 J . Org. Chem., Vol. 67, No. 8, 2002
Black et al.
68%), mp 249-251 °C. 1H NMR (CDCl3) δ 3.65 (s, 3H), 3.91
(s, 3H), 3.97 (d, J 2.0 Hz, 1H), 4.44 (d, J 2.0 Hz, 1H), 6.16 (s,
1H), 7.14 (d, J 2.1 Hz, 1H), 7.28-7.59 (m, 9H), 10.88 (br s,
1H); 13C NMR (CDCl3) δ 55.42, 56.31, 58.36, 65.18, 86.93,
103.38, 110.5, 112.06, 118.88, 126.07, 127.18, 127.72, 128.79,
129.50, 134.35, 135.43, 135.67, 138.74, 160.84, 161.52, 191.63;
IR 3320 (br s), 1640 (s); UV 220 (14900), 255 (15100), 337
(7200), 364 (6400); MS 433.1100 (M+, 35Cl, 25). Calcd for
15a was obtained as a yellow powder (0.14 g, 82%), mp 250
1
°C. H NMR (CDCl3) δ 4.02 (s, 3H), 4.19 (s, 3H), 6.55 (s, 1H),
7.18 (s, 1H), 7.29-7.69 (m, 10H); 13C NMR (CDCl3) δ 55.87,
56.79, 90.70, 103.98, 108.04, 120.23, 123.97, 125.20, 127.12,
128.01, 128.82, 129.06, 129.54, 129.69, 130.32, 133.43, 133.79,
141.34, 160.42, 162.10, 170.63; IR 3400 (br w), 3340 (w), 1610
(s); UV 244 (33300), 317 (9900), 356 (14700), 378 (11300); MS
(electrospray) 398 (M+, 100). Anal. Calcd for C25H19NO4 (398)
C, 75.6; H, 4.8; N, 3.5. Found: C, 75.2; H, 5.1; N, 3.4.
C
25H20ClNO4 433.1081. Anal. Calcd for C25H20ClNO4‚1/2H2O:
C, 67.8; H, 4.8; N, 3.2. Found: C, 67.4; H, 5.0; N, 3.1.
7,9-Dim eth oxy-4-(3,4-d im eth oxyp h en yl)-5-h yd r oxy-1-
ph en yl-6-oxo-6H-pyr r olo[3,2,1-ij]qu in olin e (15b). This was
prepared as described for the pyrroloquinoline 15a from indole
epoxide 14b (0.11 g, 0.24 mmol) and aqueous tetrahydrofuran
(15 mL) to which were added saturated potassium hydroxide
solution (3 mL) and solid potassium hydroxide (0.3 g, 5.3
mmol). After flash column chromatography (97:3 of dichlo-
romethane/methanol) and recrystallization (dichloromethane/
petroleum ether), the indole flavonol 15b was obtained as a
yellow powder (0.07 g, 60%), mp 298 °C. 1H NMR (CDCl3) δ
3.92 (s, 3H), 3.96 (s, 3H), 4.02 (br s, 3H), 4.17 (br s, 3H), 6.55
(br s, 1H), 7.02-7.61 (m, 9H); 13C NMR (CDCl3) δ 55.85, 56.01,
56.15, 56.77, 90.73, 103.81, 108.12, 111.25, 113.30, 120.28,
121.81, 123.19, 125.21, 127.10, 128.02, 129.04, 133.41, 133.81,
141.30, 149.10, 150.09, 160.42, 162.06, 170.58; IR 3200 (br m),
1640 (m), 1600 (s); UV 243 (10600), 332 (4600), 358 (5600),
405 (3650); MS 457 (M+, 100). Anal. Calcd for C27H23NO6 (457)
C, 70.9; H, 5.1; N, 3.1. Found: C, 70.8; H, 5.4; N, 2.8.
1-(4,6-Dim eth oxy-2,3-d ip h en ylin d ol-7-yl)-3-p h en yl-2,3-
ep oxyp r op a n -1-on e (16). This compound was prepared as
described for the indole chalcone epoxide 14a from indole
chalcone 13e (0.026 g, 0.057 mmol), saturated sodium hydrox-
ide solution (5 mL), and hydrogen peroxide solution (5 mL,
30%) in anhydrous tetrahydrofuran (15 mL). After flash
column chromatography (dichloromethane) and recrystalliza-
tion (dichloromethane/petroleum ether), the indole chalcone
epoxide 16 was obtained as a pale yellow powder (0.02 g, 80%),
1
mp 226-228 °C. H NMR (CDCl3) δ 3.63 (s, 3H), 3.78 (s, 3H),
4.02 (d, J 2.1 Hz, 1H), 4.52 (d, J 2.1 Hz, 1H), 6.11 (s, 1H),
7.19-7.43 (m, 15H), 11.03 (br s, 1H); 13C NMR (CDCl3) δ 55.39,
56.20, 59.06, 65.04, 87.12, 103.26, 113.24, 114.48, 125.83,
126.26, 127.26, 127.50, 127.75, 128.50, 131.36, 132.25, 133.21,
135.54, 137.02, 137.85, 160.87, 161.41, 192.12; IR 3320 (br m),
1610 (m), 1600 (s); UV 251 (48820), 266 (50190), 312 (41390),
328 (42830), 367 (26330); MS 475 (M+, 60). Anal. Calcd for
C
30H25NO4 (475): C, 77.6; H, 5.7; N, 2.9. Found: C, 77.7; H,
7,9-Dim eth oxy-5-h ydr oxy-4-(4-m eth oxyph en yl)-1-ph en -
yl-6-oxo-6H-p yr r olo[3,2,1-ij]q u in olin e (15c). This com-
pound was prepared as described for the pyrroloquinoline 15a
from indole epoxide 14c (0.09 g, 0.2 mmol) and aqueous
tetrahydrofuran (10 mL) to which were added saturated
potassium hydroxide solution (2 mL) and solid potassium
hydroxide (0.2 g, 3.6 mmol). After flash column chromatogra-
phy (97:3 of dichloromethane/methanol) and recrystallization
(dichloromethane/petroleum ether), the indole flavonol 15c was
obtained as a yellow powder (0.05 g, 56%), mp 278-280 °C
(decomp). 1H NMR (CDCl3) δ 3.90 (s, 3H), 4.01 (s, 3H), 4.19
(s, 3H), 6.53 (s, 1H), 7.06 (d J 6.7 Hz, 2H), 7.20 (s, 1H), 7.32-
7.61 (m, 5H), 7.59 (d J 6.7 Hz, 2H); 13C NMR (CDCl3) δ 55.37,
55.79, 56.72, 90.71, 103.73, 107.77, 114.21, 120.17, 121.46,
124.11, 127.07, 127.96, 128.99, 131.65, 133.10, 133.68, 160.34,
160.47, 162.06, 169.96; IR 2930 (w), 2820 (w), 1630 (w), 1600
(s); UV 241 (5900), 328 (2300), 357 (3000), 380 (2200); HRMS
calcd for C26H21NO5 427.1420, found 427.1424.
4-(4-Ch lor op h en yl)-7,9-d im eth oxy-5-h yd r oxy-1-p h en -
yl-6-oxo-6H-p yr r olo[3,2,1-ij]qu in olin e (15d ). This com-
pound was prepared as described for compound 15a from
indole epoxide 14d (0.15 g, 0.34 mmol) and aqueous tetrahy-
drofuran (10 mL) to which were added saturated potassium
hydroxide solution (2 mL) and solid potassium hydroxide (0.2
g, 3.6 mmol). After flash column chromatography (97:3 of
dichloromethane/methanol) and recrystallization (dichlo-
romethane/petroleum ether), the indole flavonol 15d was
obtained as a yellow powder (0.08 g, 54%), mp 266-268 °C.
1H NMR (CDCl3) δ 4.02 (s, 3H), 4.17 (s, 3H), 6.54 (s, 1H), 7.14
(s, 1H), 7.27-7.61 (m, 5H), 7.50 (d J 8.3 Hz, 2H), 7.65 (d J 8.3
Hz, 2H); 13C NMR (CDCl3) δ 55.87, 56.81, 90.80, 103.83,
108.08, 119.83, 123.90, 124.25, 127.20, 128.07, 128.51, 129.05,
129.16, 131.71, 133.53, 133.67, 135.82, 141.50, 160.60, 162.21,
170.48; IR 1640 (m), 1610 (s); UV 246 (12000), 319 (3500), 357
(5500); HRMS calcd for C25H18NO4Cl 431.0924, found 431.0897
(Cl35).
5.4; N, 3.0.
1-(4,6-Dim e t h oxy-3-p h e n ylin d ol-2-yl)-3-p h e n yl-2,3-
ep oxyp r op a n -1-on e (17). This compound was prepared as
described for the indole chalcone epoxide 14a from indole
chalcone 8 (0.06 g, 0.15 mmol), saturated sodium hydroxide
solution (2 mL), and hydrogen peroxide solution (5 mL, 30%)
in anhydrous tetrahydrofuran (30 mL). After flash column
chromatography (dichloromethane) and recrystallization (dichlo-
romethane/petroleum ether), the indole chalcone epoxide 17
was obtained as a pale yellow powder (0.06 g, 94%), mp 195
1
°C. H NMR (CDCl3) δ 3.56 (s, 3H), 3.86 (s, 3H), 3.32 (d, J 1.5
Hz, 1H), 3.99 (d, J 2.1 Hz, 1H), 6.09 (d, J 2.0, 1H), 6.51 (d, J
1.5 Hz, 1H), 6.93-7.35 (m, 10H), 9.72 (br s, 1H); 13C NMR
(CDCl3) δ 55.12, 55.61, 59.98, 60.81, 85.59, 93.35, 113.51,
125.91, 127.15, 127.26, 128.31, 128.63, 130.03, 130.71, 134.40,
135.48, 138.88, 157.07, 161.76, 184.84; IR 3300 (br m), 1620
(s); UV 260 (23190), 346 (20030); MS 399 (M+, 21). Anal. Calcd
for C25H21NO4 (399): C, 75.1; H, 5.6; N, 3.5. Found: C, 75.2;
H, 5.3; N, 3.5.
1-(4,6-Dim eth oxy-3-ph en ylin dol-7-yl)-2-h ydr oxy-3-m eth -
oxy-3-p h en ylp r op a n -1-on e (18). Concentrated HCl (5 drops)
was added to a solution of indole epoxide 14a (0.2 g, 0.5 mmol)
in methanol (20 mL), and the solution was allowed to stir for
2h. Water (100 mL) was added, and the resulting precipitate
was filtered, washed, dried, and recrystallized (dichloromethane/
petroleum ether) to give the methoxy alcohol 18 (0.17 g, 80%)
1
as a pale yellow powder, mp 217-219 °C. H NMR (CDCl3) δ
3.07 (s, 3H), 3.95 (s, 3H), 4.10 (s, 3H), 4.24 (d, J 8.2 Hz, 1H),
4.66 (d, J 1.5 Hz, 1H), 5.32 (dd, J 2.1 Hz, 1.5 Hz, 1H), 6.3 (s,
1H), 7.16 (d J 2.1 Hz, 1H), 7.28-7.65 (m, 10H), 11.01 (br s,
1H); 13C NMR (CDCl3) δ 55.37, 56.23, 57.61, 79.35, 83.64,
87.23, 101.60, 110.95, 118.80, 122.05, 126.04, 127.43, 127.71,
128.26, 128.44, 128.52, 129.52, 135.48, 139.33, 160.64, 198.02;
IR 3380 (br m), 1580 (s); UV 333 (13600), 256 (14800); MS
431 (M+, 3). Anal. Calcd for C25H21NO4 (431) C, 75.5; H, 5.6;
N, 3.5. Found: C, 75.2; H, 5.3; N, 3.5.
5-Acetoxy-7,9-d im eth oxy-1,4-d ip h en yl-6-oxo-6H-p r yr -
r olo[3,2,1-ij]qu in olin e (24). Acetic anhydride (15 mL) was
added to pyrroloquinoline 15a (0.15 g, 0.63 mmol), and the
mixture was allowed to stir for 4 h. Water was added, and the
resulting pale yellow precipitate was filtered, washed with
acetic acid and water, and then dried to yield the acetylated
indole flavonol 24 (0.14 g, 86%), mp 209-211 °C, which could
Gen er a l Meth od for Cycliza tion of In d ole Ep oxid es.
5-Hyd r oxy-7,9-d im eth oxy-1,4-d ip h en yl-6-oxo-6H-p yr r olo-
[3,2,1-ij]qu in olin e (15a ). Indole epoxide 14a (0.17 g, 0.42
mmol) was dissolved in aqueous tetrahydrofuran (13 mL) to
which saturated potassium hydroxide solution (3 mL) and solid
potassium hydroxide (0.3 g, 5.3 mmol) were added. The
reaction mixture was allowed to stir at room temperature for
4 h. Water was added, and the resulting pale yellow precipitate
was filtered, washed, dried, and flash column chromato-
graphed (97:3 of dichloromethane/methanol). After recrystal-
lization (dichloromethane/petroleum ether), the indole flavonol
1
not be obtained analytically pure. H NMR (CDCl3) δ 2.20 (s,
3H), 3.99 (s, 3H), 4.13 (s, 3H), 6.54 (s, 1H), 6.95 (s, 1H), 7.31-
7.58 (m, 10H); 13C NMR (CDCl3) δ 20.40, 55.85, 56.78, 91.53,
107.02, 108.55, 119.65, 125.29, 127.32, 128.00, 128.85, 129.11,
129.51, 130.29, 133.54, 135.92, 137.215, 138.03, 141.26, 160.14,

Synthesis of Pyrroloquinolines
J . Org. Chem., Vol. 67, No. 8, 2002 2473
162.34,169.23,170.14);HRMS calcd for C27H21NO5Na 462.131179,
found 462.131387.
128.10, 129.13, 129.22, 130.28, 132.81, 133.67, 137.99, 145.94,
159.58, 161.78, 177.87; IR 1630 (s); UV 217 (31200), 241
(29000), 270 (13400), 340 (17400), 364 (8800); HRMS calcd for
C25H19NO3 381.1365, found 381.1366.
7,9-Dim eth oxy-1,4-d ip h en yl-4,5-d ih yd r o-6-oxo-6H-p yr -
r olo[3,2,1-ij]qu in olin e (25a ). Indole chalcone 13a (0.21 g,
0.55 mmol) was dissolved in anhydrous tetrahydrofuran (20
mL) to which sodium hydride (80%) (0.04 g, 1.2 mmol) was
added. The solution was brought to reflux for 1 h. After cooling,
the solution was added to ice-water (50 mL) containing
ammonium chloride solution (10 mL). The resulting yellow
gum was extracted with dichloromethane, the extract dried
(MgSO4), and the solvent removed under reduced pressure to
give the crude product. Preparative chromatography (97:3 of
dichloromethane/methanol) afforded the title compound as a
pale yellow powder (0.12 g, 56%), mp 97-99 °C. 1H NMR
(CDCl3) δ 3.21 (d, J 7.2 Hz, 2H), 3.95 (s, 3H), 4.04 (s, 3H),
5.50 (t, J 7.2 Hz, 1H), 6.27 (s, 1H), 6.75 (s, 1H), 7.22-7.58 (m,
10H); 13C NMR (CDCl3) δ 47.25, 55.42, 56.55, 59.38, 87.93,
101.81, 109.09, 119.76, 123.13, 126.10, 126.83, 127.80, 128.61,
129.12, 134.97, 139.23, 142.22, 158.66, 160.44, 188.47; IR 1660
(s); UV 218 (27600), 259 (23800), 283 (6500), 352 (8800); HRMS
calcd for C25H21NO3 383.1521, found 383.1519.
7,9-Dim et h oxy-4-(3,4-d im et h oxyp h en yl)-1-p h en yl-6-
oxo-6H-p yr r olo[3,2,1-ij]qu in olin e (26b). This compound
was prepared as described for the indole flavone 26a from
indole flavanone 25b (0.12 g, 0.27 mmol), in anhydrous
dichloromethane (25 mL), to which was added DDQ (0.14 g,
0.60 mmol) and refluxed for 1 h. Preparative chromatography
(97:3 of dichloromethane/methanol) gave the indole flavone 26c
as a pale yellow powder (0.02 g, 16%) mp 324-326 °C (dec).
1H NMR (CDCl3) δ 3.88 (s, 3H), 3.89 (s, 3H), 3.94 (s, 3H), 4.12
(s, 3H), 6.34 (s, 1H), 6.51 (s, 1H), 6.91-7.08 (m, 3H), 7.36-
7.51 (m, 5H); 13C NMR (CDCl3) δ 55.79, 55.99, 56.13, 56.77,
91.76, 107.21, 108.16, 110.59, 112.71, 120.46, 122.27, 125.48,
127.62, 127.68, 130.61, 131.72, 136.74, 141.59, 146.17, 148.48,
150.21, 158.83, 161.56, 167.55, 177.09; IR 1620 (s); UV 239
(25000), 270 (10000), 335 (13500), 366 (6900); MS 441.1892
(M+, 100). Calcd for C27H23NO5 441.1576. Anal. Calcd for
C
27H23NO5‚1/2H2O (441) C, 72.0; H, 5.4; N, 3.1. Found: C, 72.1;
7,9-Dim eth oxy-4-(3,4-d im eth oxyp h en yl)-4,5-d ih yd r o-1-
ph en yl-6-oxo-6H-pyr r olo[3,2,1-ij]qu in olin e (25b). This was
prepared as described for the indole flavanone 25a from indole
chalcone 13b (0.25 g, 0.56 mmol) and anhydrous tetrahydro-
furan (30 mL) to which was added sodium hydride (80%) (0.04
g, 1.24 mmol). The solution was refluxed for 75 min and gave
the indole flavanone 25b after preparative chromatography
(97:3 of dichloromethane/methanol) as a yellow powder (0.13
g, 50%), mp 126-128 °C. 1H NMR (CDCl3) δ 3.06-3.26 (m,
2H), 3.81 (s, 3H), 3.87 (s, 3H), 3.94 (s, 3H), 4.03 (s, 3H), 5.38
(dd J 10.2 Hz, 5.1 Hz, 1H), 6.24 (s, 1H), 6.73 (s, 1H), 6.80-
6.82 (m, 3H), 7.30-7.55 (m, 5H); 13C NMR (CDCl3) δ 47.29,
55.29, 55.85, 56.41, 59.08, 87.99, 101.61, 108.97, 109.79,
111.41, 119.63, 123.08, 126.08, 127.80, 129.09, 131.24, 134.90,
142.10, 149.15, 149.32, 158.55, 160.25, 188.64; IR 1650 (s); UV
227 (28000), 259 (23000), 280 (12800), 332 (9000), 354 (9100);
HRMS calcd for C27H25NO3 443.1733, found 443.1735.
7,9-Dim eth oxy-1,4-d ip h en yl-6-oxo-6H-p yr r olo[3,2,1-ij]-
qu in olin e (26a ). Indole flavanone 25a (0.10 g, 0.26 mmol)
was dissolved in anhydrous dichloromethane (20 mL) to which
was added DDQ (0.12 g, 0.56 mmol). The solution was brought
to reflux for 1 h. After cooling, the solution was added to ice
water (50 mL), and 20% Na2S2O5 solution (10 mL) was added.
The resulting yellow brown precipitate was extracted with
dichloromethane, the dichloromethane layer dried (MgSO4),
and the solvent removed under reduced pressure to give the
crude product as a yellow brown powder. Preparative chro-
matography (97:3 of dichloromethane/methanol) afforded the
title compound as a pale yellow powder (0.03 g, 25%) (dichlo-
H, 5.5; N, 3.0.
5-Ben zyliden e-7,9-dim eth oxy-1,4-diph en yl-4,5-dih ydr o-
6-oxo-6H-p yr r olo[3,2,1-ij]qu in olin e (27). Indole flavanone
25a (0.11 g, 0.29 mmol) was dissolved in anhydrous tetrahy-
drofuran (20 mL) under N2. To this solution sodium hydride
(80%) (0.02 g, 0.6 mmol) was added. After 5 min benzaldehyde
(0.1 mL, 1.4 mmol) was added and the solution brought to
reflux for 1 h. After cooling, the solution was added to ice-
water (50 mL) containing ammonium chloride solution (10
mL). The resulting yellow gum was extracted with dichlo-
romethane, the extract dried (MgSO4), and the solvent re-
moved under reduced pressure to give the crude product.
Preparative chromatography (97:3 of dichloromethane/metha-
nol) afforded the title compound as a bright yellow powder
(0.09 g, 63%), mp 236-238 °C. 1H NMR (CDCl3) δ 3.93 (s, 3H),
4.09 (s, 3H), 6.28 (s, 1H), 6.53 (s, 1H), 7.06 (s, 1H), 7.19-7.58
(m, 15H), 7.96 (s, 1H); 13C NMR (CDCl3) δ 55.40, 56.62, 59.61,
88.39, 101.30, 108.94, 119.87, 122.74, 126.09, 126.40, 127.82,
128.26, 128.65, 128.74, 129.10, 129.30, 134.93, 135.43, 136.30,
137.72, 140.03, 140.87, 159.86, 160.64, 181.02; IR 1640 (m),
1590 (m), 1560 (s); UV 228 (13000), 282 (7900), 344 (2900);
HRMS calcd for C32H29NO3 requires 471.1834, found 471.1649.
Ack n ow led gm en t. We thank the Australian Re-
search Council for financial support.
Su p p or tin g In for m a tion Ava ila ble: Full 1H NMR and
13C NMR with assignments, complete listing of IR peaks, UV
absorptions, and MS fragments of compounds 5, 7-18, 25a ,b,
26a ,b, and 27. This material is available free of charge via
the Internet at http://pubs.acs.org.
1
romethane/petroleum ether), mp 288-290 °C (dec). H NMR
(CDCl3) δ 3.99 (s, 3H), 4.14 (s, 3H), 6.46 (s, 1H), 6.54 (s, 1H),
7.22 (s, 1H), 7.32-7.64 (m, 10H); 13C NMR (CDCl3) δ 55.74,
56.82, 91.57, 107.52, 108.83, 117.50, 119.62, 125.34, 127.40,
J O010915B