Diversity-Oriented Synthesis of Calothrixins and Ellipticines

Article abstract of DOI:10.1002/ejoc.201402837

The divergent synthesis of calothrixins and ellipticines has been accomplished by utilising the one-pot formation of o-diacylarenes as a key intermediate through rearrangement of o-hydroxy ketone monoacyl hydrazones by lead tetraacetate mediated oxidation. The divergent synthesis of calothrixins and ellipticines has been accomplished by utilising the one-pot formation of o-diacylarenes as a key intermediate through rearrangement of o-hydroxy ketone monoacyl hydrazones by lead tetraacetate mediated oxidation.

Full text of DOI:10.1002/ejoc.201402837

Job/Unit: O42837
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Date: 18-09-14 17:48:34
Pages: 11
FULL PAPER
DOI: 10.1002/ejoc.201402837
Diversity-Oriented Synthesis of Calothrixins and Ellipticines
Dattatraya H. Dethe*[a] and Ganesh M. Murhade[b]
Keywords: Natural products / Nitrogen heterocycles / Quinones / Rearrangement / Oxidation
The divergent synthesis of calothrixins and ellipticines has
been accomplished by utilising the one-pot formation of o-
diacylarenes as a key intermediate through rearrangement of
o-hydroxy ketone monoacyl hydrazones by lead tetraacetate
mediated oxidation.
Introduction
In 1959, Goodwin and colleagues reported the isolation
and structure determination of ellipticine (1) and 9-meth-
oxyellipticine (2) 6H-pyrido[4,3-b]carbazole alkaloids from
the leaves of Ochrosia elliptica Labill (family Apocynaceae)
(Figure 1).[1] The promising antitumor activity of ellip-
ticines prompted several groups to explore the synthesis and
pharmacological properties of such compounds.[2] Several
ellipticine derivatives (e.g., 2) have been used in clinical
trials.[3] Calothrixin A (4) and B (5) are two naturally occur-
ring pentacyclic isoquinoline alkaloids that were isolated
from cyanobacterium of the genus Calothrix in 1999.[4] The
discovery of their antimalarial and antiproliferative proper-
ties against several cancer cell lines as well as human DNA
topoisomerase I poisoning activity has led to an explosion
of synthetic,[5] biological, and pharmacological studies.[4,6]
Reactions mediated by lead tetraacetate (LTA) and other
metallic acetates with nitrogen-containing derivatives of
carbonyl compounds have been the subject of extensive re-
search.[7,8] Kotali et al. have discovered an interesting re-
arrangement of o-hydroxy ketone monoacyl hydrazones by
LTA-mediated oxidation, resulting in an unusual replace-
ment of the phenolic hydroxyl group with an acyl substitu-
ent to give o-diacylbenzene.[7a] The mechanistic studies per-
formed by Kotali and Katritzky showed that this rearrange-
ment occurs through 1,3,4-oxadiazoline and 1,3-dioxane in-
termediates.[7b] Einhorn et al.[8a] and Dong et al.[8b] also
utilised this method for the synthesis of a range of o-diacyl-
benzenes. Although there are various reports on the forma-
tion of o-diacylbenzenes by LTA-mediated oxidation, as
Figure 1. Structures of the natural products.
mentioned above,[7] so far this reaction has not been ex-
plored with heterocyclic aromatic compounds such as ind-
oles, quinoline, and pyridines. In this article, we report a
concise five-step total synthesis of calothrixins B (5) and a
range of analogues by using LTA-mediated rearrangement
of suitable o-hydroxy aryl ketone monoacylhydrazone di-
rectly into the corresponding quinone as the key step.
Results and Discussion
It was envisioned that both ellipticines quinone (3) and
calothrixin (5) could be obtained from key intermediate 6/
7 by Lewis-acid mediated intramolecular nucleophilic at-
tack of C-3 indole onto aldehyde followed by oxidation
(Scheme 1). Compounds 8 (hydrazone derivatives of pyr-
idine) and 9 (hydrazone derivatives of quinoline) could be
synthesised by coupling hydrazide derivatives of ethyl 1H-
indole-2-carboxylate 10 with either pyridine derivative 11
or quinoline derivative 12, followed by LTA-mediated re-
arrangement. The latter pyridine and quinoline derivatives
11 and 12 were prepared in two steps by reported pro-
cedures.[9] Compound 10, on treatment with hydrazine
[a] Department of Chemistry, Indian Institute of Technology
Kanpur,
Kanpur 208016, India
E-mail: ddethe@iitk.ac.in
http://home.iitk.ac.in/~ddethe/
[b] Department of Chemistry, Indian Institute of Technology
Kanpur,
Kanpur 208016, India
E-mail: gmurhade@iitk.ac.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402837.
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D. H. Dethe, G. M. Murhade
FULL PAPER
Scheme 1. Retrosynthetic analysis of calothrixin and ellipticine quinone.
Scheme 2. Formal synthesis of ellipticine and its analogue.
Scheme 3. Synthesis of isocalothrixins and its analogues.
2
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Diversity-Oriented Synthesis of Calothrixins and Ellipticines
hydrate in ethanol, generated indolyl-hydrazide 13 LTA-mediated oxidative rearrangement of 21a afforded key
(Scheme 2), which was used in next step without further intermediate keto-aldehyde 22a (Scheme 4). BF3·OEt2 cata-
purification. Condensation of 13 with 11 afforded hydraz- lysed cyclisation by intramolecular nucleophilic attack of C-
one 8. To our surprise, LTA-mediated oxidative rearrange- 3 of indole on aldehyde followed by concomitant oxidation
ment of acyl-hydrazone 8 afforded the keto alcohol 15a di- of the alcohol thus directly afforded quinone 23a in 74%
rectly. Contrary to our expectation, LTA-mediated re- yield. Ellipticines quinone 23a has previously been trans-
arrangement of compound 8 produced the aldehyde in situ, formed into ellipticines 1,[4,10] thus this reaction completes
which, on intramolecular nucleophilic attack of indole ni- the second formal total synthesis of ellipticine 1. It was sur-
trogen on aldehyde instead of C-3 of indole, afforded the prising that in the presence of BF3·OEt2, 22a generated
keto alcohol 15a. Oxidation of the secondary alcohol by quinone 23a directly instead of the corresponding keto
using 2-iodoxybenzoic acid (IBX) afforded isoellipticine alcohol as in the synthesis of isoellipticine quinone 16a
quinone 16a in 87% yield. Conversion of the latter quinone (Scheme 2) by further oxidation of alcohol to ketone. The
16a into ellipticines 1 has already been described,[10] thus
this approach constitutes a formal synthesis of ellipticine 1.
The benzene analogue 16b of isoellipticine quinone was also
synthesised by using salicylaldehyde 14 (Scheme 2). Simi-
larly, condensation of various indolyl-hydrazides (13 and
13a–c) with quinoline derivative 12 followed by LTA-medi-
ated oxidative rearrangement and IBX-mediated oxidation
afforded isocalothrixin analogues 18a–d in very good over-
all yield (Scheme 3).
Considering the observed attack of the indole nitrogen
on the aldehyde formed in situ, we decided to protect the
indole nitrogen of ethyl 1H-indole-2-carboxylate. To this
end, reaction of indole 10 with benzyl bromide in the pres-
ence of NaH generated the N-benzyl protected indole 19.
Compound 19, on treatment with hydrazine hydrate and
heating to reflux with ethanol, generated N-protected
indolyl-hydrazide 20, which was used in next step without
further purification. Condensation of 20 with pyridine de-
rivative 11 afforded acyl-hydrazone 21a. To our delight, Scheme 4. Synthesis of ellipticine quinone and its analogue.
Scheme 5. Total synthesis of calothrixin B and its analogues.
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D. H. Dethe, G. M. Murhade
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filtered and washed with water. The solid was taken into a round-
bottomed flask, methanol was added and the mixture was heated
to reflux for another 15 min. The solid was filtered again, washed
with methanol and dried under vacuum.
same strategy was used for the synthesis of benz-ellipticine
quinone 23b from salicylaldehyde 14. Similarly, condensa-
tion of N-PMB protected indole derivative 19a (obtained
by reaction of ethyl 1H-indole-2-carboxylate 10 with PMB-
Cl in the presence of NaH) with quinoline derivative 12,
followed by LTA-mediated oxidative rearrangement,
BF3·OEt2-mediated cyclisation, and deprotection of the
PMB group, afforded calothrixin B (5) in 39.1% overall
yield from 10 (Scheme 5 and Scheme 6). A range of ana-
logues of calothrixin (26a–e) were made by using same
strategy, as shown in Scheme 5.
(E)-NЈ-[(4-Hydroxypyridin-3-yl)methylene]-1H-indole-2-carbohydraz-
ide (8): According to General Procedure A, 1H-indole-2-carbo-
hydrazide (13; 1.1 g, 6.20 mmol) and aldehyde 11 (773 mg,
6.20 mmol) in ethanol (25 mL) were used to furnish product 8
(1.66 mg, 96%) as a light-yellow solid; m.p. 250–255 °C. IR (neat):
ν
˜
= 3444, 2922, 1626, 1542, 1455, 1321, 1270 cm–1. 1H NMR
max
(500 MHz, [D6]DMSO): δ = 4.64 (br. s, 1 H), 7.06–7.23 (m, 3 H),
7.44 (s, 1 H), 7.66 (s, 1 H), 8.31 (s, 1 H), 8.76 (s, 2 H), 11.90 (s, 1
H), 12.40 (br. s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
104.5, 112.5, 115.2, 120.1, 120.7, 122.0, 124.2, 127.0, 129.6, 137.0,
138.5, 140.3, 140.8, 157.7, 171.3 ppm. HRMS: m/z calcd. for
C15H13N4O2 [M + H]+ 281.1039; found 281.1039.
(E)-NЈ-(2-Hydroxybenzylidene)-1H-indole-2-carbohydrazide
(8a):
According to General Procedure A, 1H-indole-2-carbohydrazide
(13; 300 mg, 1.71 mmol) and aldehyde 14 (0.2 mL, 1.71 mmol) in
ethanol (10 mL) were used to furnish product 8a (443 mg, 93%) as
Scheme 6. Synthesis of calothrixin B.
a light-yellow solid; m.p. 266 °C; IR (neat): ν
= 3295, 1653,
˜
max
1616, 1576, 1537, 1486, 1443, 1346, 1308, 1268, 1239 cm–1. 1H
NMR (400 MHz, [D6]DMSO): δ = 6.94 (m, 2 H), 7.08 (t, J =
7.3 Hz, 1 H), 7.23 (t, J = 7.3 Hz, 1 H), 7.28–7.33 (m, 2 H), 7.48 (d,
J = 7.8 Hz, 1 H), 7.59 (d, J = 7.3 Hz, 1 H), 7.69 (d, J = 7.8 Hz, 1
H), 8.66 (s, 1 H), 11.19 (s, 1 H), 11.85 (s, 1 H), 12.15 (s, 1 H) ppm.
13C NMR (125 MHz, [D6]DMSO): δ = 103.8, 112.5, 116.4, 118.9,
119.4, 120.1, 121.9, 124.0, 127.0, 129.2, 129.7, 131.4, 136.9, 147.2,
157.3, 157.4 ppm. HRMS: m/z calcd. for C16H14N3O2 [M + H]+
280.1086; found 280.1082.
Conclusions
We have demonstrated a novel approach for the synthesis
of calothrixin B, ellipticine, and their various analogues
in excellent overall yield by using the rearrangement of
o-hydroxy ketone monoacyl hydrazones induced by lead
tetraacetate as a key step.
(E)-NЈ-[(4-Hydroxyquinolin-3-yl)methylene]-1H-indole-2-carbo-
hydrazide (9): According to General Procedure A, 1H-indole-2-
carbohydrazide (13; 500 mg, 2.85 mmol) and aldehyde 12 (494 mg,
2.85 mmol) in ethanol (15 mL) were used to furnish product 9
(893 mg, 95%) as a light-yellow solid; m.p. 296–298 °C. IR (neat):
Experimental Section
General: All reactions were carried out under either a nitrogen or
argon atmosphere with anhydrous solvents under anhydrous condi-
tions, unless otherwise mentioned. Anhydrous THF and diethyl
ether were distilled from sodium benzophenone, and dichloro-
methane was distilled from calcium hydride, yields refer to chro-
matographically pure material, unless otherwise stated.
ν
= 3230, 3055, 1620, 1575, 1520, 1557, 1475, 1359, 1316,
˜
max
1214 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 7.06 (m, 1 H),
7.21 (m, 1 H), 7.35 (s, 1 H), 7.40–7.47 (m, 2 H), 7.66–7.71 (m, 3
H), 8.21 (d, J = 7.9 Hz, 1 H), 8.54 (s, 1 H), 8.82 (s, 1 H), 11.76 (s,
1 H), 11.82 (s, 1 H), 12.39 (br. s, 1 H) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 103.3, 112.7, 113.8, 119.0, 119.9, 121.7, 123.7,
124.3, 125.2, 125.7, 127.1, 130.2, 132.2, 136.8, 137.0, 139.3, 143.2,
157.3, 175.0 ppm. HRMS: m/z calcd. for C19H15N4O2 [M + H]+
331.1195; found 331.1198.
Reactions were monitored by thin-layer chromatography (TLC)
carried out on 0.25 mm Merck silica gel plates (60F254) using UV
light as a visualising agent and an p-anisaldehyde or ninhydrine
stain, and heat as developing agents. Merck silica gel (particle size
100–200 and 230–400 mesh) was used for flash column chromatog-
raphy.
(E)-NЈ-[(4-Hydroxyquinolin-3-yl)methylene]-5-methoxy-1H-indole-
2-carbohydrazide (9a): According to General Procedure A, 5-meth-
oxy-1H-indole-2-carbohydrazide (13a; 270 mg, 1.31 mmol) and al-
dehyde 12 (173 mg, 1.31 mmol) in ethanol (10 mL) were used to
furnish product 9a (448 mg, 95%) as a light-yellow solid; m.p. 288–
Reagents were purchased at the highest commercial quality and
used without further purification, unless otherwise stated. NMR
spectra were recorded with either a Bruker Avance 200 (1H:
200 MHz, 13C: 50 MHz), Bruker Avance 400 (1H: 400 MHz, 13C:
100 MHz), Bruker Avance 500 (1H: 500 MHz, 13C: 125 MHz), or
JEOL ECX 500 (1H: 500 MHz, 13C: 125 MHz). The following ab-
breviations were used to explain the multiplicities in the NMR
spectra: s = singlet, d = doublet, t = triplet, q = quartet, dd =
doublet of doublet, ddd = doublet of a doublet of a doublet, dm
= doublet of a multiplet, m = multiplet, br = broad. Mass spectro-
metric data were obtained with a WATERS-Q-Tof Premier-ESI-
MS.
292 °C. IR (neat): νmax = 3334, 1626, 1558, 1518, 1476, 1446, 1386,
˜
1249 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 3.78 (s, 3 H),
6.87 (d, J = 7.9 Hz, 1 H), 7.13 (s, 1 H), 7.26 (s, 1 H), 7.35 (d, J =
8.5 Hz, 1 H), 7.41 (m, 1 H), 7.66–7.71 (m, 2 H), 8.20 (d, J = 7.3 Hz,
1 H), 8.53 (s, 1 H), 8.81 (s, 1 H), 11.60 (s, 1 H), 11.17 (s, 1 H),
12.36 (s, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 55.3,
102.1, 103.0, 113.1, 113.9, 115.0, 119.0, 124.3, 125.2, 125.7, 127.4,
130.5, 132.1, 136.9, 139.2, 143.1, 153.8, 157.2, 175.0 ppm. HRMS:
m/z calcd. for C20H17N4O3 [M + H]+ 361.1301; found 361.1299.
Preparation of Acylhydrazones 8 and 9. General Procedure A: Ind-
ole-2-carbohydrazide was added at room temperature to a solution
of the desired aldehyde in ethanol. The reaction mixture was heated
to reflux for 30 min, poured on ice, and the resulting solid was
(E)-5-(Benzyloxy)-NЈ-[(4-hydroxyquinolin-3-yl)methylene]-1H-ind-
ole-2-carbohydrazide (9b): According to General Procedure A, 5-
(benzyloxy)-1H-indole-2-carbohydrazide (13b; 354 mg, 1.25 mmol)
and aldehyde 12 (217 mg, 1.25 mmol) in ethanol (15 mL) were used
4
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Diversity-Oriented Synthesis of Calothrixins and Ellipticines
to furnish product 9b (523 mg, 96%) as a light-yellow solid; m.p.
1.00 mmol) and Pb(OAc)4 (443 mg, 1.00 mmol) in THF (15 mL)
254 °C. IR (neat): ν
= 1643, 1569, 1475, 1451, 1261, 1218 cm–1. were used to furnish product 17a (240 mg, 80%) as a yellow solid;
˜
max
1H NMR (500 MHz, [D6]DMSO): δ = 5.11 (s, 2 H), 6.96 (s, 1 H),
m.p. 172 °C; R = 0.30 (EtOAc/hexane, 50:50). IR (neat): ν
=
˜
f
max
7.24–7.48 (m, 9 H), 7.67 (m, 1 H), 8.20 (s, 1 H), 8.54 (s, 1 H), 8.81
3127, 1658, 1570, 1523, 1320, 1241 cm–1. 1H NMR (400 MHz, [D6]-
(s, 1 H), 11.62 (s, 1 H), 11.76 (s, 1 H), 12.37 (br. s, 1 H) ppm. 13C DMSO): δ = 7.19 (d, J = 10.1 Hz, 1 H), 7.25 (t, J = 7.8 Hz, 1 H),
NMR (125 MHz, [D6]DMSO): δ = 69.6, 103.1, 103.7, 113.2, 113.9, 7.43–7.49 (m, 2 H), 7.51 (s, 1 H), 7.81–7.91 (m, 4 H), 8.17 (d, J =
115.5, 119.0, 124.3, 125.2, 125.7, 127.3, 127.7, 128.4, 130.6, 132.2,
136.9, 137.6, 139.3, 143.1, 152.9, 157.2, 175.0 ppm. HRMS: m/z
calcd. for C26H21N4O3 [M + H]+ 437.1614; found 437.1614.
7.8 Hz, 1 H), 9.32 (s, 1 H), 9.62 (d, J = 8.3 Hz, 1 H) ppm. 13C
NMR (125 MHz, [D6]DMSO): δ = 72.5, 108.1, 112.5, 121.9, 122.9,
123.2, 126.3, 126.4, 127.3, 129.1, 129.7, 130.2, 132.9, 134.9, 137.4,
148.2, 151.5, 178.8 ppm. HRMS: m/z calcd. for C19H13N2O2 [M +
H]+ 301.0977; found 301.0973.
(E)-5-Chloro-NЈ-[(4-hydroxyquinolin-3-yl)methylene]-1H-indole-2-
carbohydrazide (9c): According to General Procedure A, 5-chloro-
1H-indole-2-carbohydrazide (13c; 310 mg, 1.48 mmol) and alde-
hyde 12 (256 mg, 1.48 mmol) in ethanol (15 mL) were used to fur-
nish product 9c (511 mg, 95%) as a light-yellow solid; m.p. 294–
7-Hydroxy-11-methoxybenzo[f]indolo[1,2-b][2,7]naphthyridin-
14(7H)-one (17b): According to General Procedure B, compound
9a (200 mg, 0.55 mmol) and Pb(OAc)4 (246 mg, 0.55 mmol) in
296 °C. IR (neat): ν
= 3384, 3268, 1624, 1578, 1473, 1272 cm–1. THF (10 mL) were used to furnish product 17b (135 mg, 75%) as
˜
max
1H NMR (500 MHz, [D6]DMSO): δ = 7.21 (m, 1 H), 7.32 (s, 1 H),
a yellow solid; m.p. 170–175 °C; Rf = 0.33 (EtOAc/hexane, 40:60).
7.40–7.47 (m, 2 H), 7.65–7.75 (m, 3 H), 8.20 (m, 1 H), 8.57 (s, 1
IR (neat): ν
= 3169, 2925, 1659, 1537, 1456 cm–1. 1H NMR
˜
max
H), 8.80 (s, 1 H), 11.92 (s, 1 H), 11.98 (s, 1 H), 12.44 (br. s, 1 (500 MHz, [D6]DMSO): δ = 3.82 (s, 3 H), 7.16 (m, 2 H), 7.28 (m,
H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 103.1, 113.9, 1 H), 7.42 (m, 1 H), 7.76 (d, J = 9.2 Hz, 1 H), 7.85 (m, 1 H), 7.91
114.1, 119.1, 120.9, 123.9, 124.5, 124.6, 125.4, 125.8, 128.2, 131.8,
132.3, 135.3, 137.3, 139.4, 143.8, 157.2, 175.2 ppm. HRMS: m/z
calcd. for C19H14ClN4O2 [M + H]+ 365.0805; found 365.0800.
(m, 1 H), 8.15 (m, 1 H), 9.32 (s, 1 H), 9.65 (d, J = 9.8 Hz, 1 H) ppm.
13C NMR (125 MHz, [D6]DMSO): δ = 55.3, 72.5, 102.7, 107.54,
113.5, 118.1, 122.9, 126.5, 127.9, 129.1, 129.7, 129.7, 130.2, 132.8,
133.2, 135.0, 148.2, 151.4, 155.1, 178.5 ppm. HRMS: m/z calcd. for
C20H13N2O3 [M + H]+ 329.0926; found 329.0922.
Preparation of Keto Alcohol 15 and 17. General Procedure B: At
room temperature, the appropriate hydrazone was dissolved in
THF (analytical grade). At 0 °C, lead tetraacetate was gradually
added to the solution. The resulting mixture was stirred for 3–4 h
at room temp., and the progress of the reaction was monitored by
the evolution of nitrogen. The solvent was removed under reduce
pressure. Ethyl acetate was added to the residue and the suspension
was filtered through Celite. The organic layer was washed with a
saturated solution of NaHCO3 then brine, and dried with Na2SO4.
The solvent was removed under vacuo and the residue was purified
on a silica gel column using EtOAc/hexane as eluent to furnish the
product.
11-(Benzyloxy)-7-hydroxybenzo[f]indolo[1,2-b][2,7]naphthyridin-
14(7H)-one (17c): According to General Procedure B, compound
9b (200 mg, 0.458 mmol) and Pb(OAc)4 (202 mg, 0.458 mmol) in
THF (10 mL) were used to furnish product 17c (150 mg, 81%) as
a yellow solid; m.p. 178 °C; Rf = 0.30 (EtOAc/hexane, 20:80). IR
(neat): ν
= 3429, 2923, 1653, 1450, 1354, 1205, 1025 cm–1. 1H
˜
max
NMR (400 MHz, [D6]DMSO): δ = 5.16 (s, 2 H), 7.15 (d, J = 10 Hz,
1 H), 7.24 (dd, J = 2.5, 9.1 Hz, 1 H), 7.32–7.45 (m, 6 H), 7.50 (m,
2 H), 7.77 (d, J = 9.1 Hz, 1 H), 7.83–7.92 (m, 2 H), 8.18 (dd, J =
1.4, 8.4 Hz, 1 H), 9.31 (s, 1 H), 9.64 (dd, J = 1.2, 8.4 Hz, 1 H) ppm.
13C NMR (125 MHz, [D6]DMSO): δ = 69.6, 72.5, 104.3, 107.5,
113.6, 118.5, 122.9, 126.5, 127.7, 127.8, 127.9, 128.5, 129.1, 129.7,
129.7, 130.2, 133.0, 133.3, 135.0, 137.2, 148.2, 151.4, 154.1,
178.5 ppm. HRMS: m/z calcd. for C26H19N2O3 [M + H]+ 407.1396;
found 407.1393.
12-Hydroxyindolo[1,2-b][2,7]naphthyridin-5(12H)-one (15a): Ac-
cording to General Procedure B, compound 8 (300 mg, 1.07 mmol)
and Pb(OAc)4 (474 mg, 1.07 mmol) in THF (15 mL) were used to
furnish product 15a (208 mg, 78%) as a yellow solid; m.p. 180 °C;
R = 0.40 (EtOAc/hexane, 50:50). IR (neat): ν
= 3413, 1660,
˜
f
max
1532, 1440, 1466, 1290, 1250 cm–1
DMSO): δ = 7.14 (d, J = 9.7 Hz, 1 H), 7.25 (t, J = 7.2 Hz, 1 H),
7.37 (d, J = 10.0 Hz, 1 H), 7.50 (t, J = 8.0 Hz, 1 H), 7.54 (s, 1 H), (300 mg, 0.824 mmol) and Pb(OAc)4 (365 mg, 0.824 mmol) in THF
7.84 (m, 2 H), 7.98 (d, J = 4.9 Hz, 1 H), 8.89 (d, J = 4.9 Hz, 1 H), (15 mL) were used to furnish product 17d (212 mg, 77%) as a yel-
9.10 (s, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 72.3, low solid; m.p. 185 °C; Rf = 0.30 (EtOAc/hexane, 20:80). IR (neat):
.
1H NMR (500 MHz, [D6]- 11-Chloro-7-hydroxybenzo[f]indolo[1,2-b][2,7]naphthyridin-14(7H)-
one (17d): According to General Procedure B, compound 9c
108.2, 112.7, 118.0, 122.0, 123.2, 126.5, 127.2, 131.7, 134.6, 135.3,
137.9, 150.5, 151.1, 175.8 ppm. HRMS: m/z calcd. for C15H10N2O2
[M + H]+ 251.0821; found 251.0820.
ν
= 3113, 2848, 1660, 1524, 1524, 1444, 1427, 1355, 1316, 1273,
˜
max
1175 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 7.18 (m, 1 H),
7.45–7.52 (m, 3 H), 7.82–7.91 (m, 4 H), 8.17 (d, J = 7.9 Hz, 1 H),
9.30 (s, 1 H), 9.58 (d, J = 8.5 Hz, 1 H) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 72.6, 107.2, 114.2, 122.1, 122.7, 126.3, 126.3,
126.4, 128.2, 128.8, 129.7, 129.8, 130.2, 133.9, 134.8, 135.6, 148.1,
151.3, 178.7 ppm. HRMS: m/z calcd. for C19H12ClN2O2 [M + H]+
335.0587; found 335.0580.
6-Hydroxyindolo[1,2-b]isoquinolin-11(6H)-one (15b): According to
General Procedure B, compound 8a (260 mg, 0.98 mmol) and
Pb(OAc)4 (434 mg, 0.98 mmol) in THF (10 mL) were used to fur-
nish product 15b (190 mg, 78%) as a yellow solid; m.p. 132–136 °C;
R = 0.40 (EtOAc/hexane, 50:50). IR (neat): ν
= 3275, 1632,
˜
f
max
1598, 1530, 1354, 1275, 1197 cm–1. 1H NMR (500 MHz, CDCl3): Oxidation of Alcohol 16 and 18. General Procedure C: Compound
δ = 3.36 (br. s, 1 H), 6.86 (d, J = 8.5 Hz, 1 H), 7.25 (m, 1 H), 7.39
(s, 1 H), 7.48 (t, J = 7.0 Hz, 1 H), 7.55 (t, J = 7.0 Hz, 1 H), 7.70–
was dissolved in a mixture of ethyl acetate and DMSO (2:1) and
IBX was added. The reaction mixture was heated to reflux for 8 h.
7.75 (m, 2 H), 7.81 (t, J = 8.5 Hz, 2 H), 8.19 (d, J = 7.0 Hz, 1 After completion of reaction, aq. NaHCO3 was added and the mix-
H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 73.9, 107.2, 112.8, ture was extracted with ethyl acetate (3ϫ 15 mL). The organic ex-
121.8, 123.1, 125.9, 127.3, 129.1, 129.3, 129.8, 132.2, 134.0, 137.8,
141.3, 176.7 ppm. HRMS: m/z calcd. for C16H11NNaO2 [M + of the solvent and purification of the residue on a silica gel column
Na]+ 272.0687; found 272.0680.
using EtOAc/hexane as eluent furnished the product.
tract was washed with brine and dried with Na2SO4. Evaporation
7-Hydroxybenzo[f]indolo[1,2-b][2,7]naphthyridin-14(7H)-one (17a): Indolo[1,2-b][2,7]naphthyridine-5,12-dione (16a): According to Ge-
According to General Procedure B, compound 9 (330 mg, neral Procedure C, compound 15a (25 mg, 0.10 mmol), IBX
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5

Job/Unit: O42837
/KAP1
Date: 18-09-14 17:48:34
Pages: 11
D. H. Dethe, G. M. Murhade
(74 mg, 0.30 mmol) and a mixture of EtOAc (4 mL) and DMSO δ = 70.7, 105.4, 111.0, 113.3, 115.6, 117.8, 119.0, 122.6, 123.5,
FULL PAPER
(2 mL) were used to furnish product 16a (21 mg, 87%) as a yellow
125.3, 127.3, 128.4, 128.6, 129.1, 129.8, 130.2, 131.0, 134.0, 135.7,
solid; m.p. 190 °C; R = 0.34 (EtOAc/hexane, 20:80). IR (neat): ν
137.5, 139.9, 141.2, 145.1, 154.8, 158.1, 173.9 ppm. HRMS: m/z
˜
f
max
= 1651, 1477, 1050, 1004 cm–1. H NMR (500 MHz, [D6]DMSO): calcd. for C26H17N2O3 [M + H]+ 405.1239; found 405.1238.
1
δ = 7.44 (t, J = 7.9 Hz, 1 H), 7.67 (d, J = 7.9 Hz, 1 H), 7.83 (s, 1
11-Chlorobenzo[f]indolo[1,2-b][2,7]naphthyridine-7,14-dione (18d):
H), 7.90 (d, J = 7.9 Hz, 1 H), 8.02 (d, J = 4.9 Hz, 1 H), 8.51 (d, J
According to General Procedure C, compound 17d (100 mg,
= 8.2 Hz, 1 H), 9.14 (d, J = 4.9 Hz, 1 H), 9.48 (s, 1 H) ppm. 13C
0.29 mmol), IBX (222 mg, 0.89 mmol) and a mixture of EtOAc
(8 mL) and DMSO (2 mL) were used to furnish product 18d
(77 mg, 80 %) as a light-orange solid; m.p. 249 °C; Rf = 0.33
NMR (125 MHz, [D6]DMSO): δ = 116.4, 116.4, 118.3, 124.2,
124.8, 125.4, 128.3, 130.1, 133.7, 136.4, 138.9, 150.1, 155.3, 158.5,
174.8 ppm. HRMS: m/z calcd. for C15H9N2O2 [M + H]+ 249.0664;
(EtOAc/hexane, 20:80). IR (neat): ν
= 2923, 1691, 1654, 1541,
˜
max
found 249.0666.
1419, 1385, 1322, 1280, 1177 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 7.56 (dd, J = 2.3, 9.2 Hz, 1 H), 7.62 (s, 1 H), 7.73 (d, J =
1.7 Hz, 1 H), 7.82–7.86 (m, 1 H), 7.92–7.96 (m, 1 H), 8.25 (d, J =
7.4 Hz, 1 H), 8.52 (d, J = 9.2 Hz, 1 H), 9.69 (d, J = 9.7 Hz, 1 H),
9.91 (s, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 116.4,
118.2, 122.6, 123.0, 123.3, 127.8, 129.8, 130.3, 130.6, 130.9, 131.4,
132.0, 132.7, 133.9, 134.9, 149.4, 151.8, 158.3, 177.6 ppm. HRMS:
m/z calcd. for C19H10ClN2O3 [M + H]+ 333.0431; found 333.0432.
Indolo[1,2-b]isoquinoline-6,11-dione (16b): According to General
Procedure C, compound 15b (40 mg, 0.16 mmol), IBX (119 mg,
0.48 mmol) and a mixture of EtOAc (4 mL) and DMSO (2 mL)
were used to furnish product 16b (34 mg, 87%) as a yellow solid;
m.p. 140–144 °C; R = 0.34 (EtOAc/hexane, 20:80). IR (neat): ν
˜
f
max
= 1688, 1662, 1552, 1444, 1372, 1247 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 7.38 (t, J = 7.2 Hz, 1 H), 7.59 (t, J = 7.2 Hz, 1 H),
7.66 (s, 1 H), 7.75 (d, J = 7.9 Hz, 1 H), 7.80–7.86 (m, 2 H), 8.30
(m, 1 H), 8.44 (m, 1 H), 8.63 (d, J = 8.3 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 116.5, 117.2, 123.7, 125.3, 126.9, 128.6,
129.3, 129.8, 131.2, 133.5, 134.1, 134.4, 137.2, 159.2, 175.6 ppm.
HRMS: m/z calcd. for C16H10NO2 [M + H]+ 248.0712; found
248.0719.
Preparation of Acylhydrazone 21 and 24. General Procedure D: The
N-alkylated indole-2-carbohydrazide was added at room tempera-
ture to a solution of the desired aldehyde in ethanol. The reaction
mixture was heated to reflux for 30 min, poured on ice, and the
resulting solid was filtered and washed with water. The solid was
taken into a round-bottomed flask, methanol was added, and the
mixture was heated to reflux for another 15 min. The solid was
filtered again, washed with methanol, and dried under vacuum.
Benzo[f]indolo[1,2-b][2,7]naphthyridine-7,14-dione (18a): According
to General Procedure C, compound 17a (74 mg, 0.24 mmol), IBX
(183 mg, 0.73 mmol) and a mixture of EtOAc (9 mL) and DMSO
(3 mL) were used to furnish product 18a (60 mg, 85%) as a yellow
(E)-1-Benzyl-NЈ-[(4-hydroxypyridin-3-yl)methylene]-1H-indole-2-
carbohydrazide (21a): According to General Procedure D, 1-benzyl-
1H-indole-2-carbohydrazide (20; 500 mg, 1.88 mmol) and aldehyde
11 (232 mg, 1.88 mmol) in ethanol (20 mL) were used to furnish
solid; m.p. 249 °C; R = 0.30 (EtOAc/hexane, 20:80). IR (neat): ν
˜
f
max
= 1698, 1656, 1573, 1419, 1382, 1235 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.37 (t, J = 7.1 Hz, 1 H), 7.60 (t, J = 7.1 Hz, 1 H),
7.67 (s, 1 H), 7.73 (d, J = 7.8 Hz, 1 H), 7.81 (t, J = 8.5 Hz, 1 H),
7.91 (t, J = 8.5 Hz, 1 H), 8.23 (d, J = 8.5 Hz, 1 H), 8.56 (d, J =
8.5 Hz, 1 H), 9.70 (d, J = 8.7 Hz, 1 H), 9.91 (s, 1 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 117.1, 117.9, 122.6, 123.3, 123.9,
125.7, 127.8, 128.6, 130.3, 130.5, 130.7, 132.4, 133.8, 134.0, 136.7,
149.5, 151.7, 158.3, 177.6 ppm. HRMS: m/z calcd. for C19H11N2O2
[M + H]+ 299.0821; found 299.0825.
product 21a (660 mg, 95%) as a white solid; m.p. 254–256 °C. IR
1
(neat): ν
= 3190, 1635, 1522, 1494, 1452, 1215 cm–1. H NMR
˜
max
(500 MHz, [D6]DMSO): δ = 4.62 (br. s, 1 H), 5.90 (s, 2 H), 7.07 (s,
2 H), 7.19–7.29 (m, 6 H), 7.50 (s, 1 H), 7.57 (s, 1 H), 7.74 (s 1 H),
8.42 (s, 1 H), 8.71 (s, 1 H), 8.83 (s, 1 H) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 47.0, 107.1, 111.3, 112.07, 116.2, 121.0, 122.3,
124.7, 125.9, 126.6, 127.2, 128.6, 129.7, 138.8, 140.1, 141.7, 149.3,
159.8, 173.0 ppm. HRMS: m/z calcd. for C22H19N4O2 [M + H]+
371.1508; found 371.1501.
11-Methoxybenzo[f]indolo[1,2-b][2,7]naphthyridine-7,14-dione (18b):
According to General Procedure C, compound 17b (98 mg,
0.29 mmol), IBX (220 mg, 0.89 mmol) and a mixture of EtOAc
(8 mL) and DMSO (2 mL) were used to furnish product 18b
(77 mg, 81%) as a red solid; m.p. 206 °C; Rf = 0.30 (EtOAc/hexane,
(E)-1-Benzyl-NЈ-(2-hydroxybenzylidene)-1H-indole-2-carbohydraz-
ide (21b): According to General Procedure D, 1-benzyl-1H-indole-
2-carbohydrazide (20; 500 mg, 1.9 mmol) and aldehyde 14 (0.2 mL,
1.9 mmol) in ethanol (15 mL) were used to furnish product 21b
20:80). IR (neat): ν
= 1689, 1650, 1570, 1477, 1240 cm–1. 1H
˜
(666 mg, 95%) as a white solid; m.p. 180–182 °C. IR (neat): ν
˜
max
max
= 3217, 1646, 1543, 1488, 1451, 1350, 1274, 1207 cm–1. H NMR
(500 MHz, CDCl3): δ = 5.81 (s, 2 H), 6.90 (t, J = 7.3 Hz, 1 H),
7.00 (d, J = 8.2 Hz, 1 H), 7.09 (d, J = 7.4 Hz, 3 H), 7.15–7.27 (m,
5 H), 7.31 (t, J = 8.2 Hz, 1 H), 7.37 (d, J = 8.2 Hz, 1 H), 7.69 (d,
J = 7.9 Hz, 1 H), 8.27 (br. s, 1 H), 9.25 (br. s, 1 H), 10.88 (s, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 47.9, 111.0, 117.3,
119.3, 121.2, 122.2, 125.2, 126.1, 126.4, 127.3, 128.6, 130.9, 132.0,
137.9, 139.2, 147.8, 154.5, 158.2, 161.5 ppm. HRMS: m/z calcd. for
C23H20N3O2 [M + H]+ 370.1556; found 370.1551.
1
NMR (500 MHz, CDCl3): δ = 3.90 (s, 3 H), 7.16 (m, 1 H), 7.23
(m, 1 H), 7.63 (s, 1 H), 7.83 (m, 1 H), 7.93 (m, 1 H), 8.25 (d, J =
8.5 Hz, 1 H), 8.47 (d, J = 9.2 Hz, 1 H), 9.73 (d, J = 8.5 Hz, 1 H),
9.92 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 55.7, 105.1,
117.6, 118.0, 120.2, 122.7, 123.4, 127.8, 129.7, 130.3, 130.7, 131.6,
132.4, 134.0, 149.4, 151.8, 157.8 ppm. HRMS: m/z calcd. for
C20H13N2O3 [M + H]+ 329.0926; found 329.0928.
11-(Benzyloxy)benzo[f]indolo[1,2-b][2,7]naphthyridine-7,14-dione
(18c): According to General Procedure C, compound 17c (190 mg,
0.46 mmol), IBX (348 mg, 1.40 mmol) and a mixture of EtOAc
(E)-NЈ-[(4-Hydroxyquinolin-3-yl)methylene]-1-(4-methoxybenzyl)-
(10 mL) and DMSO (5 mL) were used to furnish product 18c 1H-indole-2-carbohydrazide (24a): According to General Procedure
(145 mg, 78%) as a red solid; m.p. 230–235 °C; Rf = 0.30 (EtOAc/ D, 1-(4-methoxybenzyl)-1H-indole-2-carbohydrazide (20a; 1 g,
hexane, 30:70). IR (neat): ν = 1686, 1654, 1573, 1539, 1442, 3.38 mmol) and aldehyde 12 (586 mg, 3.38 mmol) in ethanol
˜
max
1460, 1392, 1255 cm–1. 1H NMR [500 MHz, CDCl3 + TFA (10:1)]: (25 mL) were used to furnish product 24a (1.39 g, 92%) as a light-
δ = 4.94 (dd, J = 11.5, 25.8 Hz, 2 H), 6.87 (s, 1 H), 7.21–7.31 (m, yellow solid; m.p. 305–310 °C. IR (neat): ν
= 3406, 1614, 1554,
˜
max
6 H), 8.00 (t, J = 8.0 Hz, 1 H), 8.25 (t, J = 8.0 Hz, 1 H), 8.54 (d, 1473, 1313, 1248 cm–1. H NMR (500 MHz, [D6]DMSO): δ = 3.63
J = 8.6 Hz, 1 H), 8.69 (d, J = 9.2 Hz, 1 H), 9.71 (d, J = 8.6 Hz, 1 (s, 3 H), 5.78 (s, 2 H), 6.78 (d, J = 8.6 Hz, 2 H), 7.04–7.10 (m, 2
H), 10.16 (s, 1 H) ppm. 13C NMR [125 MHz, CDCl3 + TFA (10:1)]: H), 7.22 (m, 1 H), 7.31 (s, 1 H), 7.37 (m, 1 H), 7.54–7.69 (m, 5 H),
1
6
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Date: 18-09-14 17:48:34
Pages: 11
Diversity-Oriented Synthesis of Calothrixins and Ellipticines
8.15 (d, J = 8.02 Hz, 1 H), 8.47 (s, 1 H), 8.74 (s, 1 H), 11.86 (s, 1
H), 12.36 (br. s, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ =
46.2, 55.0, 106.1, 111.1, 113.8, 118.9, 120.4, 121.8, 124.0, 124.2,
125.2, 125.6, 125.8, 128.0, 130.2, 130.6, 132.1, 132.2, 136.9, 138.3,
139.2, 143.5, 155.7, 158.0, 158.3, 174.9 ppm. HRMS: m/z calcd. for
C27H23N4O3 [M + Na]+ 451.1770; found 451.1778.
105.6, 112.8, 113.7, 119.0, 121.0, 124.2, 124.3, 125.1, 125.2, 125.7,
126.4, 126.9, 127.1, 128.5, 131.7, 132.2, 136.7, 137.0, 138.4, 139.2,
143.9, 157.5, 174.9 ppm. HRMS: m/z C26H19ClN4NaO2 [M +
Na]+ 477.1094; found 477.1098.
Preparation of Keto-aldehyde 22 and 25. General Procedure E: At
room temperature, the appropriate hydrazone was dissolved in
THF (analytical grade). At 0 °C, lead tetraacetate was gradually
added to the solution. The resulting mixture was stirred for 3–4 h
at room temp. and the progress of the reaction was monitored by
the evolution of nitrogen. The solvent was removed under reduce
pressure. Ethyl acetate was added to the residue and the suspension
was filtered through Celite. The organic layer was washed with a
saturated solution of NaHCO3 then brine, and dried with Na2SO4.
The solvent was removed under vacuo and the residue was purified
on a silica gel column using EtOAc/hexane as eluent to furnish the
product.
(E)-1-Benzyl-NЈ-[(4-hydroxyquinolin-3-yl)methylene]-1H-indole-2-
carbohydrazide (24b): According to General Procedure D, 1-benzyl-
1H-indole-2-carbohydrazide (20; 150 mg, 0.86 mmol) and aldehyde
12 (230 mg, 0.86 mmol) in ethanol (10 mL) were used to furnish
product 24b (335 mg, 93%) as a light-yellow solid; m.p. 288 °C. IR
(neat): νmax = 3406, 2922, 1630, 1517, 1477, 1451, 1222, 1106 cm–1.
˜
1H NMR (500 MHz, [D6]DMSO): δ = 5.90 (s, 2 H), 7.08–7.15 (m,
4 H), 7.19–7.27 (m, 4 H), 7.40 (s, 2 H), 7.56 (m, 1 H), 7.65 (m, 1
H), 7.71 (m, 2 H), 8.19 (d, J = 7.9 Hz, 1 H), 8.50 (s, 1 H), 8.77 (s,
1 H), 11.92 (s, 1 H), 12.37 (br. s, 1 H) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 46.9, 106.3, 111.1, 113.9, 119.0, 120.6, 122.0,
124.2, 124.4, 125.3, 125.7, 125.9, 126.5, 127.0, 128.5, 130.3, 132.2,
137.0, 138.4, 138.8, 139.3, 143.6, 158.0, 175.0 ppm. HRMS: m/z
calcd. for C26H20N4NaO2 [M + Na]+ 443.1484; found 443.1483.
4-(1-Benzyl-1H-indole-2-carbonyl)nicotinaldehyde (22a): According
to General Procedure E, compound 21a (400 mg, 1.08 mmol) and
Pb(OAc)4 (478 mg, 1.08 mmol) in THF (15 mL) were used to fur-
nish 22a (268 mg, 73%) as a light-orange solid; m.p. 225–230 °C;
R = 0.40 (EtOAc/hexane, 50:50). IR (neat): ν
= 1701, 1647,
˜
f
max
(E)-1-Benzyl-NЈ-[(4-hydroxyquinolin-3-yl)methylene]-5-methoxy-
1H-indole-2-carbohydrazide (24c): According to General Procedure
D, 1-benzyl-5-methoxy-1H-indole-2-carbohydrazide (20b; 285 mg,
0.96 mmol) and aldehyde 12 (167 mg, 0.96 mmol) in ethanol
(15 mL) were used to furnish product 24c (401 mg, 93%) as a white
1510, 1496, 1456, 1403, 1259 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 5.96 (s, 2 H), 6.78 (s, 1 H), 7.14–7.30 (m, 7 H), 7.36–7.47 (m,
3 H), 7.61 (d, J = 8.3 Hz, 1 H), 8.91 (d, J = 4.9 Hz, 1 H), 9.18 (s,
1 H), 9.97 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 48.4,
111.1, 117.7, 121.7, 122.3, 123.5, 126.0, 126.5, 127.4, 127.7, 128.7,
128.8, 133.6, 137.7, 141.0, 148.4, 151.4, 154.0, 185.6, 189.2 ppm.
HRMS: m/z calcd. for C22H17N2O2 [M + H]+ 341.1290; found
341.1291.
solid; m.p. 285 °C. IR (neat): ν
= 3450, 1641, 1552, 1474, 1451,
˜
max
1230, 1165 cm–1. H NMR (500 MHz, [D6]DMSO): δ = 3.78 (s, 3
H), 5.86 (s, 2 H), 6.91 (t, J = 7.9 Hz, 1 H), 7.06 (m, 2 H), 7.23 (m,
5 H), 7.44 (m, 2 H), 7.66 (m, 2 H), 8.20 (d, J = 7.49 Hz, 1 H), 8.49
(s, 1 H), 8.77 (s, 1 H), 11.85 (s, 1 H), 12.34 (br. s, 1 H) ppm. 13C
NMR (125 MHz, [D6]DMSO): δ = 46.9, 55.4, 102.5, 105.8, 112.0,
113.9, 115.1, 119.0, 124.3, 125.2, 125.7, 126.2, 126.4, 127.0, 128.4,
130.4, 132.1, 133.1, 133.7, 136.9, 138.9, 139.2, 143.4, 154.3, 157.9,
174.9 ppm. HRMS: m/z calcd. for C27H23N4O3 [M + H]+ 451.1770;
found 451.1778.
1
2-(1-Benzyl-1H-indole-2-carbonyl)benzaldehyde (22b): According to
General Procedure E, compound 21b (490 mg, 1.32 mmol) and
Pb(OAc)4 (584 mg, 1.32 mmol) in THF (15 mL) were used to fur-
nish 22b (313 mg, 70%) as a yellow solid; m.p. 134 °C; Rf = 0.25
(EtOAc/hexane, 10:90). IR (neat): ν
= 1698, 1650, 1512, 1453,
˜
max
1204 cm–1. H NMR (500 MHz, CDCl3): δ = 6.01 (s, 2 H), 6.85 (s,
1 H), 7.16–7.25 (m, 4 H), 7.31 (m, 2 H), 7.39 (m, 1 H), 7.45 (m, 1
H), 7.64 (m, 2 H), 7.67 (m, 2 H), 8.03 (m, 1 H), 9.97 (s, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 48.2, 111.0, 117.3, 121.3, 123.3,
126.0, 126.5, 127.0, 127.3, 128.6, 129.0, 129.1, 130.5, 133.0, 135.0,
135.2, 138.0, 140.6, 142.4, 188.1, 190.4 ppm. HRMS: m/z calcd. for
C23H17NNaO2 [M + Na]+ 362.1157; found 362.1150.
1
(E)-1-Benzyl-5-(benzyloxy)-NЈ-[(4-hydroxyquinolin-3-yl)methylene]-
1H-indole-2-carbohydrazide (24d): According to General Procedure
D, 1-benzyl-5-(benzyloxy)-1H-indole-2-carbohydrazide (20c;
200 mg, 0.53 mmol) and aldehyde 12 (93 mg, 0.53 mmol) in ethanol
(15 mL) were used to furnish product 24d (251 mg, 90%) as a white
solid; m.p. 286–290 °C. IR (neat): ν
= 3227, 1643, 1569, 1475,
˜
max
1451, 1278 cm–1. H NMR (500 MHz, [D6]DMSO): δ = 5.12 (s, 2
H), 5.86 (s, 2 H), 7.00 (d, J = 8.6 Hz, 1 H), 7.00 (d, J = 7.4 Hz, 2
H), 7.19 (m, 1 H), 7.25 (m, 5 H), 7.32 (t, J = 6.87 Hz, 1 H), 7.39
(m, 3 H), 7.47 (m, 3 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.71 (t, J =
6.87 Hz, 1 H), 8.19 (d, J = 7.45 Hz, 1 H), 8.49 (s, 1 H), 8.76 (s, 1
H), 11.87 (s, 1 H), 12.4 (br. s, 1 H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 46.9, 69.8, 104.0, 105.8, 112.0, 113.8, 115.6, 119.0,
124.3, 125.2, 125.7, 126.1, 126.4, 126.9, 127.6, 128.4, 130.5, 132.1,
133.8, 136.9, 137.5, 138.8, 139.2, 143.4, 153.3, 174.9 ppm. HRMS:
m/z calcd. for C33H27N4O3 [M + H]+ 527.2083; found 527.2082.
1
4-[1-(4-Methoxybenzyl)-1H-indole-2-carbonyl]quinoline-3-carbalde-
hyde (25a): According to General Procedure E, compound 24a (1 g,
2.20 mmol) and Pb(OAc)4 (974 mg, 2.20 mmol) in THF (25 mL)
were used to furnish 25a (683 mg, 74%) as a red solid; m.p. 190–
192 °C; R = 0.33 (EtOAc/hexane, 20:80). IR (neat): ν
= 1697,
˜
f
max
1647, 1512, 1477, 1456, 1403, 1248 cm–1 1H NMR (500 MHz,
.
CDCl3): δ = 3.80 (s, 3 H), 6.02 (s, 2 H), 6.86 (s, 1 H), 6.88 (d, J =
8.5 Hz, 2 H), 7.14 (t, J = 7.3 Hz, 1 H), 7.19 (d, J = 8.9 Hz, 2 H),
7.42–7.49 (m, 2 H), 7.53 (t, J = 8.5 Hz, 3 H), 7.85 (m, 1 H), 8.23
(d, J = 8.2 Hz, 1 H), 9.45 (s, 1 H), 10.06 (s, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 48.0, 55.3, 111.1, 114.1, 118.4, 121.7, 123.6,
124.5, 126.2, 126.8, 127.9, 128.2, 128.4, 130.0, 132.7, 134.7, 141.1,
149.0, 149.1, 150.3, 159.1, 186.3, 189.1 ppm. HRMS: m/z calcd. for
C27H21N2O3 [M + H]+ 421.1552; found 421.1556.
(E)-1-Benzyl-5-chloro-NЈ-[(4-hydroxyquinolin-3-yl)methylene]-1H-
indole-2-carbohydrazide (24e): According to General Procedure D,
1-benzyl-5-chloro-1H-indole-2-carbohydrazide (20d; 250 mg,
0.83 mmol) and aldehyde 12 (143 mg, 0.83 mmol) in ethanol
(12 mL) were used to furnish product 24e (342 mg, 91%) as a white
4-(1-Benzyl-1H-indole-2-carbonyl)quinoline-3-carbaldehyde (25b):
solid; m.p. 284–285 °C. IR (neat): ν
= 3139, 3040, 1644, 1557, According to General Procedure E, compound 24b (180 mg,
˜
max
1475, 1458, 1258 cm–1. H NMR (500 MHz, [D6]DMSO): δ = 5.90 0.43 mmol) and Pb(OAc)4 (190 mg, 0.43 mmol) in THF (10 mL)
1
(s, 2 H), 7.70 (d, J = 7.3 Hz, 2 H), 7.18–7.28 (m, 4 H), 7.35 (s, 1
H), 7.41 (t, J = 6.9 Hz, 1 H), 7.60–7.72 (m, 3 H), 7.82 (s, 1 H), 8.18
(d, J = 6.87 Hz, 1 H), 8.49 (s, 1 H), 8.77 (s, 1 H), 11.97 (s, 1 H),
were used to furnish 25b (124 mg, 74%) as a red solid; m.p. 142 °C;
R = 0.40 (EtOAc/hexane, 40:60). IR (neat): ν = 1695, 1643,
˜
f
max
1562, 1511, 1452, 1247 cm–1. 1H NMR (500 MHz, CDCl3): δ =
12.36 (br. s, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 47.0, 6.11 (s, 2 H), 6.69 (s, 1 H), 7.15 (t, J = 7.7 Hz, 1 H), 7.23 (m, 2 H),
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O42837
/KAP1
Date: 18-09-14 17:48:34
Pages: 11
D. H. Dethe, G. M. Murhade
FULL PAPER
7.29–7.37 (m, 3 H), 7.41–7.57 (m, 5 H), 7.85 (t, J = 7.7 Hz, 1 H),
and BF3·OEt2 (0.032 mL, 0.264 mmol) in CH2Cl2 (7 mL) were used
8.23 (d, J = 8.3 Hz, 1 H), 9.45 (s, 1 H), 10.06 (s, 1 H) ppm. 13C to furnish 23a (33 mg, 74%) as a light-orange solid; m.p. 252 °C;
NMR (125 MHz, CDCl3): δ = 48.5, 111.0, 118.3, 121.7, 123.5,
124.5, 124.5, 126.1, 126.6, 126.7, 127.5, 127.9, 128.4, 128.7, 129.8,
132.7, 134.6, 137.8, 141.1, 148.9, 149.0, 150.2, 186.2, 188.9 ppm.
HRMS: m/z calcd. for C26H19N2O2 [M + H]+ 391.1447; found
391.1457.
R = 0.33 (EtOAc/hexane, 20:80). IR (neat): ν
= 1654, 1511,
max
˜
f
1260, 1207 cm–1. H NMR (500 MHz, CDCl3): δ = 5.99 (s, 2 H),
7.19 (d, J = 6.7 Hz, 2 H), 7.26–7.31 (m, 3 H), 7.42–7.47 (m, 1 H),
7.49 (m, 2 H), 7.93 (d, J = 4.8 Hz, 1 H), 8.51 (d, J = 7.9 Hz, 1 H),
9.03 (d, J = 4.6 Hz, 1 H), 9.46 (s, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 48.6, 111.7, 118.7, 119.6, 123.9, 124.3, 125.3, 126.7,
128.0, 128.5, 129.0, 136.2, 139.1, 140.3, 148.5, 155.0, 177.8,
180.8 ppm. HRMS: m/z calcd. for C22H15N2O2 [M + H]+ 339.1134;
found 339.1130.
1
4-(1-Benzyl-5-methoxy-1H-indole-2-carbonyl)quinoline-3-carbalde-
hyde (25c): According to General Procedure E, compound 24c
(170 mg, 0.37 mmol) and Pb(OAc)4 (167 mg, 0.37 mmol) in THF
(10 mL) were used to furnish 25c (105 mg, 68%) as a dark-red so-
lid; m.p. 200–202 °C; Rf = 0.2 (EtOAc/hexane, 20:80). IR (neat):
5-Benzyl-5H-benzo[b]carbazole-6,11-dione (23b): According to Ge-
neral Procedure F, compound 22b (40 mg, 0.117 mmol) and
BF3·OEt2 (0.029 mL, 0.235 mmol) in CH2Cl2 (7 mL) were used to
furnish 23b (31 mg, 74%) as a yellow solid; m.p. 130–132 °C; Rf =
ν
= 1697, 1643, 1572, 1517, 1454, 1244, 1211 cm–1. 1H NMR
˜
max
(400 MHz, CDCl3): δ = 3.76 (s, 3 H), 6.06 (s, 2 H), 6.57 (s, 1 H),
6.87 (d, J = 2.2 Hz, 1 H), 7.11 (dd, J = 2.2, 9.3 Hz, 1 H), 7.19 (d,
J = 6.8 Hz, 2 H), 7.30–7.41 (m, 4 H), 7.48 (t, J = 7.3 Hz, 1 H),
7.56 (d, J = 7.8 Hz, 1 H), 7.85 (t, J = 7.1 Hz, 1 H), 8.22 (d, J =
8.5 Hz, 1 H), 9.44 (s, 1 H), 10.05 (s, 1 H) ppm. 13C NMR
(500 MHz, CDCl3): δ = 48.7, 55.6, 102.4, 112.2, 117.6, 120.4, 124.5,
124.5, 126.4, 126.6, 126.8, 127.6, 128.4, 128.8, 129.9, 132.7, 134.8,
136.9, 137.9, 148.8, 149.3, 150.3, 155.2, 185.8, 189.0 ppm. HRMS:
m/z calcd. for C27H21N2O3 [M + H]+ 421.1552; found 421.1559.
0.33 (EtOAc/hexane, 20:80). IR (neat): ν
= 1652, 1596, 1516,
˜
max
1466, 1340, 1303 cm–1. H NMR (400 MHz, CDCl3): δ = 5.98 (s,
2 H), 7.17–7.30 (m, 5 H), 7.37–7.45 (m, 3 H), 7.66 (t, J = 7.3 Hz,
1 H), 7.71 (t, J = 7.3 Hz, 1 H), 8.13 (d, J = 7.3 Hz, 1 H), 8.21 (d,
J = 7.8 Hz, 1 H), 8.48 (d, J = 7.8 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 48.4, 111.4, 119.3, 123.9, 124.0, 124.6,
126.2, 126.5, 126.6, 127.6, 127.7, 128.8, 132.8, 133.5, 133.8, 134.0,
134.7, 136.5, 139.7, 178.9, 181.2 ppm. HRMS: m/z calcd. for
C23H16NO2 [M + H]+ 362.1157; found 362.1150.
1
4-[1-Benzyl-5-(benzyloxy)-1H-indole-2-carbonyl]quinoline-3-carb-
aldehyde (25d): According to General Procedure E, compound 24d
(180 mg, 0.34 mmol) and Pb(OAc)4 (150 mg, 0.34 mmol) in THF
(10 mL) were used to furnish product 25d (119 mg, 71%) as a red
solid; m.p. 140–142 °C; Rf = 0.33 (EtOAc/hexane, 20:80). IR (neat):
12-(4-Methoxybenzyl)-7H-indolo[3,2-j]phenanthridine-7,13(12H)-di-
one (26a): According to General Procedure F, compound 25a
(200 mg, 0.476 mmol) and BF3·OEt2 (0.116 mL, 0.952 mmol) in
CH2Cl2 (15 mL) were used to furnish 26a (159 mg, 80%) as a red
ν
˜
= 1698, 1628, 1573, 1495, 1453, 1242 cm–1 1H NMR
.
max
(400 MHz, CDCl3): δ = 5.01 (s, 2 H), 6.06 (s, 2 H), 6.55 (s, 1 H),
6.93 (m, 1 H), 7.19 (m, 3 H), 7.29–7.42 (m, 9 H), 7.48 (m, 1 H),
7.55 (m, 1 H), 7.85 (m, 1 H), 8.22 (d, J = 8.0 Hz, 1 H), 9.43 (s, 1
H), 10.05 (s, 1 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 48.6,
70.4, 104.0, 112.1, 117.6, 120.8, 124.5, 124.5, 126.4, 126.6, 127.3,
127.6, 127.9, 128.4, 128.5, 128.7, 129.8, 132.7, 134.8, 136.8, 137.9,
148.8, 149.2, 150.2, 154.3, 185.8, 189.0 ppm. HRMS: m/z calcd. for
C33H25N2O3 [M + H]+ 497.1865; found 497.1866.
solid; m.p. 243 °C; R = 0.33 (EtOAc/hexane, 20:80). IR (neat): ν
˜
f
max
= 1650, 1609, 1512, 1497, 1512, 1238 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 3.74 (s, 3 H), 5.91 (s, 2 H), 6.82 (d, J = 8.2 Hz, 2 H),
7.19 (d, J = 8.2 Hz, 2 H), 7.38–7.49 (m, 3 H), 7.73 (t, J = 7.3 Hz,
1 H), 7.81 (t, J = 7.3 Hz, 1 H), 8.17 (d, J = 8.2 Hz, 1 H), 8.43 (d,
J = 8.2 Hz, 1 H), 9.55 (d, J = 8.5 Hz, 1 H), 9.77 (s, 1 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 48.0, 55.2, 111.6, 114.2, 117.6, 123.1,
123.3, 123.9, 124.5, 125.1, 127.7, 127.9, 128.1, 128.3, 130.1, 130.3,
131.4, 133.3, 135.1, 140.0, 147.9, 152.1, 159.2, 181.0, 182.0 ppm.
HRMS: m/z calcd. for C27H19N2O3 [M + H]+ 419.1396; found
419.1396.
4-(1-Benzyl-5-chloro-1H-indole-2-carbonyl)quinoline-3-carbaldehyde
(25e): According to General Procedure E, compound 24e (230 mg,
0.50 mmol) and Pb(OAc)4 (221 mg, 0.50 mmol) in THF (10 mL)
were used to furnish 25e (150 mg, 71%) as a red solid; m.p. 136–
12-Benzyl-7H-indolo[3,2-j]phenanthridine-7,13(12H)-dione (26b):
According to General Procedure F, compound 25b (107 mg,
0.278 mmol) and BF3·OEt2 (0.068 mL, 0.556 mmol) in CH2Cl2
(10 mL) were used to furnish 26b (85 mg, 79%) as a red solid; m.p.
140 °C; R = 0.25 (EtOAc/hexane, 20:80). IR (neat): ν
= 1697,
˜
f
max
1648, 1562, 1508, 1452, 1403, 1246 cm–1 1H NMR (400 MHz,
.
CDCl3): δ = 6.08 (s, 2 H), 6.56 (s, 1 H), 7.20 (d, J = 6.9 Hz, 2 H),
7.31–7.38 (m, 5 H),7.47–7.54 (m, 3 H), 7.86 (m, 1 H), 8.24 (d, J =
8.7 Hz, 1 H), 9.44 (s, 1 H), 10.07 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 48.7, 112.3, 116.6, 122.5, 124.5, 126.6,
126.8, 127.3, 127.7, 128.3, 128.6, 128.8, 130.0, 132.9, 135.4, 137.4,
139.2, 148.4, 149.4, 150.3, 188.6, 189.0 ppm. HRMS: m/z calcd. for
C26H18ClN2O2 [M + H]+ 425.1057; found 425.1051.
230 °C; R = 0.25 (EtOAc/hexane, 20:80). IR (neat): ν
= 1653,
˜
f
max
1525, 1495, 1454, 1241 cm–1. 1H NMR (500 MHz, CDCl3): δ =
6.00 (s, 2 H), 7.22 (m, 2 H), 7.27–7.32 (m, 3 H), 7.40–7.47 (m, 3
H), 7.72 (m, 1 H), 7.82 (m, 1 H), 8.18 (d, J = 8.3 Hz, 1 H), 8.45
(d, J = 8.3 Hz, 1 H), 9.53 (d, J = 8.3 Hz, 1 H), 9.78 (s, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 48.5, 111.6, 117.7, 123.1, 123.3,
123.9, 124.5, 125.2, 126.6, 127.7, 127.9, 128.0, 128.9, 130.1, 130.3,
131.4, 133.3, 135.1, 136.2, 140.1, 147.9, 152.2, 181.0, 182.0 ppm.
HRMS: m/z calcd. for C26H17N2O2 [M + H]+ 389.1290; found
389.1290.
Cyclisation Reaction for the Preparation of 23 and 26. General Pro-
cedure F: Under an inert atmosphere of argon, to a stirred solution
of keto-aldehyde in CH2Cl2, BF3·OEt2 (1 equiv.) was added at 0 °C
and the mixture was stirred for 1 h at room temp. The progress of
the reaction was monitored by TLC and, upon completion, the
reaction was quenched by the addition of sodium bisulfate. The
mixture was extracted with CH2Cl2 and the combined organic lay-
ers were washed with brine and dried with anhydrous Na2SO4. The
solvent was removed under reduced pressure and the crude product
was purified on silica gel column chromatography using EtOAc/
hexane as eluent to furnish the product.
12-Benzyl-9-methoxy-7H-indolo[3,2-j]phenanthridine-7,13(12H)-di-
one (26c): According to General Procedure F, compound 25c
(53 mg, 0.126 mmol) and BF3·OEt2 (0.031 mL, 0.25 mmol) in
CH2Cl2 (7 mL) were used to furnish 26c (42 mg, 80%) as a red
solid; m.p. 218–220 °C; Rf = 0.30 (EtOAc/hexane, 20:80). IR (neat):
ν
˜
= 1648, 1614, 1496, 1517, 1474, 1237 cm–1 1H NMR
.
max
(500 MHz, CDCl3): δ = 3.92 (s, 3 H), 5.96 (s, 2 H), 7.05 (d, J =
8.5 Hz, 1 H), 7.20 (m, 2 H), 7.24–7.31 (m, 4 H), 7.24–7.31 (m, 4
H), 7.71 (m, 1 H), 7.80 (m, 2 H), 8.17 (d, J = 8.5 Hz, 1 H), 9.55
6-Benzyl-5H-pyrido[4,3-b]carbazole-5,11(6H)-dione (23a): Accord-
ing to General Procedure F, compound 22a (45 mg, 0.132 mmol)
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42837
/KAP1
Date: 18-09-14 17:48:34
Pages: 11
Diversity-Oriented Synthesis of Calothrixins and Ellipticines
(d, J = 8.5 Hz, 1 H), 9.76 (s, 1 H) ppm. 13C NMR (400 MHz,
CDCl3): δ = 48.7, 55.8, 102.8, 112.7, 117.1, 120.3, 123.3, 124.3,
124.7, 126.6, 127.9, 127.9, 128.9, 130.0, 130.1, 131.5, 133.7, 134.8,
135.5, 136.1, 147.5, 158.3, 168.4, 180.7, 181.3 ppm. HRMS: m/z
calcd. for C27H19N2O3 [M + H]+ 419.1396; found 419.1392.
cial support from the Indian Institute of Technology Kanpur is
gratefully acknowledged.
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12-Benzyl-9-(benzyloxy)-7H-indolo[3,2-j]phenanthridine-7,13(12H)-
dione (26d): According to General Procedure F, compound 25d
(48 mg, 0.096 mmol) and BF3·OEt2 (0.023 mL, 0.193 mmol) in
CH2Cl2 (10 mL) were used to furnish 26d (36 mg, 77%) as a red
solid; m.p. 226 °C; R = 0.30 (EtOAc/hexane, 20:80). IR (neat): ν
˜
f
max
= 1654, 1524, 1496, 1461, 1240 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 5.19 (s, 2 H), 5.98 (s, 2 H), 7.16–7.22 (m, 3 H), 7.28–7.34 (m,
3 H), 7.36 (d, J = 9.2 Hz, 2 H), 7.43 (t, J = 7.4 Hz, 2 H), 7.52 (d,
J = 7.4 Hz, 2 H), 7.73 (m, 1 H), 7.82 (m, 1 H), 7.94 (d, J = 2.2 Hz,
1 H), 8.19 (d, J = 8.5 Hz, 1 H), 9.57 (d, J = 9.2 Hz, 1 H), 9.79 (s,
1 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 48.8, 70.6, 104.2,
112.9, 120.7, 123.3, 124.4, 124.7, 126.7, 127.8, 128.0, 128.2, 128.7,
129.0, 130.1, 130.4, 131.5, 133.6, 134.6, 135.7, 136.3, 136.7, 148.0,
152.2, 153.2, 157.5, 166.4, 168.7, 180.7, 181.7 ppm. HRMS: m/z
calcd. for C33H23N2O3 [M + H]+ 495.1709; found 495.1704.
12-Benzyl-9-chloro-7H-indolo[3,2-j]phenanthridine-7,13(12H)-dione
(26e): According to General Procedure F, compound 25e (50 mg,
0.118 mmol) and BF3·OEt2 (0.029 mL, 0.236 mmol) in CH2Cl2
(10 mL) were used to furnish 26e (37 mg, 75%) as an orange solid;
m.p. 243 °C; R = 0.40 (EtOAc/hexane, 20:80). IR (neat): ν
=
˜
f
max
2921, 1742, 1656, 1523, 1455, 1343, 1236 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 5.97 (s, 2 H), 7.18 (m, 2 H), 7.27–7.33 (m,
4 H), 7.37 (m, 2 H), 7.72 (m, 1 H), 7.82 (m, 1 H), 8.41 (s, 1 H),
9.50 (d, J = 8.5 Hz, 1 H), 9.76 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 48.7, 112.8, 116.9, 123.0, 123.1, 124.0, 124.2, 126.5,
127.6, 128.1, 128.6, 129.0, 130.3, 131.2, 131.6, 133.2, 135.7, 135.8,
138.3, 147.7, 152.1, 180.6, 181.8 ppm. HRMS: m/z calcd. for
C26H16ClN2O2 [M + H]+ 423.0900; found 423.0902.
7H-Indolo[3,2-j]phenanthridine-7,13(12H)-dione (5): A solution of
26a (72 mg, 0.172 mmol) in anhydrous anisole (3 mL) was added
dropwise to a stirred suspension of AlCl3 (114 mg, 0.861 mmol) in
anhydrous anisole (2 mL) at 0 °C, and the resulting reaction mix-
ture was stirred at room temp. for 6 h. After the addition of water,
the mixture was extracted with ethyl acetate and the combined or-
ganic layers were washed with 5% aqueous NaHCO3 and brine
successively, then dried with anhydrous Na2SO4. The solvent was
removed under reduced pressure to give an oil, which was purified
by a silica gel column using EtOAc/hexane as eluent to furnished
the product 5 (34 mg, 78%) as a red solid; m.p. 170–175 °C; Rf =
0.30 (EtOAc/hexane, 20:80). IR (neat): ν
= 3428, 1651, 1050,
˜
max
1026 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 7.40 (t, J =
7.4 Hz, 1 H), 7.48 (t, J = 7.4 Hz, 1 H), 7.61 (t, J = 8.0 Hz, 1 H),
7.89 (t, J = 8.0 Hz, 1 H), 7.96 (t, J = 8.0 Hz, 1 H), 8.17 (d, J =
8.0 Hz, 2 H), 9.57 (d, J = 8.6 Hz, 1 H), 9.61 (s, 1 H) ppm. 13C
NMR (125 MHz, [D6]DMSO): δ = 114.1, 115.7, 122.5, 122.8,
123.5, 124.5, 125.0, 127.3, 130.0, 130.4, 131.7, 132.7, 138.1, 138.6,
147.7, 151.4, 180.5, 181.0 ppm. HRMS: m/z calcd. for C19H11N2O2
[M + H]+ 299.0821; found 299.0824.
Supporting Information (see footnote on the first page of this arti-
1
cle): Experimental details as well as H and 13C NMR spectra of
all the compounds reported in this article.
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Acknowledgments
G. M. thanks the Council of Scientific and Industrial Research
(CSIR), New Delhi, for the award of a research fellowship. Finan-
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Job/Unit: O42837
/KAP1
Date: 18-09-14 17:48:34
Pages: 11
D. H. Dethe, G. M. Murhade
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Date: 18-09-14 17:48:34
Pages: 11
Diversity-Oriented Synthesis of Calothrixins and Ellipticines
Natural Products
D. H. Dethe,* G. M. Murhade ........ 1–11
Diversity-Oriented Synthesis of Calothrix-
ins and Ellipticines
Keywords: Natural products / Nitrogen het-
erocycles / Quinones / Rearrangement /
Oxidation
The divergent synthesis of calothrixins and
ellipticines has been accomplished by utilis-
ing the one-pot formation of o-diacylarenes
as a key intermediate through rearrange-
ment of o-hydroxy ketone monoacyl
hydrazones by lead tetraacetate mediated
oxidation.
Eur. J. Org. Chem. 0000, 0–0
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11