Indole as a tool in synthesis. Algorithmic construction of a family of compounds with all ring sizes ranging from 10 to 16

Article abstract of DOI:10.1016/S0040-4020(00)00912-1

An iterating two-step ring extension process including indolisation-oxidation by ozone applied to an eight membered cyclanone allowed the preparation of seven compounds with ring sizes ranging from 10 to 16. The structure of all derivatives were assigned

Full text of DOI:10.1016/S0040-4020(00)00912-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9641±9646
Indole as a Tool in Synthesis. Algorithmic Construction of a
Family of Compounds with all Ring Sizes Ranging from 10 to 16
*
Fran cË oise Sigaut, Betty Didierdefresse and Jean L e vy
UPRESA CNRS 6013, Isolement, Structure, Transformations et Synth eÁ se de Substances Naturelles,
IFR 53 `Biomol e cules' Facult e de Pharmacie, 3 rue du Mar e chal Juin, F-51096 Reims cedex, France
Received 12 July 2000; revised 11 September 2000; accepted 29 September 2000
AbstractÐAn iterating two-step ring extension process including indolisation±oxidation by ozone applied to an eight membered cyclanone
allowed the preparation of seven compounds with ring sizes ranging from 10 to 16. The structure of all derivatives were assigned by
1
13
spectroscopic data, particularly by H and C NMR, COSY, HMBC and HMQC experiments. q 2000 Elsevier Science Ltd. All rights
reserved.
1
Some time ago we reported the synthesis of compound 5
with a 14-membered ring by means of an iterating Fischer's
indolisations and oxidations via 3±4 starting from cyclo-
octanone 1 (Scheme 1). It soon became apparent that 5
was prone to two different modes of intramolecular cycli-
sations. Heating 5 in acidic medium gave the benzodiazo-
cine 14 resulting from a cyclization between the reactive
with phenylhydrazine in AcOH±H SO thus produced the
2 4
10-membered indolo±quinazolinone compound 7. It is
interesting to note that some of these compounds were
related to the cyclic polyanthranilates, synthesized by
using a more classical approach.
Ollis and collaborators2
,3,4,5
In our case, ring extension by reduction of the quinazo-
6
,7
linone 7 with BH is possible leading to the 1,5-diamine 16
3
C -keto group and N15a±H. Formation of the 7-phenyl-
7
(Scheme 1).
hydrazone 15 prevented cyclisation while the 1,6 relation-
ship between the C -carbonyl and N prompted the well
precedented formation of a quinazolinone under the acidic
conditions used in the Fischer's indole synthesis. Heating 5
The novel indole appendage in 7 seemed to allow the con-
tinuation of the indolisation±oxidation process with a
`chemical algorithm' in mind that would possibly generate
1
15b
3 3 2 2 3 2 4 3
Scheme 1. (a) O , (CH ) S. (b) PhNHNH . (c) CH COOH/H SO . (d) BH ±DMS.
Keywords: macrocycles; quinazolinones; indolisation; ozonolysis.
*
Corresponding author. Tel.: 133-3-26-91-20-27; fax: 133-3-26-91-80-29; e-mail: francoise.sigaut@univ-reims.fr
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00912-1

9
642
F. Sigaut et al. / Tetrahedron 56 (2000) 9641±9646
Scheme 2. `Chemical algorithm'.
a series of compounds with ring sizes ranging from 10 to as
high as possible.
insolubility in commonly used solvents. From the mother
liquors, we were able to isolate compound 18 which had lost
an anthranilic unit. This regression to the 12-membered ring
is thought to result from fragmentation of intermediate 17.
Each oxidation±indolization step would increase the ring
size by 3 units. After two repetitions of such a sequence
the 1,6 relationship of NH and CO functions would be set
up, thus allowing cyclisation to a quinazolinone core with
concomitant regression of the central macrocycle by 4 units
The structure of all derivatives was ascertained by their
1
13
spectroscopic data, particularly by H and C NMR. The
assignments were based on COSY, HMBC and HMQC
experiments.
(
Scheme 2).
Ozonolysis of 7 gave the keto-lactam 8 (13-membered ring),
which was subjected to Fischer indolisation conditions to
generate the indolo±quinazolinone 9. Further oxidation of
this latter smoothly afforded macrocycle 10 (16-membered
ring) (Scheme 3).
For homogeneity, we decided to use a biogenetic-like
numbering, which means that each atom keeps its original
number after transformation.
In each indolisation seven further atoms are incorporated
which have the same number but are distinguished by letters
referring to the successive indolisation: a for the ®rst indo-
lisation, b for the second one, and so on. An illustration of
this particular numbering for 10 is as shown in Scheme 4.
In order to complete the collection, the 16-membered
macrocycle 10 was submitted to indolisation to lead to 11
(25%) (16-membered ring) and 12 (15%) with a 12
membered central ring system.
1 13
For the simplest structures (2±10) each H and C NMR
The regression of the ring by 4 units is due to a stereo-
electronically favoured cyclization to a quinazolinone.
However, this cyclization did not abort the synthesis, as
further oxidation of 12 could be performed allowing the
preparation of the 15-membered ring compound 13. On
the contrary, ozonolysis of 11 was not feasable due to its
signal could be individually attributed (Table 1 and Table 2)
but the complexity of spectra, in particular, H NMR of the
1
aromatic region, did not allow a full individual assignment
for higher homologs like 11, 12 and 13 (separate description
1
3
in the Experimental part). On the contrary, C NMR data
completed by HMBC and HMQC experiments led to a full

F. Sigaut et al. / Tetrahedron 56 (2000) 9641±9646
9643
3 3 2 2 3 2 4
Scheme 3. (a) O , 2808, (CH ) S. (b) PhNHNH . (c) CH COOH/H SO .
assignment of all the carbons in the molecules even if some
signals remained interchangeable.
strategy, although using unnatural building blocks and
constructing unnatural products. Thus repetition of a few
unitary processes and serial introduction of a building
block (Ph±±N from phenylhydrazine) leads to a series of
This approach is proposed as a model of a biosynthetic
Scheme 4. Example for numbering of macrocycle 10.

9
644
F. Sigaut et al. / Tetrahedron 56 (2000) 9641±9646
1
Table 1. H NMR data of macrocycles 2±10
related compounds with structural relationships resembling
those in such families of natural products as terpenes or
polyketides. In analogy with natural processes, deviations
from the standard algorithm are observed in the cases when
it leads to a peculiar organization of the molecule respon-
sible for anecdotic events.
H
2
3
4
5
6
7
9
10
2
3
4
5
6
7
2.8 2.3 2.2 2.3 2.5
1.7 1.7 1.7 1.8 1.3, 1.8 1.4
1.4 1.4 1.3 1.5 1.8
1.5 1.4 1.4 1.8 2.4
1.7 1.7 2.6 3.2
2.3, 2.5 1.2
2.2
2.2, 2.9 1.7, 2.6
2.8
1.4
2.4, 2.9
1.7, 2.6
2.7 2.7
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0a
7.5 7.5 7.7 8.0 8.15
7.0 7.3 7.2 7.5 7.4
7.0 7.3 7.4 8.2 7.7
7.2 7.2 7.3 7.2 7.5
8.1
7.5
7.8
7.6
8.1
7.5
7.8
7.6
8.15
7.5
7.8
7.7
1a
2a
3a
Experimental
Melting points were determined on a Reichert apparatus and
were uncorrected. UV spectra (nm) were recorded in MeOH
solutions with Philips Unicam SP 8700 spectrophotometer
and IR spectra were recorded on a Bomen spectro-
5a 10.0 10.0 10.6 11.2
0b
1b
2b
3b
5b
0c
1c
2c
3c
5c
0d
1d
2d
3d
5d
7.5 7.7 7.3
7.1 7.5 7.6
6.9 7.5 7.6
7.4 7.3 7.7
8.4 10.8
7.5
7.0
8.1
7.7
7.8
7.6
7.8
7.6
7.7
7.6
7.9
7.6
7.7
7.5
2
1
photometer, wavenumbers are expressed in cm . Mass
spectra (EIMS and HREIMS) were recorded on a VG Auto-
spec X101 instrument. H NMR spectra were measured at
7.5
7.3
7.5
7.4
7.4
7.3
7.3
7.5
10.1
7.6
6.9
7.1
8.1
7.2
7.5
7.8
10.9
7.8
7.3
7.6
7.6
11.5
1
7.1
7.2
9.4
13
3
3
00 MHz and C NMR spectra at 75 MHz on a Bruker AC
00 spectrometer using DMSO-d as solvent; chemical
6
10.6
shifts are reported in ppm taking the signal of DMSO as
internal reference. Analytical thin layer chromatographies
were performed on pre-coated plates (Kieselgel 60 F254)
and were visualized by UV; for column chromatographies
Kieselgel 60, 70±230 mesh was used.
7.3
11.0
1
3
13
Table 2. C NMR data of macrocycles 2±13 (For compounds 11 and 12 C NMR were measured at 3538K; italicized signals may be interchanged
q: quaternary C))
(
C
2
3
4
5
7
8
9
10
11
12
13
1
2
3
4
5
6
7
8
136.0
22.0
29.0
25.0
25.0
172.4
36.1
22.2
24.3
25.5
172.5
36.2
25.5
26.8
35.5
170.7
37.3
23.1
25.0
22.3
156.5
29.6
26.4
25.4
19.8
155.0
31.5
23.0
22.2
42.5
155.2
37.0
26.5
155.6
34.0
18.8
157.0
29.0
38.0
157.0
29.2
32.8
155.0
31.1
32.0
23.6
38.3
111.0
136.0
171.1
163.0
161.5
120.5
126.4
126.4
134.6
127.1
147.0
134q
118.6
120.9
122.2
128.6
136q
140q
129.2
131.5
132.5
134.1
146q
123.9
130.8
118.5
130.8
130.8
136.0
127.9
115.0
118.2
116.3
11.3
115.8
136.3
161.0
151.0
164.0
120.5
126.4
126.4
134.7
127.1
147.0
136q
125.4
127.0
129.1
129.3
135q
122.0
125.2
125.4
133.1
127.2
145.7
134q
129.6
130.3
130.7
131.4
134q
125.0
115.2
116.7
115.5
115.0
129.3
168.2
164.0
161.0
151.6
161.0
122.0
126.0
127.0
135.0
129.0
148.0
132q
124.0
125.1
125.6
127.9
132q
121.1
127.3
127.0
134.0
129.1
147.0
134q
128.2
129.1
129.4
130.0
135q
136q
130.0
131.0
131.5
133.3
138q
112.2
130.6
164.5
162.2
120.7
126.6
126.4
134.4
126.9
147.3
134.1
128.8
129.3
131.8
130.3
135.6
131.7
131.7
125.6
127.8
127.8
135.1
128.1
119.0
118.5
121.3
111.2
136.8
202.0
167.8
164.2
161.4
120.6
126.6
126.6
127.1
127.1
147.2
134.2
128.9
129.9
132.4
130.9
135.7
134.2
128.7
124.2
123.4
123.4
138.1
133.4
128.8
126.1
126.7
132.5
135.5
29.0
25.0
23.2
38.8
26.8
36.1
114.0
130.5
163.0
119.5
126.2
126.1
134.8
126.5
147.0
133.2
130.0
130.0
130.0
128.4
137.8
127.1
118.5
118.8
121.8
111.2
135.8
203.5
164.5
162.0
120.5
126.5
126.0
134.0
127.0
147.2
132.5
129.0
130.0
132.0
131.0
136.5
134.5
129.5
126.5
131.5
128.5
135.0
113.0
131.0
127.0
128.0
131.5
124.6
125.8
137.0
129.0
118.5
120.0
120.0
111.2
136.3
203.3
167.0
122.0
128.7
132.4
122.1
123.1
138.8
133.7
127.2
131.1
122.7
126.0
136.5
111.0
128.0
117.0
119.0
120.0
110.0
135.0
205.0
127.4
127.4
127.4
131.1
126.4
138.8
9
1
1
1
1
1
9
1
1
1
1
1
9
1
1
1
1
1
9
1
1
1
1
1
9
1
1
1
1
1
a
0a
1a
2a
3a
4a
b
0b
1b
2b
3b
4b
c
0c
1c
2c
3c
4c
d
0d
1d
2d
3d
4d
e
0e
1e
2e
3e
4e
133.1

F. Sigaut et al. / Tetrahedron 56 (2000) 9641±9646
9645
General procedure for indole synthesis
4. Amorphous; UV: 205, 224, 285, 293; IR (®lm): 3400,
3
1
300, 1650; EIMS: 304 (100) [M ], 276, 247, 219.
A mixture of the ketone and phenylhydrazine (97%),
(
0.5 mL for 2 mmol) was stirred at room temperature.
5. Amorphous; UV: 220, 250, 300; IR (KBr): 3260, 1740,
1600; EIMS: 336 (30) [M ], 120 (100); HREIMS: calcd for
C H N O : 336.1473, found: 336.1498.
20 20 2 3
1
After complete conversion of the ketone into the hydra-
zones, the mixture was diluted with CH Cl (20 mL) and
washed with 20% H SO (50 mL for 2 mmol). The organic
2
2
2
4
phase was then dried (MgSO ) ®ltered and concentrated in
4
7. Amorphous; UV: 222, 270, 280; IR (KBr): 3280, 1660;
EIMS: 391 (30) [M ], 362 (20), 336 (28), 302 (35), 259
1
vacuo. The residue was used without further puri®cation.
The crude phenylhydrazone was then diluted with glacial
CH COOH (5 mL for 10 mmol) and cooled to 108C in an
(50), 221 (100); HREIMS: calcd for
391.1681, found: 391.1669.
C H N O:
26 21 3
3
ice±water bath. Indolisation of the hydrazones was started
by dropwise addition of 98% H SO (1 mL for 10 mmol).
8. Amorphous; UV: 225, 265, 305, 318; IR (KBr): 3150,
1650; EIMS: 423 (25) [M ], 300 (25), 120 (100); HREIMS:
calcd for C26H N O : 423.1578, found: 423.1560.
21 3 3
2
4
1
Stirring was continued at room temperature. For compounds
and 4 the reaction mixture was diluted with H O and
extracted with CH Cl . The combined organic layers were
2
2
2
2
washed with saturated NaHCO solution, dried (MgSO ),
3
9. Amorphous; UV: 225, 278, 300; IR (®lm): 3210, 1660;
EIMS: 496 (40) [M ], 150 (100); HREIMS: calcd for
4
1
®
ltered and concentrated in vacuo. The reaction products
were separated by column chromatography (eluent: 2:
hexane, hexane/CH Cl 4:1; 4: CH Cl ). Compounds 7, 9,
C H N O : 496,1894, found: 496,2026.
32 24 4 2
2
2
2
2
11 and 12 were precipitated by water and isolated by ®ltra-
tion. The crude products were washed with CH Cl and
10. Amorphous; UV: 220, 265, 305, 320; IR (®lm): 3180,
1650; EIMS 582 (80) [M ], 394 (88), 381 (82), 235 (80),
1
2
2
dried at 608C under reduced pressure during 4 days to afford
respectively 7 and 9. For compounds 11 and 12 the crude
product were washed with CH Cl to afford 18 and then
120 (100); HREIMS: calcd for C32
found: 528.1874.
H N O : 528.1792,
24 4 4
2
2
extracted with CH Cl /MeOH 9:1 to furnish 12 and the
2
residual solid was 11. 11 and 12 were also dried under
reduced pressure at 608C during 4 days.
11. Amorphous yellow solid; UV: 226, 283, 293; IR (KBr):
3300, 3260, 1740, 1660; H NMR (3538K): 1.25 (2H, m),
2.5 (2H, m), 6.55 (1H, t), 6.75 (1H, t), 6.8±7.1 (5H), 7.2±7.9
2
1
Compounds
2
4
7
9
11
12
Reaction time hydrazone
Reaction time indole
Yield (%)
10 min
2 h
97
2 h
2 h
65
15 h
64 h
35
12 h
48 h
79
2 h
5 days
25
2 h
5 days
15
General procedure for ozonolysis
(9H), 8.0±8.1 (3H), 8.3 (1H, d), 10.0 (N±H), 10.6 (N±H);
EIMS: 601 (60) [M ], 584 (10), 510 (25), 218 (100);
1
Ozone was bubbled through a stirred solution of the indole
in CH Cl (2 mmol in 50 mL) at 2808C, until the red color
HREIMS: calcd for
601.2117.
C H O N : 601.2113, found:
38 27 3 5
2
2
of Sudan III disappeared (5 min for 1 mmol). The mixture
was then purged with N and dimethylsul®de was added
12. Amorphous; UV: 225, 278, 300; IR (KBr): 3200, 1650;
H NMR: 0.85 (2H, m), 2.85 (2H, m), 6.00 (1H, d), 6.2 (1H,
2
1
(
0.1 mL for 1 mmol). The mixture was kept cold for 1 h
and left at room temperature for 2 h. The organic solvent
was then evaporated under reduced pressure. The crude
products were puri®ed by crystallization (CR) or by column
chromatography (CC).
t), 6.6±6.9 (3H), 7.35 (1H, t), 7.45±8.1 (13H), 8.1 (1H, d),
10.0 (1H, s); EIMS: 583 (80) [M ], 422 (100); HREIMS:
1
calcd for C38
H
N
5
O
2
: 583.2008, found: 583.2014.
25
1
3. Amorphous; UV: 224, 260, 305, 320; IR (®lm): 1660; H
1
Compounds
3
5
8
10
13
Puri®cation
Solvent or
Eluent
CR
MeOH
CC
CH Cl /MeOH (98:2)
CC
CH Cl /MeOH
2 2
(98:2 to 90:10)
87
CC
CH Cl /MeOH
(98:2 to 90:10)
93
Not puri®ed
2
2
2
2
Yield (%)
72
57
90
2
2
1
. Yellow oil; UV: 204, 228, 284; IR (®lm): 3393 (NH),
900, 1600, 1450, 743; EIMS: 199 (100) [M ], 170, 156,
44, 130.
NMR: 2.5 (2H, m), 2.52 to 3 (2H, m), 7.0 (1H, t), 7.1 (1H, t),
7.2 (1H, t), 7.28 (2H, d), 7.32 (1H, t), 7.35 (2H, d), 7.41 (1H,
t), 7.48 (1H, t), 7.58 (1H, t and 2H, d), 7.60 (1H, t), 7.61 (2H,
d), 7.70 (1H, t), 7.90 (1H, d), 8.28 (N±H); EIMS: 615 (25)
1
1
3. Pale yellow crystals; mp: 1538C; UV: 204, 221, 250, 293;
IR (KBr): 3310, 1680; EIMS: 231 (45) [M ], 120 (100).
[M ], 275 (100), 247 (80); HREIMS: calcd for C H N O :
3
8
25
5
4
1
615.1863, found: 615.1807.

9
646
F. Sigaut et al. / Tetrahedron 56 (2000) 9641±9646
14. Compound 4 (120 mg, 0.36 mmol) in 1 mL CH COOH/
H SO (5:1) was stirred at room temperature for 3 h, then
the reaction mixture was diluted with H O and extracted
2
(C-11a), 116.0 (C-11b), 118.0 (C-11c), 118.5 (C-10c),
3
119.0 (C-12b), 121.0 (C-12c), 122.0 (C-9a), 128.0
(C-12a), 128.5 (C-9c), 129.0 (C-12b), 131.0 (C-10a),
131.5 (C-10b), 133.0 (C-7), 136.0 (C-14c), 147.0 (C-14b),
2
4
with CH Cl . The combined organic solvents were washed
2
2
1
with saturated NaHCO solution, dried (MgSO ), ®ltered
3
147.5 (C-14a); EIMS: 381 (70) [M ] 118 (100); HREIMS:
calcd for C H N : 381,2205, found: 381,2342.
4
and concentrated in vacuo. The crude residue was puri®ed
by preparative TLC (CH Cl /MeOH 95:5) to furnish 14
2
6
27
3
2
2
(
1
72 mg, 63%); UV: 203, 240; IR (CH Cl ): 3300, 1780,
2
18. Amorphous; UV: 224, 280, 300; IR (®lm): 3319, 1670,
1577; H NMR: 1.3 (1H, m, H-2), 2.1 (1H, m, H-2), 2.7 (1H,
2
1
720; H NMR: 1.6 (2H, m, H -4), 1.8 (2H, m, H -3), 2.3
1
2
2
(
4H, m, H -2, H -5), 3.4 (1H, s, NH-15b), 5.2 (1H, t,
2
m, H-3), 2.9 (1H, m, H-3), 6.9 (1H, H-11e), 7.1 (1H, H-12e),
7.3 (1H, H-12d), 7.3 (1H, H-11d), 7.35 (1H, H-13e), 7.4
(1H, H-10d), 7.45 (1H, H-13d), 7.5 (1H, H-11a), 7.55
(1H, H-10e), 7.6 (2H, H-13b, H-11b), 7.65 (1H, H-13a),
7.7 (1H, H-12b), 7.8 (2H, H-12a, H-10b), 8.1 (1H,
H-10a), 10.1 (1H, H-15d), 10.5 (1H, H-15e); C NMR:
23.6 (C-2), 26.5 (C-3), 111.2 (C-13e), 112.2 (C-9e), 118.5
(C-11e), 119.0 (C-10e), 120.7 (C-9a), 125.6 (C-12e, C-12d),
126.6 (C-11a), 126.9 (C-10a), 127.7 (C-11d, C-13b, C-13d),
2
Jˆ5 Hz, H-6), 7.2 (1H, H-13a), 7.23 (1H, H-11b), 7.25
(
(
1H, H-13b), 7.28 (1H, H-11a), 7.35 (1H, H-12b), 7.52
1H, H-10b), 7.53 (1H, H-12a), 7.91 (1H, H-10a);
1
3
C
NMR: 21.0 (C-5), 21.5 (C-3), 30.0 (C-4), 361 (C-2), 103.0
1
3
(
(
C-6), 122.0 (C-13b), 126.5 (C-9a), 127.5 (C-11b), 130.0
C-12b), 131.0 (C-10a), 132.0 (C-12a), 136.5 (C-14a),
139.0 (C-14b), 145.0 (C-7), 157.5 (C-8), 172.0 (C-1);
EIMS: 318 (20) [M ], 151 (100).
1
1
28.0 (C-4e, C-9d), 129.3 (C-11b), 130.5 (C-13a), 130.6
16. To a stirred solution of 7 (200 mg, 0.75 mmol) in anhy-
drous THF (15 ml) was added a solution of BH /DMS
(C-5e), 131.7 (C-12a, C-12b, C-10d), 134.1 (C-9b), 134.3
(C-10b), 135.5 (C-14d), 136.6 (C-14e,C-14b), 147.3
(C-14a), 155.2 (C-1), 162.3 (C-8), 164.6 (C-6); EIMS:
3
(
7.5 ml of 1 M solution in DMS, 7.5 mmol) under nitrogen.
1
Stirring was continued for 2 h at room temperature, and then
the mixture was heated at re¯ux for 2 h. After cooling at
room temperature water (10 ml) was added slowly to the
stirred mixture. 50% aqueous NaOH (20 ml) was then
added, and stirring was continued for 1 h. The mixture
was then extracted with CH Cl . The combined extracts
482 (30) [M ] 150 (100).
References
1. Sigaut, F.; L e vy, J. Tetrahedron Lett. 1989, 22, 2937±2940.
2. Hoofar, A.; Ollis, W. D.; Price, J. A.; Stephanidou-Stephanatou,
J.; Stoddart, J. F. J. Chem. Soc., Perkin Trans. 1 1982, 1649±1699.
3. Edge, S. J.; Ollis, W. D.; Stephanidou-Stephanatou, J.; Stoddart,
J. F. J. Chem. Soc., Perkin Trans. 1 1982, 1701±1714.
4. Ollis, W. D.; Stephanidou-Sthephanatou, J.; Stoddart, J. F.
J. Chem. Soc., Perkin Trans. 1 1982, 1715±1720.
5. Hoofar, A.; Ollis, W. D.; Stoddart, J. F. J. Chem. Soc., Perkin
Trans. 1 1982, 1721±1726.
2
2
were dried (MgSO ) and were evaporated under reduced
4
pressure to give the crude product, which was puri®ed by
column chromatography (hexane/ethyl acetate 99:1 to
8
0:20) to afford diamine 16 (90 mg, 31%); amorphous;
1
UV: 205, 225, 248, 294; IR (®lm): 3500; H NMR: 1.0±
.6 (6H, m, H -2, H -3, H -4), 2.5 (1H, m, H-5), 2.7 (1H, m,
H-5), 3.0 (2H, m, H -1), 4.8 (1H, s, NH-15a), 4.25 (2H, d,
1
2
2
2
2
H -8), 5.2 (1H, s, NH-15b), 6.4 (1H, H-13a), 7.0 (2H, H-12a,
2
H-11c), 7.1 (2H, H-10b, H-12c), 7.2 (2H, H-10a, H-12b),
6. Takeuchi, H.; Matsushita, Y.; Eguchi, S. J. Org. Chem. 1991,
56, 1535±1537.
1
3
7.3 (1H, H-13c), 7.5 (1H, H-10c); C NMR: 23.6 (C-5),
25.5 (C-3), 26.0 (C-2), 29.0 (C-4), 42.0 (C-1), 47.0 (C-8),
110.0 (C-13a, C-13b), 111.0 (C-13c), 112.5 (C-6), 115.0
7. Eguchi, S.; Matsushita, Y.; Takeuchi, H. J. Org. Chem. 1992,
57, 6975±6979.