Design and effective synthesis of the first 4-aza-2,3- didehydropodophyllotoxin rigid aminologue: A N-methyl-4-[(3,4,5- trimethoxyphenyl)amino]-1,2-dihydroquinoline-lactone

Article abstract of DOI:10.1021/jo800166b

(Chemical Equation Presented) The first N1-alkyl-4-amino-1,2- dihydroquinoline-lactone has been prepared by a five-step sequence in a 51% overall yield via the corresponding furo[3,4-b]quinolin-1(3H)-one. A new practical synthesis of this intermediate was carried out using versatile, commercially available starting materials and constitutes the shortest and highest yielding route. These synthetic pathways could be widened with a view toward the preparation of different substituted derivatives, which could be considered as rigid aminologues of 4-aza-2,3-didehydropodophyllotoxins.

Full text of DOI:10.1021/jo800166b

Design and Effective Synthesis of the First 4-Aza-
2,3-didehydropodophyllotoxin Rigid Aminologue:
A N-Methyl-4-[(3,4,5-trimethoxyphenyl)amino)]-
1,2-dihydroquinoline-lactone
Raphaël Labruère, Philippe Helissey,
Stéphanie Desbène-Finck, and Sylviane Giorgi-Renault*
Laboratoire de Chimie Thérapeutique, UMR CNRS No.
8638, UniVersité Paris Descartes, Faculté des Sciences
Pharmaceutiques et Biologiques, 4 aVenue de l’ObserVatoire,
75270 Paris Cedex 06, France
FIGURE 1. Structures of podophyllotoxin and 4-aza-2,3-didehydro-
podophyllotoxins.
NMR and X-ray studies show that podophyllotoxin adopts, in
solution, a single conformation in which the trimethoxy phenyl
ring is in a quasi-axial position and nearly perpendicular to the
tricyclic moiety, and this conformation seems to be important
for the binding of the molecule to the colchicine binding site in
tubulin.4 We have not yet investigated this point in the 4-aza-
2,3-didehydropodophyllotoxin series.
sylViane.giorgi-renault@uniV-paris5.fr
ReceiVed January 22, 2008
As part of a program directed at developing new antitumor
drugs, the great interest revealed by this category of biologically
relevant molecules prompted us to synthesize a rigid analogue
of 4-aza-2,3-didehydropodophyllotoxins (2). In this context, we
designed the aminologue 3 in which the rotation between the
tetracycle and the aryl ring is blocked by creation of an
additional pseudocycle. The central heterocyclic moiety of 3 is
constituted by a 4-amino-1,2-dihydroquinoline nucleus.
It is noteworthy that N-substituted dihydroquinolines can
potentially exist in two tautomeric forms, the 1,4-dihydroquino-
line being generally more stable than the 1,2-dihydro tautomer.
4-Aminodihydroquinolines are an exception when they are
substituted at position 3 by an acyl or a carboxylate function.
Hydrogen bonding between the NH and the CO could explain
the stabilization of the 1,2-dihydro structure, and the two types
of derivatives can be isolated depending on the synthetic method.
4-Amino-1,4-dihydroquinolines were obtained by addition of
an amine to a quinolinium salt,5 and the 1,2-dihydroanalogues
were usually prepared by reduction of the corresponding
imines.5e,6
Consequently, two routes were designed for the synthesis of
the desired N-methyl-4-anilino-1,2-dihydroquinoline lactone 3
from the quinoline-lactone 7 via the imine 4. Route A would
involve a Michaël addition of the aniline to the quinolinium
salt 6 and subsequent oxidation of the resulting N-methyl-4-
amino-1,4-dihydroquinoline 5 into 4. In route B, the 4-anilino
group would be introduced on the aromatic heterocyclic skeleton
before quaternarization and the imine 4 would be obtained by
deprotonation of the 4-anilinoquinolinium salt 8 (Scheme 1).
The first N1-alkyl-4-amino-1,2-dihydroquinoline-lactone has
been prepared by a five-step sequence in a 51% overall yield
via the corresponding furo[3,4-b]quinolin-1(3H)-one. A new
practical synthesis of this intermediate was carried out using
versatile, commercially available starting materials and
constitutes the shortest and highest yielding route. These
synthetic pathways could be widened with a view toward
the preparation of different substituted derivatives, which
could be considered as rigid aminologues of 4-aza-2,3-dide-
hydropodophyllotoxins.
We have previously described and patented a three-
component one-pot synthesis of 4-aza-2,3-didehydropodophyl-
lotoxins 2,1,2 aza-analogues of podophyllotoxin (1) (Figure 1),
which is a cytotoxic plant lignan. The 1,4-dihydroquinoline-
lactones 2 present very interesting antitumor properties.2
Podophyllotoxin (1) works by acting in the colchicine binding
site of tubulin, resulting into depolymerization of microtubules.3,4
The colchicine binding mode was recently confirmed by the
determination of an X-ray structure of R-ꢀ tubulin complexed
with DAMA-colchicine.3 Colchicine and podophyllotoxin bind
to ꢀ-tubulin at its interface with R-tubulin, the trimethoxyphenyl
nucleus being hidden into the ꢀ-subunit.3 Furthermore, dynamic
(5) (a) Gündel, W.-H.; Berenbold, H. Liebigs. Ann. Chem. 1978, 188–190.
(b) Gündel, W.-H.; Bohnert, S. Liebigs. Ann. Chem. 1986, 395–401. (c) Gündel,
W.-H.; Bohnert, S. Liebigs. Ann. Chem. 1986, 1127–1130. (d) Bohnert, S.;
Gündel, W.-H. Z. Naturforsch. 1987, 42b, 1159–1166. (e) Gündel, W.-H.;
Bohnert, S. Z. Naturforsch. 1988, 43b, 769–777. (f) Gündel, W.-H.; Bohnert, S.
Liebigs. Ann. Chem. 1988, 611–614. (g) Duchstein, H.-J.; Fenner, H.; Franck,
P.; Bauch, W. Arch. Pharm. 1990, 323, 67–72. (h) Leleu, S.; Papamicaël, C.;
Marsais, F.; Dupas, G.; Levacher, V. Tetrahedron: Asymmetry 2004, 15, 3919–
3928. (i) Leleu, S.; Penhoat, M.; Bouet, A.; Dupas, G.; Papamicaël, C.; Marsais,
F.; Levacher, V. J. Am. Chem. Soc. 2005, 127, 15668–15669.
* To whom correspondence may be addressed. Tel: 33 (0)1 53 73 96 98.
Fax: 33 (0)1 43 29 14 03.
(1) Tratrat, C.; Giorgi-Renault, S.; Husson, H.-P. Org. Lett. 2002, 4, 3187–
3189.
(2) Husson, H.-P.; Giorgi-Renault, S.; Tratrat, C.; Atassi, G.; Pierré, A.;
Renard, P.; Pfeiffer, B. Eur. Pat. Appl. EP 1.103.554, 2000. Chem. Abstr. 2001,
135, P5535u.
(3) Ravelli, R. B. G.; Gigant, B.; Curmi, P. A.; Jourdain, I.; Lachkar, S.;
Sobel, A.; Knossow, M. Nature 2004, 428, 192–202.
(4) Desbène, S.; Giorgi-Renault, S. Curr. Med. Chem.-Anti-Cancer Agents
2002, 2, 71–90, and references therein.
(6) (a) Blurton, P.; Brickwood, A.; Dhanak, D. Heterocycles 1997, 45, 2395–
2403. (b) Van Es, T.; Staskun, B. S. Afr. J. Chem. 1998, 51, 121–126.; Chem.
Abstr. 1999, 130, 52311z.
3642 J. Org. Chem. 2008, 73, 3642–3645
10.1021/jo800166b CCC: $40.75 2008 American Chemical Society
Published on Web 04/02/2008

SCHEME 1. Retrosynthesis Plans for the Synthesis of the Aminologue 3
SCHEME 2. Synthesis of the Aminologue 3
In the literature, two syntheses of the key synthon 7 have
been described starting from 6-nitropiperonal, in 4 steps and
41% overall yield for the first one,7 and in 2 steps but only
34% yield for the second one.8 To circumvent the preparation
of the unstable aminobenzaldehyde, we have elaborated a new
synthetic pathway by adaptation of the one-pot synthesis of
4-aza-2,3-didehydropodophyllotoxins1 to an aliphatic aldehyde.
Thus, the quinoline-lactone 7 was readily obtained in 50% yield
by refluxing in ethanol a mixture of 3,4-methylenedioxyaniline
(10), tetronic acid (11), and formaldehyde (12) and then, after
filtration of the resulting solid, subsequent oxidation of the
dihydroquinoline intermediate in warmed DMSO (Scheme 2).
Another interesting feature of this method is the possibility of
changing the substituent pattern on the quinolinic nucleus by
using various commercially available anilines.
Quaternarization of the quinoline-lactone 7 needs the use of
very reactive alkylating agents such as trifluoromethyl sulfonate.
The poor nucleophilicity of this quinoline could be explained
by the vinylamide character of the nitrogen. Unfortunately,
treatment of the resulting salt 6 with aniline 13 in neutral
medium or in the presence of NaH was unsuccessful, probably
because of the instability of 6 in solution. For this reason,
compound 6 was not characterized.
In light of these results, route B was investigated. The
4-chloroquinoline-lactone 15 was prepared in near quantitative
yield by reaction of POCl3 on the quinoline-N-oxide 14, which
is easily obtained by m-CPBA oxidation of the key synthon 7.
Then an aromatic nucleophilic substitution by the aniline 13
provided the phenylaminoquinoline-lactone 9, which was quar-
ternarized as before with trifluoromethyl sulfonate to afford the
quinolinium salt 8 in good yield (85%). Deprotonation of 8 was
(7) (a) Kurihara, T.; Sano, H.; Hirano, H. Chem. Pharm. Bull. 1975, 23,
1155–1157. (b) Kurihara, T.; Michida, T.; Hirano, H. Chem. Pharm. Bull. 1975,
23, 2451–2453.
(8) (a) Smith, D. G.; Seemuth, P. D.; Zimmer, H. J. Org. Chem. 1983, 48,
1914–1916. (b) Pendrak, I.; Wittrock, R.; Kingsbury, W. D. J. Org. Chem. 1995,
60, 2912–2915.
J. Org. Chem. Vol. 73, No. 9, 2008 3643

SCHEME 3. Mechanisms Proposed in the Literature for the
Reduction of 16 into 18
toxins, has been prepared via a five-step sequence in a 51%
overall yield from the quinoline-lactone 7. Furthermore, a new
practical synthesis of the previously described derivative 7 was
carried using versatile commercially available starting materials
and constitutes the shortest and highest yielding route. These
synthetic pathways could be widened with a view toward the
preparation of different substituted aminologues of 4-aza-2,3-
didehydropodophyllotoxins. Biological activities of the amino-
logues will be reported in due course.
Experimental Section
1
Melting points are uncorrected. H and 13C NMR experiments
were performed at 300 and 75 MHz, respectively, using a 300 MHz
instrument. 1H-13C HSQC and 1H-13C HMBC NMR experiments
were performed at 400 MHz.
6,7-(Methylenedioxy)furo[3,4-b]quinolin-1(3H)-one (7). A mix-
ture of tetronic acid (11) (300 mg, 3 mmol), a 37% solution of
formaldehyde 12 (730 µL, 9 mmol), and 3,4-methylenedioxyaniline
(10) (411 mg, 3 mmol) in EtOH (30 mL) was refluxed for 0.5 h.
The resulting white precipitate was filtered off and then dissolved
in DMSO (15 mL). The solution was stirred at 105 °C for 1 h.
After addition of water (150 mL), the resulting precipitate was
collected and recrystallized from EtOH to give 7 as a white powder
(345 mg, 50%): mp ) 281–282 °C (lit.,8a mp ) 284–285 °C). The
analytical data are in agreement with literature values.8a 1H NMR
(400 MHz, CDCl3) δ 8.50 (s, 1H), 7.45 (s, 1H), 7.25 (s, 1H), 6.20
(s, 2H,), 5.40 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 165.2 (CdO),
158.3 (Cq), 149.7 (Cq), 146.7 (Cq), 144.8 (Cq), 129.6 (CH), 120.8
(Cq), 111.4 (Cq), 101.5 (CH), 100.0 (CH), 98.5 (CH2), 66.4 (CH2).
4-Methyl-6,7-(methylenedioxy)-1-oxo-1,3-dihydrofuro[3,4-b]quin-
olin-4-ium trifluoromethanesulfonyl (6). To a solution of quinoline
7 (300 mg, 1.31 mmol) in CH2Cl2 (60 mL) was added a large excess
of methyl triflate (1 mL). After 48 h of stirring at rt, the resulting
solid was filtered off to afford quite pure 6 as a yellow powder
(463 mg, 90%) that is unstable in solution and was used without
further purification in the next step.
6,7-(Methylenedioxy)-4-oxyfuro[3,4-b]quinolin-1(3H)-one (14).
To a solution of quinoline 7 (1.15 g, 5.0 mmol) in CH2Cl2 (300
mL) was added m-CPBA (70% of purity) (1.8 g, 7.5 mmol). After
10 h of stirring at rt, the solvent was eliminated under reduced
pressure, and the residue was recrystallized from EtOAc to give
14 as a white powder (960 mg, 78%): mp ) 285–287 °C; 1H NMR
(300 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.93 (s, 1H), 7.70 (s, 1H),
6.37 (s, 2H), 5.51 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 168.4
(CdO), 154.4 (Cq), 150.1 (Cq), 147.4 (Cq), 142.2 (Cq), 128.1 (Cq),
122.6 (CH), 118.9 (Cq), 105.7 (CH), 104.2 (CH2), 95.8 (CH), 67.5
(CH2); Anal. Calcd for C12H7NO5 ·0.5 H2O: C, 56.70; H, 3.17; N,
5.51. Found: C, 56.85; H, 3.44; N, 5.72.
9-Chloro-6,7-(methylenedioxy)furo[3,4-b]quinolin-1(3H)-one (15).
To a solution of quinoline N-oxide 14 (960 mg g, 3.92 mmol) in
CH2Cl2 (300 mL) was added POCl3 (4 mL). After refluxing for
10 h, water (150 mL) and then a saturated aqueous solution of
NaHCO3 were added until a pH of 9 was reached. After extraction
of the aqueous layer with CH2Cl2 (3 × 50 mL), the organic phases
were dried over Na2SO4, filtered, and then the solvent was
eliminated under reduced pressure. The solid residue was recrystal-
lized from EtOAc to give 15 as a white powder (1.03 g, 100%):
mp ) 310–312 °C; 1H NMR (300 MHz, DMSO-d6) δ 7.71 (s, 1H),
7.56 (s, 1H), 6.38 (s, 2H), 5.42 (s, 2H); 13C NMR (75 MHz, DMSO-
d6) δ 167.0 (CdO), 163.8 (Cq), 154.6 (Cq), 151.2 (Cq), 150.3 (Cq),
140.2 (Cq), 123.1 (Cq), 112.7 (Cq), 105.6 (CH), 104.1 (CH2), 100.1
(CH), 69.6 (CH2); Anal. Calcd for C12H6ClNO4: C, 54.67; H, 2.29;
N, 5.31. Found: C, 54.99; H, 2.09; N, 5.22.
SCHEME 4. New Mechanism Hypothesized for the
Catalytic Hydrogenation of 4 into 3
accomplished by a weak base in heterogeneous medium; the
resulting imine 4 could be regioselectively reduced into the
aminologue 3 either by NaBH4 or by catalytic hydrogenation.
Surprisingly, the quinolinium 8 could be reduced into the
aminologue 3 in one step by treatment with NaBH4 without
preliminary formation of the imine. To our knowledge, this is
the first example of a 4-amino-1,2-dihydro-3-quinolinecarboxy-
late reduction. In both cases, the reduced derivative exists only
under the 1,2-dihydroquinoline form. HMBC spectrum of
3
compound 3 showed clearly J correlation between the proton
of N-methyl group (δ 2.68 ppm) and C-3a (δ 57.10 ppm) and
2J correlation between C-3a and both H3 of the lactone (δ 4.30
and 4.66 ppm) (see Supporting Information).
Two different mechanisms have been proposed for the
transformation of 4-iminoquinoline-3-carboxyles 16 into 4-amino-
1,2-dihydroquinolines 18 (Scheme 3). According to the litera-
ture, hydride reduction proceeds by reaction on the N1-C2
iminium double bound of the zwitterion 17, a minor mesomeric
form of 165e whereas catalytic hydrogenation of the N-C4
imine function of 16 leads to the formation of the 1,4-dihydro
intermediate 19 which is spontaneously isomerized into 18.6a
In our case, the reactivity of the quinolinium salt 8 (Scheme
2), which can be explained by addition of NaBH4 on the N+-C
double bond, corroborates the mechanism described in the
literature for hydride reduction of the imines 16. Concerning
the mechanism envisaged for the catalytic hydrogenation,6a we
proposed another hypothesis. Indeed, the transformation of the
1,4-dihydro isomer into the 1,2-dihydro derivative has never
been described for 4-aminoquinoline-3-carboxylates and both
forms can be obtained according to the synthetic method.5,6
Consequently, it seems reasonable to hypothesize a regioselec-
tive reduction of the C2-C3 double bond of 4 into the 4-imino-
2,3-dihydroquinoline 20, which was isolated in the more stable
tautomeric form 3 (Scheme 4).
9-[(3,4,5-Trimethoxyphenyl)amino]-6,7-(methylenedioxy)furo[3,4-
b]quinolin-1(3H)-one (9). A mixture of chloroquinoline 15 (1.00
g, 3.80 mmol) and 3,4,5-trimethoxyaniline (13) (1.40 g ; 7.60 mmol)
in EtOH (500 mL) was refluxed for 6 h. The resulting precipitate
In conclusion, the first potentially bioactive N-methyl-4-
amino-1,2-dihydroquinoline-lactone 3, which could be consid-
ered as a rigid aminologue of 4-aza-2,3-didehydropodophyllo-
3644 J. Org. Chem. Vol. 73, No. 9, 2008

was filtered off, washed with EtOH, and then recrystallized from
(3aRS)-4-Methyl-6,7-(methylenedioxy)-9-[(3,4,5-trimethoxyphe-
nyl)amino]-3a,4-dihydrofuro[3,4-b]quinolin-1(3H)-one (3), Pre-
pared from 4. A. A solution of iminoquinoline 4 (100 mg, 0.24
mmol) in dry MeOH (50 mL) was hydrogenated for 4 h at rt in the
presence of 10% Pd/C (20 mg) and under a pressure of 10 bar.
After filtration through a pad of Celite, the solvent was eliminated
under reduced pressure and the residue was recrystallized from
EtOH to give 3 as an orange-yellow powder (82 mg, 80%). B. To
a solution of iminoquinoline 4 (100 mg, 0.24 mmol) in dry MeOH
(50 mL) was added NaBH4 (46 mg, 1.20 mmol). After 10 h of
stirring at rt, the resulting solid was filtered off and recrystallized
EtOAc to give 9 as a pale-yellow powder (1.50 g, 96%): mp )
1
297–299 °C; H NMR (300 MHz, DMSO-d6) δ 9.08 (br s, 1H),
7.32 (s, 2H), 6.50 (s, 2H), 6.22 (s, 2H), 5.28 (s, 2H), 3.67 (s, 6H),
3.65 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 169.5 (CdO), 165.0
(Cq), 153.4 (2 × Cq), 152.6 (Cq), 151.4 (Cq), 147.6 (Cq), 146.8
(Cq), 138.1 (Cq), 134.9 (Cq), 115.1 (Cq), 106.1 (CH), 103.1 (CH2),
100.9 (CH), 100.8 (Cq), 100.3 (2xCH), 69.8 (CH2), 60.1 (CH3),
56.4 (2 × CH3); Anal. Calcd for C21H18N2O7 ·0.5 H2O: C, 60.14;
H, 4.57; N, 6.58. Found: C, 60.31; H, 4.63; N, 6.56.
4-Methyl-6,7-(methylenedioxy)-1-oxo-9-[(3,4,5-trimethoxyphe-
nyl)amino]-1,3-dihydrofuro[3,4-b]quinolin-4-ium trifluoromethane-
sulfonyl (8). To a solution of aminoquinoline 9 (560 mg, 1.37 mmol)
in CH2Cl2 (100 mL) was added a large excess of methyl triflate (1
mL). After 4 h of stirring at rt, the solvent was eliminated under
reduced pressure, and the residue was recrystallized from EtOH to
give 8 as a dark-yellow powder (665 mg, 85%): mp ) 272–274
°C; 1H NMR (300 MHz, DMSO-d6) δ 10.69 (s, 1H), 7.87 (s, 1H),
7.82 (s, 1H), 6.70 (s, 2H), 6.42 (s, 2H), 5.63 (s, 2H), 3.97 (s, 3H),
3.70 (s, 6H), 3.68 (s, 3H);13C NMR (75 MHz, DMSO-d6) δ 165.9
(CdO) 164.0 (2 × Cq), 155.7 (CF3), 153.6 (2 × Cq), 151.0 (Cq),
148.6 (Cq), 140.0 (Cq), 136.9 (Cq), 136.0 (Cq), 115.5 (Cq), 105.1
(CH), 102.4 (CH2), 102.2 (2 × CH), 100.7 (Cq), 98.0 (CH), 67.3
(CH2), 60.7 (CH3), 56.7 (2 × CH3), 38.6 (CH3); Anal. Calcd for
C23H21F3N2O10S·0.5 H2O: C, 47.34; H, 3.80; N, 4.80. Found: C,
47.30; H, 3.58; N, 4.50.
4-Methyl-6,7-(methylenedioxy)-9-[(3,4,5-trimethoxyphenyl)imi-
no]4,9-dihydrofuro[3,4-b]quinolin-1(3H)-one (4). To a solution of
aminoquinolinium 8 (300 mg, 0.52 mmol) in dry acetone (50 mL)
was added K2CO3 (72 mg, 0.52 mmol). After 3 h of stirring at rt,
the resulting solid was filtered off and recrystallized from EtOH to
afford 4 as a yellow powder (217 mg, 98%): mp ) 284–286 °C;
1H NMR (300 MHz, DMSO-d6) δ 7.85 (s, 1H), 7.31 (s, 1H), 6.19
(s, 2H), 6.02 (s, 2H), 5.21 (s, 2H), 3.66 (s, 6H), 3.60 (s, 3H), 3.52
(s, 3H);13C NMR (75 MHz, DMSO-d6) δ 167.1 (CdO), 164.4 (Cq),
153.0 (Cq), 151.2 (Cq), 149.8 (2 × Cq), 146.4 (Cq), 146.1 (Cq),
136.0 (Cq), 132.7 (Cq), 122.6 (Cq), 104.1 (CH), 102.9 (CH2), 97.7
(2 × CH, Cq), 96.9 (CH), 65.4 (CH2), 60.5 (CH3), 56.1 (2 × CH3),
35.6 (CH3); Anal. Calcd for C22H20N2O7 ·0.5 H2O: C, 60,97; H,
4.88; N, 6.46. Found: C, 61.08; H, 4.52; N, 6.84.
1
to afford 3 (82 mg, 80%): mp ) 220 °C; H NMR (300 MHz,
CDCl3) δ 8.34 (s, 1H), 6.64 (s, 1H), 6.41 (s, 1H), 6.12 (s, 2H),
5.90 (s, 2H), 4.66 (m, 1H), 4.30 (m, 2H), 3.81 (s, 3H), 3.71 (s,
6H), 2.68 (s, 3H);13C NMR (75 MHz, CDCl3) δ 170.5 (CdO),
153.4 (2 × Cq), 151.2 (Cq), 147.4 (Cq), 146.7 (Cq), 140.0 (Cq),
137.2 (Cq), 134.6 (Cq), 110.3 (Cq), 108.1 (CH), 101.5 (CH2), 100.2
(2 × CH), 95.4 (CH), 94.0 (Cq), 71.9 (CH2), 61.0 (CH3), 57.1 (CH),
56.1 (2 × CH3), 35.3 (CH3); Anal. Calcd for C22H22N2O7: C, 61,97;
H, 5.20; N, 6.57. Found: C, 62.05; H, 5.42; N, 6.29.
(3aRS)-4-Methyl-6,7-(methylenedioxy)-9-[(3,4,5-trimethoxyphe-
nyl)amino]-3a,4-dihydrofuro[3,4-b]quinolin-1(3H)-one (3), Pre-
pared from 8. The same procedure as previously was used starting
from the aminoquinolinium 8 (120 mg, 0.21 mmol) in dry MeOH
(50 mL) and NaBH4 (40 mg, 1.05 mmol) to afford 3 (72 mg, 80%).
The analytical data were identical to those described for 3 prepared
from 4.
Acknowledgment. R. Labruère was supported by a fellow-
ship from MNSER.
1
Supporting Information Available: Copies of H NMR
spectrum and proton-decoupled 13C NMR spectrum for each
new compound, along with two-dimensional 1H-13C HSQC 1J
1
1
correlation for compound 4 and H-13C HSQC J correlation
3
and HMBC J correlation for compound 3. Complete IR peak
listings for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.
JO800166B
J. Org. Chem. Vol. 73, No. 9, 2008 3645