A carbohydrate-based approach for the total synthesis of 1,3-polyol/α-pyrone antifungal natural products

Full text of DOI:10.1021/jo050972v

A Carbohydrate-Based Approach for the
Total Synthesis of 1,3-Polyol/r-Pyrone
Antifungal Natural Products
C. V. Ramana,* Burgula Srinivas,
Vedavati G. Puranik, and Mukund K. Gurjar
National Chemical Laboratory, Dr. Homi Bhabha Road,
Pune - 411 008, India
vr.chepuri@ncl.res.in
Received May 16, 2005
FIGURE 1. Representative skipped polyol natural products
with an integrated R-pyrone moiety.
An elimination and stereoselective hydrogenation of R-D-
glucoheptonic-γ-lactone derivative has been applied to pre-
pare a differentially protected anti,anti-1,3,5-triol system,
the utility of which has been extended for the total synthesis
of anti-fungal 1,3-polyol/R-pyrone natural products.
FIGURE 2. Retrosynthetic strategy for the key syn,syn-1,3,5-
triol synthesis and of the R-pyrone moiety.
The 5,6-dihydro-δ-pyrones with an integrated 1,3-
skipped polyol system form a basic skeleton of several
natural products represented by cryptocarya diacetate
(1),1 passifloricin (2),2 1,3-polyol/R-pyrones (3 and 4),3 and
strictifolione (5)4 (Figure 1). The broad range of biological
activities associated with these natural products was
ascribed to their inherent ability to act as good Michael
acceptors.5 Natural products 3 and 4,3 isolated from
Ravensara anisata, possess inhibitory activity against C.
cucumerinum which was comparable to miconazole and
propiconazole. The synthesis of 3 and 4 reported by
Shibasaki and co-workers turned out to be their enanti-
omers.6 Herein, we report the first synthesis of the
natural occurring 3 and 4 by adopting the chiral pool
approach.
The structural analysis of 3 and 4 revealed that the
diacetonide (10)7 of commercially available R-D-glucohep-
tonic-γ-lactone would be an ideal starting point as
depicted in Figure 2. The deoxygenation at C-3 by base-
mediated elimination and stereocontrolled reduction8 and
Barton-McCombie radical deoxygenation9 of C-5 followed
by an inversion at C-4 are the key steps to secure the
preparation of the key intermediate (7). Coupling reaction
between the advanced intermediate (6) and methyl
propiolate by the Yamaguchi method,10 partial hydroge-
* Corresponding author. Tel: +91-20-25882456. Fax: +91-20-
25893614.
(1) (a) Collett, L. A.; Davies-Coleman, M. T.; Rivett, D. E. A.; Drewes,
S. E.; Horn, M. M. Phytochemistry 1997, 44, 935. (b) Hunter, T. J.;
O’Doherty, G. A. Org. Lett. 2001, 3, 2777. (c) Smith, C. M.; O’Doherty,
G. A. Org. Lett. 2003, 5, 1959.
(2) (a) Echeverri, F.; Arango, V.; Quin˜ones, W.; Torres, F.; Escobar,
G.; Rosero, Y.; Archbold, R. Phytochemistry 2001, 56, 881. For
synthesis, see: (b) Murga, J.; Garc´ıa-Fortanet, J.; Carda, M.; Marco,
J. A. Tetrahedron Lett. 2003, 44, 7909. (c) Murga, J.; Garc´ıa-Fortanet,
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A.; Aimi, N. Phytochemistry 2000, 54, 989. (b) Juliawaty, L. D.;
Watanabe, Y.; Kitajima, M.; Achmad, S. A.; Takayama, H.; Aimi, N.
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2003, 5, 495.
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341. (b) Shing, T. K. M.; Tsui, H. C.; Zhou, Z.-H.; Mak, T. C. W. J.
Chem. Soc., Perkin Trans. 1 1992, 887. (c) Baudat, A.; Picasso, S.;
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10.1021/jo050972v CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/07/2005
8216
J. Org. Chem. 2005, 70, 8216-8219

SCHEME 1. Synthesis of the Epoxide 6a
SCHEME 2. Total Synthesis of Anti-fungal
Natural Products 3/4a
a Reagents and conditions: (a) methyl propiolate, n-BuLi,
BF3‚Et2O, THF, -78 °C, 1 h, 93%; (b) H2, Pd/CaCO3, quinoline,
benzene, 1 NTP, 0.5-1 h, 72%, followed by PPTS, CHCl3, reflux,
6 h, 95%; (c) TFA, DCM, 0 °C, 0.5 h, 78% (18/19 and 20) and 90%
(3/4); (d) Ac2O, Et3N, DMAP, CH2Cl2, rt, 6 h, 94%.
a Reagents and conditions: (a) Ag2O, BnBr, CH2Cl2, reflux, 6
h, 84%; (b) KO-t-Bu, THF, -78 °C, 0.25 h, 81%; (c) NaBH4,
NiCl2‚6H2O, methanol, 0 °C, 1.5 h, 61%; (d) NaH, CS2, MeI, THF,
-15 °Cfrt, 12 h, 93%, followed by n-Bu3SnH, AIBN, toluene,
reflux, 5 h, 71%; (e) DIBAL-H, CH2Cl2, -78 °C, 0.5 h, followed by
[C6H5CH2CH2CH2PPh3]+I-, n-BuLi, THF, 0 °C f rt, 12 h, 93%;
(f) DEAD, TPP, benzoic acid, THF, 0 °C, 2 h, 69%; (g) H2-Raney-
Ni, ethanol, 20 psi, 12 h, followed by NaOMe, MeOH, rt, 2 h, 91%;
(h) NaH, PMBCl, DMF, 0°C f rt, 6 h, followed by PPTS, methanol,
24 h, 85%; (i) (i) TsCl, Bu2SnO (cat.), triethylamine, DMAP,
CH2Cl2, rt, 1 h, followed by (ii) K2CO3, MeOH, 0 °Cfrt, 0.5 h, 78%.
olate was reacted with the epoxide 6 in THF at -78 °C
to furnish the â-hydroxy alkyne derivative 16. The latter
compound (16) was successively subjected to partial
reduction in the presence of Lindlar catalyst and lacton-
ization resulting in the formation of the R-pyrone inter-
mediate 17.
Attempted deprotection of PMB ethers of 17 using TFA
in dichloromethane provided a (1:1) regiomeric mixture
of mono-PMB ethers 18 and 19 along with the diol 20.
The diol 20 was converted to the diacetate 21 which
showed spectral data identical with the reported values.7
The acetylation of 18/19 followed by treatment with TFA
gave a mixture of 3 and 4 (3:1), separated by preparative
HPLC. The spectral and analytical data of 3 and 4 were
identical with the data reported for the natural products.
nation, and lactonization should complete the total
synthesis of the natural products 3 and 4.
Protection of the hydroxyl group at C-2 with silver
oxide and benzyl bromide gave the benzyl ether 11. After
substantial experimentation of the elimination step, we
concluded that potassium tert-butoxide provided satisfac-
tory yield.7d,8 Selective conjugate reduction of the lactone
9 with -OBn intact was achieved with NiCl2-NaBH4.11
The spectral and analytical data of 12 were in agreement
with the assigned structure, which was further substan-
tiated by single-crystal X-ray crystallography.12 Subse-
quent reduction of 8 with DIBAL-H and Wittig olefina-
tion with 3-phenylpropyltriphenylphosphorane furnished
13. The Z-configuration of 13 was evident from the
coupling constant (J ) 10.3 Hz). Mitsunobu reaction of
13 using DEAD and benzoic acid was facile to give the
benzoate derivative 14. Hydrogenation of the double bond
present in 14 by using Raney-Ni followed by saponifica-
tion with catalytic NaOMe gave the diol 7. The diol 7
was protected with p-methoxybenzyl chloride-NaH, and
then the 1,2-isopropylidene group hydrolyzed in the
presence of PPTS in MeOH to obtain the terminal diol
15. The primary hydroxyl group of 15 was selectively
tosylated by using TsCl, Bu2SnO, and triethylamine in
dichloromethane followed by cyclization with K2CO3 in
methanol to afford the epoxide 6 (Scheme 1).
1
Notably, a periodic examination of H NMR spectra of
pure isomers 3 and 4 indicated the migratory aptitudes
of acetyl group in these compounds, however with dif-
ferent rate of migration. For example, the interconversion
of 4 f 3 was substantially faster than 3 f 4 (Scheme 2).
In summary, we report a simple strategy for the
synthesis of anti,anti- and syn,syn-1,3,5-polyol systems
using a chiral pool approach. This study enabled us to
carry out the first total synthesis of antifungal natural
1,3-polyol/R-pyrones 3 and 4.
Experimental Section
2-Benzyloxy-3-deoxy-6,7-O-isopropylidine-D-arabino-
hept-2-enoic-γ-lactone (9). At -78 °C, a suspension of KO-t-
Bu (1.48 g, 13.2 mmol) in anhydrous THF (50 mL) was treated
with a solution of 11 (5 g, 13.2 mmol) in anhydrous THF (80
mL) and stirred for 15 min at -78 °C. The reaction mixture was
quenched with a solution of acetic acid (0.8 mL, 13.2 mmol) in
THF (5 mL) and allowed to reach rt. The contents were filtered
(Celite) and concentrated, and the crude product was purified
by crystallization from ethyl acetate/hexane (1:3) to procure 9
(3.43 g, 81%) as a colorless solid. Mp: 162 °C. [R]25D ) +31.7 (c
) 1, CHCl3). IR (CHCl3): ν 3420, 3020, 2400, 1760, 1652, 1381,
1215, 1059, 756, 668 cm-1. 1H NMR (200 MHz, CDCl3) δ: 7.40-
7.36 (m, 5H), 6.17 (d, J ) 2.1 Hz, 1H), 5.09 (dd, J ) 4.1, 2.1 Hz,
1H), 5.02 (s, 2H), 4.16 (dd, J ) 6.2, 4.1 Hz, 1H), 4.12 (dt, J )
6.2, 3.5 Hz, 1H), 3.99 (dd, J ) 7.6, 3.5 Hz, 1H), 3.55 (dd, J )
Our next concern involved the construction of the key
pyrone ring for which the lithium salt of methyl propi-
(11) (a) Satoh, T.; Nanba, K.; Suzuki, S. Chem. Pharm. Bull. 1971,
19, 817. (b) Kinoshita, A.; Mori, M. J. Org. Chem. 1996, 61, 8356.
(12) G. M. Sheldrick, SHELX-97 Program for Crystal Structure
Solution and Refinement, University of Gottingen, Germany, 1997.
J. Org. Chem, Vol. 70, No. 20, 2005 8217

7.6, 4.1 Hz, 1H), 2.40 (br.s, 1H), 1.37 (s, 3H), 1.35 (s, 3H). 13C
NMR (50 MHz) δ: 25.1 (q), 26.7 (q), 67.1 (t), 72.8 (t), 73.1 (d),
75.3 (d), 79.5 (d), 109.7 (s), 115.9 (d), 127.6 (d), 128.5 (d), 128.6
(d), 134.7 (s), 145.9 (s), 167.8 (s) ppm. Anal. Calcd for C17H20O6:
C, 63.74; H, 6.29. Found: C, 63.80; H, 6.03.
142.3 (s), 153.8 (s), 159.2 (s), 159.4 (s) ppm. Anal. Calcd for
C36H44O7: C, 73.44; H, 7.53. Found: C, 73.14; H, 7.80.
PMB Deprotection of 17. A solution of compound 17 (145
mg, 0.26 mmol) in CH2Cl2 (10 mL) at 0 °C was treated with TFA
(50 µL) and stirred for 30 min at 0 °C. The reaction was
quenched by addition of saturated bicarbonate solution, and the
aqueous layer was extracted with CH2Cl2. The combined organic
layer was washed with brine, dried (Na2SO4), and concentrated.
The crude product was purified by column chromatography (40%
f 50% ethyl acetate in petroleum ether) to afford a 1:1 mixture
of alcohols 18 and 19 (61 mg, 54%) and diol 20 (20 mg, 24%).
2-O-Benzyl-3-deoxy-6,7-O-isopropylidine-D-gluco-heptoic-
γ-lactone (12). At 0 °C, a solution of 9 (1 g, 3.1 mmol) in
methanol (30 mL) was treated with NiCl2‚6H2O (220 mg, 0.9
mmol) and stirred for 30 min. To this solution were added
NaBH4 (342 mg, 9.1 mmol) and acetic acid (to maintain pH )
7) in three portions during a 10 min interval. After the addition
was complete, stirring was continued for another 30 min at 0
°C. The contents were filtered (Celite), concentrated, dissolved
in ethyl acetate (25 mL), washed with water and brine, dried
(Na2SO4), and concentrated to get a white solid. The crude
product was purified by crystallization in CH2Cl2/hexane to get
Data for 18 and 19. [R]25 ) +54.8 (c ) 1, CHCl3). IR
D
(CHCl3): ν 3462, 3019, 2937, 2860, 1719, 1612, 1514, 1454, 1390,
1251, 1215, 1035, 757, 668 cm-1. 1H NMR (200 MHz, CDCl3) δ:
7.19-7.07 (m, 7H), 6.82-6.70 (m, 3H), 5.96-5.88 (m, 1H), 4.59-
4.21 (m, 3H), 3.92-3.77 (m, 1H), 3.71 (s, 3H), 3.68-3.54 (m, 1H),
2.59-2.49 (m, 2H), 2.33-2.18 (m, 2H), 2.14-1.67 (m, 2H), 1.67-
1.45 (m, 6H), 1.41-1.28 (m, 3H). 13C NMR (50 MHz) δ: 24.1 (t),
25.1 (t), 29.1 (t), 29.7 (t), 31.5 (t), 31.6 (t), 33.1 (t), 35.8 (t), 35.9
(t), 37.6 (t), 38.8 (t), 40.7 (t), 41.8 (t), 55.1 (q), 68.0 (d), 70.2 (t),
70.4 (t), 70.6 (d), 74.7 (d), 75.2 (d), 75.5 (d), 79.5 (d), 113.9 (d),
121.2 (d), 121.4 (d), 125.6 (d), 125.7 (d), 128.2 (d), 128.3 (d), 129.5
(d), 129.6 (d), 129.8 (s), 142.2 (s), 142.5 (s), 144.8 (d), 145.2 (d),
159.3 (s), 159.4 (s), 163.9 (s), 164.3 (s) ppm. Anal. Calcd for
C27H34O5: C, 73.94; H, 7.81. Found: C, 74.05; H, 7.63.
a white crystalline solid 12 (615 mg, 61%). Mp: 116 °C. [R]25
)
D
+32.4 (c ) 1, CHCl3). IR (CHCl3): ν 3442, 2992, 2881, 1787,
1455, 1370, 1216, 848, 755 cm-1. 1H NMR (200 MHz, CDCl3) δ:
7.38-7.32 (m, 5H), 4.96 (d, J ) 11.8 Hz, 1H), 4.75 (d, J ) 11.8
Hz, 1H), 4.59 (ddd, J ) 8.9, 6.4, 2.9 Hz, 1H), 4.24 (dd, J ) 9.2,
8.4 Hz, 1H), 4.19-3.96 (m, 3H), 3.45 (br.d, J ) 4.4 Hz, 1H), 2.51
(ddd, J ) 13.1, 8.3, 6.4 Hz, 1H), 2.30 (dt, J ) 13.1, 9.1 Hz, 1H),
1.38 (s, 3H), 1.33 (s, 3H). 13C NMR (75 MHz) δ: 25.1 (q), 26.7
(q), 31.1 (t), 67.2 (t), 72.1 (t), 72.9 (d), 73.2 (d), 75.3 (d), 76.4 (d),
109.4 (s), 128.0 (d), 128.4 (d), 136.9 (s), 174.5 (s) ppm. Anal. Calcd
for C17H22O6: C, 63.34; H, 6.88. Found: C, 63.38; H, 7.14.
Crystal Data. A colorless platelike crystal of approximate
size 0.48 × 0.24 × 0.02 mm was used for data collection on a
Bruker SMART APEX CCD diffractometer using Mo KR radia-
tion with fine focus tube with 50 kV and 30 mA. Crystal to
detector distance 6.05 cm, 512 × 512 pixels/frame, multiscan
data acquisition. Total scans ) 3, total frames ) 1212, oscilla-
tion/frame -0.3°, exposure/frame ) 10.0 s/frame, maximum
detector swing angle ) -30.0°, beam center ) (260.2, 252.5), in
plane spot width ) 1.24, SAINT integration, θ range ) 2.52-
25.0°, completeness to θ of 23.33° is 99.2%. SADABS correction
applied, C17H22O6, M ) 322.35. Crystals belong to monoclinic,
space group P21, a ) 9.195(1) Å, b ) 6.1777(8) Å, c ) 15.004(2)
Data of Diol 20. [R]25 ) +62.1 (c ) 1, CHCl3). IR (CHCl3):
D
ν 3684, 3020, 2934, 1725, 1522, 1476, 1215, 1055, 759, 669 cm-1
.
1H NMR (200 MHz, CDCl3) δ: 7.30-7.11 (m, 5H), 6.89 (dt, J )
9.8, 4.5, 3.8 Hz, 1H), 6.02 (dt, J ) 9.8, 1.8 Hz, 1H), 4.72-4.57
(br.ddt, J ) 8.9, 7.5, 5.5 Hz, 1H), 4.15-4.03 (m, 1H), 3.90-3.79
(m, 1H), 3.50 (b, 2H), 2.62 (t, J ) 7.5 Hz, 2H), 2.45-2.39 (m,
2H), 2.08-1.94 (m, 1H), 1.81-1.32 (m, 9H). 13C NMR (50 MHz)
δ: 24.9 (t), 29.4 (t), 31.4 (t), 35.8 (t), 38.1 (t), 42.3 (t), 42.7 (t),
69.5 (d), 72.7 (d), 76.2 (d), 121.2 (d), 125.7 (d), 128.2 (d), 128.3
(d), 142.4 (s), 145.4 (d), 164.2 (s) ppm. Anal. Calcd for C19H26O4:
C, 71.66; H, 8.23. Found: C, 71.39; H, 8.81.
Diacetate 21. Treatment of 20 (29 mg, 0.09 mmol) in CH2-
Cl2 (6 mL) with Ac2O (85 µL, 0.91 mmol), triethylamine (126
µL, 0.91 mmol), and DMAP (5 mg) and usual workup after 6 h
of stirring followed by purification by column chromatography
(30% ethyl acetate in petroleum ether) gave 21 (34 mg, 94%) as
a yellow oil: [R]25D ) +48.6 (c ) 1, CHCl3). IR (CHCl3): ν 3020,
2936, 2861, 1730, 1496, 1374, 1242, 1216, 1152, 1038, 758, 668
Å, â ) 93.846(2)°, V ) 850.4 (2) Å3, Z ) 2, Dc ) 1.259 mg m-3
,
µ (Mo KR) ) 0.095 mm-1, T ) 295(2) K, 4283 reflections
measured, 2795 unique [I > 2σ(I)], R value 0.0594, wR2 )
0.1375. All of the data were corrected for Lorentzian, polariza-
tion, and absorption effects. SHELX-97 (ShelxTL)12 was used
for structure solution and full-matrix least-squares refinement
on F2. Hydrogen atoms were included in the refinement as per
the riding model.
1
cm-1. H NMR (500 MHz, CDCl3) δ: 7.28-7.25 (m, 2H), 7.18-
7.15 (m, 3H), 6.87-6.84 (m, 1H), 6.02-6.00 (dd, J ) 9.7, 1.9 Hz,
1H), 5.07-5.02 (m, 1H), 4.95-4.90 (m, 1H), 4.50-4.45 (m, 1H),
2.61-2.58 (t, J ) 7.5 Hz, 2H), 2.46-2.40 (m, 1H), 2.33-2.27 (m,
1H), 2.16-2.10 (m, 1H), 2.05 (s, 3H), 2.03 (s, 3H), 1.99-1.89 (m,
2H), 1.84-1.79 (m, 1H), 1.66-1.57 (m, 4H), 1.39-1.28 (m, 2H).
13CNMR (125 MHz, CDCl3) δ: 21.1 (q), 24.6 (t), 29.1 (t), 31.0
(t), 34.1 (t), 35.6 (t), 38.9 (t), 38.9 (t), 67.8 (d), 70.8 (d), 74.9 (d),
121.3 (d), 125.7 (d), 128.2 (d), 128.4 (d), 142.3 (s), 144.7 (d), 163.7
(s), 170.6 (s), 170.8 (s) ppm. MALDI-TOF (MS): calcd for
Treatment of Epoxide 6 with Methyl Propiolate. Methyl
propiolate (590 µL, 6.6 mmol) was taken in a flame-dried two-
neck round-bottom flask (50 mL) and dissolved in anhydrous
THF (15 mL). The reaction mixture was cooled to -78 °C, treated
with n-BuLi (4.2 mL, 6.64 mmol, 1.6 M in hexane) dropwise,
stirred for 15 min, treated with BF3‚Et2O (0.84 mL, 6.6 mmol),
and stirred for an additional 15 min. Once the formation of dark
black alkyne borane was observed, a solution of epoxide 6 (335
mg, 0.66 mmol) in anhydrous THF (10 mL) was added and
stirred for 30 min at -78 °C. The reaction was quenched at -78
°C by addition of satd Na2SO4 (20 mL) and taken in ethyl
acetate-water, and the aqueous phase was extracted with ethyl
acetate. The combined organic phase was washed with brine,
dried (Na2SO4), and concentrated. Purification by column chro-
matography (20% ethyl acetate in petroleum ether) gave 16 (365
C
23H30O6Na 425.19, found 425.19 (M + Na). Anal. Calcd for
C23H30O6: C, 68.64; H, 7.51. Found: C, 68.89; H, 7.61.
Synthesis of R-Pyrone Natural Products 3 and 4. In a
manner similar to that used in the deprotection of 17, treatment
of 18-Ac/19-Ac (58 mg, 0.12 mmol) in CH2Cl2 (6 mL) with TFA
(20 µL), stirring at 0 °C for 30 min, usual workup, and
purification by column chromatography (40% ethyl acetate in
petroleum ether) gave an equilibrium mixture of natural regioi-
somers 3 and 4 (39 mg, 90%) as a yellow oil. [R]25 ) +39 (c )
mg, 93%). [R]25 ) +56.7 (c ) 1, CHCl3). IR (CHCl3): ν 3457,
D
D
0.4, MeOH) [lit.3 [R]25D ) +35 (c ) 0.05, MeOH)]. IR (CHCl3): ν
3440, 3019, 2934, 2859, 1724, 1513, 1496, 1384, 1250, 1216,
1043, 757, 668 cm-1. MALDI-TOF (MS): calcd for C21H28O5Na
383.18, found 383.17 (M + Na). Anal. Calcd for C21H28O5: C,
69.98; H, 7.83. Found: C, 69.79; H, 7.96.
3011, 2936, 2859, 2238, 1714, 1612, 1586, 1513, 1454, 1435,
1302, 1250, 1075, 1035, 822, 755, 667 cm-1. 1H NMR (200 MHz,
CDCl3) δ: 7.31-7.14 (m, 9H), 6.83 (br.d, J ) 8.4 Hz, 4H), 4.52
(d, J ) 11.2 Hz, 1H), 4.47 (d, J ) 11.2 Hz, 1H), 4.30 (d, J ) 11.2
Hz, 1H), 4.27 (d, J ) 11.2 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H),
3.90-3.73 (m, 2H), 3.71 (s, 3H), 3.44-3.33 (m, 1H), 2.66-2.58
(t, J ) 7.5 Hz, 2H), 2.47-2.26 (m, 2H), 2.03-1.90 (m, 1H), 1.71-
1.33 (m, 10H). 13C NMR (50 MHz) δ: 24.6 (t), 27.3 (t), 31.6 (t),
33.9 (t), 35.9 (t), 38.3 (t), 39.9 (t), 52.4 (q), 55.1 (q), 69.3 (d), 70.0
(t), 70.5 (t), 74.5 (s), 74.8 (d), 76.4 (d), 86.2 (s), 113.7 (d), 113.9
(d), 125.7 (d), 128.3 (d), 128.4 (d), 129.6 (d), 129.7 (d), 130.5 (s),
A portion of the 3/4 mixture was subjected to preparative
1
HPLC separation, and the H and 13C NMR of the separated 3
and 4 were recorded. In case of the minor isomer 4, we found
the equilibration is facile and the difference in the ratio of 4/3
changed from 1:0.14 (1H NMR) to ∼1:0.75 (13C NMR), the later
being recorded overnight.
8218 J. Org. Chem., Vol. 70, No. 20, 2005

Major Isomer 3. [R]25D ) +33 (c ) 0.3, MeOH) [lit.4 [R]25
)
21.3 (q), 25.0 (t), 29.2 (t), 31.3 (t), 35.8 (t), 37.7 (t), 39.3 (t), 41.7
(t), 69.0 (d), 69.2 (d), 75.1 (d), 121.4 (d), 125.7 (d), 128.3 (d), 128.4-
(d), 142.4(s), 144.7 (d), 163.9 (s), 170.9 (s).
D
+35 (c ) 0.05, MeOH)]. 1H NMR (500 MHz, CDCl3) δ: 7.27-
7.24 (m, 2H), 7.18-7.14 (m, 3H), 6.87 (dt, J ) 9.8, 4.2 Hz, 1H),
6.01 (br dt, J ) 9.5, 1.7 Hz, 1H), 4.97-4.92 (m, 1H), 4.66-4.60
(m, 1H), 3.90-3.86 (m, 1H), 2.59 (t, J ) 7.5 Hz, 2H), 2.40-2.37
(m, 2H), 2.02 (s, 3H),1.95-1.41 (m, 10H). 13C NMR (125 MHz)
δ: 21.3 (q), 24.8 (t), 29.4 (t), 31.1 (t), 34.5 (t), 35.7 (t), 41.7 (t),
42.3 (t), 67.0 (d), 72.3 (d), 76.6 (d), 121.2 (d), 125.7 (d), 128.3 (d),
128.4 (d), 142.3 (s), 145.2 (d), 163.9 (s), 171.3 (s) ppm.
Acknowledgment. B.S. thanks CSIR, New Delhi,
for the financial assistance in the form of a research
fellowship.
Supporting Information Available: Experimental pro-
cedures and spectral and analytical data for all new com-
pounds (3/4, 6-21), representative 1H, 13C, and DEPT spectra
(3/4, 6-8, 12, 13, 17, 20, and 21), and crystallographic
information file (CIF) of 12. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
Minor Isomer 4. H NMR (500 MHz, CDCl3): δ 7.27-7.24
(m, 2H), 7.18-7.14 (m, 3H), 6.87-6.84 (ddd, J ) 9.7, 6.1, 2.4
Hz, 1H), 6.01 (ddd, J ) 9.7, 2.6, 0.7 Hz, 1H), 5.24-5.19 (m, 1H),
4.54-4.48 (m, 1H), 3.72-3.67 (m, 1H), 2.61 (t, J ) 7.5 Hz, 2H),
2.48-2.43 (m, 1H), 2.34-2.26 (m, 1H), 2.18 (ddd, J ) 14.6, 8.4,
6.3 Hz, 1H), 2.05 (s, 3H), 1.95 (ddd, J ) 14.6, 6.8, 4 Hz, 1H),
1.82-1.71 (m, 2H), 1.66-1.42 (m, 6H). 13C NMR (125 MHz) δ:
JO050972V
J. Org. Chem, Vol. 70, No. 20, 2005 8219