Stereoselective synthesis of a tetrahydropyranyl diarylheptanoid, ent-diospongin A

Article abstract of DOI:10.1016/j.tetasy.2011.10.006

The stereoselective synthesis of the unnatural enantiomer of a cyclic diarylheptanoid, diospongin A is described. The salient feature of this synthesis is the formation of a tetrahydropyran ring via the AgOTf-catalysed intramolecular oxa-Michael addition

Full text of DOI:10.1016/j.tetasy.2011.10.006

Tetrahedron: Asymmetry 22 (2011) 1725–1728
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Tetrahedron: Asymmetry
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Stereoselective synthesis of a tetrahydropyranyl diarylheptanoid,
ent-diospongin A
⇑
Chada Raji Reddy , Guvvala Balakrishna Reddy, Boinapally Srikanth
Organic Chemistry Division-I, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The stereoselective synthesis of the unnatural enantiomer of a cyclic diarylheptanoid, diospongin A is
described. The salient feature of this synthesis is the formation of a tetrahydropyran ring via the
AgOTf-catalysed intramolecular oxa-Michael addition of a b-hydroxy ynone followed by hydrogenation
Ó 2011 Elsevier Ltd. All rights reserved.
Received 25 August 2011
Accepted 14 October 2011
Available online 15 November 2011
1. Introduction
OH
O
OH
O
Tetrahydropyranyl diarylheptanoids are an important class of
natural products and have received considerable attention due to
their wide range of biological activities.1 Diospongins A and B
(Fig. 1) are tetrahydropyranyl diarylheptanoids, which were
isolated from the rhizomes of Dioscorea Spongiosa by Kadota and
co-workers in 2004.2 Although they possess structural similarity,
containing two phenyl rings and three asymmetric centers, dio-
spongin B, which has a 2,6-trans tetrahydropyran (THP) ring,
exhibits potent anti-osteoporotic activity in a bone organ culture,
while its stereoisomer diospongin-A, which has a 2,6-cis tetrahy-
dropyran ring, did not show any activity. This interesting biological
profile combined with its structural simplicity has not only led to a
number of total syntheses but also the synthesis of their stereoiso-
O
O
Diospongin A 1
Diospongin B 2
OH
4
3
5
O
6
O
2
mers.3 The formation of the tetrahydropyran ring in these strate-
1
3b–d,i
gies can be carried out by oxa-Michael reactions,
Prins
cyclisations,3e,g Pd-catalyzed stereospecific cyclisations,3f three-
component coupling/hydrogenations,3h tandem cross-metathesis/
thermal SN2 reactions,3j hetero-Diels–Alder reactions3k–m amongst
others.3a
ent-Diospongin A ent-1
Figure 1. Structure of diospongin A and B and their enantiomers.
We considered that our recent work on the synthesis of the THP
subunit of (ꢀ)-dactylolide4 using the AgOTf-catalysed oxa-Michael
addition of a b-hydroxy ynone followed by a hydrogenation might
be useful and applicable for the synthesis of ent-diospongin A ent-1
(Fig. 1). Furthermore, this reaction sequence has not been utilized
for the synthesis of the diospongins. In continuation of our interest
in the synthesis of tetrahydropyranyl diarylheptanoids and their
analogues,5 we herein report the stereoselective synthesis of ent-
diospongin A.
2. Results and discussion
The synthesis of ent-diospongin A is shown in Scheme 1. The
synthesis began from the known hydroxy Weinreb amide 3, which
can be readily obtained in four steps from L-malic acid following a
literature protocol.6 In the first step, Weinreb amide 3 was treated
with phenyl acetylene in the presence of n-BuLi as a base, which
provided the desired b-hydroxyalkynone 4, a precursor for oxa-
Michael cyclisation. Next, the b-hydroxyalkynone 4 was subjected
to cyclisation by treatment with AgOTf in dichloromethane at
room temperature to obtain the dihydropyranone 5 in 85% yield.7
⇑
Corresponding author.
E-mail address: rajireddy@iict.res.in (C.R. Reddy).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.10.006

1726
C. R. Reddy et al. / Tetrahedron: Asymmetry 22 (2011) 1725–1728
O
O
O
OH
O
OH
O
OH
ref.6
a
b
c
OH
OTBDPS
MeO
OTBDPS
HO
N
OTBDPS
O
Ph
3
Ph
4
L-malic acid
5
OCOPh-4-NO2
OH
OCOPh-4-NO2
OH
g
h
f
e
ent-1
OH
O
OTBDPS
OTBDPS
Ph
Ph
Ph
O
Ph
O
Ph
O
Ph
8
6
7
9
+
O
(E/Z = 1:9 )
(9:1)
d
OTBDPS
6a
O
Scheme 1. Reagents and conditions: (a) phenyl acetylene, n-BuLi, THF, 0 to ꢀ78 °C to rt, 8 h, 74%; (b) AgOTf (1 mol %), CH2Cl2, rt, 30 min, 85%; (c) 10% Pd–C, Et3N, EtOH, H2
(gas), rt, 8 h, 70%; (d) NaBH4, CeCl3, MeOH, ꢀ78 °C, 82%; (e) DEAD, p-nitrobenzoic acid, PPh3, toluene, rt, 30 min, 80%; (f) TBAF, THF, 0 °C to rt, 1 h, 82%; (g) (i) DMP, CH2Cl2,
0 °C to rt, 8 h (ii) PhCHPPh3þBrꢀ, n-BuLi, THF, ꢀ78 °C to rt, 4 h, 60% (over two steps); (h) PdCl2 (50 mol %), CuCl, O2, DMF/H2O (1:1), 50 °C, 3 days, 52%.
Next, we focused our attention on the formation of the cis-tetrahy-
dropyran ring and the creation of a C4 stereocenter via a stereose-
lective controlled reduction of the C5–C6 double bond in
compound 5. The hydrogenation of 5 in the presence of palladium
on charcoal provided cis-tetrahydropyranol 6, along with the cis-
tetrahydropyranone 6a in a 9:1 ratio8 (the minor pyranone 6a
was reduced to pyranol 6 using NaBH4/CeCl3). The cis-stereochem-
istry in compound 6 was confirmed by nOe studies.9 As ent-dio-
spongin A required the apposite stereocenter at C4, we decided
to employ Mitsunobu inversion using p-nitrobenzoic acid, which
would also temporarily block the hydroxyl group in further trans-
formations. Thus, compound 6 was reacted with p-nitrobenzoic
acid and PPh3/DEAD in toluene at room temperature to afford ben-
zoate 7 in 80% yield. Next, the deprotection of tert-butyldiphenyl-
silyl group was accomplished by using TBAF in THF at 0 °C to afford
alcohol 8 in 82% yield. Oxidation of alcohol 8 using Dess–Martin
periodinane to the aldehyde and subsequent Wittig reaction with
benzyltriphenylphosphonium bromide salt in the presence of n-
BuLi in THF at ꢀ78 °C gave the tetrahydropyranol 9 as a 1:9 E/Z
mixture of compounds.10 The hydrolysis of benzoate ester also oc-
curred during the Wittig reaction under basic conditions, which is
an added advantage. Finally, Wacker oxidation was carried out on
the mixture of E/Z isomers of 9 which produced the desired ent-
diospongin A ent-1 in 52% yield, which was fully characterized
by 1H, 13C NMR, mass spectrometry and specific rotation. The spec-
troscopic data (IR, 1H and 13C NMR) of the obtained ent-1 were
identical while the specific rotation observed for ent-1,
4. Experimental
4.1. General
1H NMR and 13C NMR spectra were recorded in CDCl3 solvent on
300 or 75 MHz spectrometer at ambient temperature. The
chemical shifts (d) are reported in ppm downfield from TMS as
the internal standard; signal patterns are indicated as follows: s,
singlet; d, doublet; dd, doublet of doublet; dt, doublet of triplet;
t, triplet; m, multiplet; br s, broad singlet. Coupling constants J
are in Hz. FTIR spectra were recorded as KBr thin films or neat.
For low (MS) and high (HRMS) resolution, m/z ratios are reported
as values in atomic mass units. All reagents and solvents were of
reagent grade and used without further purification unless speci-
fied otherwise. Technical grade ethyl acetate and hexanes used
for column chromatography were distilled prior to use. Column
chromatography was carried out using silica gel (60–120 mesh)
packed in glass columns. All of the reactions were performed under
an atmosphere of nitrogen in flame-dried or oven-dried glassware
with magnetic stirring.
4.1.1. (S)-6-(tert-Butyldiphenylsilyloxy)-5-hydroxy-
1-phenylhex-1-yn-3-one 4
To
a stirred solution of the phenyl acetylene (0.77 mL,
6.85 mmol) in THF at 0 °C was added n-BuLi (2.74 mL, 6.85 mmol,
2.5 M in hexane) dropwise over a period of 10 min. After 30 min of
additional stirring, Weinreb amide (2.5 g, 6.23 mmol) in THF was
slowly added at -78 °C and stirred for 8 h at rt under an N2 atmo-
sphere. The mixture was quenched with saturated aq NH4Cl
(20 mL) at 0 °C, extracted with EtOAc (2 ꢂ 20 mL), dried over
Na2SO4 and purified by column chromatography (20% EtOAc in
½
a 2D7
ꢁ
¼ þ19:2 (c 0.26, CHCl3), was comparable with the reported
data {lit: ½a 2D8
ꢁ
¼ þ23:3 (c 0.2, CHCl3)}.3k
hexanes) to give 4 (2 g, 74%) as a yellowish liquid. ½a D28
ꢁ
¼ ꢀ4:6 (c
3. Conclusion
1.0, CHCl3); IR (Neat): mmax 3451, 2927, 2856, 2202, 1665, 1110,
757, 701 cmꢀ1 1H NMR (300 MHz, CDCl3): d 7.70–7.60 (m, 4H),
;
In conclusion, a stereoselective total synthesis of ent-diospongin
A has been accomplished using the AgOTf-catalyzed oxa-Michael
addition of a b-hydroxy ynone followed by stereoselective hydro-
genation for the formation of the 2,6-cis tetrahydropyran ring.
The synthetic sequence is new and unique, and can also be used
for the synthesis of diospongin A (starting from the other isomer
of the Weinreb amide) as well as other analogues.
7.57 (t, J = 1.7 Hz, 1H), 7.50 (d, J = 1.7 Hz, 1H), 7.50–7.30 (m, 9H),
4.36–4.20 (m, 1H), 3.74–3.59 (m, 2H), 2.88 (dd, J = 1.3, 6.7 Hz,
2H), 2.66 (d, J = 4.9 Hz,1H), 1.09 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 186.0, 135.4, 133.2, 133.0, 132.8, 130.8, 129.8, 128.5, 127.7,
119.6, 91.4, 87.8, 68.1 66.8, 48.7, 29.6, 26.7; HRMS (ESI):(m/z) calcd
for C28H30NaO3Si, 465.1856 [M+Na]+; found, 465.1817.

C. R. Reddy et al. / Tetrahedron: Asymmetry 22 (2011) 1725–1728
1727
4.1.2. (S)-2-((tert-Butyldiphenylsilyloxy)-6-phenyl-2H-pyran-
4(3H)-one 5
129.6, 128.3, 127.8, 127.6, 125.8, 123.6, 123.5, 74.3, 73.6, 69.9,
66.9, 37.5, 31.7, 26.8, 19.3; HRMS (ESI): (m/z) calcd for C35H37Na-
NO6Si, 618.2282 [M+Na]+; found, 618.2278.
To a stirred solution of ynone 4 (2.8 g, 6.3 mmol) in dichloro-
methane (14 mL) was added silvertrifluoromethanesulfonate
(16 mg, 0.06 mmol) at rt in the absence of light and the resultant
solution was stirred for 30 min. The mixture was filtered through
a pad of Celite and the filtrate was concentrated and purified by
flash chromatography (10% ethyl acetate in hexanes) to give 5
4.1.6. (2S,4R,6R)-2-(Hydroxymethyl)-6-phenyltetrahydro-2H-
pyran-4-yl-4-nitrobenzoate 8
To a stirred solution of silylated ester 7 (1.2 g, 2 mmol) in THF
(10 mL) was added a solution of TBAF (1 M in THF, 2.4 mL) at rt.
After 4 h of additional stirring, the reaction mixture was diluted
with water (10 mL) and extracted with EtOAc (2 ꢂ 20 mL). The or-
ganic extracts were washed with brine solution (20 mL) and dried
over Na2SO4. After evaporation of the solvent, the residue was puri-
fied by column chromatography (30% of EtOAc in hexanes) to af-
ford alcohol 9 (0.56 g, 78%) as an off-white solid, M.P: 86–88 °C;
(2.38 g, 85%) as a yellow oil: ½a D28
ꢁ
¼ þ36:3 (c 1.0, CHCl3); IR (Neat):
mmax 3068, 2930, 2857, 1659, 1597, 1109, 742, 701 cmꢀ1
;
1H NMR
(300 MHz, CDCl3): d 7.76–7.66 (m, 6H), 7.51–7.31 (m, 9H), 5.98 (s,
1H), 4.69–4.58 (m, 1H), 4.02 (dd, J = 3.7, 11.3 Hz, 1H), 3.95 (dd,
J = 5.2, 11.3 Hz, 1H), 2.79 (dd, J = 13.5, 16.6 Hz, 1H), 2.47 (dd,
J = 2.6, 16.6 Hz, 1H), 1.08 (s, 9H); 13C NMR (75 MHz, CDCl3): d
193.1, 169.9, 135.5, 132.9, 132.5, 131.5 129.8, 128.5, 127.7, 126.5,
101.8, 79.5, 64.9, 37.5, 26.6, 19.1; HRMS (ESI): (m/z) calcd for
½
a 2D8
ꢁ
¼ ꢀ34:0 (c 1.0, CHCl3); IR (KBr): mmax 3334, 2956, 2923,
2853, 1722, 1277, 1101, 1061, 721 cmꢀ1 1H NMR (300 MHz,
;
C
28H31O3Si, 443.2037 [M+H]+; found, 443.2009.
CDCl3): d 8.30 (d, J = 8.7 Hz, 2H), 8.27 (d, J = 8.7 Hz, 2H), 7.42–
7.20 (m, 5H), 5.62 (t, J = 2.9 Hz, 1H), 4.89 (dd, J = 1.9, 11.6 Hz,
1H), 4.17–4.09 (m, 1H), 3.73 (d, J = 12.6 Hz, 1H), 3.64 (dd, J = 5.8,
10.6 Hz, 1H), 2.08–1.80 (m, 4H); 13C NMR (75 MHz, CDCl3): d
159.1, 141.6, 130.4, 129.0, 128.5, 128.3, 127.6, 126.0, 113.8, 77.8,
74.1, 69.2, 65.9, 39.8, 33.6; HRMS (ESI): (m/z) calcd for
4.1.3. ((2S,4R,6R)-2-((tert-Butyldiphenylsilyloxy)methyl)-6
phenyltetrahydro-2H-pyran-4-ol 6
At first, 10% palladium on carbon (400 mg, 10 mol %) was added
to a solution of enone 5 (1.8 g, 4 mmol) and Et3N (1.14 mL, 8 mmol)
in ethanol (20 mL). The reaction mixture was stirred for 6 h at rt
under a hydrogen atmosphere and the filtrate was concentrated
and purified by flash chromatography (20% ethyl acetate in hex-
anes) to give the mixture of products 6 and 6a with a 9: 1 ratio
of silylated alcohol and silylated ketone. Compound 6: Yield:
C
19H19NO6, 380.1106 [M+H]+; found, 380.1102.
4.1.7. (2R,4R,6S)-2-Phenyl-6-styryltetrahydro-2H-pyran-4-ol 9
To a stirred solution of alcohol 8 (250 mg, 07 mmol) in 5 mL of
dichloromethane was added NaHCO3 (293 mg, 3.5 mmol) at 0 °C.
After 10 min. of additional stirring, Dess–Martin periodinane
(445 mg, 1.05 mmol) was added and stirred for 2 h at rt. Reaction
mixture was quenched with a saturated aqueous hypo solution
(10 mL), extracted with dichloromethane (3 ꢂ 10 mL), dried over
sodium sulphate, filtered and concentrated under reduced pressure
to give a crude aldehyde (200 mg), which was used for the Wittig
reaction without purification.
Benzyl triphenyl phosphonium bromide (365 mg, 0.83 mmol)
was dissolved in freshly distilled THF (3 mL) and n-BuLi (0.33 mL,
0.83 mmol, 2.5 M in hexanes) was added to the above solution at
0 °C. After 20 min. of additional stirring at rt, the reaction temper-
ature was lowered to ꢀ78 °C and the crude aldehyde (200 mg,
0.55 mmol) in THF (2 mL) was added to the above solution and
stirred for 30 min. After 1 h, the reaction mixture was warmed to
rt, quenched with ether (10 mL) and a saturated aqueous sodium
bicarbonate solution (10 mL). This mixture was extracted with
ether (3 ꢂ 10 mL), washed with brine (10 mL), dried over sodium
sulphate, filtered, concentrated under reduced pressure and puri-
fied through column chromatography (20% ethyl acetate in hex-
anes) to give 9 (117 mg, 60% over two steps) as a pale-yellow oil.
1H NMR for the major Z-isomer: (500 MHz, CDCl3): d 7.43–7.18
(m, 10H), 6.53 (d, J = 11.8 Hz, 1H), 5.71 (dd, J = 11.8, 8.9 Hz 1H),
4.98–4.87 (m, 2H), 4.35 (t, J = 3.0 Hz, 1H), 1.94–1.76 (m, 4H); MS
(ESI): (m/z) 303 (M+Na)+.
1.27 g, (70%); yellow liquid, ½a D28
ꢁ
¼ þ31:4 (c 1.0, CHCl3); IR (Neat):
mmax 3383, 3067, 2930, 2857, 1109, 701 cmꢀ1
;
1H NMR (300 MHz,
CDCl3): d 7.69–7.62 (m, 4H), 7.41–7.27 (m, 11H), 4.33 (dd, J = 2.2,
11.3 Hz, 1H), 4.02- 3.87 (m, 1H), 3.81 (AB, J = 9.8 Hz, 1H, A of AB),
3.68 (AB, J = 9.8 Hz, 1H, B of AB), 3.65–3.58 (m, 1H), 2.20–2.07
(m, 2H), 1.50–1.30 (m, 2H) 1.05 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 141.9, 135.6, 133.5, 129.5, 128.2, 127.5, 127.4, 125.9, 77.6, 77.4,
68.4, 66.8, 43.1, 37.5, 26.8, 19.2; HRMS (ESI): (m/z) calcd for
C
28H34NaO3Si, 469.2169 [M+Na]+; found, 469.2161.
4.1.4. (2S,6R)-2-((tert-Butyldiphenylsilyloxy)methyl)-6-phenyl-
dihydro-2H-pyran-4(3H)-one 6a
White solid, M.P: 90–92 °C; ½a D28
ꢁ
¼ þ41:5 (c 1.0, CHCl3); IR
(KBr): mmax 3064, 2931, 2854, 1711, 1111, 747, 701 cmꢀ1
;
1H
NMR (300 MHz, CDCl3): d 7.67 (t, J = 8.3 Hz, 4H), 7.43–7.27 (m,
11H), 4.64 (dd, J = 3.2, 10.9 Hz, 1H), 3.96–3.87 (m, 1H), 3.85 (d,
J = 4.3 Hz, 2H), 2.68–2.45 (m, 4H), 1.07 (s, 9H); 13C NMR (75 MHz,
CDCl3): d 206.9, 140.6, 135.5, 133.2, 129.6, 128.5, 127.9, 127.6,
125.6, 78.7, 77.5, 66.3, 49.6, 44.0, 26.7, 19.2; HRMS (ESI): (m/z)
calcd for C28H32NaO3Si, 467.2013 [M+Na]+; found, 467.2019.
4.1.5. (2S,4R,6R)-2-((tert-Butyldiphenylsilyloxy)methyl)-6-
phenyltetrahydro-2H-pyran-4-yl-4-nitrobenzoate 7
To a stirred mixture of alcohol 6 (1.15 g, 2.57 mmol), triphenyl-
phosphine (815 mg, 3 mmol) and p-nitrobenzoic acid (516 mg,
3 mmol) in toluene (12 mL) was added dropwise diethylazodicarb-
oxylate (0.60 mL, 3 mmol) at rt. After 15 min, the orange solution
became homogenous (orange–yellow), which indicated the com-
pletion of the reaction. The mixture was concentrated under re-
duced pressure to give a residue, which was purified by column
chromatography (10% EtOAc in hexanes) to give 7 (1.22 g, 80%)
4.1.8. 2-((2S,4R,6R)-4-Hydroxy-6-phenyltetrahydro-2H-pyran-2-
yl)-1-phenylethanone ent-1
A mixture of alkene 9 (100 mg, 0.35 mmol), PdCl2 (15.8 mg,
0.08 mmol) and CuCl (23.9 mg, 0.17 mmol) in DMF (3 mL) and
H2O (3 mL) was stirred at 50 °C for 3 days under an oxygen atmo-
sphere. Evaporation of the solvent in vacuo and purification of the
residue by column chromatography on silica gel eluted with 20% of
EtOAc in hexanes gave phenyl ketone 7 (55 mg, 52%) as a white so-
as a light yellow oil. ½a D28
ꢁ
¼ ꢀ15:7 (c 1.0, CHCl3); IR (KBr): mmax
2962, 2924, 2853, 1724, 1272, 709 cmꢀ1
;
1H NMR (300 MHz,
CDCl3): d 8.41–8.18 (m, 5H), 7.70 (dt, J = 1.5, 8.3 Hz, 4H), 7.45–
7.28 (m, 10H), 5.63 (t, J = 4.8 Hz, 1H), 4.85 (dd, J = 2.2, 12.0 Hz,
1H), 4.16–4.06 (m, 1H), 3.86 (dd, J = 5.2, 10.5 Hz,1H), 3.78 (dd,
J = 5.2, 10.5 Hz,1H), 2.20 (d, J = 14.3 Hz,1H), 2.08 (d,
J = 14.3 Hz,1H), 1.98–1.84 (m, 2H), 1.06 (s, 9H); 13C NMR
(75 MHz, CDCl3): d 163.8, 150.6, 141.9, 135.6, 133.5, 130.7, 130.6,
lid, M.P: 98–100 °C; ½a D27
ꢁ
¼ þ19:2 (c 0.26, CHCl3); IR (KBr): mmax
1H
7.98 (d, J = 7.7 Hz, 2H), 7.55 (t,
J = 7.7 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.40–7.20 (m, 5H), 4.93
3453, 2962, 2077, 1735, 1639, 1442, 1288, 1180, 689 cmꢀ1
;
NMR (300 MHz, CDCl3):
d

1728
C. R. Reddy et al. / Tetrahedron: Asymmetry 22 (2011) 1725–1728
3456; (d) Bates, R. W.; Song, P. Tetrahedron 2007, 63, 4497–4499; (e) Hiebel,
M.-A.; Pelotier, B.; Piva, O. Tetrahedron 2007, 63, 7874–7878; (f) Kawai, N.;
Hande, S.-M.; Uenishi, J. Tetrahedron 2007, 63, 9049–9056; (g) Yadav, J. S.;
Padmavani, B.; Reddy, B. V. S.; Venugopal, C.; Rao, A. B. Synlett 2007, 2045–
2048; (h) Wang, H.; Shuhler, B. J.; Xian, M. Synlett 2008, 2651–2654; (i) Sabitha,
G.; Padmaja, P. Helv. Chim. Acta 2008, 91, 2235–2239; (j) Lee, K.; Kim, H.; Hong,
J. Org. Lett. 2009, 11, 5202–5205; (k) Kumaraswamy, G.; Ramakrishna, G.;
Naresh, P.; Jagadeesh, B.; Sridhar, B. J. Org. Chem. 2009, 74, 8468–8471; (l)
Anada, M.; Washio, T.; Watanabe, Y.; Takeda, K.; Hashimoto, S. Eur. J. Org. Chem.
2010, 6850–6854; (m) More, J. D. Synthesis 2010, 2419–2423.
(dd, J = 1.9, 11.6 Hz, 1H), 4.69–4.61 (m, 1H), 4.28–4.19 (m, 1H), 3.40
(dd, J = 5.8, 16.5 Hz, 1H), 3.06 (dd, J = 6.8, 15.5 Hz, 1H),
1.99–1.90 (m, 2H), 1.80–1.64 (m, 2H); 13C NMR (75 MHz, CDCl3):
d 198.2, 142.6, 137.4, 133.0, 128.5, 128.3, 128.2, 127.2, 125.7,
73.7, 69.0, 64.7, 45.1, 42.1, 38.5; HRMS (ESI): (m/z) calcd for
C
19H20NaO3, 319.1305 [M+Na]+; found, 319.1297.
Acknowledgement
4. Reddy, Ch. R.; Srikanth, B. Synlett 2010, 1536–1538.
5. (a) Reddy, Ch. R.; Madhavi, P. P.; Chandrasekhar, S. Synthesis 2011, 123–126; (b)
Reddy, Ch. R.; Madhavi, P. P.; Chandrasekhar, S. Tetrahedron: Asymmetry 2010,
21, 103–105; (c) Reddy, Ch. R.; Rao, N. N.; Srikanth, B. Eur. J. Org. Chem. 2010,
345–351; (d) Chandrasekhar, S.; Babu, G. S. K.; Reddy, Ch. R. Tetrahedron:
Asymmetry 2009, 20, 2216–2219; (e) Reddy, Ch. R.; Madhavi, P. P.;
Chandrasekhar, S. Synthesis 2008, 2939–2942.
G.B.R. and B.S. thank Council of Scientific and Industrial Re-
search (CSIR), New Delhi for research fellowship.
References
6. Shioiri, T.; McFarlane, N.; Hamada, Y. Heterocycles 1998, 47, 73–76.
7. (a) Wang, C.; Forsyth, C. J. Org. Lett. 2006, 8, 2997–3000; (b) Nicolaou, K. C.;
Cole, K. P.; Frederick, M. O.; Aversa, R. J.; Denton, R. M. Angew. Chem., Int. Ed.
2007, 46, 8875–8879.
1. (a) De Albuquerque, I. L.; Galeffi, C.; Casinovi, C. G.; Marini-Bettolo, G. B. Gazz.
Chim. Ital. 1964, 94, 287–295; (b) Galeffi, C.; Casinovi, C. G.; Marini-Bettolo, G.
B. Gazz. Chim. Ital. 1965, 95, 95–100; (c) Craveiro, A. A.; Prado, A. d. C.; Gottlieb,
O. R.; Welerson de Albuquerque, P. C. Phytochemistry 1970, 9, 1869–1875; (d)
Jurd, L.; Wong, R. Y. Aust. J. Chem. 1984, 37, 1127–1133; (e) Jiang, Z. H.; Tanaka,
T.; Kirata, H.; Fukuoka, R.; Kuono, I. Phytochemistry 1996, 43, 1049–1054; (f)
Prasain, J. K.; Li, J. X.; Tezuka, Y.; Tanaka, K.; Basnet, P.; Dong, H.; Namba, T.;
Kadota, S. J. Nat. Prod. 1998, 61, 212–216; (g) Araujo, C. A. C.; Alefrio, L. V.; Leon,
L. L. Phytochemistry 1998, 49, 751–754; (h) DeC Alcantara, A. F.; Souza, M. R.;
Pilo-Veloso, D. Fitoterapia 2000, 71, 613–615; (i) Ali, M. S.; Tezuka, Y.; Banskota,
A. H.; Kadota, S. J. Nat. Prod. 2001, 64, 491–496; (j) He, W.; Wei, X.; Li, L.; Li, Y.;
Guo, S.; Guo, B. Zhiwu Xuebao 2001, 43, 757–759; (k) Jin, W. Y.; Cai, X. F.; Na, M.;
Lee, J. J.; Bae, K. Arch Pharm. Res. 2007, 30, 412–418; (l) Jin, W. Y.; Cai, X. F.; Na,
M.; Lee, J. J.; Bae, K. Biol. Pharm. Bull. 2007, 30, 810–813.
8. Lei, M.; Gao, L.; Yang, J. S. Tetrahedron Lett. 2009, 50, 5135–5138.
9. An nOe experiment has been carried out on compound
enhancements are shown below.
6 and key nOe
nOe enhancements
H
H
H
OH
O
2. Yin, J.; Kouda, K.; Tezuka, Y.; Le Tran, Q.; Miyahara, T.; Chen, Y.; Kadota, S.
Planta Med. 2004, 70, 54–58.
3. (a) Jennings, M. P.; Sawant, K. B. J. Org. Chem. 2006, 71, 7911–7914; (b)
Chandrasekhar, S.; Shyamsunder, T.; Prakash, S. J.; Prabhakar, A.; Jagadeesh, B.
Tetrahedron Lett. 2006, 47, 47–49; (c) Allais, F.; Cossy, J. Synlett 2006, 3455–
OTBDPS
10. Harris, J. M.; O’Doherty, G. A. Tetrahedron 2001, 57, 5161–5173.