Facile enantiospecific synthesis of (-)-muricatacin

Article abstract of DOI:10.1016/j.tetasy.2008.11.004

A facile approach for the enantiospecific synthesis of the bioactive butanolide (-)-muricatacin from l-(+)-tartaric acid is presented. Pivotal reaction sequence includes the elaboration of γ-hydroxy amide derived from tartaric acid and ring-closing metathesis.

Full text of DOI:10.1016/j.tetasy.2008.11.004

Tetrahedron: Asymmetry 19 (2008) 2616–2619
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Facile enantiospecific synthesis of (ꢀ)-muricatacin
*
Kavirayani R. Prasad , Vasudevarao Gandi
Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 October 2008
Accepted 7 November 2008
A facile approach for the enantiospecific synthesis of the bioactive butanolide (ꢀ)-muricatacin from
L-(+)-
tartaric acid is presented. Pivotal reaction sequence includes the elaboration of
from tartaric acid and ring-closing metathesis.
c-hydroxy amide derived
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Annonaceae acetogenins from the Annonaeceae plants are
shown to possess diverse biological profile including cytotoxic
activity.1 Muricatacin 1, isolated as a mixture of enantiomers from
the seeds of Anona muricata L.,2 is a simple butanolide possessing
potent cytotoxicity toward several human tumor cell lines. While
the diastereomers of muricatacin had no significant effect on bio-
activity, it was shown that altering the alkyl side chain influenced
the activity.3 Several syntheses of muricatacin and its congeners
were developed in recent years.4
We have recently demonstrated the use of novel building block
-hydroxy butyramides derived from tartaric acid in the total syn-
c
thesis of natural products.5 Herein, we report the facile synthesis
of (ꢀ)-muricatacin which is general and applicable for the synthe-
sis of a number of analogues. Our approach toward the synthesis
of muricatacin is depicted in Scheme 1. It is based on the hydro-
genation of butenolide 2, the synthesis of which is anticipated by
ring-closing metathesis of the acrloyl ester 3 derived from the
allylic alcohol 4. The formation of 4 is envisaged via Boord type
fragmentation of the isopropylidinedioxy iodide 5.
c-Hydroxy
OH
amide 6 was identified as the ideal precursor for the synthesis
of 5. The synthesis of 6 from the bis-Weinreb amide 7 of tartaric
acid involving a combination of controlled addition of Grignard
reagent and stereoselective reduction is a procedure established
in our laboratory.6
O
muricatacin 1
O
BnO
C12H25
R
R
O
O
R
O
O
O
O
OH
OBn
OH
OBn
2
1
3
4
R = C12H25
OH
O
Me
N
BnO
O
O
O
Me
N
I
R
OMe
MeO
R
N
OMe
O
O
O
5
Me
O
O
7
6
Scheme 1. Retrosynthesis for the synthesis of (ꢀ)-muricatain.
* Corresponding author. Tel.: +91 80 22932524; fax: +91 80 23600529.
E-mail address: prasad@orgchem.iisc.ernet.in (K. R. Prasad).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.11.004

K. R. Prasad, V. Gandi / Tetrahedron: Asymmetry 19 (2008) 2616–2619
2617
Accordingly, the synthesis of muricatacin commenced with the
4.1.1. Preparation of (4R,5R)-N-methoxy-N,2,2-trimethyl-5-
controlled addition of n-dodecylmagnesium bromide to the bis-
Weinreb amide 77 resulting in the formation of the mono keto
amide 8 in 82% yield. Stereoselective reduction of the keto group
in 8 with K-Selectride furnished alcohol 6 in 93% yield. The protec-
tion of the hydroxyl group in 6 as the corresponding benzyl ether 9
was accomplished in 71% yield (94% yield based on recovery of the
starting compound) by treating with BnBr/Ag2O. Reduction of the
Weinreb amide in 9 with NaBH4 afforded the primary alcohol 10
in 92% yield. Reaction of the primary alcohol 10 with PPh3/I2
provided the iodide 5 in 86% yield. Refluxing an ethanol solution
of iodide 5 with activated Zn cleanly produced the allylic alcohol
4 in 99% yield. Acrloylation of 4 afforded ester 3 in 88% yield, which
on ring-closing metathesis with Grubbs second generation catalyst
(10 mol %) furnished the butenolide in 91% yield. Hydrogenation of
2 with Pd/C afforded muricatacin 1 in 97% yield, the physical and
spectroscopic data of which are in complete agreement with those
reported in the literature.8
tridecanoyl-1,3-dioxolane-4-carboxamide 8
In a two-necked 50 mL, round-bottomed flask equipped with a
magnetic stir bar, rubber septum, and argon inlet was placed 7
(0.5 g, 1.81 mmol), which was dissolved in 6 mL of THF and cooled
to ꢀ15 °C. A freshly prepared THF solution of dodecylmagnesium
bromide (7.2 mL of 0.5 M solution in THF, 3.6 mmol) was added
at a rate that the internal temperature did not rise above ꢀ10 °C.
The progress of the reaction was monitored by TLC and after the
reaction was complete (0.5 h), it was cautiously quenched by addi-
tion of saturated solution of NH4Cl (5 mL). It was then poured into
water (10 mL) and extracted with ethyl acetate (2 ꢁ 10 mL). The
combined ethyl acetate extracts were washed with brine (10 mL)
and dried over Na2SO4. Evaporation of the solvent and silica gel
column chromatography of the residue with petroleum ether/
EtOAc (70:30) as eluent yielded 8 (0.57 g, 82%) as a colorless oil.
½
a D
ꢂ
¼ þ4:4 (c 1.1, CHCl3); IR (neat) 2926, 1721, 1675, 1378,
1082, 863 cmꢀ1 1H NMR (400 MHz, CDCl3) d 5.03 (d, J = 5.6 Hz,
;
1H), 4.81 (d, J = 5.6 Hz, 1H), 3.70 (s, 3H), 3.22 (s, 3H), 2.74–2.51
(m, 2H), 1.61–1.51 (m, 2H), 1.49 (s, 3H), 1.43 (s, 3H), 1.29–1.22
(m, 18H), 0.87 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
208.5, 169.8, 112.7, 82.3, 73.9, 61.7, 39.3, 32.5, 31.9, 29.62, 29.6,
29.46, 29.38, 29.3, 29.1, 26.7, 26.2, 23.1, 22.7, 14.1; HRMS for
C21H39NO5 + Na (M+Na) calcd 408.2726; found 408.2734.
3. Conclusion
In conclusion,
(ꢀ)-muricatacin, was accomplished from the chiral pool material
-(+)-tartaric acid. The synthetic sequence presented is highly
a
facile synthesis of bioactive lactone,
L
diastereoselective and is amenable to the synthesis of a number
of functionalized and non-functionalized derivatives of muri-
catacin (Scheme 2).
4.1.2. Preparation of (4R,5S)-5-((R)-1-hydroxytridecyl)-N-
methoxy-N,2,2-trimethyl-1,3-dioxolane-4-carboxamide 6
To a pre-cooled solution of 8 (0.5 g, 1.3 mmol) in THF(4 mL) at
ꢀ78 °C was added K-Selectride (2 mL, 1 M solution in THF, 2 mmol)
dropwise over a period of 10 min, under an argon atmosphere and
stirred at the same temperature. The progress of the reaction was
monitored by TLC and after the reaction was complete (0.5 h), it
was cautiously quenched by the dropwise addition of water
(2 mL) at ꢀ78 °C and extracted with ethyl acetate (2 ꢁ 10 mL).
The combined organic layer was washed with brine (5 mL) and
dried over Na2SO4. Evaporation of the solvent and silica gel column
chromatography of the resulting residue with petroleum ether/
EtOAc (1:1) as eluent afforded 6 (0.43 g, 86%) as a colorless oil;
4. Experimental
4.1. General procedures
Column chromatography was performed on silica gel, Acme
grade 100–200 mesh. TLC plates were visualized either with UV,
in an iodine chamber, or with phosphomolybdic acid spray, unless
noted otherwise. Unless stated otherwise, all reagents were pur-
chased from commercial sources and used without additional puri-
fication. THF was freshly distilled over Na-benzophenone ketyl.
Melting points are uncorrected. Unless stated otherwise, all the
reactions were performed under an inert atmosphere. Optical rota-
tions were measured on a JASCO DIP-370 digital polarimeter mea-
sured at 25 °C.
½
aꢂD
¼ ꢀ4:3 (c 1.1, CHCl3); IR (neat) 3454, 2925, 2853, 1667,
1594, 1378, 1068 cmꢀ1 1H NMR (400 MHz, CDCl3) d 4.76 br s,
;
1H), 4.36 (br s, 1H), 3.73 (s, 3H), 3.62–3.55 (m, 1H), 3.22 (br s,
3H), 1.96 (d, J = 8.8 Hz, 1H), 1.75–1.38 (m, 8 H), 1.37–1.17 (br s,
OH
O
Me
N
O
O
Me
N
O
O
Me
N
C12H25MgBr
THF, -15 ºC
0.5 h, 82%
K-Selectride
THF, −78 ºC
2.5 h, 86%
MeO
R
OMe
N
OMe
R
OMe
O
O
6
Me
O
O
O
O
8
R = C12H25
7
Ag2O, BnBr
Toluene, reflux
26 h, 94%
BnO
R
O
BnO
O
Me
N
PPh3, Imidazole
I2, Toluene, reflux
3 h, 86%
NaBH4/ MeOH
0 ºC to rt, 3 h
92%
OH
O
R
OMe
O
O
O
9
10
O
Cl
BnO
R
BnO
R
O
Grubbs 2nd gen cat
Toluene, Δ , 5 h, 91%
Zn, EtOH
reflux, 1 h
99%
Et3N, DMAP
CH2Cl2, 0 ºC
1 h, 88%
R
I
O
OBn
OH
O
5
3
4
H2, Pd/C
EtOAc, 2 h
97%
R
O
O
O
O
OH
1
OBn
2
Scheme 2. Synthesis of (ꢀ)-muricatacin.

2618
K. R. Prasad, V. Gandi / Tetrahedron: Asymmetry 19 (2008) 2616–2619
20H) 0.86 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 170.6,
111.0, 80.9, 73.8, 70.3, 61.7, 34.6, 32.4, 31.9, 29.67 (2xC), 29.64,
29.59, 29.5, 29.3, 27.0, 26.1, 25.8, 25.6, 22.7, 14.1; HRMS calcd
for C21H41NO5+Na (M+Na) 410.2882; found 410.2887.
(0.13 g, 84%) as a colorless oil; ½a D
ꢂ
¼ ꢀ7:4 (c 2, CHCl3); IR (neat)
1H NMR
3032, 2925, 2854, 1458, 1373, 1068, 883 cmꢀ1
;
(400 MHz, CDCl3) d 7.38–7.24 (m, 5H), 4.63 (m, 2H), 3.92 (dd,
J = 7.5, 3.9 Hz, 1H), 3.85 (td, J = 7.5, 2.9 Hz, 1H), 3.55 (td, J = 8.8,
4.2 Hz, 1H), 3.34 (dd, J = 10.7, 4.2 Hz, 1H), 3.22 (dd, J = 10.7,
5.1 Hz, 1H), 1.68–1.52 (m, 2H), 1.47 (s, 3H), 1.43 (s, 3H), 1.38–
1.24 (m, 20H), 0.89 (t, J = 6.3 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 138.2, 128.4, 128.1, 127.8, 109.3, 81.8, 77.8, 75.5, 72.8, 31.9,
30.4, 29.69, 29.66, 29.60, 29.59, 29.40, 27.5, 27.3, 26.0, 22.7, 14.1,
7.5 HRMS calcd for C26H43IO3+Na 553.2155; found 553.2150.
4.1.3. Preparation of (4R,5S)-5-((R)-1-(benzyloxy)tridecyl)-N-
methoxy-N,2,2-trimethyl-1,3-dioxolane-4-carboxamide 9
To a solution of 8 (0.15 g, 0.38 mmol) in toluene (3 mL) was
added Ag2O (0.18 g, 0.77 mmol) under an argon atmosphere at
room temperature. The reaction mixture was stirred at reflux for
1 h, and then cooled to room temperature. Benzyl bromide
(0.07 mL, 0.57 mmol) was then introduced into the reaction mix-
ture, and was allowed to reflux for additional 23 h. Progress of
the reaction was monitored by TLC and after the reaction was com-
plete, the reaction mixture was filtered through a short pad of Cel-
ite and the Celite pad was washed with CH2Cl2 (2 ꢁ 5 mL).
Evaporation of the solvent and silica gel column chromatography
of the residue with petroleum ether/EtOAc (70:30) as an eluent
4.1.6. Preparation of (3R,4R)-4-(benzyloxy)hexadec-1-en-3-ol 4
To a solution of the iodide 5 (0.12 g, 0.22 mmol) was added acti-
vated zinc dust (0.12 g, 1.8 mmol) in absolute ethanol (4 mL) at
room temperature and stirred for 1 h at 80 °C. Progress of the reac-
tion was followed by TLC. After completion of the reaction, it was
filtered through a short pad of Celite and the Celite pad was
washed with Et2O (2 ꢁ 5 mL). Evaporation of the solvent followed
by silica gel column chromatography of the crude residue with
furnished 9 0.14 g as a colorless oil; ½a D
ꢂ
¼ þ6:5 (c 1.4, CHCl3); IR
(neat) 3031, 2926, 2851, 1671, 1376, 1070 cmꢀ1
;
1H NMR
petroleum ether/ethyl acetate (9:1) as eluent furnished
(0.076 g, 99%) as a colorless oil. ½a D ¼ ꢀ3:6 (c 1.7, CHCl3); IR (neat)
3465, 2925, 2855, 1460, 1219, 1099 cmꢀ1 1H NMR (300 MHz,
4
(400 MHz, CDCl3) d 7.36–7.24 m, 5H), 4.76–4.70 (m, 2H), 4.64
and 4.59 (AB q, J = 11.5 Hz, 2H), 3.65 (s, 3H), 3.57 (dd, J = 10.7,
6.2 Hz, 1H), 3.18 (s, 3H), 1.57 (q, J = 7.2 Hz, 2H), 1.48 (s, 3H), 1.47
(s, 3H), 1.30–1.22 (m, 20H), 0.88 (t, J = 6.5 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 170.4, 138.6, 128.2, 127.9, 127.7, 127.5,
110.1, 80.3, 79.2, 78.0, 72.2, 61.7, 32.3, 31.9, 30.1, 29.67, 29.61,
29.58, 29.38, 27.1, 26.2, 25.8, 22.7, 14.1; HRMS calcd for
C28H47NO5+Na 500.3352; found 500.3338.
ꢂ
;
CDCl3) d 7.38–7.24 m, 5H), 5.88 (ddd, J = 16.8 Hz, 10.5 Hz, 6.3 Hz,
1H), 5.36 (dt, J = 17.1 Hz, 1.5 Hz, 1H), 5.22 (dt, J = 10.5 Hz, 1.5 Hz,
1H), 4.64 and 4.54 (AB q, J = 11.4 Hz, 2H), 4.0–4.2 (m, 1H), 3.35
(dd, J = 11.1 Hz, 6.0 Hz, 1H), 2.49 (d, J = 4.5 Hz, 1H), 1.68–1.48 (m,
3 1.47–1.24 (m, 19H), 0.88 (t, J = 6.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 138.3; 137.7, 128.4, 127.9, 127.8, 116.8, 82.4, 74.4, 72.6,
31.9, 30.4, 29.9, 29.70, 29.66, 29.61, 29.60, 29.4, 25.1, 22.7, 14.1
YRMS calcd for M+Na (C23H38O2+Na) 369.2770; found 369.2751.
4.1.4. Preparation of (4S,5S)-5-((R)-1-(benzyloxy)tridecyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)methanol 10
In a single-necked round-bottomed flask equipped with a mag-
netic stir bar and guard tube was placed a solution of 9 (0.150 g,
0.31 mmol) in MeOH (2 mL). NaBH4 (0.024 g, 0.62 mmol) was
introduced into the solution at 0 °C. The reaction mixture was
slowly warmed up to room temperature and stirred for 3 h at the
same temperature. After the reaction was complete (TLC), most
of the methanol was removed under reduced pressure and water
(3 mL) was added to the reaction mixture and extracted with ethyl
acetate (2 ꢁ 10 mL). The combined organic layers were washed
with brine (5 mL) and dried over Na2SO4. Evaporation of solvent
followed by silica gel column chromatography of the crude residue
with petroleum ether/ethyl acetate (7:3) as eluent furnished 10
4.1.7. Preparation of (3R,4R)-4-(benzyloxy)hexadec-1-en-3-yl
acrylate 3
To an ice-cold solution of 4 (0.03 g, 0.08 mmol) in CH2Cl2 (2 mL)
was added DMAP (0.01 g, 0.08 mmol) and Et3N (0.03 mL,
0.26 mmol) and stirred for 15 min at the same temperature. Acry-
loyl chloride (0.02 mL, 0.26 mmol) was added to the reaction mix-
ture at 0 °C and stirred at the same temperature for 1 h. After the
reaction was complete (TLC), it was poured into water (5 mL)
and extracted with ethyl acetate (2 ꢁ 5 mL). The combined organic
layers were washed with brine (5 mL) followed by saturated
sodium bicarbonate solution (5 mL) and dried over Na2SO4. Evapo-
ration of solvent followed by silica gel column chromatography of
the crude residue with petroleum ether/ethyl acetate (95:5) as elu-
ent resulted in the acryloyl ester 3 (0.028 g, 88%) as a colorless oil;
(0.12 g, 92%) as a colorless oil; ½a D
ꢂ
¼ þ9:7 (c 1.5, CHCl3); IR(neat)
3467, 3031, 2925, 2856, 1459, 1374, 1070 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) d 7.36–7.23 m, 5H), 4.63 (s, 2H), 4.2–3.96 (m,
2H), 3.73–3.50 (m, 3H), 2.39 (t, J = 4.2 Hz, 1H), 1.42 (s, 3H), 1.40
(m, 2H), 1.78–1.37 (m, 2H), 1.37–1.20 (m, 22H), 0.88 (t,
J = 6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3), d 138.0, 128.4, 128.2,
128.0, 127.9, 108.8, 78.8, 78.2, 77.2, 73.0, 62.8, 31.9, 30.3, 29.70,
29.67, 29.61, 29.60, 29.38, 27.1, 26.1, 22.7, 14.1. HRMS for
C26H44O4+Na calcd 443.3137; found 443.3127.
½ ꢂ ¼ þ21:6 (c 0.8, CHCl3); IR (neat) 3090, 3033, 2925, 1730, 1635,
a D
1404, 1265, 1099 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 7.36–7.24 (m,
5H), 6.45 (dd, J = 17.3, 1.39 Hz, 1H), 6.17 (dd, J = 17.2, 10.3 Hz, 1H),
5.93–5.87 (m, 1H), 5.86 (dd, J = 10.3, 1.4 Hz, 1H), 5.55–5.50 (m, 1H),
5.36–5.23 (m, 2H), 4.65 and 4.58 (AB q, J = 11.5 Hz, 2H), 3.52 (dd,
J = 12.1, 5.4 Hz, 1H), 1.56–1.41 (m, 4H), 1.39–1.15 (m, 18H), 0.88
(t, J = 6.6 Hz, 3H);13CNMR (100 MHz, CDCl3) d 165.3, 138.4, 133.0,
131.0, 128.5, 128.3, 128.0, 127.7, 118, 79.8, 75.4, 72.8, 31.9, 30.4,
29.69, 29.66, 29.62, 29.6, 29.5, 29.4, 25.4, 22.7, 14.1. HRMS calcd
for C26H40O3+Na 423.2875; found 423.2874.
4.1.5. Preparation of (4S,5R)-4-((R)-1-(benzyloxy)tridecyl)-5-
(iodomethyl-2,2-dimethyl-1,3-dioxolane 5
To a solution of 10 (0.12 g, 0.28 mmol), in dry toluene (6 mL),
was added PPh3 (0.23 g, 0.85 mmol), imidazole (0.058 g,
0.85 mmol), and iodine (0.066 g, 0.52 mmol), under argon atmo-
sphere at room temperature. The reaction mixture was then stirred
at reflux for 1 h. After the reaction was complete (TLC), it was
cooled to room temperature and poured into water (5 mL) and
extracted with ether (2 ꢁ 10 mL). The combined ethereal layers
were washed with brine (5 mL) followed by saturated solution of
sodium thiosulfate (5 mL) and dried over Na2SO4. Evaporation of
solvent followed by silica gel column chromatography of the crude
residue with petroleum ether/ether (95:5) as eluent afforded 5
4.1.8. Preparation of (R)-5-(R-1-(benzyloxy)tridecyl)furan-
2(5H)-one 2
A mixture of the diene 3 (0.02 g, 0.05 mmol) and Grubbs 2nd
generation catalyst (0.004 g, 0.005 mmol, 10 mol %) in 1 mL of tol-
uene was stirred at reflux for 4 h. It was then cooled to room tem-
perature and most of the toluene evaporated off. Column
chromatography of the resultant residue using petroleum ether/
ethyl acetate (9:1) as eluent afforded 2 in 91% (0.017g) yield
½
aꢂD
¼ þ104:5 (c 1.1, CHCl3); IR (neat) 2924, 2853, 1783, 1757,
1160, 1070, 823, 771 cmꢀ1 1H NMR (400 MHz, CDCl3) d 7.46 (dd,
;

K. R. Prasad, V. Gandi / Tetrahedron: Asymmetry 19 (2008) 2616–2619
2619
J = 5.7 Hz, 1.4 Hz, 1H), 7.38–7.24 (m, 5H), 6.17 (dd, J = 5.7 Hz,
References
1.7 Hz, 1H), 5.14–5.08 (m, 1H), 4.69 and 4.61 (AB q, J = 11.5 Hz,
2H), 3.68–3.59 (m, 1H), 1.50–1.34 (m, 4H), 1.32–1.15 (m, 18H),
0.88 (t, J = 6.5 Hz, 3H);13CNMR (100 MHz, CDCl3) d 172.9, 154.0,
137.8, 128.5, 128.0, 122.7, 84.6, 78.8, 73.4, 31.9, 30.6, 29.7, 29.65,
29.62, 29.56, 29.49, 29.4, 25.6, 22.7, 14.1; HRMS calcd for
C24H36O3+Na 395.2562; found 395.2548.
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Synlett 2007, 1112; (h) Prasad, K. R.; Anbarasan, P. Synlett 2006, 2087; (i) Prasad,
K. R.; Gholap, S. L. J. Org. Chem. 2006, 71, 3643; (j) Prasad, K. R.; Anbarasan, P.
Tetrahedron: Asymmetry 2006, 17, 1146; (k) Prasad, K. R.; Anbarasan, P.
Tetrahedron 2006, 62, 8303; (l) Prasad, K. R.; Anbarasan, P. Tetrahedron:
Asymmetry 2006, 17, 850; (m) Prasad, K. R.; Anbarasan, P. Tetrahedron Lett.
2006, 47, 1433; (n) Prasad, K. R.; Gholap, S. L. Synlett 2005, 2260.
4.1.9. Preparation of muricatacin 1
To a solution of 2 (0.016 g, 0.04 mmol) in 1 mL of EtOAc at room
temperature was added 10% activated Pd/C (50 mg). The reaction
mixture was stirred for 2 h under a hydrogen atmosphere (balloon)
at the same temperature. After the reaction was complete (TLC), it
was filtered through a short pad of Celite and the Celite pad was
washed with EtOAc (2 ꢁ 5 mL). The residue obtained after evapo-
ration of the solvent was purified by column chromatography
using petroleum ether/ethyl acetate (1:1) as eluent to yield muri-
catacin 1 (0.011 g, 97%) as a white solid. mp 67–69 °C; lit.8 mp
67–68 °C ½a D
ꢂ
¼ ꢀ23:9 (c 0.8, CHCl3); lit.8
½
aꢂD
¼ ꢀ23:3 (c 1.8,
CHCl3); IR (KBr) 3441, 3401, 2956, 1743, 1471, 1196 cmꢀ1
;
1H
NMR (400 MHz, CDCl3) d 4.41 (td, J = 7.2 Hz, 4.4 Hz, 1H), 3.62–
3.53 (br m, 1H), 2.68–2.45 (m, 2H), 2.28–2.21 (m, 1H), 2.16–2.06
(m, 1H)1.89 (br s, 1H), 1.61–1.46 (m, 2H), 1.41–1.24 (m, 20H),
0.88 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 177.2, 83.0,
73.7, 33.0, 31.9, 29.66, 29.64, 29.57, 29.50, 29.3, 28.7, 25.5, 24.1,
22.7, 14.1; Anal. calcd for C17H32O2: C, 71.79; H, 11.34. Found: C,
71.70: H, 11.10.
6. Prasad, K. R.; Chandrakumar, A. Tetrahedron 2007, 63, 1798.
7. (a) Nugiel, D. A.; Jakobs, K.; Worley, T.; Patel, M.; Kaltenbach, R. F., III.; Meyer, D.
T.; Jadhav, P. K.; De Lucca, G. V.; Smyser, T. E.; Klabe, R. M.; Bacheler, L. T.;
Rayner, M. M.; Seitz, S. P. J. Med. Chem. 1996, 39, 2156–2169; (b) McNulty, J.;
Grunner, V.; Mao, J. Tetrahedron Lett. 2001, 42, 5609.
8. Marshall, J. A.; Welmaker, G. S. J. Org. Chem. 1994, 59, 4122.
Acknowledgments
We thank DST and DBT, New Delhi, for funding of this project.
V.G. thanks CSIR for a junior research fellowship.