Efficient stereoselective total synthesis of (+)-cryptofolione and the first synthesis of (-)-cryptocaryalactone

Article abstract of DOI:10.1055/s-0030-1260246

The stereoselective syntheses of the naturally occurring -pyrone derivatives (+)-cryptofolione and (-)-cryptocaryalactone were efficiently accomplished by using propane-1,3-diol as the starting material. Keck allylation, Mitsunobu center inversion, and ol

Full text of DOI:10.1055/s-0030-1260246

3706
PAPER
Efficient Stereoselective Total Synthesis of (+)-Cryptofolione and the First
Synthesis of (–)-Cryptocaryalactone1
S
ynthesisof (+
.
)
-Cryptofol
B
a
l
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160512; E-mail: biswanathdas@yahoo.com
Received 1 July 2011; revised 22 August 2011
O
Abstract: The stereoselective syntheses of the naturally occurring
2
a-pyrone derivatives (+)-cryptofolione and (–)-cryptocaryalactone
OH OH
O
8'
2'
were efficiently accomplished by using propane-1,3-diol as the
6
4'
6'
starting material. Keck allylation, Mitsunobu center inversion, and
olefin cross metathesis were used as the key steps. (–)-Cryptocarya-
lactone was synthesized here for the first time.
7'
1'
1
O
O
Key words: total synthesis, lactones, natural products, Keck allyla-
tion, Mitsunobu center inversion, olefin cross metathesis
OAc
O
OAc
O
Naturally occurring a,b-unsaturated d-lactones (e.g., sty-
ryllactones) and derivatives (a-pyrone derivatives) exhib-
it various biological activities such as cytotoxic, anti-
inflammatory, antitumor, antiviral, and antibacterial prop-
erties.2 The unsaturated moiety plays an important role in
biological activity, as it acts as an Michael accepter in the
presence of protein functional groups.3 Over the past two
decades an increasing number of a-pyrone derivatives
have been isolated from different sources.4 (+)-Cryptofo-
lione (1) (Figure 1), an unsaturated a-pyrone derivative,
was isolated from the bark of Cryptocarya latifolia and
Cryptocarya myrtifolia.5 Cryptocarya species have been
used as traditional medicine in South Africa for their anti-
inflammatory and other different activies.6 (+)-Cryptofo-
lione showed activity towards Trypanosoma cruzi tryp-
mastigotes, reducing their number by 77% at 250 mg/mL.7
It is also an inhibitor of the G2 check point.8 Thus, the syn-
thesis of this compound has recently attracted much atten-
tion from organic chemists.9
2
3
Figure 1
the best of our knowledge, there is no straightforward syn-
thesis of this compound, and only enantiomer 3 of this
compound has been synthesized.11
In continuation of our work12 on the synthesis of natural
a-pyrone, we have synthesized (+)-cryptofolione (1) and
(–)-cryptocaryalactone (2) by a facile straightforward ap-
proach starting from propane 1,3-diol; we report this syn-
thesis here.
Retrosynthetic analysis (Scheme 1) demonstrates that
compound 1 can be obtained from intermediate 4, which
can be prepared from propargyl alcohol 6, generated from
phenylacetylene and alcohol 7. Alcohol 7 can, in turn, be
prepared from propane-1,3-diol (8).
The synthesis of (+)-cryptofolione (1) was started from
mono-TBS-protected propane-1,3-diol 9 (Scheme 2).
Compound 9 was subjected to oxidation with pyridinium
chlorochromate followed by Keck allylation13 with binol
(–)-Cryptocaryalactone (2) (Figure 1), another related un-
saturated a-pyrone derivative, was isolated from Crypto-
carya moschata.10 It exhibits anti-germination activity. To
O
O
OH OH
O
O
O
O
+
Ph
Ph
4
1
5
OH OTBDPS
OTBDPS
HO
OH
HO
Ph
8
7
6
Scheme 1 Retrosynthetic analysis of (+)-cryptofolione (1)
SYNTHESIS 2011, No. 22, pp 3706–3710
x
x.
x
x
.
2
0
1
1
Advanced online publication: 29.09.2011
DOI: 10.1055/s-0030-1260246; Art ID: Z65911SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of (+)-Cryptofolione and (–)-Cryptocaryalactone
3707
complex (S,S)-18 (Figure 2) and allyltributyltin, to pro- ed with 2,2-dimethoxypropane and pyridinium p-toluene-
duce the chiral homoallylic alcohol 10 in 82% yield and sulfonate in dichloromethane to produce the acetonide 4.
96% ee. This chiral homoallylic alcohol 10 was protected The 1,3-anti relationship in 4 was established by analysis
as the corresponding TBDPS ether 11 with imidazole and of the 13C NMR spectrum (Figure 3). The methyl carbon
tert-butyldiphenylsilyl chloride in dichloromethane and values appeared at d = 25.0 and 25.6 ppm and the ace-
then treated with pyridinium p-toluenesulfonate in metha- tonide carbon at d = 100.3 ppm. The optical rotation,
nol to yield the free primary alcohol 7. Oxidation of 7 with physical, and spectroscopic properties of compound 4
2-iodoxybenzoic acid (IBX) in dimethyl sulfoxide formed were identical to those reported earlier.9b
the corresponding aldehyde, which was subsequently
δ 25.6
treated with phenylacetylene in the presence of n-butyl-
lithium in tetrahydrofuran at –20 °C to form the propargyl
alcohol in a diastereomeric ratio of 71:29. Purification of
the diastereomers by column chromatography gave the re-
quired chiral propargyl alcohol 6. The undesired diaste-
reomer 12 was converted into 6 under standard Mitsunobu
conditions14 to give 6 in high yield.
δ 25.0
δ 100.3
O
O
Ph
4
Figure 3
Finally, the olefin cross-metathesis reaction of 4 with the
known vinyl lactone12a 5 in the presence of the Grubbs
second-generation catalyst (Figure 4) in dichloromethane
yielded9b the required cross-coupled product 14
(Scheme 2), the treatment of which with hydrochloric
acid generated the naturally occurring (+)-cryptofolione
(1). The physical and spectroscopic properties of this
compound were identical to those reported earlier.9b,d
O
Oi-Pr
Ti
O
O
O
Ti
i-PrO
(S,S)-18
O
The synthesis of (–)-cryptocaryalactone (2) (Scheme 3)
was initiated from propane-1,3-diol by converting it into
the homoallylic alcohol 15 according to our previously re-
ported method.9d Compound 15 was esterified with acry-
loyl chloride in the presence of triethylamine and 4-(N,N-
dimethylamino)pyridine in dichloromethane to give the
acryloyl ester in 85% yield, which underwent ring-closing
metathesis16 in the presence of the Grubbs first-generation
Figure 2
Compound 6 was treated with sodium bis(2-methoxy-
ethoxy)aluminum hydride (Red-Al) in tetrahydrofuran to
produce diol 13 in high yield (Scheme 2). The relative ste-
reochemistry of the 1,3-diol 13 was confirmed by
Rychnovsky’s acetonide method.15 The diol 13 was treat-
OR
OTBDPS
a
b
d
HO
OH
HO
OTBS
8
9
TBSO
c
HO
7
10 R = H
11 R = TBDPS
OH OTBDPS
OH OTBDPS
OH OH
e
g
+
Ph
Ph
Ph
12
6
13
29:71
f
O
O
O
O
h
j
5
O
O
O
O
OH OH
O
O
i
Ph
Ph
Ph
1
4
14
Scheme 2 Reagents and conditions: (a) NaH, TBSCl, THF, 0 °C to r.t., 3.5 h, 91%; (b) 1. PCC, Celite, CH2Cl2, r.t., 2 h, 89%; 2. binol complex
(S,S)-18 (10 mol%), AllSnBu3, 4 Å MS, CH2Cl2, –20 °C, 36 h, 82%, 96% ee; (c) TBDPSCl, imidazole, DMAP (cat.), CH2Cl2, 0 °C to r.t., 4 h,
88%; (d) PPTS, MeOH, 0 °C to r.t., 6 h, 86%; (e) 1. IBX, CH2Cl2–DMSO, 0 °C to r.t., 6 h, 87%; 2. PhC≡CH, n-BuLi, anhyd THF, –20 °C, 3
h, 86%; (f) 1. 4-O2NC6H4CO2H, tetraphenylporphyrin (TPP), DIAD, anhyd THF, 0 °C to r.t., 12 h, 89%; 2. K2CO3, MeOH, 1 h, 92%; (g) Red-
Al, anhyd THF, 0 °C to r.t., 6 h, 93%; (h) 2,2-dimethoxypropane, PPTS, CH2Cl2, 0 °C, 30 min, 91%; (i) Grubbs II cat. (10 mol%), CH2Cl2,
reflux, 4 h, 69%; (j) MeCN, 4 N aq HCl, 0 °C, 30 min, 92%.
Synthesis 2011, No. 22, 3706–3710 © Thieme Stuttgart · New York

3708
P. Balasubramanyam et al.
PAPER
O
O
OAc OH
a
ref. 9d
b
HO
OH
OAc
O
OAc O
Ph
Ph
Ph
6
15
17
2
Scheme 3 Reagents and conditions: (a) H2C=CHCOCl, Et3N, DMAP, CH2Cl2, 0 °C, 1 h, 85%; (b) Grubbs I cat. (10 mol%), CH2Cl2, reflux,
8 h, 61%.
ane, 1:30); this afforded the corresponding aldehyde (8.68 g), which
was used as such for further reaction.
PCy3
Ru
N
N
Cl
Cl
A mixture of (S)-BINOL (1.33 g, 4.74 mmol) and Ti(Oi-Pr)4 (1.5 g,
4.755 mmol) in CH2Cl2 (60 mL) in the presence of 4 Å MS (6 g) was
stirred under reflux. After 1 h, the reaction mixture was cooled to
r.t. and the previously prepared aldehyde (8.68 g, 46.17 mmol) in
anhyd CH2Cl2 was added to it, and the resulting mixture was stirred
for 10 min. The mixture was then cooled to –78 °C and AllSnBu3
(18.87 g, 57.06 mmol) was added to it; stirring was continued at
–20 °C for 36 h. After completion of the reaction (according to
TLC), the reaction was quenched with sat. aq NaHCO3 (30 mL) and
the reaction mixture was stirred for an additional 30 min and ex-
tracted into CH2Cl2 (50 mL). The organic phase was washed with
brine (30 mL) and dried (Na2SO4), and the solvent was removed un-
der reduced pressure to give a crude residue, which was purified by
column chromatography (silica gel; EtOAc–hexane, 1:20); this af-
forded homoallylic alcohol 10.
Yield: 8.72 g (82%); [a]D30 –3.10 (c 1.5, CHCl3).
IR (film): 3454, 2931, 2859, 1738, 1640, 1467, 1095 cm–1.
1H NMR (200 MHz, CDCl3): d = 5.89–5.75 (m, 1 H), 5.14–5.03 (m,
2 H), 3.92–3.74 (m, 3 H), 3.40 (br s, 1 H), 2.29–2.18 (m, 2 H), 1.69–
1.62 (m, 2 H), 0.88 (s, 9 H), 0.06 (s, 6 H).
Cl
Ru
Cl
Ph
Ph
PCy3
(Cy)3P
Grubbs II catalyst
Grubbs I catalyst
Figure 4
catalyst (Figure 4) to furnish (–)-cryptocaryalactone (2) in
61% yield. The spectral data of 2 were identical with those
of the reported natural product.10
In conclusion, we have described the synthesis of two nat-
ural a-pyrone derivatives, (+)-cryptofolione, and (–)-
cryptocaryalactone. The later was synthesized here for the
first time. The synthetic strategy involves Keck allylation,
Mitsunobu center inversion, and olefin cross-metathesis
as the key steps.
13C NMR (50 MHz, CDCl3): d = 134.94, 117.20, 71.13, 62.49,
Reactions were conducted under N2 in anhyd solvents. All reactions
were monitored by TLC on silica gel GF254 precoated plates; visu-
alization was accomplished with UV light and/or with appropriate
stains. The spectra were recorded with the following instruments:
IR: Perkin-Elmer RX FT-IR spectrophotometer; NMR: Varian
Gemini 200 MHz (1H) and 50 MHz (13C) spectrometer; ESI-MS:
VG-Autospec micromass. Optical rotations were measured on a
JASCO DIP 300 digital polarimeter.
41.92, 37.75, 25.81, 18.08, –5.62.
ESI-MS: m/z (%) = 253 [M + Na]+.
(S)-1-(tert-Butyldimethylsiloxy)-3-(tert-butyldiphenyl-
siloxy)hex-5-ene (11)
Imidazole (2.35 g, 41.4 mmol), DMAP (cat.), and TBDPSCl (10.37
g, 37.87 mmol) were added to a stirred soln of compound 10 (8.72
g, 37.87 mmol) in anhyd CH2Cl2 (35 mL) at 0 °C. Stirring was con-
tinued for 3 h and then the mixture was diluted with CH2Cl2 (15
mL). The organic layer was washed with brine (25 mL) and then
dried (Na2SO4). Evaporation of the solvent under reduced pressure
followed by column chromatography (silica gel; EtOAc–hexane,
1:30) afforded the silyl ether 11.
3-(tert-Butyldimethylsiloxy)propan-1-ol (9)
Propane-1,3-diol (4.0 g, 52.63 mmol) was dissolved in anhyd THF
(50 mL). NaH (60% dispersion in mineral oil; 2.1 g, 52.63 mmol)
was added to it portionwise at 0 °C. The reaction mixture was
stirred at 0 °C for 30 min. TBSCl (7.92 g, 52.63 mmol) was added
to the mixture, which was then warmed to r.t. The reaction mixture
was stirred for a further 3 h at r.t. Ice water (15 mL) was added care-
fully to the reaction mixture to quench any excess of NaH. The re-
action mixture was extracted with EtOAc (50 mL). The organic
layer was washed with H2O (30 mL) and brine (20 mL). Evapora-
tion of the solvents and purification of the residue by chromatogra-
phy (silica gel; EtOAc–hexane, 1:9) afforded 9.
Yield: 15.58 g (88%).
1H NMR (200 MHz, CDCl3): d = 7.73–7.62 (m, 4 H), 7.44–7.31 (m,
6 H), 5.73 (m, 1 H), 4.95–4.86 (m, 2 H), 3.94 (m, 1 H), 3.71–3.54
(m, 2 H), 2.17 (m, 2 H), 1.71 (m, 2 H), 1.07 (s, 9 H), 0.85 (s, 9 H),
0.02 (s, 6 H).
13C NMR (50 MHz, CDCl3): d = 135.88, 134.69, 129.45, 127.45,
116.92, 70.37, 59.93, 41.34, 39.13, 26.99, 25.89, 19.37, 18.21, –5.3.
Yield: 9.88 g (91%).
1H NMR (200 MHz, CDCl3): d = 3.81–3.63 (m, 4 H), 2.71 (br s, 1
H), 1.78–1.66 (m, 2 H), 0.89 (s, 9 H), 0.03 (s, 6 H).
ESI-MS: m/z (%) = 491 [M + Na]+.
13C NMR (50 MHz, CDCl3): d = 62.4, 61.8, 34.3, 25.9, 18.2, –5.5.
ESI-MS: m/z (%) = 213 [M + Na]+.
(S)-3-(tert-Butyldiphenylsiloxy)hex-5-en-1-ol (7)
PPTS (419 mg, 1.67 mmol) was added to a stirred soln of 11 (15.58
g, 33.36 mmol) in MeOH (45 mL) at 0 °C; the mixture was allowed
to warm to r.t. and stirred for 6 h before it was evaporated. The
crude mass was diluted with EtOAc (25 mL) and the mixture was
washed with brine (20 mL) and subsequently dried (Na2SO4). Evap-
oration of the solvent under reduced pressure followed by column
chromatography (silica gel; EtOAc–hexane, 1:9) afforded alcohol
7.
(S)-1-(tert-Butyldimethylsiloxy)hex-5-en-3-ol (10)
Celite (60 g) and PCC (19.89 g, 71.83 mmol) were added to a stirred
soln of 9 (9.88 g, 47.89 mmol) in anhyd CH2Cl2 (80 mL) at 0 °C and
the mixture was stirred for 1.5 h at r.t. The mixture was diluted with
Et2O (50 mL) and passed through a column (silica gel; EtOAc–hex-
Synthesis 2011, No. 22, 3706–3710 © Thieme Stuttgart · New York

PAPER
Synthesis of (+)-Cryptofolione and (–)-Cryptocaryalactone
3709
Yield: 10.15 g (86%); [a]D30 +12.11 (c 2.0, CHCl3).
IR (film): 3419, 2932, 2857, 1752, 1591, 1430, 1109 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.77–7.65 (m, 5 H), 7.44–7.33 (m,
5 H), 5.66–5.52 (m, 1 H), 4.96–4.83 (m, 2 H), 4.02–3.93 (m, 1 H),
3.80–3.57 (m, 2 H), 2.33–2.12 (m, 2 H), 1.87–1.60 (m, 2 H), 1.07
(S, 9 H).
13C NMR (50 MHz, CDCl3): d = 135.89, 135.84, 134.76, 134.17,
133.90, 133.61, 117.31, 71.63, 59.66, 41.03, 37.48, 26.98, 19.24.
ESI-MS: m/z (%) = 377 [M + Na]+.
(4S,6R)-4-Allyl-2,2-dimethyl-6-styryl-1,3-dioxane (4)
PPTS (20 mg, 0.08 mmol) followed by 2,2-dimethoxypropane (1.0
mL, 8 mmol) were added to a stirred soln of 13 (0.55 g, 2.5 mmol)
in anhyd CH2Cl2 (5 mL) under N2 at 0 °C. The soln was stirred for
30 min and then quenched with solid NaHCO3 powder (30 mg). The
mixture was filtered, the filtrate was concentrated under reduced
pressure, and the residue was subjected to column chromatography
(silica gel; EtOAc–hexane, 1:20); this afforded pure 4.
Yield: 0.53 g (91%); [a]D29 +42.9 (c 1.5, CHCl3).
1H NMR (200 MHz, CDCl3): d = 7.34–7.12 (m, 5 H), 6.49 (d,
J = 18.0 Hz, 1 H), 6.16 (dd, J = 18.0, 8.0 Hz, 1 H), 5.79 (m, 1 H),
5.12–5.04 (m, 2 H), 4.49 (m, 1 H), 3.96 (m, 1 H), 2.42–2.16 (m, 2
H), 1.89–1.70 (m, 2 H), 1.39 (s, 6 H).
(3R,5S)-5-(tert-Butyldiphenylsiloxy)-1-phenyloct-7-en-1-yn-3-
ol (6)
A soln of 7 (2.0 g, 5.6 mmol) in anhyd CH2Cl2 was added to an ice-
cold soln of IBX (3.1 g, 11.2 mol) in DMSO (6 mL); the reaction
mixture was warmed to r.t. over 3 h. The mixture was diluted with
CH2Cl2 (5 mL), and the soln was stirred for 3 h, before it was fil-
tered through a Celite pad, which was washed with CH2Cl2 (10 mL).
The combined filtrates were washed with H2O (10 mL), dried
(Na2SO4), and concentrated under reduced pressure; this afforded
the intermediate aldehyde (1.73 g, 87%) which was used directly af-
ter flash chromatography (silica gel; EtOAc–hexane, 1:30) for the
next reaction.
13C NMR (50 MHz, CDCl3): d = 136.5, 134.2, 130.6, 130.0, 128.5,
127.7, 126.3, 116.9, 100.3, 67.8, 66.1, 40.1, 37.6, 25.6, 25.0.
ESI-MS: m/z (%) = 281 [M + Na]+.
(R)-6-{(E)-3-[(4S,6R)-2,2-Dimethyl-6-styryl-1,3-dioxan-4-
yl]prop-1-enyl}-5,6-dihydro-2H-pyran-2-one (14)
N2 was bubbled through a soln of 4 (0.12 g, 0.512 mmol) and 5
(0.045 g, 0.362 mmol) in anhyd CH2Cl2 (5 mL); then the Grubbs II
cat. (15 mg, 0.03 mmol) was added at once, and the resulting mix-
ture was heated under N2 at 50 °C for 4 h. After the mixture had
cooled, the solvent was evaporated in vacuo. The residue was puri-
fied by column chromatography (silica gel; EtOAc–hexane, 3:7);
this afforded pure 14.
A 2.0 M soln of n-BuLi in hexane (3.5 mL, 7.0 mmol) was added to
a soln of phenylacetylene (0.6 mL, 5.89 mmol) in anhyd THF (10
mL) at –20 °C. After 30 min, the intermediate aldehyde (1.73 g, 4.9
mmol) was added dropwise. The mixture was stirred for 3 h,
quenched with sat. aq NH4Cl (10 mL), and extracted with EtOAc
(3 × 15 mL). The combined organic extracts were washed with
brine (10 mL), dried (Na2SO4), and concentrated in vacuo. Purifica-
tion of the residue by column chromatography (silica gel; EtOAc–
hexane, 1:30) afforded 6 as pure diastereomer.
Yield: 0.125 g (69%); [a]D29 +50.2 (c 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 7.40–7.16 (m, 5 H), 6.86 (m, 1 H),
6.53 (d, J = 18.0 Hz, 1 H), 6.18 (dd, J = 16.0, 6.0 Hz, 1 H), 6.06 (d,
J = 8.0 Hz, 1 H), 5.84 (m, 1 H), 5.67 (dd, J = 18.0, 6.0 Hz, 1 H), 4.88
(q, J = 6.0 Hz, 1 H), 4.50 (q, J = 6.0 Hz, 1 H), 3.94 (m, 1 H), 2.50–
2.18 (m, 4 H), 1.94–1.48 (m, 2 H), 1.42 (s, 3 H), 1.40 (s, 3 H).
Yield: 1.37 g (86%); [a]D30 –9.17 (c 2.0, CHCl3).
The remaining isomer 12 was also converted into the required iso-
13C NMR (50 MHz, CDCl3): d = 164.1, 144.6, 131.0, 129.9, 129.7,
129.3, 128.8, 128.5, 127.6, 126.5, 121.5, 100.4, 77.9, 67.5, 65.8,
39.3, 38.5, 37.3, 25.6, 25.0.
mer 6 under standard Mitsunobu conditions.14
IR (film): 3438, 2928, 2857, 1724, 1466, 1107 cm–1.
ESI-MS: m/z (%) = 377 [M + Na]+.
1H NMR (200 MHz, CDCl3): d = 7.76–7.70 (m, 5 H), 7.43–7.28 (m,
10 H), 5.63–5.48 (m, 1 H), 4.97–4.82 (m, 3 H), 4.19 (m, 1 H), 2.97
(br s, 1 H), 2.31–2.15 (m, 2 H), 2.04–1.97 (m, 2 H), 1.08 (s, 9 H).
13C NMR (50 MHz, CDCl3): d = 135.89, 134.75, 133.68, 131.61,
129.86, 129.75, 128.20, 127.71, 127.57, 117.68, 90.01, 84.85,
71.10, 60.05, 42.62, 41.22, 26.94, 19.26.
(R)-6-[(1E,4S,6R,7E)-4,6-Dihydroxy-8-phenylocta-1,7-dienyl]-
5,6-dihydro-2H-pyran-2-one (1; Cryptofolione)
A 4 N aq HCl soln (0.5 mL) was added dropwise over 5 min to a
soln of 14 (0.12 g, 0.338 mmol) in MeCN (4 mL) at 0 °C. The mix-
ture was stirred at 0 °C for 0.5 h, and then quenched with sat. aq.
NaHCO3 (10 mL) and extracted with EtOAc (4 × 10 mL). The com-
bined organic layer was washed with brine (2 × 10 mL), dried
(Na2SO4), and concentrated. The residue was subjected to column
chromatography (silica gel; EtOAc–hexane, 5:5); this afforded pure
1.
ESI-MS: m/z (%) = 477 [M + Na]+.
(3R,5S,E)-1-Phenylocta-1,7-diene-3,5-diol (13)
Red-Al (4.2 mmol) was added to a stirred soln of 6 (1.25 g, 2.75
mmol) in anhyd THF (10 mL) under N2 at 0 °C. After stirring for 6
h, the reaction mixture was quenched with sodium potassium tar-
trate soln. The residue was washed with EtOAc (15 mL) and the
EtOAc layer was concentrated under reduced pressure. The crude
product was purified by column chromatography (silica gel;
EtOAc–hexane, 2:8); this gave pure diol 13.
Yield: 0.0979 g (92%); [a]D29 +44.2 (c 0.5, CHCl3).
IR (film): 2957, 1713, 1643, 1387, 1249, 1123 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.39–7.13 (m, 5 H), 6.82 (m, 1 H),
6.60 (d, J = 16.0 Hz, 1 H), 6.22 (dd, J = 16.0, 7.0 Hz, 1 H), 5.99 (d,
J = 8.0 Hz, 1 H), 5.86 (m, 1 H), 5.61 (dd, J = 16.0, 7.0 Hz, 1 H), 4.85
(m, 1 H), 4.60 (m, 1 H), 4.03, (m, 1 H), 3.25 (br s, 2 H), 2.42–2.31
(m, 2 H), 2.25 (t, J = 7.0 Hz, 2 H), 1.80–1.61 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 164.1, 145.0, 136.5, 132.1, 131.2,
130.1, 129.9, 128.9, 127.8, 126.7, 121.5, 76.5, 70.2, 68.0, 42.2,
40.1, 29.6.
Yield: 0.55 g (93%); [a]D29 +29.71 (c 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 7.34–7.18 (m, 5 H), 6.62 (d,
J = 18.0 Hz, 1 H), 6.22 (dd, J = 18.0, 6.0 Hz, 1 H), 5.86–5.70 (m, 1
H), 5.15–5.01 (m, 2 H), 4.62 (m, 1 H), 3.94 (m, 1 H), 3.38 (br s, 2
H), 2.18 (m, 2 H), 1.75–1.60 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 136.4, 134.4, 131.8, 129.9, 128.6,
127.6, 126.2, 118.2, 70.2, 68.0, 42.1, 41.9.
ESI-MS: m/z (%) = 337 [M + Na]+.
ESI-MS: m/z (%) = 241 [M + Na]+.
(3R,5S,E)-3-Acetoxy-1-phenylocta-1,7-dien-5-yl Acrylate (17)
Et3N (0.25 mL, 3.5 mmol) and DMAP (cat.), followed by acryloyl
chloride (0.08 mL, 0.9 mmol) were added to a stirred soln of 15
Synthesis 2011, No. 22, 3706–3710 © Thieme Stuttgart · New York

3710
P. Balasubramanyam et al.
PAPER
(0.14 g, 0.445 mmol) in anhyd CH2Cl2 (5 mL) at 0 °C. Stirring was
continued for 60 min and then the mixture was diluted with CH2Cl2
(10 mL). The organic layer was washed with NaHCO3 (10 mL) and
dried (Na2SO4). Evaporation of the solvent under reduced pressure
followed by column chromatography (silica gel; EtOAc–hexane,
1:9) afforded 17.
Yield: 0.148 g (85%); [a]D27 –37.6 (c 0.6, CHCl3).
IR (film): 2923, 2856, 1742, 1673, 1490, 1439, 1248, 1035 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.38–7.23 (m, 5 H), 6.59 (d,
J = 18.0 Hz, 1 H), 6.39 (m, 1 H), 6.18–6.06 (m, 2 H), 5.84–5.71 (m,
2 H), 5.48 (m, 1 H), 5.18–5.03 (m, 3 H), 2.41–2.30 (m, 2 H), 2.16–
1.91 (m, 5 H).
O.; Hofer, E.; Scheper, T.; Beil, W. ChemBioChem 2001, 2,
709. (b) Kalesse, M.; Christmann, M. Synthesis 2002, 981.
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(d) Buck, S. B.; Hardouin, C.; Ichikawa, S.; Soenen, D. R.;
Gauss, C.-M.; Hwang, I.; Swingle, M. R.; Bonness, K. M.;
Honkanen, R. E.; Boger, D. L. J. Am. Chem. Soc. 2003, 125,
15694.
(4) (a) Bohlmann, F.; Suwita, A. Phytochemistry 1979, 18, 677.
(b) Juliawata, L. D.; Kitajima, M.; Takayama, H.; Achmad,
S. A.; Aimi, N. Phytochemistry 2000, 54, 989. (c) Drewes,
S. E.; Sehlapelo, B. M.; Horn, M. M.; Scott-Shaw, R.;
Sander, O. Phytochemistry 1995, 38, 1427. (d) Drewes, S.
E.; Horn, M. M.; Scott-Shaw, R. Phytochemistry 1995, 40,
321.
(5) (a) Sehlapelo, B. M.; Drewes, S. E.; Scott-Shaw, R.
Phytochemistry 1994, 37, 847. (b) Cavalheiro, A. J.;
Yoshida, M.; Jodynis-Liebert, J.; Murias, M.; Bloszyk, E.
Phytochemistry 2000, 53, 811.
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2000, 71, 473. (b) Drewes, S. E.; Horn, M. H.; Mavi, S.
Phytochemistry 1997, 44, 437.
(7) Schemda-Hirschmann, G.; Astuddillo, L.; Bastida, J.;
Codina, C.; De Arias, A. R.; Ferrira, M. E.; Inchaustti, A.;
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ESI-MS: m/z (%) = 337 [M + Na]+.
(R,E)-1-[(S)-6-Oxo-3,6-dihydro-2H-pyran-2-yl]-4-phenylbut-3-
en-2-yl Acetate [2; (–)-Cryptocaryalactone]
Grubbs I cat. (21 mg, 0.025 mmol) was added to a soln of the acry-
late ester 17 (0.08 g, 0.279 mmol) in CH2Cl2 (20 mL) under an ar-
gon atmosphere, and the mixture was refluxed for 8 h. After
completion of the reaction, the solvent was removed by evapora-
tion, and the residue thus obtained was purified by column chroma-
tography (silica gel; EtOAc–hexane, 3:7); this gave 2.
Yield: 0.044 g (61%); [a]D27 –18.3 (c 0.2, CHCl3).
IR (film): 2921, 2859, 1728, 1508, 1454, 1376, 1232, 1019 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.42–7.21 (m, 5 H), 6.85 (m, 1 H),
6.69 (d, J = 18.0 Hz, 1 H), 6.12 (dd, J = 18.0, 8.0 Hz, 1 H), 6.04 (m,
1 H), 5.63 (m, 1 H), 4.51 (m, 1 H), 2.42–2.31 (m, 2 H), 2.01–2.19
(m, 5 H).
13C NMR (50 MHz, CDCl3): d = 170.1, 163.7, 144.8, 135.8, 133.2,
128.7, 128.2, 126.7, 126.4, 121.6, 74.2, 70.8, 39.9, 29.4, 21.2.
(9) (a) Matsuoka, Y.; Aikawa, K.; Irie, R.; Katsuki, T.
Heterocycles 2005, 66, 187. (b) Sabitha, G.; Reddy, S. S. S.;
Reddy, D. V.; Bhaskar, V.; Yadav, J. S. Synthesis 2010,
3453. (c) Kumar, R. N.; Mesham, H. M. Tetrahedron Lett.
2011, 52, 1003. (d) Das, B.; Nagendra, S.; Reddy, C. R.
Tetrahedron: Asymmetry 2011, 22, 1249.
(10) (a) Spencer, G. F.; England, R. E.; Wolf, R. B.
Phytochemistry 1984, 23, 2499. (b) Drewes, S. E.; Horn, M.
M.; Ramesar, N. S.; Ferreira, D.; Nel, R. J.-J.; Hutchings, A.
Phytochemistry 1998, 49, 1683.
(11) (a) Mori, Y.; Furukawa, H. Chem. Pharm. Bull. 1994, 42,
2161. (b) Sabitha, G.; Bhaskar, V.; Reddy, S. S. S.; Yadav,
J. S. Tetrahedron 2008, 64, 10207. (c) Radhakrishna, P.;
Krishnarao, L.; Reddy, K. L. N. Beilstein J. Org. Chem.
2009, 5, 14. (d) Sabitha, G.; Bhaskar, V.; Reddy, S. S. S.
Helv. Chim. Acta 2010, 93, 329.
ESI-MS: m/z (%) = 309 [M + Na]+.
Acknowledgment
The authors thank CSIR and UGC New Delhi for financial assi-
stance.
References
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Synthesis 2011, No. 22, 3706–3710 © Thieme Stuttgart · New York