Stereoselective total synthesis of bioactive styryllactones: 9-Deoxygoniopypyrone, goniopypyrone and 7-epi-goniofufurone

Article abstract of DOI:10.1055/s-2007-990866

Stereoselective synthesis of the bioactive styryllactones (+)-9-deoxygoniopypyrone, (+)-goniopypyrone and (+)-7-epi-goniofufurone has been achieved from D-(-)-tartaric acid. The key step involves the elaboration of a trihydroxy ester to the title compound

Full text of DOI:10.1055/s-2007-990866

PAPER
3697
Stereoselective Total Synthesis of Bioactive Styryllactones:
9-Deoxygoniopypyrone, Goniopypyrone and 7-epi-Goniofufurone
S
ynthesis of Bioac
a
tive Styryll
vactones irayani R. Prasad,* Madhuri G. Dhaware
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Fax +91(80)23600529; E-mail: prasad@orgchem.iisc.ernet.in
Received 2 August 2007
With warmth and affection, dedicated to Professor G. S. R. Subbarao on the occasion of his 70th birthday
H
H
Abstract: Stereoselective synthesis of the bioactive styryllactones
(+)-9-deoxygoniopypyrone, (+)-goniopypyrone and (+)-7-epi-go-
niofufurone has been achieved from D-(–)-tartaric acid. The key
step involves the elaboration of a trihydroxy ester to the title com-
pounds utilizing high-yielding stereoselective transformations.
H
H
O
O
HO
Ph
O
Ph
O
Ph
HO
O
O
O
O
O
HO
HO
HO
H
H
9-deoxygoniopypyrone (1)
goniopypyrone (2)
7-epi-goniofufurone (3)
Key words: styryllactone, goniopypyrone, 7-epi-goniofufurone,
tartaric acid
O
O
H
O
OH
O
OH
O
Trees of the genus Goniothalamus of the plant family An-
nonaceae have been known for a long time in folk medi-
cine for their use in the treatment of various ailments.
Extensive investigations by the research group of
McLaughlin and others led to the isolation of a large num-
ber of styryllactones, possessing marginal to significant
cytotoxic, antitumour, pesticidal, and embryotoxic activi-
ties (Figure 1).1 These styryllactones can be mainly clas-
sified into two groups, related to the size of the lactone
(five-membered furone or six-membered pyrone). The
bioactivity and structural diversity associated with these
compounds has invigorated considerable interest in their
Ph
O
Ph
Ph
O
HO
OH
goniodiol (5)
OH
H
leiocarpin (4)
7-epi-goniodiol (6)
Figure 1 Bioactive styryllactones
a facile synthesis of (+)-9-deoxygoniopypyrone (1), (+)-
goniopypyrone (2) and (+)-7-epi-goniofufurone (3) in-
volving ring-closing metathesis (RCM) as the key step.4
Our approach for the synthesis of 9-deoxygoniopypyrone
synthesis from a large number of groups.2 As part of our (1) and goniopypyrone (2) is based on a Michael-type cy-
program involving the stereoselective synthesis of natural clization of the lactones 15 and 23, which can be prepared
products from chiral pool precursors, we have recently ac- by RCM of acrylate esters 14 and 22, respectively
complished the synthesis of a number of styryllactones.3 (Scheme 1). Synthesis of 14 and 22 is anticipated from the
In a continuation of our efforts, herein we report in detail extension of protected trihydroxy ester 10 that can be ob-
O
O
H
O
O
O
O
O
Ph
R
O
Ph
O
Ph
O
R
HO
H
O
R
1 R = H
2 R = OH
15 R = H
23 R = OMOM
14 R = H
22 R = OMOM
O
OH
OH
O
O
O
OMe
NMe2
NMe2
Ph
Ph
Me2N
O
O
O
O
O
O
10
8
7
Scheme 1 Retrosynthesis for 9-deoxygoniopypyrone (1) and goniopypyrone (2)
SYNTHESIS 2007, No. 23, pp 3697–3705
x
x.
x
x
.
2
0
0
7
Advanced online publication: 31.10.2007
DOI: 10.1055/s-2007-990866; Art ID: P09707SS
© Georg Thieme Verlag Stuttgart · New York

3698
K. R. Prasad, M. G. Dhaware
PAPER
HO
O
O
O
PTSA (1.5 equiv)
ref. 3a
NMe2
NMe2
Ph
Me2N
O
MeOH–C6H6 (1:1)
reflux, 5 h, 88%
O
O
O
8
7
MeO
MeO
PTSA (10 mol%)
OH OH
O
OH
OMe
OMe
Ph
Ph
CH2Cl2, r.t., 1 h, 96%
OH
O
O
O
9
10
i) TBDMSCl, imidazole
O
OTBDMS
OH
DMAP, DMF, r.t., 12 h, 98%
Ph
ii) DIBAL-H, toluene
O
–78 °C to r.t., 1 h, 94%
11
Scheme 2 Synthesis of the protected methyl a,b,g-trihydroxy-g-phenylbutanoate
tained by elaboration of the g-hydroxy-g-phenylbutyr- droxy group in 10 as the corresponding tert-butyl-
amide 8. Synthesis of 8 from bis(dimethylamide) 7 dimethylsilyl ether, followed by reduction of the ester
derived from tartaric acid has been established previously group, furnished the alcohol 11 in good yield. Alcohol 11
in our laboratory.3a
served as the intermediate of divergence for the synthesis
of (+)-9-deoxygoniopypyrone (1), (+)-goniopypyrone (2)
and (+)-7-epi-goniofufurone (3) which was accomplished
as outlined below.
Thus, the synthetic sequence commenced with the prepa-
ration of the g-hydroxybutyramide 8, readily obtained
from the bis(dimethylamide) 7, employing a combination
of selective Grignard addition and stereoselective reduc- For the synthesis of 9-deoxygoniopypyrone (1),5 alcohol
tion.3a Hydrolysis of the amide to the methyl ester with 11 was converted into the epoxide 12 (Scheme 3). Selec-
concomitant deprotection of the acetonide in 8 was tive opening of the epoxide 12 with vinylmagnesium bro-
achieved in refluxing methanol–benzene containing an mide in the presence of copper(I) iodide resulted in the
equivalent amount of p-toluenesulfonic acid, which af- homoallylic alcohol 13 in 93% yield. Reaction of alcohol
forded the trihydroxy ester 9 in 88% yield (Scheme 2). 13 with acryloyl chloride furnished the ester 14 in 75%
Reaction of 9 with 2,2-dimethoxypropane and a catalytic yield. Reaction of ester 14 with Grubbs’ first-generation
amount of p-toluenesulfonic acid resulted in the a-hy- catalyst resulted in the lactone 15 in 52% yield, while em-
droxy ester 10 in 96% yield. Protection of the free hy- ployment of Grubbs’ second-generation catalyst afforded
i) TsCl (2 equiv), py
r.t., 12 h, 98%
MgBr
O
O
OTBDMS
OH
CuI, THF
O
Ph
Ph
Ph
Ph
ii) TBAF (2 equiv), THF
0 °C to r.t., 11 h, 96%
–30 °C
1 h, 93%
O
O
12
11
O
Grubbs II cat.
(3 mol%)
H2C=CHCOCl
O
OH
O
O
Et3N, DMAP
toluene, reflux
8 h, 76%
Ph
CH2Cl2, 0 °C
2 h, 75%
O
O
14
13
O
O
TFA (2 equiv)
DBU (cat.)
O
O
OH
O
(+)-1
CH2Cl2, 0 °C
30 min, 88%
THF, r.t.
24 h, 91%
Ph
O
15
OH
16
Scheme 3 Synthesis of (+)-9-deoxygoniopypyrone (1)
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

PAPER
Synthesis of Bioactive Styryllactones
3699
the lactone in 76% yield. Deprotection of the acetonide in 24 in 86% yield. Finally, treatment of triol 24 with DBU
15 afforded the known lactone 16, which on treatment afforded goniopypyrone (2) in 83% yield.
with DBU furnished 9-deoxygoniopypyrone (1) in 91%
Divergence to the synthesis of 7-epi-goniofufurone (3)8
yield.
began with the conversion of alcohol 19 into the corre-
The synthesis of goniopypyrone (2)6 was accomplished as sponding acrylate ester 25 by reaction with acryloyl chlo-
follows. Oxidation of alcohol 11 with 2-iodoxybenzoic ride in the presence of triethylamine and 4-(N,N-
acid (IBX) furnished the corresponding aldehyde 17 in dimethylamino)pyridine (Scheme 5). RCM of ester 25
92% yield (Scheme 4). Addition of vinylmagnesium bro- employing Grubbs’ second-generation catalyst furnished
mide to 17 afforded an inseparable diastereomeric mix- the lactone 26 in 63% yield. Deprotection of the acetonide
ture of alcohols in a 5:1 ratio,7 which was oxidized with and tert-butyldimethylsilyl groups in 26 was achieved by
IBX to give ketone 18. Reduction of 18 with sodium boro- treatment with 2 N hydrochloric acid to afford the known
hydride in the presence of cerium(III) chloride resulted in triol 27 in 84% yield. Subsequent reaction of the triol 27
alcohol 19 as a single diastereomer in 94% yield. Protec- with DBU furnished 7-epi-goniofufurone (3) in 68%
tion of the hydroxy group in 19 using chloromethyl meth- yield.
yl ether furnished the methoxymethyl ether 20 in 90%
In conclusion, a facile synthesis of the bioactive styryllac-
yield. Deprotection of the silyl group in 20 with tetra-
tones 9-deoxygoniopypyrone (1), goniopypyrone (2) and
butylammonium fluoride gave the alcohol 21 in 97%
7-epi-goniofufurone (3) has been accomplished employ-
yield, which on subsequent reaction with acryloyl chlo-
ing ring-closing metathesis as the key step. The common
ride furnished the acrylate ester 22 in 75% yield. RCM of
intermediate for the synthesis of these styryllactones was
prepared from D-(–)-tartaric acid. The synthetic sequence
is highly diastereoselective and operationally simple with
the ester 22 with Grubbs’ second-generation catalyst af-
forded the lactone 23 in 86% yield. Reaction of lactone 23
with iron(III) chloride cleanly produced the known triol
good overall yields.
i) H2C=CHMgBr
THF, –78 °C
O
OR
O
OR
IBX, DMSO
r.t., 3 h, 92%
R = TBDMS
H
Ph
Ph
1 h, 92%
ii) IBX, DMSO
r.t., 4 h, 97%
O
OH
O
O
O
11
17
OR
MOMCl, i-Pr2NEt
O
OR
NaBH4, CeCl3
Ph
Ph
CH2Cl2, 0 °C to r.t.
5 h, 90%
MeOH, –78 °C
1 h, 94%
O
OH
O
O
19
18
H2C=CHCOCl
Et3N, DMAP
O
OH
TBAF, THF
O
OR
Ph
Ph
CH2Cl2, 0 °C to r.t.
2 h, 75%
0 °C to r.t., 5 h
O
OMOM
97%
O
OMOM
20
21
O
O
O
Grubbs II cat.
(10 mol%)
FeCl3·6H2O
O
O
O
CH2Cl2, r.t.
5 h, 86%
toluene, reflux
21 h, 86%
Ph
Ph
O
OMOM
22
O
OMOM
23
H
O
O
DBU (cat.), THF
r.t., 4 h, 83%
OH
O
Ph
HO
O
O
Ph
HO
H
OH OH
(+)-2
24
Scheme 4 Synthesis of (+)-goniopypyrone (2)
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

3700
K. R. Prasad, M. G. Dhaware
PAPER
H2C=CHCOCl
Et3N, DMAP
Grubbs II cat.
(10 mol%)
O
OR
O
OR
Ph
Ph
CH2Cl2, 0 °C
2 h, 71%
toluene, reflux
8 h, 63%
O
OH
O
O
19
25
O
R = TBDMS
O
OR
OH OH
DBU (2.5 equiv)
2 N HCl, THF
r.t., 10 h, 84%
Ph
3
Ph
THF, r.t., 24 h
68%
O
O
OH
O
26
O
O
27
Scheme 5 Synthesis of (+)-7-epi-goniofufurone (3)
1H and 13C NMR spectra were recorded on JNM l-300 and Bruker
AMX 400 spectrometers using TMS as an internal standard. IR
spectra were obtained using a Jasco 410 spectrophotometer. HRMS
were recorded with a Micromass Q-TOF spectrometer in electron
spray ionization mode. Optical rotations were measured using a
Jasco DIP-370 or a Jasco P-1020 digital polarimeter. Microanalyses
were performed on a Carlo Erba 1106 CHN elemental analyzer.
Melting points are uncorrected. Column chromatography was per-
formed on silica gel, Acme grade 100–200 mesh. TLC plates were
visualized either with UV light, in an iodine chamber or with phos-
phomolybdic acid spray. Unless stated otherwise, all reagents were
purchased from commercial sources and used without additional
purification. THF was freshly distilled over sodium benzophenone
ketyl. Unless stated otherwise, all the reactions were performed un-
der an inert atmosphere. Compound 8 was synthesized employing a
procedure described by us previously.3a,b
of Celite® topped with silica gel and the Celite® pad was washed
with Et2O (3 × 5 mL). The organic layers were combined and the
solvent was evaporated off. Silica gel column chromatography of
the resulting residue (petroleum ether–EtOAc, 5:1) afforded 10
(0.22 g, 96%) as a colorless oil.
[a]D +44.7 (c 0.9, CHCl3).
IR (neat): 3496, 2987, 1747, 1380, 1249, 1065, 755 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.50–7.20 (m, 5 H), 5.12 (d,
J = 8.4 Hz, 1 H), 4.11 (d, J = 9.0 Hz, 1 H), 4.04 (d, J = 9.0 Hz, 1 H),
3.76 (s, 3 H), 3.17 (d, J = 9.0 Hz, 1 H), 1.56 (s, 3 H), 1.51 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.8, 136.9, 128.7, 128.5, 126.7,
109.8, 88.6, 78.4, 67.6, 52.7, 27.2, 26.6.
HRMS: m/z calcd for C14H18O5 + Na: 289.1054; found: 289.1052.
(2R)-2-(tert-Butyldimethylsilyloxy)-2-[(4R,5S)-2,2-dimethyl-5-
phenyl-1,3-dioxolan-4-yl]ethanol (11)
(2S,3R,4S)-Methyl 2,3,4-Trihydroxy-4-phenylbutanoate (9)
To a soln of 8 (0.3 g, 1.1 mmol) in anhyd MeOH–benzene (1:1, 6.0
mL) was added PTSA (0.3 g, 1.6 mmol) and the mixture was re-
fluxed. The progress of the reaction was monitored by TLC and, af-
ter the reaction was complete (~5 h), the reaction mixture was
cooled to r.t., K2CO3 (0.2 g, 1.6 mmol) was added and the mixture
was stirred for 15 min. Et2O (10 mL) was then added and the mix-
ture was filtered through a short pad of Celite®. The Celite® pad was
washed with Et2O (15 mL) and the combined ethereal layers were
concentrated under reduced pressure to give a thick yellow oil. Sil-
ica gel column chromatography of the crude residue (petroleum
ether–EtOAc, 1:4) afforded 9 (0.22 g, 88%) as a colorless viscous
mass.
To a magnetically stirred soln of 10 (0.2 g, 0.75 mmol) in anhyd
DMF (2 mL) under an argon atmosphere were added imidazole
(0.15 g, 2.3 mmol) and DMAP (0.02 g, 0.15 mmol) at r.t. The reac-
tion mixture was stirred for 15 min at r.t. and TBDMSCl (0.17 g, 1.1
mmol) was introduced into the mixture. It was then stirred at r.t. for
12 h. After the reaction was complete (indicated by TLC), the mix-
ture was poured into H2O (8 mL) and extracted with Et2O (30 mL).
The ethereal layers were combined, washed with brine (10 mL) and
dried (Na2SO4). Evaporation of solvent and silica gel column chro-
matography of the resulting residue (petroleum ether–EtOAc, 95:5)
yielded the corresponding silyl ether (0.3 g, 98%) as a white solid.
Mp 58–60 °C; [a]D –19.6 (c 0.2, CHCl3).
[a]D –14.2 (c 1.4, CHCl3).
IR (KBr): 3034, 2953, 2858, 1765, 1370, 1071, 883, 779 cm–1.
IR (neat): 3436, 2954, 1741, 1454, 1440, 1278, 1226, 1128, 765
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45–7.25 (m, 5 H), 4.85 (d,
J = 7.2 Hz, 1 H), 4.00–3.91 (m, 2 H), 3.71 (s, 3 H), 3.45 (br s, 3 H,
exchangeable).
13C NMR (75 MHz, CDCl3): d = 173.6, 139.8, 128.5, 128.1, 126.9,
76.5, 74.7, 71.1, 52.7.
1H NMR (300 MHz, CDCl3): d = 7.30–7.15 (m, 5 H), 4.95 (d,
J = 8.1 Hz, 1 H), 4.15 (d, J = 2.7 Hz, 1 H), 4.05 (dd, J = 8.4, 2.7 Hz,
1 H), 3.53 (s, 3 H), 1.42 (s, 3 H), 1.37 (s, 3 H), 0.82 (s, 9 H), 0.01 (s,
3 H), –0.04 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 171.6, 137.6, 128.5, 128.4, 127.2,
109.7, 84.2, 78.8, 51.9, 27.3, 26.6, 25.7, 18.3, –4.8, –5.2.
HRMS: m/z calcd for C20H32O5Si + Na: 403.1919; found: 403.1917.
HRMS: m/z calcd for C11H14O5 + Na: 249.0741; found: 249.0739.
Anal. Calcd for C20H32O5Si: C, 63.12; H, 8.48. Found: C, 63.23; H,
8.43.
Methyl (2S)-2-[(4S,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]-2-hydroxyacetate (10)
To a soln of the silyl ether (0.2 g, 0.5 mmol) in anhyd toluene (3.0
mL), cooled to –78 °C under an argon atmosphere, was added drop-
wise 1 M DIBAL-H in toluene (1 mL, 1 mmol). The reaction mix-
ture was allowed to warm to r.t. and was stirred for 1 h at r.t. After
the reaction was complete (TLC), it was cautiously quenched by the
addition of H2O (1 mL), then the mixture was diluted with Et2O (10
mL) and further stirred for 0.5 h. The precipitated salts were filtered
To a stirred soln of 9 (0.2 g, 0.9 mmol) in anhyd CH2Cl2 (4.0 mL)
were added PTSA (0.02 g, 0.1 mmol) and 2,2-dimethoxypropane
(0.2 mL, 1.0 mmol) at r.t. The reaction mixture was stirred for 1 h
at r.t. After the reaction was complete (TLC), K2CO3 (0.01 g, 0.08
mmol) and Et2O (10 mL) were added and the mixture was stirred for
15 min. The reaction mixture was then filtered through a short pad
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

PAPER
Synthesis of Bioactive Styryllactones
3701
through a short pad of Celite® and the Celite® pad was washed with
Et2O (3 × 10 mL). Evaporation of solvent and silica gel column
chromatography of the crude residue (petroleum ether–EtOAc, 9:1)
furnished 11 (0.17 g, 94%) as a colorless oil.
(1R)-1-[(4S,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl]but-3-
en-1-ol (13)
In a single-neck, 25-mL round-bottom flask containing CuI (0.02 g,
0.1 mmol) was introduced anhyd THF (2.0 mL) under an argon at-
mosphere, and the mixture was cooled to –30 °C. A 0.5 M soln of
vinylmagnesium bromide in THF (2.0 mL, 1 mmol) was added
dropwise at the same temperature and the resulting organocuprate
was stirred at –30 °C for 20 min. A soln of 12 (0.07 g, 0.3 mmol) in
anhyd THF (2.0 mL) was slowly introduced into the flask contain-
ing the cuprate. The reaction mixture was stirred for 1 h at –30 °C.
After the reaction was complete (monitored by TLC), it was cau-
tiously quenched by the addition of sat. NH4Cl (3 mL). The mixture
was then poured into H2O (10 mL) and extracted with Et2O (3 × 10
mL). The combined organic layers were washed with brine (10 mL)
and dried (Na2SO4). Evaporation of solvent and silica gel column
chromatography of the resulting residue (petroleum ether–EtOAc,
9:1) furnished 13 (0.073 g, 93%) as a colorless oil.
[a]D +8.0 (c 1.4, CHCl3).
IR (neat): 3480, 2931, 1371, 1251, 1060, 834, 777, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.50–7.10 (m, 5 H), 5.01 (d,
J = 8.4 Hz, 1 H), 3.98 (dd, J = 8.4, 3.6 Hz, 1 H), 3.86 (dd, J = 8.4,
4.2 Hz, 1 H), 3.69 (dd, J = 11.1, 4.9 Hz, 1 H), 3.61 (dd, J = 11.1, 3.6
Hz, 1 H), 2.20 (br s, 1 H), 1.55 (s, 3 H), 1.51 (s, 3 H), 0.86 (s, 9 H),
0.05 (s, 3 H), 0.01 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.9, 128.6, 128.4, 127.3, 109.2,
84.6, 78.9, 70.65, 64.2, 27.3, 26.9, 25.8, 18.2, –4.5, –4.6.
HRMS: m/z calcd for C19H32O4Si + Na: 375.1969; found: 375.1967.
(4S,5S)-2,2-Dimethyl-4-[(2R)-oxiran-2-yl]-5-phenyl-1,3-diox-
olane (12)
[a]D +18.8 (c 0.9, CHCl3).
IR (neat): 3470, 2985, 1641, 1372, 1237, 1059, 917, 887, 756 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.50–7.24 (m, 5 H), 5.84–5.68 (m,
1 H), 5.07–4.94 (m, 3 H), 3.76 (ddd, J = 8.7, 2.1, 1.2 Hz, 1 H), 3.67–
3.58 (m, 1 H), 2.34–2.14 (m, 3 H), 1.58 (s, 3 H), 1.53 (s, 3 H).
To a stirred soln of 11 (0.15 g, 0.43 mmol) in anhyd pyridine (2 mL)
was added p-toluenesulfonyl chloride (0.16 g, 0.85 mmol) and the
reaction mixture was stirred for 12 h at r.t. After the reaction was
complete (TLC), the mixture was poured into ice-cold H2O (10 mL)
and extracted with Et2O (3 × 10 mL). The ethereal layers were
washed with 2 N HCl (2 × 10 mL) and brine (2 × 10 mL), and dried
(Na2SO4). Evaporation of solvent gave a crude residue which on sil-
ica gel column chromatography (petroleum ether–EtOAc, 95:5) af-
forded the tosylate (0.21 g, 98%) as a colorless oil.
13C NMR (75 MHz, CDCl3): d = 137.6, 134.2, 128.6, 128.3, 126.9,
117.8, 109.2, 84.9, 79.3, 68.0, 39.6, 27.2, 27.0.
HRMS: m/z calcd for C15H20O3 + Na: 271.1312; found: 271.1310.
(1R)-1-[(4R,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl]but-
3-enyl Acrylate (14)
[a]D +2.4 (c 1.1, CHCl3).
IR (neat): 3716, 2954, 2857, 1598, 1459, 1369, 1253, 1070, 979,
746, 665 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66 (d, J = 8.7 Hz, 2 H), 7.30–
7.17 (m, 7 H), 4.86 (d, J = 8.7 Hz, 1 H), 4.06–3.81 (m, 3 H), 3.75
(dd, J = 8.4, 2.4 Hz, 1 H), 2.37 (s, 3 H), 1.42 (s, 3 H), 1.37 (s, 3 H),
0.79 (s, 9 H), 0.01 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 144.8, 137.6, 132.7, 129.8, 128.4,
127.9, 126.9, 109.4, 83.0, 78.3, 70.9, 68.5, 27.2, 26.8, 25.7, 21.6,
18.1, –4.3, –4.7.
To a precooled (0 °C) soln of 13 (0.03 g, 0.12 mmol) in anhyd
CH2Cl2 (2 mL) were added DMAP (3 mg, 0.03 mmol, 20 mol%),
Et3N (0.03 mL, 0.24 mmol) and acryloyl chloride (0.02 mL, 0.24
mmol), and the mixture was stirred for 2 h at 0 °C. After the reaction
was complete (TLC), the mixture was poured into H2O (5 mL) and
extracted with Et2O (3 × 5 mL). The combined organic layers were
washed with brine (10 mL) and dried (Na2SO4). Evaporation of sol-
vent and silica gel column chromatography of the crude residue (pe-
troleum ether–EtOAc, 9.5:0.5) gave 14 (0.03 g, 75%) as a colorless
oil.
HRMS: m/z calcd for C26H38O6SSi + Na: 529.2058; found:
529.2056.
[a]D –4.5 (c 1.1, CHCl3).
IR (neat): 3078, 2986, 1725, 1406, 1189, 1057, 757 cm–1.
To a precooled (0 °C) soln of the tosylate (0.15 g, 0.35 mmol) in
THF (4.0 mL) was added dropwise 1 M TBAF in THF (0.7 mL, 0.7
mmol) under an argon atmosphere. The reaction mixture was al-
lowed to warm to r.t. and was stirred for 11 h at r.t. After the reaction
was complete (indicated by TLC), the mixture was poured into H2O
(10 mL) and extracted with Et2O (3 × 10 mL). The combined organ-
ic layer was washed with brine (10 mL) and dried (Na2SO4). Evap-
oration of solvent and silica gel column chromatography of the
crude residue (petroleum ether–EtOAc, 95:5) yielded the epoxide
12 (0.08 g, 96%) as a colorless oil.
1H NMR (300 MHz, CDCl3): d = 7.43–7.24 (m, 5 H), 6.48 (dd,
J = 17.1, 1.5 Hz, 1 H), 6.18 (dd, J = 10.2, 7.1 Hz, 1 H), 5.89 (dd,
J = 10.2, 1.5 Hz, 1 H), 5.73–5.57 (m, 1 H), 5.17–4.97 (m, 3 H), 4.73
(d, J = 8.7 Hz, 1 H), 3.90 (dd, J = 8.7, 2.4 Hz, 1 H), 2.54–2.35 (m,
2 H), 1.58 (s, 3 H), 1.52 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.6, 137.3, 132.0, 131.5, 128.6,
128.4, 128.1, 126.7, 118.3, 109.4, 83.6, 78.8, 69.4, 36.3, 27.2, 26.7.
HRMS: m/z calcd for C18H22O4 + Na: 325.1418; found: 325.1416.
[a]D +10 (c 1, CHCl3).
IR (neat): 2987, 2933, 1380, 1372, 1240, 1062, 886, 756 cm–1.
(6R)-6-[(4R,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl]-5,6-
dihydro-2H-pyran-2-one (15)
To a stirred soln of 14 (0.03 g, 0.1 mmol) in anhyd toluene (10 mL)
was added Grubbs’ second-generation catalyst (3 mg, 3 mol%) and
the mixture was refluxed under an argon atmosphere. The progress
of the reaction was followed by TLC and, after the reaction was
complete (~8 h), the mixture was cooled to r.t. The solvent was re-
moved under reduced pressure and the resulting crude residue was
subjected to silica gel column chromatography (petroleum ether–
EtOAc, 5:2) to yield 15 (0.02 g, 76%) as a colorless oil.
1H NMR (300 MHz, CDCl3): d = 7.50–7.25 (m, 5 H), 4.92 (d,
J = 9.0 Hz, 1 H), 3.63 (dd, J = 9.0, 5.4 Hz, 1 H), 3.08 (ddd, J = 6.9,
4.5, 3.0 Hz, 1 H), 2.76 (dd, J = 5.1, 3.9 Hz, 1 H), 2.49 (dd, J = 5.1,
2.4 Hz, 1 H), 1.57 (s, 3 H), 1.52 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.3, 128.7, 128.5, 126.4, 109.9,
83.2, 80.0, 50.3, 43.8, 27.0, 26.7.
HRMS: m/z calcd for C13H16O3 + Na: 243.0999; found: 243.0997.
[a]D +5.0 (c 0.4, CHCl3).
IR (neat): 2986, 2932, 1732, 1380, 1241, 1062, 760 cm–1.
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

3702
K. R. Prasad, M. G. Dhaware
PAPER
1H NMR (400 MHz, CDCl3): d = 7.43–7.31 (m, 5 H), 6.87 (ddd,
J = 9.6, 5.9, 2.5 Hz, 1 H), 6.04 (dd, J = 9.6, 2.5 Hz, 1 H), 5.24 (d,
J = 8.6 Hz, 1 H), 4.42 (ddd, J = 11.7, 4.2, 2.5 Hz, 1 H), 3.82 (dd,
J = 8.6, 2.0 Hz, 1 H), 2.78–2.63 (m, 1 H), 2.40–2.23 (m, 1 H), 1.59
(s, 3 H), 1.55 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 163.6, 144.8, 137.1, 128.8, 128.7,
126.8, 121.2, 110.0, 83.9, 77.5, 73.5, 27.3, 26.8, 26.7.
were washed with brine (20 mL) and dried (Na2SO4). Evaporation
of solvent under reduced pressure gave a crude residue which on sil-
ica gel column chromatography (petroleum ether–EtOAc, 95:5)
gave 17 (0.23 g, 92%) as a colorless oil.
[a]D –15.62 (c 1.6, CHCl3).
IR (neat): 2857, 2721, 1737, 1461, 1253, 1070, 836, 779 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.57 (d, J = 1.2 Hz, 1 H), 7.28–
7.18 (m, 5 H), 4.93 (d, J = 8.4 Hz, 1 H), 4.02 (dd, J = 8.4, 2.1 Hz, 1
H), 3.93 (s, 1 H), 1.42 (s, 3 H), 1.39 (s, 3 H), 0.85 (s, 9 H), 0.01 (s,
6 H).
HRMS: m/z calcd for C16H18O4 + Na: 297.1105; found: 297.1103.
8-epi-Goniodiol (16)
To a precooled (0 °C) soln of 15 (0.02 g, 0.07 mmol) in anhyd
CH2Cl2 (2.0 mL) was added TFA (0.01 mL, 0.13 mmol) dropwise
under an argon atmosphere. The reaction mixture was stirred for 0.5
h at 0 °C. After the reaction was complete (TLC), it was cautiously
quenched with sat. NaHCO3, and the mixture was poured into H2O
(5 mL) and extracted with EtOAc (3 × 5 mL). The combined organ-
ic layers were washed with brine (10 mL), dried (Na2SO4) and con-
centrated. The crude residue was subjected to silica gel column
chromatography (petroleum ether–EtOAc, 3:7) to furnish 16 (15
mg, 88%) as a colorless oil.
[a]D –12.8 (c 0.7, CHCl3) [Lit.5a [a]D –13.7 (c 0.8, CHCl3)].
IR (neat): 3424, 2924, 1702, 1638, 1263, 1116, 764 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.48–7.24 (m, 5 H), 6.87 (ddd,
J = 9.9, 6.3, 2.1 Hz, 1 H), 5.96 (dd, J = 9.9, 3.0 Hz, 1 H), 4.98 (d,
J = 7.5 Hz, 1 H), 4.22 (ddd, J = 12.9, 4.2, 2.4 Hz, 1 H), 3.65 (t,
J = 5.4 Hz, 1 H), 3.34 (br s, 1 H), 3.23 (br s, 1 H), 2.84 (ddt,
J = 18.6, 12.9, 2.7 Hz, 1 H), 2.14 (ddd, J = 18.6, 6.3, 3.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 202.5, 137.2, 128.7, 128.6, 127.0,
110.0, 83.8, 78.3, 75.6, 26.6, 25.7, 18.2, –4.3, –4.9.
HRMS: m/z calcd for C19H30O4Si + K: 389.1550; found: 389.1550.
(1S)-1-(tert-Butyldimethylsilyloxy)-1-[(4R,5S)-2,2-dimethyl-5-
phenyl-1,3-dioxolan-4-yl]but-3-en-2-one (18)
To a precooled (–78 °C) soln of 17 (0.2 g, 0.6 mmol) in anhyd THF
(2.0 mL) was added 0.5 M vinylmagnesium bromide in THF (1.2
mL, 0.6 mmol) under an argon atmosphere. The mixture was stirred
at –78 °C for 1 h. The reaction was then cautiously quenched by the
addition of sat. NH4Cl (4 mL) and the mixture was poured into H2O
(5 mL). The mixture was extracted with Et2O (3 × 15 mL) and the
extracts were washed with brine (2 × 10 mL) and dried (Na2SO4).
Removal of solvent under reduced pressure gave a crude residue
which on silica gel column chromatography (petroleum ether–
EtOAc, 9.5:0.5) gave a mixture of diastereomers (5:1) of the alcohol
(0.2 g, 92%) as a colorless oil.
13C NMR (75 MHz, CDCl3): d = 163.7, 145.9, 139.9, 128.7, 128.3,
To a soln of the alcohol (0.2 g, 0.5 mmol) in DMSO (4 mL) was
added IBX (0.17 g, 0.6 mmol) and the mixture was stirred at r.t. for
4 h. After the reaction was complete (TLC), it was quenched by the
addition of ice-cold sat. NaHCO3 (to pH ~7) and the mixture was
poured into H2O (15 mL). The mixture was then extracted with Et2O
(3 × 20 mL). The combined organic layers were washed with brine
(2 × 15 mL), dried (Na2SO4) and concentrated. Silica gel column
chromatography of the crude residue (petroleum ether–EtOAc,
9.5:0.5) gave 18 (0.2 g, 97%) as a colorless oil.
126.9, 120.6, 77.0, 76.5, 74.1, 26.0.
HRMS: m/z calcd for C13H14O4 + Na: 257.0792; found: 257.0790.
(+)-9-Deoxygoniopypyrone (1)
A soln of 16 (11 mg, 0.05 mmol) in THF (5.0 mL) containing DBU
(0.01 mL, 0.005 mmol) was stirred at r.t. for 24 h under an argon at-
mosphere. The reaction mixture was filtered through a short pad of
Celite® topped with silica gel and the Celite® pad was washed with
EtOAc (20 mL). After concentration under reduced pressure, the
residue was subjected to silica gel column chromatography (petro-
leum ether–EtOAc, 4:6) to afford 1 (10 mg, 91%) as a crystalline
solid.
[a]D –19 (c 2.0, CHCl3).
IR (neat): 2981, 1701, 1253, 1068, 863 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34–7.10 (m, 5 H), 6.69 (dd,
J = 17.7, 10.8 Hz, 1 H), 6.18 (dd, J = 17.7, 1.8 Hz, 1 H), 5.57 (dd,
J = 10.2, 1.5 Hz, 1 H), 4.90 (d, J = 8.1 Hz, 1 H), 4.07 (d, J = 2.7 Hz,
1 H), 3.92 (dd, J = 8.4, 2.7 Hz, 1 H), 1.44 (s, 6 H), 0.85 (s, 9 H), 0.02
(s, 3 H), –0.07 (s, 3 H).
Mp 204–206 °C (Lit.8a mp 203–204 °C); [a]D +12 (c 0.5, EtOH)
[Lit.8a [a]D +12 (c 0.1, EtOH)].
IR (KBr): 3452, 2915, 1719, 1186, 1057, 726 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.45–7.24 (m, 5 H), 4.97 (s, 1 H),
4.88 (t, J = 3.7 Hz, 1 H), 4.54 (s, 1 H), 3.96 (br s, 1 H), 3.00 (d,
J = 19.3 Hz, 1 H), 2.88 (dd, J = 19.3, 5.1 Hz, 1 H), 2.60 (dt,
J = 14.1, 2.0 Hz, 1 H), 1.85 (dd, J = 14.1, 3.7 Hz, 1 H), 1.62 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 199.9, 137.4, 132.2, 128.8, 128.6,
128.5, 127.3, 109.9, 84.6, 78.5, 76.6, 27.3, 25.8, 18.2, –4.6, –4.9.
HRMS: m/z calcd for C21H32O4Si + Na: 399.1969; found: 399.1968.
13C NMR (100 MHz, CDCl3): d = 169.2, 136.7, 128.9, 128.4, 126.1,
74.7, 70.5, 68.3, 66.1, 36.3, 23.9.
(1R,2S)-1-(tert-Butyldimethylsilyloxy)-1-[(4R,5S)-2,2-dimethyl-
5-phenyl-1,3-dioxolan-4-yl]but-3-en-2-ol (19)
To a precooled (–78 °C) soln of 18 (0.2 g, 0.5 mmol) in MeOH (2.0
mL) was added CeCl3·7H2O (0.22 g, 0.6 mmol) and the mixture was
stirred for 15 min. NaBH4 (0.023 g, 0.6 mmol) was added portion-
wise over a 30-min period and the mixture was stirred at –78 °C for
1 h. Then, the reaction was cautiously quenched by the addition of
H2O (5 mL) and the mixture was extracted with Et2O (3 × 15 mL).
The combined organic layers were washed with brine (20 mL),
dried (Na2SO4) and concentrated. Silica gel column chromatogra-
phy of the crude residue (petroleum ether–EtOAc, 9.5:0.5) fur-
nished 19 (0.18 g, 94%) as a colorless oil.
HRMS: m/z calcd for C13H14O4 + Na: 257.0792; found: 257.0790.
Anal. Calcd for C13H14O4: C, 66.66; H, 6.02. Found: C, 66.51; H,
6.24.
(2S)-2-(tert-Butyldimethylsilyloxy)-2-[(4R,5S)-2,2-dimethyl-5-
phenyl-1,3-dioxolan-4-yl]acetaldehyde (17)
To a stirred soln of 11 (0.25 g, 0.71 mmol) in DMSO (5.0 mL) was
added IBX (0.24 g, 0.85 mmol) at r.t. and the mixture was stirred at
r.t. The progress of the reaction was monitored by TLC and, after
completion of the reaction (~3 h), the mixture was cooled to 0 °C
and the reaction was cautiously quenched by the addition of ice-
cold H2O (10 mL). The mixture was neutralized with sat. NaHCO3
to pH ~7 and extracted with Et2O (5 × 10 mL). The organic layers
[a]D +10 (c 0.3, CHCl3).
IR (neat): 3540, 2954, 1371, 1250, 1061, 698 cm–1.
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

PAPER
Synthesis of Bioactive Styryllactones
3703
1H NMR (300 MHz, CDCl3): d = 7.50–7.10 (m, 5 H), 5.82 (ddd,
J = 17.1, 10.5, 4.8 Hz, 1 H), 5.29 (dd, J = 17.1, 1.8 Hz, 1 H), 5.18
(m, 2 H), 4.28–4.21 (m, 1 H), 4.00 (dd, J = 8.4, 4.5 Hz, 1 H), 3.84
(dd, J = 4.5, 1.8 Hz, 1 H), 2.48 (d, J = 9.0 Hz, 1 H, exch. D2O), 1.53
(s, 3 H), 1.49 (s, 3 H), 0.70 (s, 9 H), 0.01 (s, 3 H), –0.09 (s, 3 H).
into H2O (10 mL) and extracted with Et2O (3 × 20 mL). The com-
bined ethereal extracts were washed with brine (25 mL) and dried
(Na2SO4). Evaporation of solvent followed by silica gel column
chromatography of the residue (petroleum ether–EtOAc, 9.5:0.5)
yielded 22 (0.043 g, 75%) as a white solid.
13C NMR (75 MHz, CDCl3): d = 139.3, 137.9, 128.5, 128.3, 127.6,
115.4, 108.5, 83.6, 79.2, 73.9, 70.7, 27.3, 27.0, 25.7, 18.0, –4.3,
–4.7.
Mp 59–60 °C; [a]D +48.6 (c 0.7, CHCl3).
IR (KBr): 2935, 1729, 1406, 1189, 1029, 758, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.43–7.28 (m, 5 H), 6.57 (dd,
J = 17.2, 1.2 Hz, 1 H), 6.29 (dd, J = 17.2, 10.2 Hz, 1 H), 5.95 (dd,
J = 10.4, 1.3 Hz, 1 H), 5.56 (ddd, J = 17.2, 10.4, 7.8 Hz, 1 H), 5.36
(dd, J = 17.2, 0.7 Hz, 1 H), 5.29 (dd, J = 10.4, 1.3 Hz, 1 H), 5.14
(dd, J = 8.7, 1.3 Hz, 1 H), 4.69 (d, J = 8.7 Hz, 1 H), 4.61 (d, J = 6.8
Hz, 1 H), 4.48 (d, J = 6.8 Hz, 1 H), 4.36 (t, J = 7.8 Hz, 1 H), 3.90
(dd, J = 8.7, 1.3 Hz, 1 H), 3.27 (s, 3 H), 1.57 (s, 3 H), 1.30 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.6, 137.1, 133.5, 131.8, 128.6,
128.3, 128.2, 126.6, 120.8, 109.5, 93.8, 81.6, 78.6, 77.4, 70.4, 55.5,
27.0, 26.7.
HRMS: m/z calcd for C21H34O4Si + Na: 401.2126; found: 401.2124.
(4R,5S)-4-[(1R,2S)-1-(tert-Butyldimethylsilyloxy)-2-(methoxy-
methoxy)but-3-enyl]-2,2-dimethyl-5-phenyl-1,3-dioxolane (20)
To a soln of 19 (0.2 g, 0.5 mmol) in anhyd CH2Cl2 (2 mL) were add-
ed DIPEA (0.1 mL, 0.6 mmol) and MOMCl (40 mL, 0.6 mmol) at 0
°C. After being stirred for 15 min at 0 °C, the reaction mixture was
warmed to r.t. and stirred at r.t. for 5 h. After the reaction was com-
plete (indicated by TLC), the mixture was poured into H2O (10 mL)
and extracted with Et2O (3 × 10 mL). The combined ethereal ex-
tracts were washed with brine (20 mL) and dried (Na2SO4). Evapo-
ration of solvent and silica gel column chromatography of the
residue (petroleum ether–EtOAc, 9.5:0.5) yielded 20 (0.2 g, 90%)
as a colorless oil.
HRMS: m/z calcd for C20H26O6 + Na: 385.1629; found: 385.1627.
Anal. Calcd for C20H26O6: C, 66.28; H, 7.26. Found: C, 66.29; H,
7.45.
[a]D +7.6 (c 1.3, CHCl3).
IR (neat): 3034, 2930, 2893, 1472, 1369, 1251, 1030, 834, 775 cm–1.
(5S,6R)-6-[(4R,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl]-5-
(methoxymethoxy)-5,6-dihydro-2H-pyran-2-one (23)
To a soln of 22 (0.032 g, 0.09 mmol) in anhyd toluene (9.0 mL) was
added Grubbs’ second-generation catalyst (7 mg, 0.009 mmol) and
the mixture was refluxed under an argon atmosphere for 21 h. The
mixture was cooled to r.t. and the solvent was removed under re-
duced pressure. The resulting crude residue was purified by silica
gel column chromatography (petroleum ether–EtOAc, 5:1) to fur-
nish 23 (0.025 g, 86%) as a white solid.
1H NMR (400 MHz, CDCl3): d = 7.50–7.10 (m, 5 H), 5.80–5.70 (m,
1 H), 5.30–5.18 (m, 2 H), 4.98 (d, J = 8.5 Hz, 1 H), 4.54 (d, J = 6.5
Hz, 1 H), 4.40 (d, J = 6.5 Hz, 1 H), 4.08–4.01 (m, 2 H), 3.74 (dd,
J = 5.6, 2.9 Hz, 1 H), 3.20 (s, 3 H), 1.52 (s, 6 H), 0.94 (s, 9 H), 0.14
(s, 6 H).
13C NMR (100 MHz, CDCl3): d = 138.4, 135.4, 128.4, 127.4, 118.4,
108.9, 94.9, 82.7, 80.5, 78.9, 72.7, 55.5, 27.2, 26.1, 18.4, –3.9, –4.4.
Mp 137–138 °C; [a]D +45 (c 0.4, CHCl3).
IR (KBr): 2934, 1731, 1380, 1241, 1030, 761, 702 cm–1.
HRMS: m/z calcd for C23H38O5Si + Na: 445.2388; found: 445.2386.
1H NMR (400 MHz, CDCl3): d = 7.47–7.24 (m, 5 H), 6.78 (dd,
J = 9.9, 3.9 Hz, 1 H), 6.03 (dd, J = 9.9, 0.9 Hz, 1 H), 4.95 (d, J = 9.0
Hz, 1 H), 4.48 (t, J = 4.4 Hz, 1 H), 4.32 (dd, J = 9.0, 3.9 Hz, 1 H),
4.28 (d, J = 7.1 Hz, 1 H), 4.20 (d, J = 3.9 Hz, 1 H), 3.95 (d, J = 7.1
Hz, 1 H), 3.02 (s, 3 H), 1.58 (s, 3 H), 1.49 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 162.7, 143.9, 136.7, 128.9, 128.8,
127.6, 121.9, 110.3, 96.7, 80.2, 79.5, 76.3, 68.1, 55.6, 27.3, 26.7.
(1R,2S)-1-[(4S,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl]-2-
(methoxymethoxy)but-3-en-1-ol (21)
To a precooled (0 °C) soln of 20 (0.17 g, 0.4 mmol) in anhyd THF
(4 mL) was added 1 M TBAF in THF (0.6 mL, 0.6 mmol) under an
argon atmosphere. The mixture was allowed to slowly warm to r.t.
and stirred for 5 h at r.t. H2O (5 mL) was added to the reaction mix-
ture which was stirred for 10 min. It was then extracted with Et2O
(3 × 15 mL). The combined ethereal extracts were washed with
brine (20 mL) and dried (Na2SO4). Evaporation of solvent and silica
gel column chromatography of the residue (petroleum ether–
EtOAc, 5:1) yielded 21 (0.12 g, 97%) as a colorless oil.
HRMS: m/z calcd for C18H22O6 + Na: 357.1316; found: 357.1314.
Anal. Calcd for C18H22O6: C, 64.66; H, 6.63. Found: C, 64.35; H,
6.79.
[a]D +70 (c 0.6, CHCl3).
IR (neat): 3487, 2933, 1379, 1372, 1238, 1028, 757 cm–1.
(5S,6R)-6-[(1R,2S)-1,2-Dihydroxy-2-phenylethyl]-5-hydroxy-
5,6-dihydro-2H-pyran-2-one (24)
1H NMR (300 MHz, CDCl3): d = 7.50–7.10 (m, 5 H), 5.72–5.58 (m,
1 H), 5.34–5.23 (m, 2 H), 5.07 (d, J = 8.7 Hz, 1 H), 4.66 (d, J = 6.6
Hz, 1 H), 4.54 (d, J = 6.6 Hz, 1 H), 4.08 (t, J = 7.5 Hz, 1 H), 3.81 (d,
J = 8.7 Hz, 1 H), 3.53 (t, J = 6.6 Hz, 1 H), 3.30 (s, 3 H), 2.74 (d,
J = 7.5 Hz, 1 H, OH), 1.54 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 137.5, 134.3, 128.5, 128.2, 126.7,
119.9, 109.2, 94.5, 82.0, 80.3, 79.0, 69.5, 55.6, 27.1, 26.8.
To a stirred soln of 23 (0.01 g, 0.03 mmol) in anhyd CH2Cl2 (3 mL)
was added FeCl3·6H2O (0.024 g, 0.09 mmol) at r.t. The reaction
mixture was stirred for 5 h at r.t. After the reaction was complete
(indicated by TLC), the yellow reaction mixture was diluted with
Et2O (10 mL) and solid NaHCO3 (0.03 g) was added. The mixture
was stirred until the yellow color disappeared (~0.5 h). It was then
filtered through a pad of Celite® and the Celite® pad was washed
with Et2O (15 mL). Evaporation of solvent and silica gel column
chromatography of the resulting residue (petroleum ether–EtOAc,
3:7) yielded 24 (6 mg, 86%) as a colorless oil.
[a]D +87 (c 0.5, CHCl3) [Lit.6a [a]D +88 (c 0.5, EtOH)].
IR (neat): 3384, 1717, 1384, 1264, 1100, 829, 708 cm–1.
1H NMR (400 MHz, CD3OD): d = 7.38–7.11 (m, 5 H), 6.96 (dd,
J = 9.7, 5.4 Hz, 1 H), 6.00 (d, J = 9.7 Hz, 1 H), 4.91 (d, J = 3.0 Hz,
1 H), 4.32 (dd, J = 5.8, 2.7 Hz, 1 H), 4.28 (dd, J = 5.8, 2.7 Hz, 1 H),
4.01 (dd, J = 7.0, 3.0 Hz, 1 H).
HRMS: m/z calcd for C17H24O5 + Na: 331.1523; found: 331.1521.
(1R,2S)-1-[(4R,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl]-2-
(methoxymethoxy)but-3-enyl Acrylate (22)
To a precooled (0 °C) soln of 21 (0.05 g, 0.16 mmol) under an argon
atmosphere were added Et3N (20 mL, 0.32 mmol), DMAP (4 mg,
0.03 mmol) and acryloyl chloride (20 mL, 0.32 mmol). The reaction
mixture was allowed to warm to r.t. and was stirred for 2 h at r.t. Af-
ter the reaction was complete (monitored by TLC), it was quenched
by the cautious addition of H2O (3 mL). The mixture was poured
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

3704
K. R. Prasad, M. G. Dhaware
PAPER
13C NMR (100 MHz, CDCl3): d = 164.2, 144.6, 141.7, 127.2, 126.4,
at r.t. After the reaction was complete (TLC), the volatiles were re-
moved under reduced pressure and the resulting residue was puri-
fied by silica gel column chromatography (petroleum ether–EtOAc,
2:8) to give 27 (0.016 g, 84%) as a white solid.
125.8, 121.0, 81.0, 73.6, 71.9, 59.6.
HRMS: m/z calcd for C13H14O5 + Na: 273.0741; found: 273.0739.
(+)-Goniopypyrone (2)
Mp 142–144 °C (Lit.9 mp 143–145 °C); [a]D –82.7 (c 0.2, MeOH)
A soln of triol 24 (0.006 g, 0.024 mmol) in anhyd THF (10 mL) con-
taining DBU (0.001 mL, 0.006 mmol) was stirred at r.t. for 4 h. Af-
ter the reaction was complete (TLC), the reaction mixture was
filtered through a short pad of silica gel topped with Celite®. The
residue obtained after removal of solvent from the filtrate under re-
duced pressure gave a white solid, which was further purified by sil-
ica gel column chromatography (petroleum ether–EtOAc, 3:7) to
yield 2 (0.005 g, 83%) as a white solid.
[Lit.9 [a]D –85 (c 0.3, EtOH)].
IR (neat): 3405, 1748, 1453, 1172, 1056, 822 cm–1.
1H NMR (300 MHz, CDCl3 + CD3OD): d = 7.58 (d, J = 5.7 Hz, 1
H), 7.46–7.28 (m, 5 H), 6.11 (dd, J = 5.7, 2.1 Hz, 1 H), 5.19 (dt,
J = 5.7, 1.5 Hz, 1 H), 4.82 (d, J = 6.6 Hz, 1 H), 3.66 (dd, J = 6.6, 2.4
Hz, 1 H), 3.50 (dd, J = 5.4, 2.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3 + CD3OD): d = 173.8, 154.4, 140.3,
128.3, 127.9, 126.6, 121.7, 85.7, 74.9, 74.3, 71.6.
Mp 179–182 °C (Lit.8b mp 182–184 °C); [a]D +52.8 (c 0.5, EtOH)
[Lit.8b [a]D +54 (c 0.4, EtOH)].
HRMS: m/z calcd for C13H14O5 + Na: 273.0741; found: 273.0739.
IR (neat): 3397, 2919, 1741, 1453, 1224, 1057, 733 cm–1.
(+)-7-epi-Goniofufurone (3)
1H NMR (300 MHz, CDCl3): d = 7.48–7.32 (m, 5 H), 5.02 (s, 1 H),
4.81 (dd, J = 5.9, 3.4 Hz, 1 H), 4.48 (d, J = 2.5 Hz, 1 H), 4.14–4.03
(m, 3 H), 3.10 (dd, J = 19.5, 1.7 Hz, 1 H), 3.05–2.98 (m, 1 H), 2.15
(s, 1 H).
13C NMR (75 MHz, CDCl3): d = 167.8, 135.8, 129.1, 128.7, 126.2,
72.6, 70.9, 70.3, 70.2, 64.5, 35.2.
A soln of 27 (0.006 g, 0.024 mmol) in THF (3.0 mL) containing
DBU (0.01 mL, 0.06 mmol) was stirred at r.t. for 24 h. After the re-
action was complete (monitored by TLC), the reaction mixture was
filtered through a short pad of silica gel and the silica gel pad was
washed with EtOAc (25 mL). After concentration of the filtrate un-
der reduced pressure, the residue was chromatographed on silica gel
(petroleum ether–EtOAc, 3:7) to afford 3 (0.004 g, 68%) as a crys-
talline solid.
HRMS: m/z calcd for C13H14O5 + Na: 273.0741; found: 273.0739.
(1S,2S)-1-(tert-Butyldimethylsilyloxy)-1-[(4R,5S)-2,2-dimethyl-
5-phenyl-1,3-dioxolan-4-yl]but-3-en-2-yl Acrylate (25)
Compound 25 was synthesized using a procedure similar to that de-
scribed for compound 22.
Mp 192–193 °C (Lit.8a mp 190–192 °C); [a]D +107.7 (c 0.2, EtOH)
[Lit.8a [a]D +108 (c 0.2, EtOH)].
IR (KBr): 3354, 1752, 1454, 1371, 1197, 1044, 902, 765 cm–1.
1H NMR (300 MHz, CDCl3 + D2O): d = 7.45–7.33 (m, 5 H), 5.14–
5.06 (m, 2 H), 4.90 (d, J = 4.5 Hz, 1 H), 4.41 (d, J = 3.0 Hz, 1 H),
4.24 (t, J = 3.6 Hz, 1 H), 2.82–2.65 (m, 2 H).
Yield: 71%; [a]D –32.9 (c 0.3, CHCl3).
IR (neat): 3035, 2931, 1732, 1405, 1255, 1186, 833, 776 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.27–7.10 (m, 5 H), 6.22 (dd,
J = 17.4, 0.9 Hz, 1 H), 5.93 (dd, J = 17.4, 10.2 Hz, 1 H), 5.75–5.62
(m, 1 H), 5.28 (s, 1 H), 5.24 (t, J = 6.3 Hz, 1 H), 5.13 (d, J = 17.4
Hz, 1 H), 5.07 (d, J = 10.8 Hz, 1 H), 4.84 (d, J = 8.4 Hz, 1 H), 3.84
(dd, J = 8.4, 2.7 Hz, 1 H), 3.27 (dd, J = 6.3, 2.7 Hz, 1 H), 1.38 (s, 3
H), 1.37 (s, 3 H), 0.76 (s, 9 H), 0.02 (s, 3 H), –0.03 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.0, 138.0, 133.1, 131.0, 128.6,
128.5, 128.3, 127.0, 118.5, 109.2, 82.9, 78.6, 76.8, 71.8, 27.2, 27.0,
25.9, 18.4, –4.0.
13C NMR (75 MHz, CDCl3 + D2O): d = 175.0, 139.9, 128.7, 128.5,
126.5, 87.8, 82.8, 75.5, 72.7, 36.1, 29.7.
HRMS: m/z calcd for C13H14O5 + Na: 273.0741; found: 273.0739.
Acknowledgment
We thank the Department of Science and Technology (DST), New
Delhi, the Department of Biotechnology, New Delhi and the
Council of Scientific and Industrial Research (CSIR), New Delhi
for financial support. One of us (M.G.D.) thanks the University
Grants Commission (UGC), New Delhi for a junior research fel-
lowship.
HRMS: m/z calcd for C24H36O5Si + Na: 455.2232; found: 455.2230.
(5S)-5-{(S)-(tert-Butyldimethylsilyloxy)[(4R,5S)-2,2-dimethyl-
5-phenyl-1,3-dioxolan-4-yl]methyl}furan-2(5H)-one (26)
Compound 26 was synthesized using a procedure similar to that de-
scribed for compound 23.
References
Yield: 63% (88% based on recovered starting material); [a]D –66.5
(c 0.2, CHCl3).
IR (neat): 2930, 1732, 1405, 1255, 1186, 833, 776 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.77 (dd, J = 5.7, 1.8 Hz, 1
H), 7.41–7.23 (m, 5 H), 6.10 (dd, J = 5.7, 1.8 Hz, 1 H), 5.20 (t, J =
1.8 Hz, 1 H), 5.17 (d, J = 7.8 Hz, 1 H), 1.55 (s, 3 H), 1.52 (s, 3 H),
0.83 (s, 9 H), 0.11 (s, 3 H), 0.01 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.6, 154.0, 137.5, 128.7, 128.4,
127.0, 122.5, 109.3, 83.9, 83.0, 78.6, 71.2, 27.3, 26.9, 25.8, 18.2,
–4.5.
(1) For reviews on the cytotoxic activity and other bioactivity of
styryllactones, see: (a) Mereyala, H. B.; Joe, M. Curr. Med.
Chem.: Anti-Cancer Agents 2001, 1, 293. (b) Blázquez, M.
A.; Bermejo, A.; Zafra-Polo, M. C.; Cortes, D. Phytochem.
Anal. 1999, 10, 161.
(2) For a review on the synthesis of styryllactones until 2004,
see: Mondon, M.; Gesson, J.-P. Curr. Org. Synth. 2006, 3,
41.
(3) (a) Prasad, K. R.; Gholap, S. L. Synlett 2005, 2260.
(b) Prasad, K. R.; Gholap, S. L. J. Org. Chem. 2006, 71,
3643. (c) Prasad, K. R.; Anbarasan, P. Tetrahedron:
Asymmetry 2005, 16, 3951. (d) Prasad, K. R.; Anbarasan, P.
Tetrahedron Lett. 2006, 47, 1433. (e) Prasad, K. R.;
Anbarasan, P. Synlett 2006, 2087. (f) Prasad, K. R.;
Anbarasan, P. Tetrahedron: Asymmetry 2006, 17, 1146.
(g) Prasad, K. R.; Anbarasan, P. Tetrahedron 2006, 62,
8303. (h) Prasad, K. R.; Chandrakumar, A.; Anbarasan, P.
Tetrahedron: Asymmetry 2006, 17, 1979.
HRMS: m/z calcd for C22H32O5Si + Na: 427.1919; found: 427.1917.
(5S)-5-[(1S,2R,3S)-1,2,3-Trihydroxy-3-phenylpropyl]furan-
2(5H)-one (27)
To a soln of 26 (0.03 g, 0.07 mmol) in THF (2 mL) was added 2 N
HCl (2 mL) at r.t. The reaction mixture was allowed to stir for 10 h
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York

PAPER
(4) Preliminary communication: Prasad, K. R.; Dhaware, M. G.
Synthesis of Bioactive Styryllactones
3705
(8) For the isolation of goniofufurone and 7-epi-goniofufurone,
see: (a) Fang, X.-P.; Anderson, J. E.; Chang, C.-J.;
McLaughlin, J. L.; Fanwick, P. E. J. Nat. Prod. 1991, 54,
1034. (b) Fang, X.-P.; Anderson, J. E.; Chang, C.-J.;
Fanwick, P. E.; McLaughlin, J. L. J. Chem. Soc., Perkin
Trans. 1 1990, 1655. For syntheses of goniofufurone and 7-
epi-goniofufurone, see: (c) Shing, T. K. M.; Tsui, H. C.;
Zhou, Z. H. Tetrahedron 1992, 48, 8659. (d) Prakash, K. R.
C.; Rao, S. P. Tetrahedron 1993, 49, 1505. (e) Ye, J.; Bhatt,
R. K.; Falck, J. R. Tetrahedron Lett. 1993, 34, 8007.
(f) Gracza, T.; Jaeger, V. Synthesis 1994, 1359. (g) Yang,
Z.-C.; Zhou, W.-S. Tetrahedron 1995, 51, 1429. (h) Mukai,
C.; Hirai, S.; Kim, I. J.; Masaru, K.; Hanaoka, M.
Synlett 2007, 1112.
(5) For recent syntheses of 9-deoxygoniopypyrone, see:
(a) Yamashita, Y.; Saito, S.; Kobayashi, S. J. Am. Chem.
Soc. 2003, 125, 3793. (b) Ramachandran, P. V.; Chandra, J.
S.; Reddy, M. V. R. J. Org. Chem. 2002, 67, 7547.
(c) Chen, J.; Lin, G.-Q.; Wang, Z.-M.; Liu, H.-Q. Synlett
2002, 1265. (d) Tsubaki, M.; Kanai, K.; Nagase, H.; Honda,
T. Tetrahedron 1999, 55, 2493. (e) Survivet, J.-P.; Vitale,
J.-M. Tetrahedron 1999, 55, 13011. (f) Mukai, C.; Hirai, S.;
Hanaoka, M. J. Org. Chem. 1997, 62, 6619.
(6) For syntheses of goniopypyrone, see: (a) Shing, T. K. M.;
Tsui, H. C.; Zhou, Z. H. Tetrahedron Lett. 1993, 34, 691.
(b) Zhou, W.-S.; Yang, Z.-C. Tetrahedron Lett. 1993, 34,
7075. (c) Surivet, J.-P.; Vatele, J.-M. Tetrahedron Lett.
1997, 38, 819. (d) Li, H.-M.; Yang, M.; Zhao, G.; Yu, Q.-S.;
Ding, Y. Chin. J. Chem. 2000, 18, 388.
(7) The diastereomeric ratio (5:1) of the formed alcohols was
estimated by 1H NMR spectroscopy. The stereochemistry of
the alcohols was further corroborated by conversion into the
natural product. Following a sequence that is outlined for
goniopypyrone, the major product obtained in the addition of
vinylmagnesium bromide to aldehyde 17 was converted into
9-epi-goniopypyrone in 10.5% overall yield starting from
trihydroxy ester (Scheme 6).
Tetrahedron 1996, 52, 6547. (i) Yi, X.-H.; Meng, Y.; Hua,
X.-G.; Li, C.-J. J. Org. Chem. 1998, 63, 7472. (j) Bruns, R.;
Wernicke, A.; Koll, P. Tetrahedron 1999, 55, 9793.
(k) Mereyala, H. B.; Gadikota, R. R. Indian J. Chem., Sect.
B: Org. Chem. Incl. Med. Chem. 2000, 39, 166. (l) Su, Y.-
L.; Yang, C.-S.; Teng, S.-J.; Zhao, G.; Ding, Y. Tetrahedron
2001, 57, 2147. (m) Ruiz, P.; Murga, J.; Carda, M.; Marco,
J. A. J. Org. Chem. 2005, 70, 713. (n) Fernanndez de la
Pradilla, R.; Fernandez, J.; Alma, V.; Fernanndez, J.;
Gomez, A. Heterocycles 2006, 68, 1579.
(9) Shing, T. K. M.; Tsui, H. C.; Zhou, Z. H. J. Org. Chem.
1995, 60, 3121.
H
O
O
OR
Ph
HO
O
O
Ph
HO
H
O
OH
R = TBDMS
9-epi-goniopypyrone
Scheme 6
Synthesis 2007, No. 23, 3697–3705 © Thieme Stuttgart · New York