Stereoselective total synthesis of bioactive styryllactones (+)-goniofufurone, (+)7-epi-goniofufurone, (+)-goniopypyrone, (+)-goniotriol, (+)-altholactone, and (-)etharvensin

Article abstract of DOI:10.1021/jo0702342

(Chemical Equation Presented) Stereoselective total synthesis of biologically active styryllactones 7-epi-goniofufurone, goniofufurone, goniopypyrone, goniotriol, altholactone, and etharvensin was achieved in high overall yields from a common intermediate

Full text of DOI:10.1021/jo0702342

Stereoselective Total Synthesis of Bioactive Styryllactones
(+)-Goniofufurone, (+)7-epi-Goniofufurone, (+)-Goniopypyrone,
(+)-Goniotriol, (+)-Altholactone, and (-)-Etharvensin†
Kavirayani R. Prasad* and Shivajirao L. Gholap
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
prasad@orgchem.iisc.ernet.in
ReceiVed February 6, 2007
Stereoselective total synthesis of biologically active styryllactones 7-epi-goniofufurone, goniofufurone,
goniopypyrone, goniotriol, altholactone, and etharvensin was achieved in high overall yields from a
common intermediate derived from D-(-)-tartaric acid. It is based on the utility of a masked tetrol,
comprising an alkene tether and four contiguous hydroxy groups. The pivotal reaction sequence involves
hydroxy-directed lactonization via the oxidation of alkene, and subsequent elaboration to styryllactones.
The masked tetrol was prepared by the extension of γ-phenyl-γ-hydroxy butyramide, readily obtained
from the bis-dimethylamide of tartaric acid, employing a combination of selective Grignard additions
and a stereoselective reduction.
Introduction
repellant. The research group of McLaughlin et al. isolated and
characterized a series of styryllactones, possessing pesticidal,
ratogenic, embryo toxic activity, and significant to marginal
cytotoxic activity against human tumor cell lines.1 The structures
and relative configurations of these compounds were determined
Trees of genus Goniothalamus of the plant family Annon-
aceae in South East Asia have been known for a long time for
their proven use in folk medicine. The extracts and leaves from
these plants have traditionally been used as a remedy to treat
rheumatism and edema, as an abortifacient, and as a mosquito
(1) For a review 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) Bla`zquez, M. A.; Bermejo, A.; Zafra-
Polo, M. C.; Cortes, D. Phytochem. Anal. 1999, 10, 161.
† Dedicated with warmth and respect to Professor S. V. Kessar on the occasion
of his 75th birthday.
10.1021/jo0702342 CCC: $40.75 © 2008 American Chemical Society
Published on Web 05/25/2007
2
J. Org. Chem. 2008, 73, 2-11

StereoselectiVe Total Synthesis of BioactiVe Styryllactones
CHART 1. Bioactive Styryllactones 1-8 from
Goniothalamus Species
SCHEME 1. Biogenetic Pathway for Styryllactones
Proposed by Shing et al.
either by X-ray crystallography or by extensive NMR spectral
analysis. The styryllactones can mainly be classified into two
groups, related to the size of the lactone ring. Among the group
comprising the five-membered lactone rings, 7-epi-goniofufu-
rone 1 and goniofufurone 2 are moderately active, while
goniopypyrone 3, goniotriol 4, and altholactone 5 comprising
the six-membered lactone ring showed considerable anti-tumor
activity. Because of their unique and intriguing structures and
the broad spectrum of activity, these styryllactones have attracted
the attention of several synthetic groups in recent years.2
Although, there has been a number of syntheses concerning the
individual styryllactones, very few syntheses of these styryl-
lactones from a common intermediate have been reported in
the literature. Shing et al. employed D-glycero-D-gulo-heptano-
γ-lactone as a chiral source for the synthesis of 1-5,3 while
Tsubuki et al. utilized chiral lactonic aldehydes derived from
D-isopropyldinedioxy glyceraldehyde.4 Mandelic acid was used
as the chiral source in the synthesis of styryl lactones 1-4 by
Surivet and Vatele.5 While the synthesis of these compounds
reported by Shing et al. suffers from low overall yields (<5%),
the synthetic sequence by Tsubuki et al. involves cumbersome
preparation of the chiral intermediate, and separation of dia-
stereomers formed in the reaction sequence. The synthesis by
Surivet and Vatele requires separation of the mixture of
styryllactones obtained. Herein, we disclose in detail our efforts
in the practical, efficient, and enantiospecific synthesis of
styryllactones 7-epi-goniofufurone 1, goniofufurone 2, goniopy-
pyrone 3, goniotriol 4, altholactone 5, and etharvensin 6 in high
overall yields from a single chiral building block derived from
D-(-)-tartaric acid.6
SCHEME 2. Retrosynthesis for Styryllactones 1-6 from a
Common Building Block
the oxidation of alkene in 16, and subsequent elaboration to
styryllactones 1-6. The masked tetrol 16 could be obtained by
the extension of γ-phenyl-γ-hydroxy butyramide 13, prepared
by a combination of selective Grignard addition and stereose-
lective reduction from the dimethylamide 11 derived from D-
(-)-tartaric acid (Scheme 2).
It was proposed by Shing et al.3 that the biosynthesis of
styryllactones occurs via the shikimic acid pathway. This
proceeds through the formation of cinnamic acid from pheny-
lalanine, followed by the incorporation of two acetate-malonate
units activated as coenzyme A, generating the styrylpyrone,
goniothalamin 9. The styrylpyrone 9 undergoes oxidation to
goniothalamin oxide 10, which on further hydroxylation/oxida-
tion leads to the formation of styryllactones 1-8 (Scheme 1).
Our approach for the synthesis of the styryllactones is inspired
from the above biogenetic pathway. It is based on the utility of
the masked tetrol 16, comprising an alkene tether and four
contiguous hydroxy groups installed with definite configuration.
It relied on exploiting the hydroxy directed lactonization via
Results and Discussion
At the outset, we focused on the synthesis of the key building
block 16 from D-(-)-tartaric acid. The synthetic sequence
commenced with the addition of 1.5 equiv of phenylmagnesium
bromide to the diamide 11,7 resulting in γ-oxo butyramide 12
in 92% yield. Reduction of the keto group in 12 with NaBH4/
CeCl3 afforded a diastereomeric mixture of alcohols in 94:6
ratio, which after recrystallization furnished the alcohol 13 as
the major product in 86% yield. Protection of the alcohol group
in 13 as the corresponding silyl ether utilizing standard
conditions afforded the silyloxy amide 14 in 98% yield. Addition
of 3-butenylmagnesium bromide to 14 produced the ketone 15
in 93% yield, which on reduction with L-selectride yielded the
alcohol 16 in 96% yield. The key building block was thus
successfully synthesized in a facile stereoselective route from
the dimethylamide of tartaric acid (Scheme 3).
(2) For a review on the synthesis of styryllactones until 2004 see:
Mondon, M.; Gesson, J.-P. Curr. Org. Synth. 2006, 3, 175.
(3) Shing, T. K. M.; Tsui, H. C.; Zhou, Z. H. J. Org. Chem. 1995, 60,
3121.
(4) Tsubuki, M.; Kanai, K.; Nagase, H.; Honda, T. Tetrahedron 1999,
55, 2493.
(5) Surivet, J. P.; Vatele, J. M. Tetrahedron 1999, 55, 13011.
(6) Preliminary communication: Prasad, K. R.; Gholap, S. L. Synlett
2005, 2260.
(7) (a) Toda, F.; Tanaka, K. J. Org. Chem. 1988, 53, 3607. (b) Seebach,
D.; Hidber, A. Organic Syntheses; Wiley: New York, Collect. Vol. VII, p
447.
J. Org. Chem, Vol. 73, No. 1, 2008 3

Prasad and Gholap
SCHEME 3. Stereoselective Synthesis of Masked Tetrol 16
SCHEME 5. Stereoselective Synthesis of
(+)-7-epi-Goniofufurone 1
SCHEME 6. Stereoselective Synthesis of
(+)-Goniofufurone 2
SCHEME 4. Retrosynthesis for the Synthesis of
(+)-7-epi-Goniofufurone 1
Synthesis of (+)-7-epi-Goniofufurone and (+)-Goniofu-
furone. (+)-7-epi-Goniofufurone 1 and (+)-goniofufurone 2 are
the 5-membered lactones isolated from the Goniothalamus
species comprising a furano-furone motif.8 The structures of
these compounds were established by X-ray crystal data. We
envisaged the synthesis of 7-epi-goniofufurone 1 through an
intramolecular Michael reaction of the known triol butenolide
19. For the generation of 19, lactone 17 was identified as the
precursor, which could be obtained by elaboration of 16
(Scheme 4).
Thus, ozonolysis of 16 resulted in the formation of corre-
sponding lactol, which on oxidation with PCC afforded the
lactone 17 in 92% yield. Phenylselenation of the lactone 17
followed by elimination of the phenylselenyl moeity furnished
the R,â-unsaturated lactone 18 in 76% isolated yield. Reaction
of 18 with HCl-AcOH in THF resulted in the known triol 19
in 81% yield. Treatment of 19 with DBU in THF produced
7-epi-(+)-goniofufurone 1 in 69% yield (27% overall yield in
9 steps from 11), the spectral data of which are identical with
those reported in the literature (Scheme 5).
Synthesis of (+)-goniofufurone, involving similar intramo-
lecular Micheal cyclization was achieved as follows. Reaction
of lactone 17 with TBAF produced the alcohol 20 in 97% yield.
Mitsunobu inversion of the benzylic hydroxy group in 20 with
DIAD, Ph3P, and p-nitrobenzoic acid, and subsequent hydrolysis
of the p-nitrobenzoyl ester furnished the epimerized alcohol 21
in 78% yield. Phenylselenation of 21 followed by elimination
of the phenylselenyl moeity afforded the R,â-unsaturated lactone
22 in 74% yield. Deprotection of the acetonide in 22 with 2 N
HCl yielded the known triol 23 in 88% yield. Treatment of 23
with DBU in THF resulted in (+)-goniofufurone 2, in 77% yield.
Thus, natural goniofufurone was synthesized in 11 steps from
the dimethylamide 11 in 24% overall yield (Scheme 6).
Synthesis of (+)-Goniopypyrone and (+)-Goniotriol. Among
the styryllactones, (+)-goniopypyrone 3, comprising a pyrano-
pyrone moiety, is the most active compound, exhibiting
significant activity against several human tumor cell lines. The
bioactivity and the novel structural features present in goniopy-
pyrone attracted the attention of a number of synthetic groups.9
Retrosynthetic analysis based on intramolecular Michael addition
reveals the trihydroxypyrone 29 as the possible precursor.
Further evaluation of 29 leads to lactone 26, which could be
obtained by elaboration of 16 (Scheme 7).
(8) Isolation of goniofufurone and 7-epi-goniofufurone: (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.; Fanwick, P. E.;
McLaughlin, J. L. J. Chem. Soc., Perkin Trans. 1 1990, 1655. For syntheses
of goniofuruone 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. 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. Ind. J. Chem., Sect. B 2000,
39B, 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. Heterocycle 2006, 68,
1579.
Accordingly, compound 16 was converted to the benzyl ether
24 in 91% yield. Reaction of 24 with 4 N HCl in THF effected
the deprotection of the acetonide and the TBDMS group to
(9) For synthesis 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.
4 J. Org. Chem., Vol. 73, No. 1, 2008

StereoselectiVe Total Synthesis of BioactiVe Styryllactones
SCHEME 7. Rertosynthesis of (+)-Goniopypyrone 3
SCHEME 9. Synthesis of (+)-Goniotriol 4
SCHEME 8. Synthesis of (+)-Goniopypyrone 3
triol 32 was converted to (+)-goniotriol 4 the spectral data of
which are identical with those reported in the literature (Scheme
9).11 Thus, synthesis of (+)-4 was achieved in 16% overall yield
from the diamide 11 in 14 steps.
Synthesis of (+)-Altholactone and (-)-Etharvensin. Al-
tholactone 5 was isolated by Loder and Nearn from an unknown
Polyalthea species,12a while McLaughlin et al. isolated the same
from the Goniothalamus species.12b For the generation of
altholactone 5, tetrahydrofuran 36 was identified as the precur-
sor. Synthesis of 36 from 16 was accomplished by us, earlier
in our work concerning the total synthesis of related natural
product goniothalesdiol.13
Thus, alcohol 16 was converted to the tetrahydrofuran 36 by
using the procedure described by us.13 Ozonolysis of 36
furnished the corresponding lactol, which on subsequent oxida-
tion with Ag2CO3 impregnated on Celite afforded dihy-
droaltholactone 37 in 82% yield. Conversion of 37 to altholac-
tone 5 was reported by Somfai.12f The present sequence thus
constitutes a formal synthesis of altholactone. Altholactone, thus
prepared on reaction with EtOH in the presence of concentrated
H2SO4, furnished (-)-etharvensin 6 in 86% yield (Scheme 11).
In summary, a facile, practical, and efficient enantiospecific
synthesis of bioactive styryllactones 7-epi-goniofufurone, go-
niofufurone, goniopypyrone, goniotriol, altholactone, and ethar-
furnish the triol 25 in 84% yield. Ozonolysis of triol 25 produced
the corresponding lactol, which on oxidation with silvercar-
bonate impregnated on Celite10 afforded the δ-lactone 26 in 78%
yield for two steps. The secondary hydroxy groups in lactone
26 were protected as the corresponding methoxymethyl (MOM)
ethers with use of MOMCl. The resultant lactone 27 on
phenylselenation and deselenation furnished the R,â-unsaturated
lactone 28 in 69% yield. Treatment of 28 with TiCl4 in
dichloromethane underwent smooth deprotection of the MOM
and benzyl ether groups leading to the triol 29 (8-epi-goniotriol)
in 78% yield. Treatment of 29 with a catalytic amount of DBU
in THF yielded (+)-goniopypyrone 3 in 75% yield (13% overall
yield in 12 steps from 11). The spectral data are in complete
agreement with that reported in the literature (Scheme 8).
Synthesis of (+)-goniotriol 4, utilizing similar hydroxy
directed lactonization as the key step, is achieved as follows.
Treatment of 24 with TBAF produced the alcohol 30 in 94%
yield. Mitsunobu inversion of the alcohol group in 30 furnished
31 in 86% yield. Reaction of 31 with 4 N HCl in THF afforded
triol 32 in 90% yield. Following a sequence similar to that
employed for the synthesis of 8-epi-goniotriol 29 (vide supra),
(11) Isolation of goniotriol: (a) Alkofahi, A.; Ma, W.-W.; Mckenzie,
A. T.; Byan, S. R.; McLaughlin, J. L. J. Nat. Prod. 1989, 52, 1371. (b)
Talapatra, S. K.; Basu, D.; Deb, T.; Goswami, S.; Talapatra, B. Ind. J.
Chem., Sect. B 1985, 24B, 29. Synthesis of goniotriol and analogues: (c)
Shing, T. K. M.; Zhou, Z. H.; Mak, C. W. T. J. Chem. Soc., Perkin Trans.
1 1992, 1907. (d) Shing, T. K. M.; Tai, V. W.-F. J. Org. Chem. 1999, 64,
2140. (e) Srikanth, G. S. C.; Muralikrishna, U.; Trivedi, G. K.; Cannon, J.
F. Tetrahedron 2006, 62, 11165.
(12) Isolation of altholactone: (a) Loder, J. W.; Nearn, R. H. Heterocycles
1977, 7, 113. (b) El-Zayat, A. E.; Ferrigni, N. R.; McCloud, T. G.;
McKenzie, A. T.; Byrn, S. R.; Cassady, J. M.; Chang, C.; McLaughlin, J.
L. Tetrahedron Lett. 1985, 26, 955. Synthesis of altholactone: (c)
Gillhouley, J. G.; Shing, T. K. M. J. Chem. Soc., Chem. Commun. 1988,
976. (d) Kang, S. H.; Kim. W. J. Tetrahedron Lett. 1989, 30, 5915. (e)
Gesson, J. P.; Jacquesy, J. C.; Mondon, M. Tetrahedron 1989, 45, 2627.
(f) Somfai, P. Tetrahedron 1994, 50, 11315. (g) Shing, T. K. M.; Gillhouley,
J. G. Tetrahedron 1994, 50, 8685. (h) Yadav, J. S.; Rajaiah, G.; Raju, A.
K. Tetrahedon Lett. 2003, 44, 5831. (i) Yadav, J. S.; Raju, A. K.; Ponugoti,
P.; Rajaiah, G. Tetrahedron: Asymmetry 2005, 16, 3283.
(10) (a) Balogh, V.; Fetizon, M.; Golfier, M. J. Org. Chem. 1971, 36,
1339. (b) Clive, D. L. J.; Murthy, K. S. K.; Wee, A. G. H.; Prasad, J. S.;
da Silva, G. V. J.; Majewski, M.; Anderson, P. C.; Evans, C. F.; Haugen,
R. D.; Heerze, L. D.; Barrie, J. R. J. Am. Chem. Soc. 1990, 112, 3018. (c)
Chandrasekhar, M.; Chandra, K. L.; Singh, V. K. J. Org. Chem. 2003, 68,
4039.
(13) Prasad, K. R.; Gholap, S. L. J. Org. Chem. 2006, 71, 3643.
J. Org. Chem, Vol. 73, No. 1, 2008 5

Prasad and Gholap
SCHEME 10. Retrosynthesis of (+)-Altholactone 5
crystalline solid. Recrystallization from EtOAc-petroleum ether
yielded diastereomerically pure 13 in 86% yield. Mp 154-156 °C;
[R]D +31 (c 1, CHCl3); IR (neat) 3388, 2932, 1640, 1451, 1127,
885, 716 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.46-7.20 (m, 5H),
4.90-4.78 (m, 2H), 4.40 (d, J ) 6.9 Hz, 1H), 3.57 (d, J ) 6.9 Hz,
1H), 3.02 (s, 3H), 2.89 (s, 3H), 1.39 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 168.8, 140.4, 128.1, 127.7, 126.7, 110.6, 81.1, 74.5, 72.4,
37.0, 35.8, 26.8, 26.2; HRMS for C15H21NO4 + Na calcd 302.1371,
found 302.1368. Anal. Calcd for C15H21NO4: C 64.50, H 7.58.
Found: C 64.82, H 7.67.
SCHEME 11. Synthesis of (+)-Altholactone 5 and
(-)-Etharvensin 6
Preparation of (4S,5R)-5-((S)- tert-Butyldimethylsilyloxy-
(phenyl)methyl)-N,N,2,2-tetramethyl-1,3-dioxolane-4-carboxa-
mide (14). To a solution of 13 (0.75 g, 2.7 mmol) in dry DMF (8
mL) were added imidazole (0.55 g, 8.1 mmol) and DMAP (0.07 g,
20 mol %). After stirring at room temperature for 15 min TBDMSCl
(0.6 g, 4 mmol) was introduced into the reaction mixture. Progress
of the reaction was monitored by TLC. After the reaction was
complete (∼6 h), it was cooled to 0 °C and quenched by addition
of water (10 mL). It was then extracted with ether (3 × 25 mL)
and the combined ethereal extracts were washed with brine (20
mL) and dried (Na2SO4). Evaporation of solvent and silica gel
column chromatography of the resulting residue with petroleum
ether:EtOAc (4:1) as an eluent yielded the corresponding silyl ether
14 (1.04 g, 98%) as a pale yellow solid. Mp 95-97 °C; [R]D +66.2
(c 1, CHCl3); IR (neat) 2931, 2858, 1649, 1461, 1256, 1050, 778
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.54-7.30 (m, 5H), 4.96 (d,
J ) 4.5 Hz, 1H), 4.90 (dd, J ) 6.6, 4.5 Hz, 1H), 4.58 (d, J ) 6.6
Hz, 1H), 3.12 (s, 3H), 2.98 (s, 3H), 1.48 (s, 3H), 1.40 (s, 3H), 0.98
(s, 9H), 0.14 (s, 3H), 0.01 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
169.0, 140.5, 127.7, 127.5, 127.2, 110.9, 82.0, 74.0, 73.1, 36.9,
35.7, 26.7, 26.4, 25.7, 18.2, -4.9, -5.2; HRMS for C21H35NO4Si
+ Na calcd 416.2235, found 416.2235. Anal. Calcd for C21H35-
NO4Si: C 64.08, H 8.96, N 3.56. Found: C 64.10, H 9.20, N 3.64.
Preparation of 1-((4S,5R)-5-((S)-tert-Butyldimethylsilyloxy-
(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pent-4-en-1-
one (15). To a precooled (-10 °C) solution of the silyl ether 14
(1.0 g, 2.5 mmol) in dry THF (12 mL) was added a solution of
3-butenylmagnesium bromide (0.5 M solution in THF, 10.2 mL,
5.1 mmol) dropwise under argon atmosphere. The reaction mixture
was stirred for 0.5 h at the same temperature. It was then cautiously
quenched by addition of saturated NH4Cl (15 mL). The reaction
mixture was then extracted with ether (3 × 25 mL) and the
combined ethereal extracts were washed with brine (30 mL) and
dried (Na2SO4). Evaporation of the solvent and silica gel column
chromatography of the residue with petroleum ether:EtOAc (96:4)
as an eluent afforded ketone 15 (0.96 g, 93%) as a colorless oil.
[R]D +32.5 (c 1.5, CHCl3); IR (neat) 2976, 2858, 1717, 1640, 1596,
vensin was accomplished in high overall yields from a common
chiral building block derived from D-(-)-tartaric acid. The
pivotal reaction sequence includes a hydroxy group directed
lactonization of a tetrol comprising an alkene tether. The
synthetic strategies are operationally simple, selective, and
amenable to produce a number of scaffolds based on styryllac-
tone structures.
Experimental Section
Preparation of (4S,5S)-5-Benzoyl-N,N,2,2-tetramethyl-1,3-
dioxolane-4-carboxamide (12). In a two-necked, 100 mL, round-
bottomed flask equipped with a magnetic stir bar, rubber septum,
and argon inlet was placed 11 (2.0 g, 8.2 mmol). This was dissolved
in 10 mL of THF and the solution was cooled to -10 °C. A freshly
prepared THF solution of PhMgBr (12.3 mL of 1 M solution in
THF, 12.3 mmol) was added at such a rate that the internal
temperature does not rise above -10 °C. Progress of the reaction
was monitored by TLC and after the reaction was complete (0.5
h), it was cautiously quenched by addition of a saturated solution
of NH4Cl (10 mL). It was then poured into water (20 mL) and
extracted with ether (3 × 25 mL). Combined ethereal extracts were
washed with brine (30 mL) and dried (Na2SO4). Evaporation of
the solvent and silica gel column chromatography of the residue
with petroleum ether:EtOAc (3:1) as an eluent yielded 12 (2.1 g,
92%) as a pale yellow solid. Mp 79-80 °C; [R]D +23 (c 1, CHCl3);
IR (neat) 2988, 1692, 1504, 1261, 1154, 1061, 885 cm-1; 1H NMR
(300 MHz, CDCl3) δ 8.09 (d, J ) 7.2 Hz, 2H), 7.65-7.42 (m,
3H), 5.95 (d, J ) 5.1 Hz, 1H), 5.16 (d, J ) 5.1 Hz, 1H), 3.16 (s,
3H), 3.00 (s, 3H), 1.50 (s, 3H), 1.42 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 196.3, 168.2, 134.9, 133.7, 129.4, 128.5, 112.6, 79.4,
75.0, 37.1, 35.9, 26.42, 26.38; HRMS for C15H19NO4 + Na calcd
300.1214, found 300.1212. Anal. Calcd: C 64.97, H 6.91. Found:
C 65.28 H 7.02.
1472, 1380, 1253, 1091, 886, 777 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.54-7.32 (m, 5H), 5.90 (ddt, J ) 16.8, 12.9, 6.9 Hz,
1H), 5.21-4.98 (m, 2 H), 4.95 (d, J ) 3.6 Hz, 1H), 4.44 (d, J )
7.2 Hz, 1H), 4.34 (dd, J ) 7.2, 3.6 Hz, 1H), 2.73 (dt, J ) 4.5, 1.8
Hz, 2H), 2.47-2.35 (m, 2H), 1.47 (s, 6H), 1.00 (s, 9H), 0.17 (s,
3H), 0.02 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 209.0, 140.6,
136.9, 127.9, 127.7, 127.4, 115.3, 111.0, 82.0, 80.8, 74.3, 38.1,
27.0, 26.7, 25.8, 18.2, -4.8, -5.1; HRMS for C23H36O4Si + Na
calcd 427.2283, found 427.2281.
Preparation of (4S,5R)-5-((S)-Hydroxy(phenyl)methyl)-N,N,2,2-
tetramethyl-1,3-dioxolane-4-carboxamide (13). To a solution of
12 (1.5 g, 5.4 mmol) in methanol (15 mL) cooled to -78 °C was
added CeCl3‚7H2O (2.3 g, 6.5 mmol) and then the solution was
stirred for 15 min. NaBH4 (0.25 g, 6.5 mmol) was then added
portionwise over a period of 30 min and the solution was stirred at
the same temperature. After being stirring for 1.5 h, it was cautiously
quenched by addition of water (20 mL) and extracted with EtOAc
(3 × 25 mL). The combined organic layers were washed with brine
(30 mL), dried over Na2SO4, and concentrated. Silica gel column
chromatography of the crude residue obtained after evaporation of
the solvent, with petroleum ether:EtOAc (6:4) as eluent, gave a
distereomeric mixture (dr 96:4) of alcohols (1.42 g, 94%) as a white
Preparation of (S)-1-((4R,5R)-5-((S)-tert-Butyldimethylsily-
loxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pent-4-en-
1-ol (16). To a solution of 15 (0.8 g, 1.98 mmol) in dry THF (14
mL) cooled to -78 °C was added L-selectride (2.4 mL of 1 M
solution in THF, 2.4 mmol) dropwise under argon atmosphere. After
the solution was stirred for 1 h at the same temperature, it was
allowed to warm to 0 °C. The reaction mixture was quenched by
cautious addition of water (12 mL) and stirred for 30 min. It was
then extracted with ether (3 × 25 mL) and the combined ethereal
extracts were washed with brine (30 mL) and dried over Na2SO4.
Evaporation of the solvent and silica gel column chromatography
of the residue with petroleum ether:EtOAc (95:5) as eluent yielded
the alcohol 16 (0.77 g, 96%) as a colorless oil. [R]D +39.33 (c 1.5,
6 J. Org. Chem., Vol. 73, No. 1, 2008

StereoselectiVe Total Synthesis of BioactiVe Styryllactones
CHCl3); IR (neat) 3432, 2972, 2857, 1592, 1453, 1371, 1252, 1067,
7.46-7.29 (m, 5H), 7.26 (dd, J ) 5.7, 1.8 Hz, 1H), 6.07 (dd, J )
5.7, 2.4 Hz, 1H), 4.94 (d, J ) 5.7 Hz, 1H), 4.52 (dd, J ) 3.9, 2.4
Hz, 1H), 4.46 (dd, J ) 8.1, 5.7 Hz, 1H), 3.87 (dd, J ) 8.1, 2.4 Hz,
1H), 1.34 (s, 3H), 1.17 (s, 3H), 0.91 (s, 9H), 0.11 (s, 3H), 0.01 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 172.8, 153.1, 139.4, 128.0,
127.3, 122.1, 110.2, 81.5, 80.0, 75.3, 75.1, 75.0, 27.0, 26.3, 25.8,
18.3, -4.9, -5.0; Anal. Calcd for C22H32O5Si: C 65.31, H 7.97.
Found: C 65.25, H 7.80.
1
889, 777 cm-1; H NMR (300 MHz , CDCl3) δ 7.34-7.15 (m,
5H), 5.66 (ddt, J ) 17.1, 10.2, 6.9 Hz, 1H), 5.04-4.78 (m, 2H),
4.76 (d, J ) 5.1 Hz, 1H), 4.09 (dd, J ) 7.8, 5.4 Hz, 1H), 3.64 (dd,
J ) 8.1, 2.4 Hz, 1H), 3.07 (br s, 1H), 2.18-1.82 (m, 2H), 1.54-
1.28 (m, 2H), 1.32 (s, 3H), 1.10 (s, 3H), 0.83 (s, 9H), 0.01 (s, 3H),
-0.12 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 138.1, 138.0, 127.9,
127.7, 127.4, 114.7, 109.1, 80.6, 79.3, 75.6, 69.3, 33.9, 29.8, 27.4,
27.0, 25.7, 18.2, -4.9, -5.0; HRMS for C23H38O4Si + Na calcd
429.2439, found 429.2437.
Preparation of (S)-5-((1S,2R,3S)-1,2,3-Trihydroxy-3-phenyl-
propyl)furan-2(5H)-one (19). To a solution of 18 (0.06 g, 0.15
mmol) in 2 mL of THF was added AcOH (2 mL) and 1 N HCl (2
mL) at room temperature. The reaction mixture was allowed to
stirr for 6 h at the same temperature. After the reaction was complete
(TLC), the volatiles were removed under reduced pressure and the
residue obtained was purified by silica gel column chromatography
with petroleum ether:EtOAc (2:8) as an eluent to give 19 (0.026 g,
70%) as a white solid. Mp 142-144 °C; [R]D -84 (c 0.3, MeOH);
[lit.3 mp 143-145 °C; [R]D -85 (c 0.3, EtOH)]; IR (neat) 3372,
Preparation of (S)-Dihydro-5-((4R,5R)-5-((S)-tert-butyldim-
ethylsilyloxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-3H-
furan-2-one (17). Ozone was bubbled through a precooled (-78
°C) solution of 16 (0.32 g, 0.79 mmol) in a mixture of CH2Cl2:
MeOH (4:1, 15 mL) containing solid NaHCO3 (20 mg) until the
pale blue color persisted. Excess ozone was flushed off with oxygen
and Me2S (1 mL) was added. The reaction mixture was warmed to
0 °C, then stirred at the same temperature for 4 h. The reaction
mixture was concentrated under reduced pressure and filtered
through a short pad of Celite. The Celite pad was washed with
ether (25 mL). Evaporation of the solvent yielded the crude lactol,
which was subjected to the next reaction without further purification.
To a solution of crude lactol obtained above in 8 mL of CH2Cl2
was added Celite (0.4 g) and NaOAc (0.13 g, 1.58 mmol) at room
temperature and the solution was stirred for 5 min. PCC (0.34 g,
1.58 mmol) was then introduced at the same temperature and stirring
was continued for 1 h. After the reaction was complete (monitored
by TLC), it was filtered through a pad of Celite and the Celite pad
was washed with ether (25 mL). Evaporation of the solvent and
silica gel column chromatography of the residue with petroleum
ether:EtOAc (9:1) as an eluent afforded 17 (0.29 g, 92%) as a white
solid. Mp 101-103 °C; [R]D +59.6 (c 0.4, CHCl3); IR (neat) 2985,
1
2925, 1744, 1602, 1412, 1111, 1049, 822 cm-1; H NMR (300
MHz, CDCl3) δ 7.56 (dd, J ) 5.7, 1.5 Hz, 1H), 7.46-7.20 (m,
5H), 6.10 (dd, J ) 5.7, 1.8 Hz, 1H), 5.18 (m, 1H), 4.82 (d, J ) 6.6
Hz, 1H), 3.67 (dd, J ) 6.6, 2.7 Hz, 1H), 3.52 (dd, J ) 3.3, 1.5 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 173.7, 154.4, 140.3, 128.3,
127.9, 126.6, 121.7, 85.6, 74.8, 71.6; HRMS for C13H14O5 + Na
calcd 273.0741, found 273.0739.
Preparation of (+)-7-epi-Goniofufurone (1). A solution of 19
(0.03 g, 0.11 mmol) in THF (6.0 mL) containing DBU (0.01 mL,
0.06 mmol) was stirred at room temperature for 24 h. After the
reaction 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 in vacuo,
the residue was chromatographed on silica gel [petroleum ether:
EtOAc (3:7)] to afford 1 (0.02 g, 68%) as a crystalline solid. Mp
194-197 °C; [R]D +105 (c 0.8, EtOH) [lit.8a mp 190-192 °C;
[R]D +108 (c 0.2, EtOH)]; IR (neat) 3457, 2987, 1776, 1635, 1371,
1
2857, 1772, 1471, 1249, 1033, 778 cm-1; H NMR (300 MHz,
CDCl3) δ 7.45-7.24 (m, 5H), 4.91 (d, J ) 5.4 Hz, 1H), 4.34 (dd,
J ) 8.1, 5.4 Hz, 1H), 4.02 (ddd, J ) 8.4, 4.2, 1.5 Hz, 1H), 3.7 (dd,
J ) 8.4, 1.5 Hz, 1H), 2.74-2.51 (m, 1H), 2.32-2.20 (m, 1H),
2.19-2.10 (m, 2H), 1.36 (s, 3H), 1.18 (s, 3H), 0.92 (s, 9H), 0.11
(s, 3H), 0.02 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 177.7, 139.6,
127.9, 127.8, 127.3, 109.6, 79.4, 79.3, 77.3, 75.1, 27.9, 27.1, 26.5,
25.8, 24.7, 18.3, -4.9, -5.0. Anal. Calcd for C22H34O5Si: C 64.99,
H 8.43. Found: C 64.77, H 8.55.
1
1029, 765 cm-1; H NMR (300 MHz, CDCl3) δ 7.46-7.28 (m,
5H), 5.16-5.02 (m, 2H), 4.89 (dd, J ) 4.2, 0.9 Hz, 1H), 4.41 (d,
J ) 3.3 Hz, 1H), 2.23 (t, J ) 3.6 Hz, 1H), 2.83-2.63 (m, 2H); 13
C
NMR (75 MHz, CDCl3) δ 175.0, 139.9, 128.7, 128.5, 126.5, 87.8,
82.9, 75.5, 72.7, 36.1, 29.7; HRMS for C13H14O5 + Na calcd
273.0741, found 273.0739.
Preparation of (S)-5-((4R, 5R)-5-((S)-tert-Butyldimethylsily-
loxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-
one (18). To a precooled (-78 °C) solution of 17 (0.18 g, 0.44
mmol) in dry THF (4.0 mL) was added LHMDS (1.1 mL of 1 M
solution in THF, 1.1 mmol) dropwise, under argon atmosphere.
The reaction mixture was slowly warmed to -50 °C and stirred
for 1 h. It was then cooled to -78 °C and a THF (2 mL) solution
of phenylselenyl chloride (0.13 g, 0.66 mmol) was introduced
into the flask. Then the solution was stirred for 1 h at the same
temperature and after the reaction was complete (TLC), it was
quenched with saturated NH4Cl (5 mL) and extracted with
ether (3 × 15 mL). The combined ethereal extracts were washed
with brine (15 mL) and dried over Na2SO4. Evaporation of solvent
under reduced pressure at room temperature afforded the crude
selenide, which was used for the next step without further
purification.
To a cooled (0 °C) solution of crude selenide obtained above in
6 mL of CH2Cl2 were added pyridine (0.1 mL, 0.88 mmol) and
H2O2 (2 mL of 30% w/v in water) and the resulting mixture was
stirred for 0.5 h at the same temperature. After the reaction was
complete, it was poured into water (10 mL) and extracted with
CH2Cl2 (3 × 15 mL). The combined organic extracts were washed
with brine (25 mL) and dried over Na2SO4. The solvent was
removed under reduced pressure and the residue obtained was
purified by silica gel column chromatography with petroleum ether:
EtOAc (8:2) as an eluent to give 18 (0.12 g, 65%) as a white solid.
Mp 143-144 °C; [R]D +11.7 (c 0.6, CHCl3); IR (neat) 2929, 1751,
1594, 1369, 1250, 1097, 861 cm-1; 1H NMR (300 MHz, CDCl3) δ
Preparation of (S)-Dihydro-5-((4R,5R)-5-((S)-hydroxy(phe-
nyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(3H)-one (20).
To a precooled (0 °C) solution of 17 (0.42 g, 1.03 mmol) in dry
THF (10 mL) was added TBAF (1 M solution in THF, 2.1 mL,
2.1 mmol) under argon atmosphere. The reaction mixture was
slowly allowed to warm to room temperature and stirred for 1 h at
room temperature. Water (10 mL) was added to the reaction
mixture, which was stirred for 10 min. It was then extracted with
ether (3 × 20 mL). Combined ethereal extracts were washed with
brine (30 mL) and dried (Na2SO4). Evaporation of solvent and silica
gel column chromatography of the residue with petroleum ether:
EtOAc (6:4) as an eluent yielded 20 (0.29 g, 97%) as a colorless
oil. [R]D +74 (c 1, CHCl3); IR (neat) 3457, 2987, 1776, 1373, 1168,
1
1029, 887, 765 cm-1; H NMR (300 MHz, CDCl3) δ 7.52-7.16
(m, 5H), 4.65 (d, J ) 6.6 Hz, 1H), 4.35 (dd, J ) 8.1, 6.6 Hz, 1H),
3.82 (dd, J ) 8.4, 1.2 Hz, 1H), 3.68 (dt, J ) 6.6, 1.5 Hz, 1H), 2.84
(br s, 1H), 2.66-2.48 (m, 1H), 2.38-2.2 (m, 1H), 2.18-2.00 (m,
2H), 1.45 (s, 3H), 1.39 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
177.4, 138.8, 128.6, 127.0, 110.2, 80.2, 80.0, 76.3, 75.5, 27.7, 27.4,
26.4, 24.4; HRMS for C16H20O5 + Na calcd 315.1210, found
315.1208.
Preparation of (S)-Dihydro-5-((4R,5R)-5-((R)-hydroxy(phe-
nyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(3H)-one (21).
To a precooled (0 °C) solution of 20 (0.28 g, 0.96 mmol) in dry
THF (10 mL) were added triphenylphosphine (0.5 g, 1.92 mmol)
and p-nitrobenzoic acid (0.32 g, 1.92 mmol) under argon atmosphere
and the mixture was allowed to stir for 10 min. DIAD (0.3 mL,
1.44 mmol) was introduced into the reaction mixture over a period
J. Org. Chem, Vol. 73, No. 1, 2008 7

Prasad and Gholap
of 15 min at the same temperature. The reaction mixture was
warmed to room temperature and stirred for 1 h. After the reaction
was complete (TLC), the volatiles were removed under reduced
pressure and the crude residue obtained was used without further
purification in the next step.
4.06 (dd, J ) 6.0, 2.1 Hz, 1H), 3.62 (dd, J ) 8.4, 1.8 Hz, 1H),
3.30 (dd, J ) 3.3, 1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
175.7, 157.0, 144.0, 129.1, 128.6, 128.4, 122.2, 87.6, 75.0,
74.9, 72.8; HRMS for C13H14O5 + Na calcd 273.0741, found
273.0739.
To a methanol (12 mL) solution of crude ester obtained above
was added K2CO3 (0.27 g, 1.9 mmol) with stirring for 30 min at
room temperature. After the reaction was complete (TLC), the
reaction mixture was poured into water (20 mL) and extracted with
ether (3 × 20 mL). Combined ethereal extracts were washed with
brine (25 mL) and dried over Na2SO4. Evaporation of solvent and
silica gel column chromatography of the residue with petroleum
ether:EtOAc (7:3) as an eluent afforded 21 (0.22 g, 78%) as a
colorless oil. [R]D +36.2 (c 0.8, CHCl3); IR (neat) 3458, 2922,
1778, 1462, 1169, 704 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.43-
7.22 (m, 5H), 5.05 (d, J ) 2.7 Hz, 1H), 4.37 (dd, J ) 8.4, 4.2 Hz,
1H), 4.04 (d, J ) 8.4 Hz, 1H), 3.42 (dt, J ) 8.1, 4.2 Hz, 1H), 2.92
(d, J ) 9.6 Hz, 1H), 2.65-2.48 (m, 1H), 2.33-2.18 (m, 1H), 2.16-
1.99 (m, 2H), 1.45 (s, 3H), 1.36 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 177.8, 138.4, 128.5, 127.9, 125.5, 109.6, 79.3, 78.3, 77.3, 71.3,
27.7, 27.2, 26.3, 24.4; HRMS for C16H20O5 + Na calcd 315.1210,
found 315.1208.
Preparation of (S)-5-((4R,5R)-5-((R)-Hydroxy(phenyl)methyl)-
2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-one (22). To a cooled
(-78 °C) solution of 21 (0.14 g, 0.5 mmol) in dry THF (6.0 mL)
was added LHMDS (1.5 mL of 1 M solution in THF, 1.5 mmol)
dropwise, under argon atmosphere. The reaction mixture was slowly
warmed to -50 °C and stirred for 30 min at -50 °C. It was then
cooled to -78 °C and a THF (4 mL) solution of phenylselenyl
bromide (0.17 g, 0.72 mmol) was introduced into the flask. The
solution was stirred for 1 h at the same temperature and after the
reaction was complete (TLC), it was quenched with saturated NH4-
Cl (5 mL) and extracted with ether (3 × 10 mL). Combined ethereal
extracts were washed with brine (15 mL) and dried over Na2SO4.
Evaporation of solvent under reduced pressure at room temperature
afforded crude selenide, which was used in the next step without
further purification.
Preparation of (+)-Goniofufurone (2). A solution of unsatur-
ated lactone 23 (0.058 g, 0.23 mmol) in dry THF (10 mL)
containing DBU (0.02 mL, 0.12 mmol) was stirred at room
temperature for 24 h. The solution was then filtered through a short
pad of silica gel topped with Celite. A white solid obtained after
evaporation of the solvent from filtrate was further purified by silica
gel column chromatography with petroleum ether:EtOAc (3:7) as
an eluent to give 2 (0.042 g, 72%) as a white solid. Mp 150-153
°C; [R]D +9.8 (c 0.9, EtOH) [lit.8b mp 152-154 °C; [R]D +9 (c
0.5, EtOH)]; IR (neat) 3427, 2925, 1782, 1454, 1191, 1047, 701
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.52-7.22 (m, 5H), 5.18 (d,
J ) 4.8 Hz, 1H), 5.10 (t, J ) 4.5 Hz, 1H), 4.86 (d, J ) 4.5 Hz,
1H), 4.39 (d, J ) 2.4 Hz, 1H), 4.08 (dd, J ) 4.8, 3 Hz, 1H), 2.84-
2.59 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 175.8, 139.4, 129.2,
128.9, 126.3, 87.9, 83.4. 77.7, 74.8, 73.7, 36.5; HRMS for C13H14O5
+ Na calcd 273.0741, found 273.0739.
Preparation of ((S)-((4S,5R)-5-((S)-1-(Benzyloxy)pent-4-enyl)-
2,2-dimethyl-1,3-dioxolan-4-yl)(phenyl)methoxy)(tert-butyl)dim-
ethylsilane (24). In an oven-dried, 25-mL round-bottomed flask
equipped with a magnetic stir bar, septa, and argon inlet was placed
a solution of 16 (0.84 g, 2.07 mmol) in 15 mL of dry DMF. This
was cooled to 0 °C and NaH (0.17 g, 4.14 mmol, 60% suspension
in mineral oil) was added portionwise. The reaction mixture was
stirred for 0.5 h at room temperature then cooled to 0 °C, and benzyl
bromide (0.4 mL, 3.1 mmol) was then added dropwise. The reaction
mixture was warmed to room temperature and stirred at the same
temperature for 1.5 h. After the reaction was complete (monitored
by TLC), it was quenched by cautious addition of water (1 mL).
The reaction mixture was poured into water (10 mL) and extracted
with ether (3 × 20 mL). Combined ethereal extracts were washed
with brine (25 mL) and dried (Na2SO4). Evaporation of the solvent
followed by silica gel column chromatography of the residue with
petroleum ether:EtOAc (98:2) as an eluent yielded 24 (0.93 g, 91%)
as a colorless oil. [R]D +27.5 (c 0.8, CHCl3); IR (neat) 2929, 1644,
To a cooled (0 °C) solution of crude selenide obtained above in
6 mL of CH2Cl2 was added pyridine (0.1 mL, 0.96 mmol) and H2O2
(2 mL of 30% w/v in water) and the resulting mixture was stirred
for 0.5 h at the same temperature. After the reaction was complete,
water (10 mL) was added to the reaction mixture and extracted
with CH2Cl2 (3 × 10 mL). The combined organic extracts were
washed with brine (25 mL) and dried over Na2SO4. The solvent
was removed under reduced pressure and the residue thus obtained
was purified by silica gel column chromatography with petroleum
ether:EtOAc (6:4) as an eluent to give 22 (0.1 g, 74%) as a colorless
oil. [R]D +24.2 (c 1.1, CHCl3); IR (neat) 3471, 2921, 1748, 1455,
1454, 1367, 1253, 1068, 836, 777 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.38-7.10 (m, 10H), 5.68 (ddt, J ) 16.8, 10.2, 6.6 Hz,
1H), 5.02-4.84 (m, 2H), 4.70 (d, J ) 5.7 Hz, 1H), 4.46 (d, J )
11.7 Hz, 1H), 4.37 (d, J ) 11.4 Hz, 1H), 4.18 (dd, J ) 7.5, 5.1
Hz, 1H), 3.88 (dd, J ) 7.5, 3.0 Hz, 1H), 2.89 (dt, J ) 13.2, 3.3
Hz, 1H), 2.08-1.90 (m, 2H), 1.68-1.50 (m, 2H), 1.37 (s, 3H),
1.26 (s, 3H), 0.84 (s, 9H), 0.01 (s, 3H), -0.13 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 140.8, 138.7, 138.2, 128.2, 127.9, 127.7, 127.6,
127.4, 127.3, 114.8, 109.1, 80.8, 78.8, 77.5, 76.2, 72.4, 30.1, 29.8,
27.3, 27.2, 26.0, 25.8, 18.3, -4.8; HRMS for C30H44O4Si + Na
calcd 519.2909, found 519.2907.
1
1250, 1078, 704 cm-1; H NMR (300 MHz, CDCl3) δ 7.51-7.24
(m, 5H), 7.21 (ddd, J ) 6.0, 1.5, 0.9 Hz, 1H), 6.03 (dd, J ) 6.0,
2.4 Hz, 1H), 5.12 (d, J ) 4.2 Hz, 1H), 4.54 (dd, J ) 8.1, 4.5 Hz,
1H), 4.22 (dd, J ) 8.1, 1.5 Hz, 1H), 3.89 (t, J ) 1.8 Hz, 1H), 2.62
(br s, 1H), 1.44 (s, 3H), 1.36 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 172.9, 153.2, 138.2, 128.8, 128.2, 125.5, 121.9, 110.4, 81.3, 79.9,
74.3, 71.2, 27.2, 26.1; HRMS for C16H18O5 + Na calcd 313.1054,
found 313.1052.
Preparation of (1S,2R,3S,4S)-4-(Benzyloxy)-1-phenyloct-7-
ene-1,2,3-triol (25). To a solution of 24 (0.52 g, 1.05 mmol) in
THF (8 mL) was added 4 N HCl (8 mL) at room temperature. The
reaction mixture was allowed to stir for 6 h at the same temperature.
After the reaction was complete (TLC), the reaction mixture was
poured into water (20 mL) and extracted with EtOAc (3 × 20 mL).
The combined organic layers were washed with brine (30 mL) and
dried over Na2SO4. Silica gel column chromatography of the crude
residue obtained after evaporation of the solvent with petroleum
ether:EtOAc (6:4) as eluent gave 25 (0.30 g, 84%) as a colorless
oil. [R]D +24.3 (c 1, CHCl3); IR (neat) 3413, 2923, 1643, 1454,
Preparation of (S)-5-((1S,2R,3R)-1,2,3-Trihydroxy-3-phenyl-
propyl)furan-2(5H)-one (23). To a solution of 22 (0.08 g, 0.28
mmol) in THF (3 mL) was added 2 N HCl (3 mL) at room
temperature, and the mixture was stirred for 6 h at the same
temperature. After the reaction was complete (TLC) the volatiles
are removed under reduced pressure and the residue was purified
by silica gel column chromatography with petroleum ether:EtOAc
(2:8) as an eluent to afford 23 (0.026 g, 70%) as a white solid. Mp
107-110 °C; [R]D -67.4 (c 0.5, EtOAc) [lit.3 mp 109-111 °C;
[R]D -68 (c 0.6, EtOAc)]; IR (neat) 3402, 2924, 1750, 1454, 1177,
1
1074, 736 cm-1; H NMR (300 MHz, CDCl3) δ 7.44-7.20 (m,
10H), 5.70 (ddt, J ) 16.2, 9.6, 6.6 Hz, 1H), 4.95-4.84 (m, 2H),
4.75 (d, J ) 6.6 Hz, 1H), 4.59 (d, J ) 10.8 Hz, 1H), 4.39 (d, J )
11.1 Hz, 1H), 3.72-3.32 (m, 4H), 3.18 (d, J ) 6.0 Hz, 1H), 2.90
(d, J ) 4.8 Hz, 1H), 2.12-1.51 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 140.2, 137.9, 137.7, 128.6, 128.4, 128.0, 127.9, 127.8,
126.9, 115.0, 80.0, 75.4, 75.3, 72.2, 71.2, 28.8; HRMS for C21H26O4
+ Na calcd 365.1731, found 365.1729.
1
1041, 701 cm-1; H NMR (300 MHz, CDCl3) 7.75 (dd, J ) 6.0,
1.5 Hz, 1H), 7.46-7.18 (m, 5H), 6.15 (dd, J ) 5.7, 2.1 Hz, 1H),
5.25 (ddd, J ) 6.0, 3.6, 1.2 Hz, 1H), 4.70 (d, J ) 8.4 Hz, 1H),
8 J. Org. Chem., Vol. 73, No. 1, 2008

StereoselectiVe Total Synthesis of BioactiVe Styryllactones
Preparation of (5S,6S)-5-(Benzyloxy)tetrahydro-6-((1R,2S)-
1,2-dihydroxy-2-phenylethyl)pyran-2-one (26). Ozone was bubbled
through a precooled (-78 °C) solution of 25 (0.43 g, 1.26 mmol)
in a 4:1 mixture of CH2Cl2:MeOH (20 mL) containing solid
NaHCO3 (20 mg) until the pale blue color persisted. Excess ozone
was flushed off with oxygen and dimethyl sulfide (1 mL) was
added. The reaction mixture was warmed to 0 °C and stirred at the
same temperature for 6 h. Then the reaction mixture was concen-
trated under reduced pressure and filtered through a short pad of
Celite. The Celite pad was washed with EtOAc (25 mL). Evapora-
tion of the solvent yielded the crude lactol, which was subjected to
the next reaction without further purification.
stirred for 0.5 h at the same temperature. After the reaction was
complete (monitored by TLC), water (10 mL) was added to the
reaction mixture and extracted with CH2Cl2 (3 × 10 mL). The
combined organic extracts were washed with brine (25 mL) and
dried over Na2SO4. The solvent was removed under reduced
pressure and the residue thus obtained was purified by silica gel
column chromatography with petroleum ether:EtOAc (7:3) as an
eluent to give 28 (0.06 g, 69%) as a colorless oil. [R]D +20.4 (c
1.2, CHCl3); IR (neat) 2984, 1728, 1348, 1272, 1100, 874, 718
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.44-7.22 (m, 10H), 7.02
(dd, J ) 9.9, 5.7 Hz, 1H), 6.24 (d, J ) 9.9 Hz, 1H), 4.90 (d, J )
2.1 Hz, 1H), 4.76-4.44 (m, 6H), 4.40 (dd, J ) 5.4, 3.3 Hz, 1H),
4.27 (dd, J ) 8.1, 2.4 Hz, 1H), 4.18 (d, J ) 6.6 Hz, 1H), 4.05 (s,
3H), 3.0 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 162.6, 141.9, 138.0,
137.1, 128.7, 128.4, 128.3, 128.1, 127.1, 124.8, 98.1, 95.2, 80.9,
78.1, 77.2, 70.9, 65.3, 56.3, 56.1; HRMS for C24H28O7 + Na calcd
451.1735, found 451.1733.
To a solution of the crude lactol obtained above in 25 mL of
toluene was added Ag2CO3 impregnated on Celite (2.1 g, 2.52
mmol, 33% impregnation) under argon atmosphere. The reaction
mixture was kept at 110 °C and stirred at the same temperature for
0.5 h. It was then cooled to room temperature and filtered through
a pad of Celite, and the Celite pad was washed with EtOAc (25
mL). Evaporation of the solvent and silica gel column chromatog-
raphy of the residue with petroleum ether:EtOAc (4:6) as eluent
yielded 26 (0.34 g, 78%) as a colorless oil. [R]D +32.4 (c 0.8,
Preparation of (5S,6R)-5,6-Dihydro-5-hydroxy-6-((1R,2S)-1,2-
dihydroxy-2-phenylethyl)pyran-2-one (29). To a precooled (0 °C)
solution of 28 (0.07 g, 0.16 mmol) in dry CH2Cl2 (6.0 mL) was
added TiCl4 (1.6 mL of 1 M solution in CH2Cl2, 1.6 mmol). The
reaction mixture was warmed to room temperature and stirred for
1.5 h. After the reaction was complete (monitored by TLC), it was
cautiously quenched by addition of saturated NaHCO3 (4 mL). The
reaction mixture was poured into water (5 mL) and extracted with
EtOAc (4 × 10 mL). The combined organic layers were washed
with brine (10 mL), dried over Na2SO4. Evaporation of solvent
followed by column chromatography of the residue with petroleum
ether:EtOAc (2:8) as an eluent gave 29 (0.03 g, 78%) as a white
solid. Mp 126-128 °C; [R]D +86 (c 0.6, EtOH) [lit.3 mp 127-
129 °C; [R]D +88 (c 0.5, EtOH)]; IR (neat) 3401, 2919, 1715, 1264,
CHCl3); IR (neat) 3443, 2943, 1731, 1454, 1245, 1078, 700 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.44-7.21 (m, 10H), 4.78 (d, J )
5.7 Hz, 1H), 4.59 (d, J ) 11.7 Hz, 1H), 4.34 (d, J ) 11.7 Hz, 1H),
4.18 (dd, J ) 3.9, 3.0 Hz, 1H), 4.05 (dd, J ) 5.4, 4.2 Hz, 1H),
3.95-3.86 (m, 1H), 3.70 (br s, 1H), 3.45 (br s, 1H), 2.76-2.39
(m, 2H), 2.36-2.17 (m, 1H), 1.92-1.72 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 170.2, 140.2, 136.5, 128.7, 128.4, 128.3, 127.9,
126.7, 80.1, 75.0, 73.2, 70.7, 70.4, 25.5, 22.5; HRMS for C20H22O5
+ Na calcd 365.1367, found 365.1365.
Preparation of (5S,6R)-6-((1R,2S)-1,2-Bis(methoxymethoxy)-
2-phenylethyl)-5-(benzyloxy)tetrahydropyran-2-one (27). To a
solution of 26 (0.28 g, 0.82 mmol) in dry CH2Cl2 (12 mL) were
added diisopropylethylamine (0.64 g, 0.9 mL, 4.92 mmol), DMAP
(20 mg, 20 mol %), and MOMCl (0.25 mL, 3.28 mmol) at 0 °C.
After being stirred for 15 min at 0 °C, the reaction mixture was
warmed to room temperature and then refluxed for 6 h. After the
reaction was complete (indicated by TLC), it was cooled to room
temperature, poured into water (10 mL), and extracted with ether
(3 × 20 mL). Combined ethereal extracts were washed with brine
(20 mL) and dried over Na2SO4. Evaporation of solvent and silica
gel column chromatography of the residue with petroleum ether:
EtOAc (7:3) as an eluent yielded 27 (0.28 g, 80%) as a colorless
oil. [R]D +43.6 (c 1.1, CHCl3); IR (neat) 2934, 1733, 1455, 1151,
1
1026, 706 cm-1; H NMR (300 MHz, CDCl3) δ 7.48-7.18 (m,
5H), 7.09 (dd, J ) 9.6, 6.0 Hz, 1H), 6.05 (d, J ) 9.9 Hz, 1H), 5.04
(d, J ) 3.3 Hz, 1H), 4.51 (dd, J ) 6.0, 2.7 Hz, 1H), 4.35 (dd, J )
6.6, 3.0 Hz, 1H), 4.18 (dd, J ) 6.6, 3.3 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ 167.1, 148.7, 146.1, 131.4, 130.5, 130.1, 125.3,
84.4, 77.9, 75.8, 63.7; HRMS for C13H14O5 + Na calcd 273.0741,
found 273.0739.
Preparation of (+)-Goniopypyrone (3). A solution of triol 29
(0.045 g, 0.18 mmol) in dry THF (10 mL) containing DBU (0.01
mL, 0.09 mmol) was stirred at room temperature for 4 h. After the
reaction was complete (TLC), the reaction mixture was filtered
through a short pad of silica gel topped with Celite. Residue
obtained after removal of solvent from filtrate in vacuo gave a white
solid, which was further purified by silica gel column chromatog-
raphy with petroleum ether:EtOAc (3:7) as eluent to yield 3 (0.034
g, 75%) as a white solid. Mp 179-182 °C; [R]D +52.8 (c 0.5,
EtOH) [lit.8b mp 182-184 °C; [R]D +54 (c 0.4, EtOH)]; IR (neat)
1
1024, 702 cm-1; H NMR (300 MHz, CDCl3) δ 7.44-7.14 (m,
10H), 4.84-4.38 (m, 7H), 4.28-4.10 (m, 3H), 3.34 (s, 3H), 2.95
(s, 3H), 2.75-2.54 (m, 2H), 2.43-2.31 (m, 1H), 2.04-1.88 (m,
1H); 13C NMR (75 MHz, CDCl3) δ 169.9, 138.0, 137.1, 128.6,
128.3, 128.2, 128.0, 127.8, 127.0, 98.0, 95.1, 83.1, 78.9, 77.1, 70.3,
68.4, 56.3, 56.0, 25.4, 22.7; HRMS for C24H30O7 + Na calcd
453.1892, found 453.1889.
1
3397, 2919, 1741, 1453, 1224, 1057, 733 cm-1; H NMR (300
MHz, CDCl3) δ 7.53-7.32 (m, 5H), 5.03 (d, J ) 1.2 Hz, 1H),
4.82 (dd, J ) 6.0, 3.6 Hz, 1H), 4.48 (dd, J ) 4.5, 2.1 Hz, 1H),
4.16-3.98 (m, 3H), 3.10 (dd, J ) 19.5, 1.8 Hz, 1H), 3.01 (dd, J )
19.5, 4.8 Hz, 1H), 2.16 (d, J ) 3.3 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ 167.8, 135.8, 129.1, 128.7, 126.2, 72.6, 70.9, 70.3, 70.1,
64.4, 35.2; HRMS for C13H14O5 + Na calcd 273.0741, found
273.0739.
Preparation of 4(S)-((S)-1-(Hydroxy)phenylmethyl)-5(R)-((S)-
1-(benzyloxy)pent-4-enyl)-2,2-dimethyl-1,3-dioxolane (30). To a
precooled (0 °C) solution of 24 (0.92 g, 1.85 mmol) in dry THF
(18 mL) was added TBAF (3.7 mL of 1 M solution in THF, 3.7
mmol) under argon atmosphere. The reaction mixture was allowed
to warm to room temperature and stirred at the same temperature
for 1.5 h. Water (15 mL) was added to the reaction mixture with
stirring for 10 min. The reaction mixture was then extracted with
ether (3 × 25 mL). Combined ethereal extracts were washed with
brine (30 mL) and dried (Na2SO4). Evaporation of the solvent and
silica gel column chromatography of the residue with petroleum
ether:EtOAc (8:2) as an eluent yielded 30 (0.67 g, 94%) as a
colorless oil. [R]D -20 (c 1, CHCl3); IR (neat) 3453, 2919, 1637,
Preparation of (5S,6R)-6-((1R,2S)-1,2-Bis(methoxymethoxy)-
2-phenylethyl)-5-(benzyloxy)-5,6-dihydropyran-2-one (28). To a
precooled (-78 °C) solution of 27 (0.09 g, 0.21 mmol) in dry THF
(5.0 mL) was added LHMDS (0.63 mL of 1 M solution in THF,
0.63 mmol) dropwise, under argon atmosphere. The reaction
mixture was slowly warmed to -50 °C and stirred for 1 h. It was
then cooled to -78 °C and a THF (2 mL) solution of phenylselenyl
bromide (0.074 g, 0.32 mmol) was introduced. It was stirred for 1
h at the same temperature and after the reaction was complete
(TLC), it was quenched with saturated NH4Cl (5 mL) and extracted
with ether (3 × 10 mL). Combined ethereal extracts were washed
with brine (15 mL) and dried over Na2SO4. Evaporation of solvent
under reduced pressure at room temperature afforded the crude
selenide, which was used as such in the next step without further
purification.
To a precooled (0 °C) solution of crude selenide obtained above
in 6 mL of CH2Cl2 was added pyridine (0.04 mL, 0.42 mmol) and
H2O2 (1 mL of 30% w/v in water) and the resulting mixture was
J. Org. Chem, Vol. 73, No. 1, 2008 9

Prasad and Gholap
1454, 1251, 1068, 765 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.40-
7.15 (m, 10H), 5.66 (ddt, J ) 16.2, 9.6, 6.6 Hz, 1H), 4.99-4.85
(m, 2H), 4.64 (t, J ) 5.4 Hz, 1H), 4.44 (d, J ) 11.4 Hz, 1H), 4.32
(d, J ) 11.4 Hz, 1H), 4.23 (dd, J ) 7.8, 6.0 Hz, 1H), 3.99 (dd, J
) 7.8, 3.3 Hz, 1H), 3.02 (dd, J ) 5.1, 1.5 Hz, 1H), 2.90 (dt, J )
12.0, 3.3 Hz, 1H), 2.08-1.92 (m, 2H), 1.70-1.48 (m, 4H), 1.43
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 140.0, 138.2, 138.0, 128.4,
128.3, 128.1, 127.8, 127.6, 126.9, 114.9, 109.5, 80.5, 78.6, 76.9,
74.8, 72.5, 29.7, 29.6, 27.4, 27.2; HRMS for C24H30O4 + Na calcd
405.2044, found 405.2042.
72.0, 70.1, 29.0, 28.8; HRMS for C21H26O4 + Na calcd 365.1731,
found 365.1729.
Preparation of (5S,6S)-5-(Benzyloxy)tetrahydro-6-((1R,2R)-
1,2-dihydroxy-2-phenylethyl)pyran-2-one (33). 33 was synthe-
sized by using a procedure similar to that described for 26. [R]D
-17.5 (c 0.6, CHCl3); IR (neat) 2973, 1741, 1454, 1238, 1024,
919, 703 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.50-7.18 (m, 10H),
4.86 (d, J ) 7.2 Hz, 1H), 4.68 (t, J ) 2.4 Hz, 1H), 4.56 (d, J )
11.4 Hz, 1H), 4.30 (d, J ) 11.4 Hz, 1H), 4.07 (dd, J ) 7.5, 2.4
Hz, 1H), 3.92-3.84 (m, 1H), 3.69 (br s, 1H), 3.07 (br s, 1H), 2.76-
2.44 (m, 2H), 2.32-2.14 (m, 1H), 2.06-1.78 (m, 1H); 13C NMR
(75 MHz, CDCl3) δ 170.4, 141.2, 136.4, 128.7, 128.4, 128.3, 127.9,
127.8, 126.9, 78.6, 75.1, 72.9, 70.4, 25.5, 22.8; HRMS for C20H22O5
+ Na calcd 365.1367, found 365.1365.
Preparation of (5S,6R)-6-((1R,2R)-1,2-Bis(methoxymethoxy)-
2-phenylethyl)-5-(benzyloxy)tetrahydropyran-2-one (34). 34 was
synthesized by using a procedure similar to that described for 27.
[R]D -32.2 (c 0.8, CHCl3); IR (neat) 2987, 1743, 1641, 1454, 1373,
1232, 1027, 873, 703 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.46-
7.18 (m, 10H), 4.86-4.71 (m, 3H), 4.62 (d, J ) 6.3 Hz, 1H), 4.53
(d, J ) 6.3 Hz, 1H), 4.46-4.34 (m, 2H), 4.27 (dd, J ) 7.8, 2.7
Hz, 1H), 4.04 (d, J ) 11.7 Hz, 1H), 3.83 (dd, J ) 5.1, 2.7 Hz,
1H), 3.38 (s, 3H), 3.34 (s, 3H), 2.69-2.36 (m, 2H), 2.26-2.08
(m, 1H), 1.90-1.76 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 170.0,
137.9, 137.1, 128.5, 128.4, 128.2, 128.1, 127.9, 127.8, 98.0, 94.2,
81.4, 78.0, 76.8, 69.8, 68.6, 56.3, 55.7, 25.8, 22.7; HRMS for
C24H30O7 + Na calcd 453.1892, found 453.1889.
Preparation of 4(S)((R)-1-(Hydroxy)phenylmethyl)-5(R)-((S)-
1-(benzyloxy)pent-4-enyl)-2,2-dimethyl-1,3-dioxolane (31). To a
precooled (0 °C) solution of 30 (0.72 g, 1.88 mmol) in dry THF
(20 mL) were added triphenylphosphine (0.98 g, 3.76 mmol) and
p-nitrobenzoic acid (0.62 g, 3.76 mmol) under argon atmosphere
and the mixture was allowed to stir for 10 min. DIAD (0.6 mL,
2.82 mmol) was introduced into the reaction mixture over a period
of 15 min at the same temperature. The reaction mixture was
warmed to room temperature and stirred at room temperature for 1
h. After the reaction was complete (TLC), solvent was removed
under reduced pressure and the crude ester thus obtained was
purified by column chromatography to yield the corresponding
p-nitrobenzoate ester (0.94 g, 94%) as a pale yellow solid. Mp 118
°C; [R]D +48 (c 1.2, CHCl3); IR (neat) 2930, 1733, 1454, 1154,
1
1023, 763 cm-1; H NMR (300 MHz, CDCl3) δ 8.40-8.08 (m,
4H), 7.46-7.18 (m, 10H), 6.17 (d, J ) 4.8 Hz, 1H), 5.70 (ddt, J )
16.8, 10.2, 6.6 Hz), 5.16-4.86 (m, 2H), 4.68-4.35 (m, 3H), 4.12
(dd, J ) 7.5, 3.3 Hz, 1H), 3.20 (dt, J ) 12.9, 0.3 Hz, 1H), 2.22-
2.02 (m, 2H), 1.82-1.64 (m, 2H), 1.43 (s, 3H), 1.23 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 163.5, 150.6, 138.2, 137.9, 135.8, 135.2,
130.8, 128.7, 128.4, 128.3, 127.8, 127.7, 127.5, 123.5, 115.1, 110.0,
79.1, 78.3, 77.4, 76.8, 72.4, 29.9, 29.7, 27.2, 27.1; HRMS for
C31H33NO7 + Na calcd 554.2157, found 554.2155.
Preparation of (5S,6R)-6-((1R,2R)-1,2-Bis(methoxymethoxy)-
2-phenylethyl)-5-(benzyloxy)-5,6-dihydropyran-2-one (35). 35
was synthesized by using a procedure similar to that described for
28. [R]D +43.6 (c 1.1, CHCl3); IR (neat) 2931, 1729, 1454, 1255,
1
1024, 700 cm-1; H NMR (300 MHz, CDCl3) δ 7.48-7.22 (m,
10H), 6.78 (dd, J ) 9.9, 4.2 Hz, 1H), 6.05 (d, J ) 9.9 Hz, 1H),
4.81 (d, J ) 5.1 Hz, 1H), 4.73 (d, J ) 6.6 Hz, 1H), 4.68-4.28 (m,
7H), 4.21 (t, J ) 4.5 Hz, 1H), 3.34 (s, 3H), 3.15 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 157.9, 142.6, 137.9, 136.9, 128.6, 128.5, 128.3,
128.2, 128.1, 128.0, 123.4, 97.8, 94.1, 78.7, 76.9, 76.4, 70.9, 66.3,
56.1, 55.8; HRMS for C24H28O7 + Na calcd 451.1735, found
451.1733.
To a methanol (16 mL) solution of p-nitrobenzoate ester (0.94
g, 1.8 mmol) obtained above was added K2CO3 (0.5 g, 3.6 mmol)
with stirring for 0.5 h at room temperature. After the reaction was
complete (TLC), the reaction mixture was poured into water (30
mL) and extracted with ether (3 × 25 mL). Combined ethereal
extracts were washed with brine (25 mL) and dried over Na2SO4.
Evaporation of the solvent and silica gel column chromatography
of the residue with petroleum ether:EtOAc (8:2) as eluent afforded
31 (0.62 g, 92%) as a colorless oil. [R]D +12.4 (c 0.6, CHCl3); IR
Preparation of (+)-Goniotriol (4). 4 was synthesized by using
a procedure similar to that described for 29. Mp 168-170 °C; [R]D
+119 (c 0.4, MeOH) [lit.11a mp 170 °C; [R]D +121 (MeOH)]; IR
(neat) 3404, 1715, 1383, 1264, 1099, 922, 828, 705 cm-1; 1H NMR
(300 MHz, CDCl3) δ 7.51-7.22 (m, 5H), 7.02 (dd, J ) 9.9, 6.0
Hz, 1H), 6.08 (d, J ) 9.9 Hz, 1H), 4.73 (d, J ) 7.8 Hz, 1H), 4.59
(t, J ) 3.6 Hz, 1H), 4.43 (dd, J ) 5.4, 2.7 Hz, 1H), 4.17 (dd, J )
8.1, 4.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 166.0, 146.4, 143.4,
129.2, 128.9, 128.8, 123.0, 80.3, 75.6, 73.9, 63.5; HRMS for
C13H14O5 + Na calcd 273.0741, found 273.0739.
Preparation of (2R,3R,3aS,7aS)-Tetrahydro-3-hydroxy-2-
phenyl-2H-furo[3,2-b]pyran-5(6H)-one (37). Ozone was bubbled
through a precooled (-78 °C) solution of 36 (0.33 g, 1.4 mmol) in
4:1 CH2Cl2:MeOH (15 mL) containing solid NaHCO3 (0.03 g) until
the pale blue color persisted. Excess ozone was flushed off with
oxygen and Me2S (1 mL) was added. The reaction mixture was
warmed to 0 °C, then stirred at the same temperature for 6 h. The
reaction mixture was concentrated under reduced pressure and
filtered through a short pad of Celite. The Celite pad was washed
with EtOAc (25 mL). Evaporation of the solvent yielded the crude
lactol, which was subjected to the next reaction without further
purification.
1
(neat) 3423, 2927, 1621, 1452, 1199, 917, 701 cm-1; H NMR
(300 MHz, CDCl3) δ 7.44-7.18 (m, 10H), 5.73 (ddt, J ) 16.8,
10.2, 6.6 Hz, 1H), 5.10-4.88 (m, 2H), 4.85 (dd, J ) 5.1, 1.2 Hz,
1H), 4.44 (d, J ) 11.4 Hz, 1H), 4.30-4.18 (m, 2H), 4.09 (dd, J )
7.8, 2.7 Hz, 1H), 3.24 (d, J ) 1.5 Hz, 1H), 2.83 (dt, J ) 13.2, 2.7
Hz, 1H), 2.10-1.96 (m, 2H), 1.72-1.50 (m, 2H), 1.41 (s, 3H),
1.38 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 139.5, 138.0, 130.6,
128.3, 128.2,127.8, 127.7, 126.3, 123.5, 114.9, 108.9, 79.6, 78.1,
77.4, 72.9, 72.6, 29.9, 29.8, 27.1, 26.9; HRMS for C24H30O4 + Na
calcd 405.2044, found 405.2042.
Preparation of (1R,2R,3S,4S)-4-(Benzyloxy)-1-phenyloct-7-
ene-1,2,3-triol (32). To a solution of 31 (0.66 g, 1.73 mmol) in
THF (8.0 mL) was added 4 N HCl (8.0 mL) at room temperature.
The reaction mixture was stirred at room temperature for 6 h, poured
into water (10 mL), and extracted with EtOAc (3 × 20 mL). The
combined organic layers were washed with brine (30 mL), dried
over Na2SO4, and concentrated. Silica gel column chromatography
of crude residue obtained after evaporation of the solvent with
petroleum ether:EtOAc (6:4) as an eluent afforded 32 (0.52 g, 90%)
as an oil. [R]D -40.4 (c 0.8, CHCl3); IR (neat) 3419, 2928, 1640,
1453, 1093, 742, 699 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.46-
7.18 (m, 10H), 5.72 (ddt, J ) 17.1, 10.8, 6.6 Hz, 1H), 5.02-4.84
(m, 3H), 4.54 (d, J ) 11.4 Hz, 1H), 4.35 (d, J ) 11.4 Hz, 1H),
4.02-3.69 (m, 3H), 3.63-3.40 (m, 2H), 3.23 (br s, 1H), 2.18-
1.50 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 140.8, 138.0, 137.7,
128.5, 128.4, 127.9, 127.8, 127.5, 125.9, 114.9, 80.3, 76.0, 74.2,
To a solution of crude lactol obtained above in 15 mL of toluene
was added Ag2CO3 impregnated on Celite (2.3 g, 2.8 mmol, 33%
impregnation) under an argon atmosphere. The reaction mixture
was kept at 110 °C and stirred at the same temperature for 0.5 h.
It was then cooled to room temperature then filtered through a pad
of Celite and the Celite pad was washed with EtOAc (25 mL).
Evaporation of the solvent and silica gel column chromatography
of the residue with petroleum ether:EtOAc (4:6) as an eluent yielded
10 J. Org. Chem., Vol. 73, No. 1, 2008

StereoselectiVe Total Synthesis of BioactiVe Styryllactones
37 (0.27 g, 82%) as a colorless oil. [R]D +24.3 (c 0.7, CHCl3); IR
CDCl3) δ 7.42-7.22 (m, 5H), 4.90 (dd, J ) 4.8, 1.8 Hz, 1H), 4.69
(d, J ) 6.0 Hz, 1H), 4.38 (t, J ) 3.9 Hz, 1H), 4.29 (dd, J ) 6.0,
2.1 Hz, 1H), 4.02 (dt, J ) 6.0, 3.6 Hz, 1H), 3.65 (q, J ) 6.9 Hz,
2H), 3.0 (br s, 1H), 2.85 (dd, J ) 16.2, 3.6 Hz, 1H), 2.70 (dd, J )
16.2, 6.0 Hz, 1H), 1.22 (t, J ) 6.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 169.1, 128.7, 128.4, 126.1, 86.8, 86.1, 83.7, 75.9, 72.8,
65.3, 33.2, 15.3; HRMS for C15H18O5 + Na calcd 301.1054, found
301.1052.
(neat) 3400, 2922, 2851, 1740, 1633, 1453, 1165, 1057, 734 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.48-7.22 (m, 5H), 4.76 (dd, J )
5.1, 2.4 Hz, 1H), 4.62 (d, J ) 6.3 Hz, 1H), 4.44 (dd, J ) 8.7, 3.9
Hz, 1H), 4.19 (d, J ) 6.0 Hz, 1H), 3.95 (d, J ) 6.0 Hz, 1H), 2.69
(ddd, J ) 16.8, 10.5, 5.7 Hz, 1H), 2.46 (td, 17.1, 5.1 Hz, 1H),
2.28-2.02 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 171.6, 138.3,
128.6, 128.2, 126.0, 88.5, 85.1, 84.3, 72.1, 26.0, 22.9; HRMS for
C13H14O4 + Na calcd 257.0792, found 257.0790.
Acknowledgment. We thank the Department of Science and
Technology (DST) and the Department of Biotechnology (DBT),
New Delhi for funding. One of us (S.L.G.) thanks the Council
of Scientific and Industrial Research (CSIR), New Delhi for a
senior research fellowship.
Preparation of (-)-Etharvensin (6). To a precooled (0 °C)
solution of altholactone 5 (0.016 g, 0.068 mmol) in EtOH (4 mL)
was added dropwise concentrated H2SO4 (96%, 0.5 mL). The
reaction mixture was warmed to room temperature and refluxed
for 1.5 h. After reaction was complete (TLC), water (5 mL) was
added to the reaction mixture and extracted with CH2Cl2 (3 × 10
mL). The combined organic extracts were washed with brine (15
mL) and dried over Na2SO4. The solvent was removed under
reduced pressure and the residue obtained was purified by silica
gel column chromatography with petroleum ether:EtOAc (1:1) as
an eluent to give 6 (0.017 g, 89%) as a colorless oil. [R]D -6.1 (c
1.1, EtOH) [lit.14 [R]D -6.5 (c 2.0, EtOH)]; IR (neat) 3460, 2936,
Supporting Information Available: General experimental
procedures and spectroscopic data for the compounds and copies
1
of H NMR and 13C NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO0702342
(14) Bermejo, A.; Blazquez, M. A.; Serrano, A.; Zafra-Polo, M. C.;
Cortes, D. J. J. Nat. Prod. 1997, 60, 1338.
1
1732, 1611, 1514, 1250, 1055, 821 cm-1; H NMR (300 MHz,
J. Org. Chem, Vol. 73, No. 1, 2008 11