Total synthesis of four diastereoisomers of Goniofufurone from D-(-)- or L-(+)-tartaric acid

Article abstract of DOI:10.1016/S0040-4020(01)00050-3

(+) and (-)-Goniofufurones, (+) and (-)-8-epi-goniofufurones have been synthesized from D-(-) and L-(+)-tartaric acids by the addition of ethyl lithiopropiolate to a chiral aldehyde intermediate as a key step, in which LDA is the best base compared to n-BuLi plus Lewis acid YCl₃ (cat.).

Full text of DOI:10.1016/S0040-4020(01)00050-3

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 2147±2153
Total synthesis of four diastereoisomers of Goniofufurone from
d-(2)- or l-(1)-tartaric acid
Yong-Li Su, Chun-Song Yang, Shang-Jun Teng, Gang Zhaop and Yu Dingp
Shanghai Institute of Organic Chemistry, The Chinese Academy of Sciences, Academia Sinica, 354 Fenglin Lu, Shanghai 20032,
People's Republic of China
Received 2 June 2000; revised 13 December 2000; accepted 4 January 2001
AbstractÐ(1) and (2)-Goniofufurones, (1) and (2)-8-epi-goniofufurones have been synthesized from d-(2) and l-(1)-tartaric acids by
the addition of ethyl lithiopropiolate to a chiral aldehyde intermediate as a key step, in which LDA is the best base compared to n-BuLi plus
Lewis acid YCl3 (cat.). q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
diastereoisomers of Goniofufurone from commercially
available tartaric acids.
Since the ®rst styryl lactone goniothalamin was found from
the trees of genus Goniothalamus in 19721 a variety of styryl
lactones have been isolated and identi®ed within the family
Annonaceae.2,3 The styryl lactones have been categorized as
10 types based on their skeleton structure and are reported to
show cytotoxic, antitumour, pesticidal, teratogenic and
embryotoxic activities.4 Goniofufurones contain a furano-
furone bicyclic structure and show signi®cant cytotoxic
activities against several human tumour cell lines. Herein,
we would like to report our study on the synthesis of four
Due to the unique structural features and signi®cant bio-
activity, (1)-goniofufurone, (1)-8-epi-goniofufurone and
their stereoisomers have been synthesized by many groups
from different starting materials. Most of them started from
d-glucose5 and d-mannose.6 Shing et al. completed the ®rst
successful synthesis of these styryl lactones7 starting from
d-glycero-d-glyco-heptono-g-lactone. Introduction of the
desired chiral centers by asymmetric epoxidation and
dihydroxylation of cinnamyl alcohol has been successfully
used in their total syntheses.8 Recently, Koll et al. reported
an interesting route starting from a d-glucose derivative
and reaction with Meldrum's acid.9 Tsubuki et al. reported
the syntheses of 1 from 2,3-O-isopropylidene-d-glycer-
aldehyde.10 A synthesis of (1)-Goniofufurone by highly
diastereoselective allenylation of d-glucurono-6,3-lactone
was completed by Chao-jun Li.11 Surivet et al. used
mandelic acid as the starting material.12 Roberts et al.
synthesized 1 from furyl styryl ketone, which was oxidized
Scheme 1.
Scheme 2.
Keywords: lactones; alkynes; lithium and compounds; biologically active compounds.
Corresponding authors. Tel.: 186-21-64163300; fax: 186-21-64166128; e-mail: dingyu@pub.sioc.ac.cn
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00050-3

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Y.-L. Su et al. / Tetrahedron 57 (2001) 2147±2153
Table 1. Addition of ethyl lithiopropiolate to 11a
2. Results and discussion
Entry
Base
Lewis acid
Yield (%)
Retrosynthetic analysis of (1)-Goniofufurone 1 (Scheme 2)
showed that intermediate 3 could be the precursor of 1
which will be obtained by intramolecular Michael addition
and then lactonization. Compound 4 is the key intermediate
and could be obtained by the addition of ethyl lithio-
propiolate to aldehyde 5 which is easily prepared from
d-(2)-tartaric acid.
1
2
3
n-BuLi
n-BuLi
LDA
±
Very low
60.0
78.9
YCl3 (0.1 equiv.)
±
Table 2. Addition of ethyl lithiopropiolate to 11b
Entry
Base
Lewis acid
12b1112b2 (%)
12b1:12b2
Aldehyde 7, readily available from (2)-tartaric acid in ®ve
steps according to a known procedure,14 reacted with
phenylmagnesium bromide without any puri®cation to
yield the addition product diastereoisomers 8a and 8b
(ratio of 8a/8bˆ1:1), which could be separated by column
chromatography. The absolute con®gurations of newly
formed stereogenic centers were assigned after being
transformed, respectively, to target compounds later on.
Monosilylation of 8a and 8b, and then hydrogenation on
1
2
n-BuLi
LDA
Ycl3 (0.1 equiv.)
±
40
69
1:1
1.2:1
stereoselectivity using urea hydrogen peroxide with poly-
leucine as the catalyst to give a chiral epoxide.13 Here we
would like to report in detail the synthesis of four isomers of
Goniofufurone (Scheme 1).
Scheme 3. Reagents and conditions: (a) PhMgBr/THF, 2788C, 2 h, then rt 12 h; (b) TBSCl, imidazole/DMF, rt 1 day; (c) H2, Pd±C/ethyl acetate, 458C, 6 h;
i
(d) Dess±Martin periodanane/CH2Cl2 1 h; (e) ethyl propiolate, 2 M BuLi, Pr2NHTHF, 2788C, 12 h; (f) MOMCl, (iPr)2NEt/CH2Cl2, 408C, 24 h; (g) H2,
Lindlar cat./ethyl acetate, 308C, 3 days; (h) 1 M HCl/MeOH, re¯ux, 12 h; (i) DBU/THF, rt, 1 day.

Y.-L. Su et al. / Tetrahedron 57 (2001) 2147±2153
2149
Pd±C, followed by Dess±Martin oxidation, gave the key
intermediate aldehydes 11a and 11b.15
Without further puri®cation the aldehydes were treated,
respectively, with ethyl lithiopropiolate16 immediately to
give addition products 12a17 and 12b1112b2, respectively.
The results in Table 1 show that 12a was obtained in very
low yield when ethyl lithiopropiolate was used. But when a
mixture of Lewis acid YCl3 and aldehyde 11a was added
into the ethyl lithiopropiolate at 2788C dropwise, 60% yield
could be given in two steps. When LDA instead of n-BuLi
was used as a base in the absence of YCl3, 12a could be
obtained in 79% in two steps.
In contrast with 11a the addition reaction to 11b generated a
pair of diastereoisomers 12b1 and 12b2 with poor stereo-
selectivity. Once again LDA was the most effective base
with 69% yield of 12b in two steps, 12b1/12b2ˆ1.2:1
(Table 2).
Methoxymethylation of the secondary alcohol 12a and 12b2
followed by hydrogenation on Lindlar catalyst afforded 14a
and 14b, respectively.
Exposure of 14b to 1 M HCl7 yielded a crystalline product,
trihydroxybutenolide 15b, which underwent an intramole-
cular Michael-type cyclization induced by DBU to form
(1)-7-epi-Goniofufurone 2 as colorless plates. It is
interesting that when treatment of 14a with 1 M HCl 15a,
which could also be converted to 1 with DBU, and (1)-
Goniofufurone 1 could be obtained simultaneously (ratio
of 15a:1ˆ3:2) (Scheme 3). All spectroscopic data of 1
and 2 are in accord with those of the natural compound
including the sign of the optical rotation2b: 1 [a]25 ˆ19.0
D
(C 0.2 EtOH),{1 lit. [a]22 ˆ19.0 (C 0.5 EtOH)}; 2
D
[a]25 ˆ1106 (C 0.1 EtOH), {2 lit. [a]22 ˆ1103 (C 1.0
D
D
Figure 1.
EtOH)}.
Using the same strategy we have also obtained (2)-
Goniofufurone ent-1 and (2)-7-epi-Goniofufurone ent-2
from l-(1)-tartaric acid (Scheme 3). The spectroscopic
data of ent-1 and ent-2 are in accord with 1 and 2. The
H±H COSY spectrum of ent-1 showed that the coupling
constant J4/5 is 4.2 Hz indicating that 3-H and 4-H must
be cis to each other. Similarly, 7-H and 8-H (J7/8ˆ2.7 Hz)
are cis to each other. Finally, the above structural elucida-
tion of ent-1 and ent-2 were con®rmed by X-ray crystal-
lographic analysis (Fig. 1).18
4. Experimental
4.1. General
All reactions were followed by TLC on precoated silica gel
plate HSGF254 (Yantai chemical) developed with
petroleum ether (PE)/ethyl acetate (EA). Column chromato-
graphy was performed on silica gel 300±400 m (Yantai
chemical). All solvents were re¯uxed and distilled under
N2 from sodium benzophenone ketyl (THF, Et2O) or CaH2
(CH2Cl2, iPr2NH).
The optical rotation: ent-1 [a]25 ˆ210.2 (C 1.67 EtOH).
D
{1 lit. [a]22 ˆ19.0 (C 0.5 EtOH)}; ent-2 [a]25 ˆ2106 (C
Optical rotations were taken with a Perkin±Elmer 241
Autopol Polarimeter. IR spectra were measured on Digital
FTIR spectrophotometer and reported in wave numbers
D
D
0.3 EtOH) {2 lit. [a]22 ˆ1103 (C 1.0 EtOH)}.
D
(cm21). H NMR spectra were obtained on Bruker AMX-
1
300 or DRX-400 machines and reported in d units from
internal TMS. Mass spectra were measured with a Finnigan
MAT-95 spectrometer. Elemental analyses were performed
on Carlo-ERBA 1106.
3. Conclusion
In summary, (1)-Goniofufurone 1 and (1)-7-epi-Gonio-
fufurone 2 were synthesized from aldehyde 7 in nine
steps with an overall 11% yield. The unnatural
enantiomers of these styryl lactones can also be
prepared from natural l-(1)-tartaric acid for biological
evaluation.
Procedures for the syntheses of target compounds 1 and 2
from d-(2)-tartaric acid are described in detail as follows.
Their enantiomers ent-1 and ent-2 were synthesized from
l-(1)-tartaric acid using the same procedures.

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Y.-L. Su et al. / Tetrahedron 57 (2001) 2147±2153
4.1.1. 4-Hydroxy-4-phenyl-2S,3S-O-isopropylidene-butyl
benzyl ether 8a(4R), 8b(4S). The Grignard reagent
PhMgBr (1 M, 36 ml) was added to a solution of compound
7 (8.0 g, 32 mmol) in THF (30 ml) at 2788C. The mixture
was stirred at 2788C for 2 h and left to stand overnight at
room temperature to ensure reaction completion. Saturated
aqueous NH4Cl (30 ml) was added, the reaction mixture was
extracted with ether, washed with water and brine, the
combined organic layer was washed with brine and dried,
before being concentrated. The residue was puri®ed by ¯ash
column chromatography (PE/EAˆ5:1) to afford 8a and 8b,
8a/8bˆ1:1 (7.36 g, 70%).
8.67%); [a]25 ˆ138 (C 5.9 CHCl3); nmax (liquid ®lm):
D
3032, 2931, 2859, 1604, 1496, 1379, 1369, 1087 cm21; dH
(300 MHz, CDCl3) 20.08 (3H, s, tBuSiMe2O), 0.03 (3H, s,
tBuSiMe2O), 0.83 (9H, s, tBuSiMe2O), 1.20 (3H, s, Me2C),
1.44 (3H, s, Me2C), 3.22 (2H, d, Jˆ4.5 Hz, CH2OBn), 3.89
(1H, dd, Jˆ5.4, 8.4 Hz, CHOiPr), 3.97 (1H, dt, Jˆ4.5,
8.4 Hz, CHOiPr), 4.40 (1H, d, Jˆ12.4 Hz, PhCHaHbO),
4.50 (1H, d, Jˆ12.4 Hz, PhCHaHbO), 4.79 (1H, d,
Jˆ5.4 Hz, PhCHOTBS), 7.21±7.36 (10H, m, 2£Ph); m/z
(%): 428 (M1-CH3, 0.54), 221 (PhCHOTBS, 44.05), 115
(6.37), 91 (100), 73 (24.95).
4.1.3. 4-t-Butyldimethlsiloxy-4-phenyl-2S, 3S-O-isopro-
pylidene-butanol 10a(4R), 10b(4S). Compound 9a
(1.92 g, 4.33 mmol), 5% Pd±C (600 mg) in ethyl acetate
(100 ml) was stirred under a H2 atmosphere (1 atm) at
458C for 6 h. The reaction mixture was ®ltered over celite,
and concentrated in vacuo. The residue was puri®ed by ¯ash
column chromatography (PE/EAˆ10:1) to afford 10a
(1.480 g, 97%).
8a 3.16 g, yield 35%, colorless needles, mp 56.2^0.38C;
(Found: C, 73.19; H, 7.49. C20H24O4 requires C, 73.14; H,
7.38%); [a]25 ˆ27.49 (C 4.1 CHCl3); nmax (KBr): 3420,
D
3025, 2985, 2893, 1601, 1493, 1384, 1373, 1103,
1038 cm21; dH (400 MHz, CDCl3) 1.40 (3H, s, Me2C),
1.44 (3H, s, Me2C), 2.96 (1H, d, Jˆ2.0 Hz, OH), 3.08
(2H, d, Jˆ4.7 Hz, CH2OBn), 4.03 (1H, dd, Jˆ8.1, 5.0 Hz,
CHOiPr), 4.22 (1H, dt, Jˆ4.7, 8.1 Hz, CHOiPr), 4.39 (2H, s,
CH2OCH2Ph), 4.92 (1H, d, Jˆ3.6 Hz, PhCHOH), 7.23±
7.36 (10H, m, 2£Ph); m/z (%): 313 (M1-CH3, 0.79), 221
(M1-OCH2Ph, 8.65), 107 (6.40), 91 (100).
10a colorless oil; Rf (PE/EAˆ12:1) 0.3; (Found: C, 64.50;
H, 9.23. C19H32O4Si requires C, 64.72; H, 9.17%);
[a]25 ˆ220.4 (C 0.9 CHCl3); nmax (liquid ®lm):
D
3481, 3033, 2932, 2859, 1604, 1496, 1380,, 1371,
1080, 1070, 1031 cm21; dH (300 MHz, CDCl3) 20.15
(3H, s, tBuSiMe2O), 0.07 (3H, s, tBuSiMe2O), 0.90 (9H, s,
tBuSiMe2O), 1.36 (3H, s, Me2C), 1.44 (3H, s, Me2C), 2.14
(1H, br, OH), 3.19±3.23 (1H, m, CHaHbOH), 3.45±3.49
(1H, m, CHaHbOH), 3.93 (1H, dd, Jˆ5.5, 7.7 Hz, CHOiPr),
4.23 (1H, ddd, Jˆ2.9, 5.0, 7.7 Hz, CHOiPr), 4.82 (1H, d,
Jˆ5.5 Hz, PhCHOTBS), 7.24±7.33 (5H, m, 2£Ph); m/z
(%): 352 (M1, 0.34), 337 (M1-CH3, 1.74), 221
(PhCHOTBS, 100), 131 (41.11), 91 (24.29).
8b 3.20 g, yield 35%, colorless oil. Rf (PE/EAˆ5:1) 0.55;
(Found: C,72.95; H, 7.52. C20H24O4 requires C, 73.14; H,
7.38%); [a]25 ˆ223.6 (C 4.5 CHCl3); nmax (liquid ®lm)
D
3453, 3032, 2988, 2870, 1604, 1496, 1381, 1371, 1086,
1048 cm21; dH (400 MHz, CDCl3) 1.44 (6H, s, Me2C),
2.91 (1H, d, Jˆ4.6 Hz, OH), 3.02±3.05 (2H, m,
CHaHbOBn), 3.12±3.16 (1H, m, CHaHbOBn), 4.02±4.06
(2H, m, 2£CHOiPr), 4.39 (2H, s, CH2OCH2Ph), 4.66±4.68
(1H, m, PhCHOH), 7.20±7.34 (10H, m, 2£Ph); m/z (%):
313 (M1-CH3, 1.43), 221 (M1-OCH2Ph, 13.78), 107 (6.02),
91 (100).
10b 4.11g, 91%, colorless oil; Rf (PE/EAˆ7:1) 0.24;
(Found: C, 64.49; H, 9.35. C19H32O4Si requires C, 64.72;
4.1.2. 4-t-Butyldimethylsiloxy-4-phenyl-2S,3S-O-isopro-
pylidene-butyl benzyl ether 9a(4R), 9b(4S). Compound
8a (2.0 g, 6.1 mmol), imidazole (1.4 g, 22 mmol) and
t-BuMe2SiCl (1.4 g, 9.3 mmol) in DMF (15 ml) were stirred
for 1 day, then poured into water (30 ml), extracted with
ether, washed with brine, dried, and concentrated in
vacuo. The residue was puri®ed by ¯ash column chromato-
graphy (PE/EAˆ10:1) to afford 9a (2.31 g, 85.4%).
H, 9.17%); [a]25 ˆ145 (C 3.1 CHCl3); nmax (liquid ®lm):
D
3472, 3034, 2931, 2859, 1604, 1496, 1380, 1371, 1098,
1068 cm21; dH (CDCl3) 20.05 (3H, s, tBuSiMe2O), 0.08
(3H, s, tBuSiMe2O), 0.89 (9H, s, tBuSiMe2O), 1.08 (3H, s,
Me2C), 1.38 (3H, s, Me2C), 3.38 (1H, dd, Jˆ4.7, 11.5 Hz,
CHaHbOH), 3.60 (1H, dd, Jˆ4.7, 11.5 Hz, CHaHbOH), 3.78
(1H, dt, Jˆ4.7, 8.3 Hz, CHOiPr), 3.98 (1H, dd, Jˆ5.3,
8.3 Hz, CHOiPr), 4.90 (1H, d, Jˆ5.3 Hz, PhCHOTBS),
7.24±7.35 (5H, m, 2£Ph); m/z (%): 352 (M1, 0.21), 337
(M1-CH3, 1.61), 221 (PhCHOTBS, 100), 131 (44.72), 91
(19.47).
9a colorless oil; Rf (PE/EAˆ10:1) 0.87; (Found: C, 70.66;
H, 8.87. C26H38O4Si requires C, 70.54; H, 8.67%);
[a]25 ˆ218 (C 4.6 CHCl3); nmax (liquid ®lm): 3033,
D
2931, 2858, 1604, 1496, 1379, 1369, 1095, 1069 cm21; dH
(300 MHz, CDCl3) 20.16 (3H, s, tBuSiMe2O), 0.05 (3H, s,
tBuSiMe2O), 0.88 (9H, s, tBuSiMe2O), 1.34 (3H, s, Me2C),
1.43 (3H, s, Me2C), 3.17 (1H, dd, Jˆ3.7, 10.3 Hz, CHaHbO),
3.25 (1H, dd, Jˆ2.3, 10.3 Hz, CHaHbO), 3.85 (1H, dd,
Jˆ5.2, 7.8 Hz, CHOiPr), 4.32±4.38 (1H, m, CHOiPr),
4.39 (1H, d, Jˆ12.4 Hz, PhCHaHbO), 4.46 (1H, d,
Jˆ12.4 Hz, PhCHaHbO), 4.81 (1H, d, Jˆ5.2 Hz,
PhCHOTBS), 7.22±7.34 (10H, m, 2£Ph); m/z (%): 428
(M1-CH3, 0.56), 221 (PhCHOTBS, 38.04), 91 (100), 73
(23.75).
4.1.4. Ethyl 7-t-butyldimethlsiloxy-7-phenyl-5S, 6S-O-
isopropylidene-4-hydroxy-heptyn-2-oate 12a(7R, 4S),
12b1(7S, 4R), 12b2(7S, 4S). Compound 10a (600 mg,
1.7 mmol) and Dess±Martin reagent (1.5 g, 3.5 mmol) in
CH2Cl2 (75 ml) were stirred for 1 h. Saturated aqueous
Na2S2O3 and NaHCO3 were added, followed by extraction
with ether, dried, and concentrated in vacuo. The residue
was puri®ed by ¯ash column chromatography (PE/
EAˆ10:1) to afford crude aldehyde 11a.
i
A reaction ¯ask was charged with THF (2 ml) and Pr2NH
(0.13 ml). The solution was cooled to 08C, and 2 M n-BuLi
(0.44 ml) was added and stirred for 0.5 h at rt. The solution
was cooled to 2788C and ethyl propiolate (0.06 ml,
9b 4.31 g, yield 88%, colorless oil; Rf (PE/EAˆ10:1) 0.75;
(Found: C, 70.45; H, 8.63. C26H38O4Si requires C, 70.54; H,

Y.-L. Su et al. / Tetrahedron 57 (2001) 2147±2153
2151
0.58 mmol) was added. After 1 h at 2788C, aldehyde 11a
(100 mg, 0.29 mmol) was added. After 12 h at 2788C the
reaction was stopped with sat. NH4Cl, then extracted with
ethyl acetate. The combined organic layer was washed with
brine, dried with Na2SO4, before being concentrated in
vacuo. The residue was puri®ed by ¯ash column chromato-
graphy (PE/EAˆ10:1) to afford 12a (81 mg, 79%).
nmax (liquid ®lm): 3033, 2933, 2240, 1717, 1604,
1496, 1381, 1370, 1065, 1029 cm21; dH (CDCl3) 20.16
(3H, s, tBuSiMe2O), 0.1 (3H, s, tBuSiMe2O), 0.89 (9H, s,
tBuSiMe2O), 1.26 (3H, t, Jˆ7.1 Hz, OCH2CH3), 1.39 (3H,
s, Me2C), 1.41 (3H, s, Me2C), 3.27 (3H, s, OCH2OCH3),
4.14 (1H, d, Jˆ3.4 Hz, CHOMOM), 4.14±4.46 (4H, buried
m, OCH2CH3 and CHOiPr), 4.34 (1H, dd, Jˆ3.4, 6.7 Hz,
CHOiPr),4.45 (1H, d, Jˆ6.7 Hz, PhCHOTBS), 4.80±4.89
(2H, m, OCH2OCH3), 7.25±7.36 (5H, m, Ph); m/z (%):
477 (M1-CH3, 1.09), 271 (M1-PhCH2OTBS, 3.56), 221
(100), 73 (73.79).
12a yellow oil; Rf (PE/EAˆ6:1) 0.4; (Found: C, 64.40; H,
8.57. C24H36O6Si: C, 64.25; H, 8.10%); nmax (liquid
®lm): 3458, 2933, 2859, 2241, 1717, 1496, 1382, 1371,
1087, 1066, 1030 cm21; dH (300 MHz, CDCl3) 20.13
(3H, s, tBuSiMe2O), 0.09 (3H, s, tBuSiMe2O), 0.92 (9H, s,
tBuSiMe2O), 1.30 (3H, t, Jˆ7.1 Hz, OCH2CH3), 1.41 (3H,
s, Me2C), 1.48 (3H, s, Me2C), 3.97 (1H, d, Jˆ10 Hz,
CHOH), 4.14 (1H, dd, Jˆ5.6, 7.6 Hz, CHOiPr), 4.23 (2H,
q, Jˆ7.1 Hz, OCH2CH3), 4.27±4.33 (1H, m, CHOiPr), 4.83
(1H, d, Jˆ5.6 Hz, PhCHOTBS), 7.26±7.39 (5H, m, 2£Ph);
m/z (%): 448 (M1, 0.98), 434 (M111-CH3, 1.98), 221
(PhCHOTBS, 100), 115 (9.05), 91 (9.79), 73 (41.79).
13b yield 73%, colorless oil. Rf (PE/EAˆ10:1) 0.35;
(Found: C, 63.59; H, 8.36. C26H40O7Si requires C, 63.38;
H, 8.20%); [a]25 ˆ233.3 (C 1.8 CHCl3); nmax (liquid
D
®lm): 2933, 2859, 2243, 1718, 1604, 1494, 1380,
1370, 1097, 1068, 1032 cm21; dH (300 MHz, CDCl3)
20.1 (3H, s, tBuSiMe2O), 0.1 (3H, s, tBuSiMe2O), 0.9
(9H, s, tBuSiMe2O), 1.22 (3H, s, Me2C), 1.27 (3H, t,
Jˆ7.1 Hz, OCH2CH3), 1.45 (3H, s, Me2C), 3.29 (3H, s,
OCH2OCH3), 3.98 (1H, dd, Jˆ2.5, 8.3 Hz, CHOiPr),
4.14±4.26 (3H, buried m, OCH2CH3 and CHOiPr), 4.18
(1H, d, Jˆ2.5 Hz, CHOMOM), 4.51 (1H, d, Jˆ6.9 Hz,
PhCHOTBS), 4.82±4.89 (2H, m, OCH2OCH3), 7.29±7.34
(5H, m, Ph); m/z (%): 477 (M1-CH3, 0.95), 436 (M111-
MOM, 3.17), 271 (M1-PhCH2OTBS, 2.46), 221 (100), 115
(13.92), 91 (87.83), 73 (64.57).
12b1 32 mg, yield 37.4%, yellow oil. Rf (PE/EAˆ10:1)
0.42; [a]25 ˆ143.7 (C 1.5 CHCl3); nmax (liquid ®lm):
D
3404, 3034, 2933, 2859, 2241, 1717, 1604, 1496, 1381,
1371, 1088, 1067 cm21; dH (300 MHz, CDCl3) 20.01
(3H, s, tBuSiMe2O), 0.11 (3H, s, tBuSiMe2O), 0.91 (9H, s,
tBuSiMe2O), 1.06 (3H, s, Me2C), 1.30 (3H, t, Jˆ7.1 Hz,
OCH2CH3), 1.41 (3H, s, Me2C), 3.81 (1H, dd, Jˆ3.4,
8.3 Hz, CHOiPr), 3.98 (1H, d, Jˆ10.7 Hz, CHOH), 4.23
(2H, q, Jˆ7.1 Hz, OCH2CH3), 4.35 (1H, dd, Jˆ4.6,
8.3 Hz, CHOiPr), 4.42 (1H, dd, Jˆ3.4, 10.7 Hz, CHOH),
5.06 (1H, d, Jˆ4.6 Hz, PhCHOTBS), 7.26±7.39 (5H, m,
2£Ph); m/z (%): 434 (M111-CH3, 0.90), 221 (PhCHOTBS,
100), 115 (11.73), 91 (9.01), 73 (53.59).
4.1.6. Ethyl 7-t-butyldimethlsiloxy-7-phenyl-5S, 6S-O-iso-
propylidene-4-O-methoxymethyl-hepten-2Z-oate 14a(7R,
4S), 14b(7S, 4S). A suspension of Lindlar catalyst
(18 mg) in a solution of 13a (339 mg, 0.69 mmol) and quin-
oline (3.4 ml) in ethyl acetate (4.5 ml) were stirred under H2
atmosphere (1 atm) at 308C for 3 days. The mixture was
®ltered over celite and concentrated in vacuo. The crude
product was puri®ed by column chromatography (PE/
EAˆ10:1) to give 14a (319 mg, 91%).
12b2 27 mg, 31.6%, yellow oil. Rf (PE/EAˆ10:1) 0.27; nmax
(liquid ®lm): 3424, 3034, 2933, 2859, 2243, 1717, 1495,
1381, 1371, 1085, 1069, 1031 cm21; dH (300 MHz,
CDCl3) 20.04 (3H, s, tBuSiMe2O), 0.08 (3H, s, tBuSi-
Me2O), 0.90 (9H, s, tBuSiMe2O), 1.14 (3H, s, Me2C), 1.24
(3H, t, Jˆ7.1 Hz, OCH2CH3), 1.42 (3H, s, Me2C), 3.30 (1H,
d, Jˆ6.4 Hz, CHOH), 3.90 (1H, dd, Jˆ4.8, 8.2 Hz,
CHOiPr), 4.13 (1H, dd, Jˆ4.8, 8.2 Hz, CHOiPr), 4.20±
4.27 (3H, buried m, OCH2CH3 and CHOH), 4.95 (1H, d,
Jˆ4.8 Hz, PhCHOTBS), 7.1±7.5 (5H, m, Ph); m/z (%):
448(M1, 2.91), 434 (M111-CH3, 2.59), 221 (PhCHOTBS,
100), 115 (5.31), 91 (5.02), 73(18.86).
14a colorless oil, Rf (PE/EAˆ10:1) 0.42; [a]25 ˆ120.1 (C
D
1.8 CHCl3); nmax (liquid ®lm): 3030, 2933, 2859, 1720,
1651, 1496, 1380, 1370, 1089, 1064, 1031 cm21; dH
(300 MHz, CDCl3) 20.15 (3H, s, tBuSiMe2O), 0.06
(3H, s, tBuSiMe2O), 0.89 (9H, s, tBuSiMe2O), 1.27 (3H,
t, Jˆ7.1 Hz, OCH2CH3), 1.62 (3H, s, Me2C), 1.66 (3H,
s, Me2C), 3.24 (3H, s, OCH2OCH3), 4.10±4.23 (3H,
m, OCH2CH3 and CHOiPr), 4.30 (1H, d, Jˆ6.6 Hz,
OCHaHbOCH3), 4.34 (1H, t, Jˆ5.8 Hz, CHOiPr), 4.47
(1H, d, Jˆ6.6 Hz, OCHaHbOCH3), 4.85 (1H,d, Jˆ3.6 Hz,
PhCHOTBS), 5.09 (1H, dd, Jˆ5.8, 9.0 Hz, CHOMOM),
5.59 (1H, d, Jˆ11.7 Hz, vCHCO2Et), 5.71 (1H, dd,
Jˆ9.0, 11.7 Hz, CHˆCHCO2Et), 7.23±7.35 (5H, m, Ph);
m/z (%): 479 (M1-CH3, 0.96), 378 (M111-OTBS, 1.19),
221 (75.97), 91 (11.39), 73 (71.49).
4.1.5. Ethyl 7-t-butyldimethlsiloxy-7-phenyl-5S, 6S-O-iso-
propylidene-4-O-methoxymethyl-heptyn-2-oate 13a(7R,
4S), 13b(7S, 4S). To stirred solution of 12a (1.1 g,
2.45 mmol) in CH2Cl2 (15 ml) were added iPr2NEt
(0.8 ml, 4.9 mmol) and MOMCl (0.35 ml, 4.4 mmol) at
08C. The reaction mixture was stirred for 24 h at 408C.
After addition of a saturated aqueous solution of NH4Cl it
was extracted with CH2Cl2 (100 ml). The extract was
washed with brine and dried over Na2SO4. Evaporation of
the solvent gave a residue, which was puri®ed by column
chromatography (PE/EAˆ10:1) to give 13a.
14b 200 mg, yield 99%, colorless oil, Rf (PE/EAˆ9:1) 0.50;
[a]25 ˆ29.7 (C 1.8 CHCl3); nmax (liquid ®lm): 3030, 2956,
D
2933, 1719, 1652, 1494, 1380, 1369, 1099, 1032 cm21; dH
(300 MHz, CDCl3) 20.16 (3H, s, tBuSiMe2O), 0.05 (3H, s,
tBuSiMe2O), 0.90 (9H, s, tBuSiMe2O), 1.29 (3H, t,
Jˆ7.2 Hz, OCH2CH3), 1.34 (3H, s, Me2C), 1.42 (3H, s,
Me2C), 3.35 (3H, s, OCH2OCH3), 3.92 (1H, dd, Jˆ3.3,
7.8 Hz), 4.15±4.25 (2H, m), 4.35 (1H, dd, Jˆ2.8, 7.8 Hz),
4.60 (1H, d, Jˆ6.7 Hz, OCHaHbOCH3), 4.66 (1H, d,
13a 882 mg, yield 73%, colorless oil, Rf (PE/EAˆ10:1)
0.47; (Found: C, 63.39; H, 8.34. C26H40O7Si requires
C, 63.38; H, 8.20%); [a]25 ˆ122.9 (C 1.5 CHCl3);
D

2152
Y.-L. Su et al. / Tetrahedron 57 (2001) 2147±2153
Jˆ6.7 Hz, OCHaHbOCH3), 4.76 (1H, d, Jˆ3.3 Hz,
PhCHOTBS), 5.34 (1H, ddd, Jˆ0.8, 2.8, 9.0 Hz,
CHOMOM), 5.93 (1H, dd, Jˆ0.8, 11.7 Hz, ˆCHCO2Et),
6.15 (1H, dd, Jˆ9.0, 11.7 Hz, CHvCHCO2Et), 7.22±7.37
(5H, m, Ph); dc (75 MHz, CDCl3) 25.02, 24.60, 14.23,
18.30, 25.82, 25.90, 27.13, 27.29, 55.73, 60.38, 71.70,
74.54, 79.16, 82.02, 95.32, 109.80, 123.26, 127.23,
127.44, 127.54, 127.88, 128.10, 141.71, 144.48, 165.49;
m/z (%): 479 (M1-CH3, 1.51), 221 (67.56), 91 (11.84), 73
(55.94).
unsaturated lactone 15b (8 mg, 0.032 mmol) in dry 18 ml
THF containing 0.05% (v/v) DBU was stirred at room
temperature for 24 h. The solution was diluted with ethyl
acetate and washed with water, dried with Na2SO4, concen-
trated in vacuo, the residue was puri®ed by ¯ash column
chromatography (PE/EAˆ1:1) to give 2 (4 mg, 50%).
2 white solid, mp 197.5^0.38C. Rf (PE/EAˆ3:1) 0.39;
[a]25 ˆ1106 (C 0.1 EtOH). nmax (KBr): 3450, 3380,
D
3300, 3032, 2926, 2850, 1759, 1640, 1496, 1455, 1351,
1255, 1200, 1151, 1064, 1045, 1030 cm21; dH (300 MHz,
CDCl3) 2.67±2.83 (2H, m, CHaHbCv O), 4.24 (1H, t,
Jˆ3.5 Hz, CHCHOHPh), 4.43 (1H, d, Jˆ3.2 Hz, CHOH),
4.90 (1H, d, Jˆ4.4 Hz, CHOCvO), 5.08 (1H, d, Jˆ3.8 Hz,
PhCHOH), 5.10±5.14 (1H, m, CHCHaHb), 7.33±7.45 (5H,
m, Ph); m/z (%): 251 (M1, 1.53), 233 (M1H±H2O, 40.01),
215 (M1H±2H2O, 8.24), 126 (39.14), 107 (89.99), 97
(12.70), 73 (100). HRMS calcd for C13H14O5(M1):
250.0841, Found: 250.0812.
4.1.7. 7R-Pheny-5S, 6S, 7R-trihydroxy-hept-2-enono-g-
lactone 15a, (1)-goniofufurone 1, 7S-pheny-5S, 6S, 7S-
trihydroxy-hept-2-enono-g-lactone 15b. A solution of
the 14a (50 mg) in 1 M HCl (0.4 ml) and MeOH (1 ml)
was stirred at 608C for 1 day. The mixture was diluted
with ethyl acetate and washed with water and brine, dried
with Na2SO4, concentrated in vacuo to leave a residue,
which was puri®ed by column chromatography (PE/
EAˆ1:1) and then gave 1 (8 mg), 15a (12 mg), total yield
80%.
References
15a white solid; Rf (PE/EAˆ1:3) 0.17; nmax (KBr): 3420,
3100, 1735, 1600, 1496, 1179, 1108, 1040, 1050 cm21; dH
(300 MHz, CD3COCD31D2O) 3.69 (1H, dd, Jˆ2.0, 7.9 Hz,
CHOH), 4.09 (1H, dd, Jˆ2.0, 5.6 Hz, CHOH), 4.79 (1H, d,
Jˆ7.9 Hz, PhCHOH), 5.26 (1H, dt, Jˆ1.7, 5.6 Hz,
vCHOCvO), 6.14 (1H, dd, Jˆ2.0, 5.7 Hz, vCHCO2),
7.22±7.46 (5H, m, Ph), 7.81 (1H, dd, Jˆ1.7, 5.7 Hz,
vCH); m/z (%): 251(M1H, 0.23), 215 (M1H-2H2O,
4.79), 126 (29.18), 107 (100), 97 (17.68), 79 (58.02).
HRMS calcd for C13H13O4 (M1H±H2O) 233.0814, Found:
233.0798.
1. Jewers, K.; Davis, J. B.; Dougan, J.; Manchanda, A. H.;
Blunden, G.; Kyi, A.; Wetchapinan, S. Phytochemistry
1972, 11, 2025.
2. (a) Fang, X. P.; Anderson, J. E.; Chang, C. J.; Mclaughlin, J. L.
J. Chem. Soc., Perkin Trans. 1 1990, 1655. (b) Fang, X. P.;
Anderson, J. E.; Chang, C. J.; Mclaughlin, J. L. J. Nat. Prod.
1991, 54, 1034. (c) EI-Iayat, A. L.; Ferrigini, N. R.; Mclaud,
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(d) Alkofahi, A.; Ma, W. W.; Mekenzie, M. T.; Byrn, S. R.;
Mclaughlin, J. L. J. Nat. Prod. 1989, 52, 1371.
1 white solid, mp 152±1548C. Rf (PE/EAˆ3:1) 0.23;
3. (a) Bermejo, A.; Blazquez, M. A.; Rao, K. S.; Cores, D.
Phytochemistry 1998, 47, 1375. (b) Cao, Sh. G.; Wu, X. H.;
Sim, K. Y.; Tan, B. K. H.; Pereira, J. T.; Goh, S.-H.
Tetrahedron 1998, 54, 2143.
[a]25 ˆ19.0 (C 0.2 CHCl3); nmax (KBr): 3411, 3344,
D
3030, 3004, 2866, 1758, 1606, 1497, 1452, 1351, 1270,
1193, 1160, 1068, 1049, 1037 cm21; dH (300 MHz,
CDCl3) 2.69 (1H, d, Jˆ18.8 Hz, CHaHbCvO), 2.75 (1H,
dd, Jˆ5.4, 18.8 Hz CHaHbCvO), 2.88 (1H, d, Jˆ3.1 Hz,
CHOH), 4.07 (1H, dd, Jˆ2.8, 4.8 Hz, CHCHOHPh), 4.17
(1H, d, Jˆ2.9 Hz, PhCHOH), 4.40 (1H, br. s, CHOH-
CHOCvO), 4.86 (1H, d, Jˆ4.2 Hz, CHOCvO), 5.09±
5.13 (1H, m, CHCHaHb), 5.18 (1H, dd, Jˆ2.8, 4.5 Hz,
PhCHOH), 7.3±7.5 (5H,m, Ph); dc (75 MHz, CD3COCD3)
36.13, 71.47, 74.04, 77.64, 84.68, 88.27, 127.36, 127.72,
128.40, 143.23, 176.18; m/z (%): 251(M1H, 0.51), 233
(M1H±H2O, 5.54), 126 (48.76), 107 (93.56), 97 (12.07),
79 (100).
4. Blazquez, M. A.; Bermijo, A.; Zafra-Polo, M. C.; Cortes, D.
Phytochem. Anal. 1999, 10, 161.
È
5. (a) Gracza, T.; Jager, V. Synthesis 1994, 1359. (b) Cagnolini,
C.; Ferri, M.; Jones, P. R.; Murphy, P. J.; Ayres, B.; Cox, B.
Tetrahedron 1997, 53, 4815. (c) Prakash, K. R. C.; Rao, S. P.
Tetrahedron 1993, 49, 6695.
6. (a) Mereyala, H. B.; Gadikota, R. R.; Maju, J.; Arora, S. K.;
Dastida, S. G.; Agarwal, S. Bioorg. Med. Chem. 1999, 7, 2095.
(b) Shing, T. K. M.; Tsui, H. J.; Zhou, Z. H. Tetrahedron 1992,
48, 8659.
7. Shing, T. K. M.; Tsui, H.-C.; Zhou, Z.-H. J. Org. Chem. 1995,
60, 3121.
15b, yield 56.0%. nmax (liquid ®lm): 3541, 3443, 3225,
2913, 1793, 1750, 1596, 1494, 1161, 1106, 1074,
1034 cm21; dH (300 MHz, CD3COCD31D2O) 3.43 (1H,
dd, Jˆ1.5, 6.5 Hz, CHOH), 4.02 (1H, dd, Jˆ1.5, 7.9 Hz,
CHOH), 4.95 (1H, d, Jˆ7.9 Hz, PhCHOH), 5.35 (1H,dt,
Jˆ1.7, 6.5 Hz, vCHOCvO), 6.31 (1H, dd, Jˆ2.0,
5.8 Hz, vCHCO2), 7.20±7.49 (5H, m, Ph), 8.03 (1H, dd,
Jˆ1.7, 5.8 Hz, vCH); m/z (%): 233 (M1H±H2O, 0.65), 215
(M1H±2H2O, 2.44), 126 (39.13.40), 107 (100), 97 (9.15),
79 (73.49). HRMS calcd for C13H13O4 (M1H±H2O)
233.0814, Found: 233.0800.
8. Zhi-Cai, Yang; Wei-Shai, Zhou Heterocycles 1997, 45, 367.
9. Bruns, R.; Wernicke, A.; Koll, P. Tetrahedron 1999, 55, 9793.
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11. Yi, X.-H.; Meng, Y.; Hui, X. G.; Li J. Org. Chem. 1998, 63,
7472.
12. Surivet, J. P.; Vatele, J. M. Tetrahedron 1999, 55, 13011.
13. Chen, W. P.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1
1999, 103.
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687. (b) Mukaiyama, T.; Suzuki, K.; Yamada, T.; Tabusa, F.
Tetrahedron 1990, 46, 265.
4.1.8. (1)-8-epi-Goniofufurone 2. A solution of the
15. Dess, D.; Martin, J. J. Org. Chem. 1983, 48, 4155.

Y.-L. Su et al. / Tetrahedron 57 (2001) 2147±2153
2153
16. (a) Bachmann, W. E.; Raunio, E. K. J. Am Chem. Soc. 1950,
72, 2533. (b) Herrmann, J. L.; Berger, M. H.; Schlessinger,
R. H. J. Am. Chem. Soc. 1979, 101, 1544. (c) Midland, M. M.;
Tramontano, A.; Cable, J. R. J. Org. Chem. 1980, 50, 28.
17. There is small amount of its diastereoisomer in isolated 12a
18. The crystallographic data (excluding structure factors) for the
structures of compounds ent-1 and ent-2 reported in this paper
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC
150288 and CCDC 150287, respectively. Copies of the data
can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: (144)1223-336-
033; e-mail: deposit@ccdc.cam.ac.uk).
1
based on its H NMR spectrum at dH 1.30 (t, Jˆ7.1 Hz) and
4.24 (q, Jˆ7.1 Hz), which is hard to separate by column
chromatography.