Synthesis of the syributins and formal total synthesis of syringolide 1

Article abstract of DOI:10.1071/ch99170

A synthesis of syributins 1 (5) and 2 (6) from D-glyceraldehyde acetonide (12) and furans (14) and (15) is described. Compounds (5) and (6) are cometabolites of the novel non-proteinaceous C-glycosidic elicitor molecules the syringolides 1 (1) and 2 (2). Under a variety of acidic conditions, the intermediate butenolides (9) and (10) provided syributins 1 (5) and 2 (6). Similar results have been reported by Honda and coworkers who converted butenolide (20) into syringolide 1 (1). Since compound (20) was also synthesized by the present new route, a formal synthesis of syringolide 1 (1) has been achieved. CSIRO 2000.

Full text of DOI:10.1071/ch99170

C S I R O P U B L I S H I N G
Australian Journal
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Volume 53, 2000
© CSIRO 2000
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Aust. J. Chem., 2000, 53, 327–331
Synthesis of the Syributins and
Formal Total Synthesis of Syringolide 1*
Romina Di FlorioA and Mark A. RizzacasaA,B
A School of Chemistry, The University of Melbourne, Vic. 3010.
B Author to whom correspondence should be addressed.
Asynthesis of syributins 1 (5) and 2 (6) from D-glyceraldehyde acetonide (12) and furans (14) and (15) is described.
Compounds (5) and (6) are cometabolites of the novel non-proteinaceous C-glycosidic elicitor molecules the
syringolides 1 (1) and 2 (2). Under a variety of acidic conditions, the intermediate butenolides (9) and (10) provided
syributins 1 (5) and 2 (6). Similar results have been reported by Honda and coworkers who converted butenolide
(20) into syringolide 1 (1). Since compound (20) was also synthesized by the present new route, a formal synthesis
of syringolide 1 (1) has been achieved.
Keywords. Amberlyst 15; butenolide; glyceraldehyde acetonide; synthesis; syributin; syringolide.
Introduction
In plants, resistance to microbial pathogens is known as
the hypersensitive response (HR) and this can be initiated by
signal or elicitor molecules produced by the pathogens. For
example, the bacterial pathogen Pseudomonas syringae pv.
tomato illicits a hypersensitive response on soybean plants
carrying the resistance gene Rpg4. In 1993, Sims and
coworkers reported the isolation of a novel pair of C-glyco-
side elicitor molecules, the syringolides 1 (1) and 2 (2), from
P. syringae pv. tomato.1 These compounds are the first low
molecular weight non-proteinaceous elicitor molecules to be
identified and represent a new class of natural product. The
biological activity of the syringolides as well as their novel
tricyclic ring system have made these compounds important
targets for synthesis and a number of total syntheses have
been reported.2–9
Along with the syringolides, a group of structurally
related compounds the secosyrins 1 (3) and 2 (4) and the
syributins 1 (5) and 2 (6) have also been isolated by Sims et
al.10 Although these compounds do not possess any elicitor
activity, they are important as they may provide clues to the
biosynthesis of the syringolides. Several syntheses of both
the syributins and secosyrins have also been reported.5,11–15
All the syntheses of the syringolides thus far rely on a
biomimetic-type cyclization as the key step. This involves an
acid-catalysed Michael cyclization of a ꢀ-keto butenolide
precursor (7) or its protected equivalent followed by ketal-
ization (Scheme 1). This cyclization provides the
syringolides in low yields as the major products.
butenolide precursor such as (8), which is structurally related
to the syributins, could cyclize to the secosyrins (path A) and
then onto the syringolides via a Michael addition followed
by Dieckmann-type condensation. However, if path C is fol-
lowed, the syributins would be produced. This would then
suggest that the secosyrins and syributins are a result of
decomposition of the syringolides and are not intermediates
in the biosynthesis.
Initially, we and others5 proposed that the secosyrins
could be converted into the syringolides via an intramolecu-
lar Claisen condensation (path B, Scheme 2). In turn, a
* Dedicated to Professor Don Cameron on the occasion of his 65th birthday.
Manuscript received 3 December 1999
© CSIRO 2000
10.1071/CH99170
0004-9425/00/040327

328
R. Di Florio and M. A. Rizzacasa
than that for t-butyldimethylsilyl-protected furan (14);
however, yields and stereoselectivities were not improved by
the use of other bases (ButLi or BusLi), large excesses of
anion or variations in solvent and temperature. Since the
aldehyde (12) is known to form a hydrate,19 it was freshly
distilled and dried over molecular sieves prior to use but this
protocol also did not improve yields. In one experiment, the
anion derived from (14) was quenched with MeOD and 92%
deuterium incorporation was detected by n.m.r. spec-
troscopy. This indicated that the anion was successfully gen-
erated and that the furan adducts were probably somewhat
unstable to the isolation or chromatographic purification
procedures.
We therefore targeted the acetonides (9) and (10) as pre-
cursors to (8) and it was envisaged that these compounds
could be synthesized in a rapid manner by addition of a
butenolide-equivalent furan anion (11)16,17 to aldehyde (12)
followed by acylation and desilylation to unveil the buteno-
lide system (Scheme 3). We now wish to report a new and
short synthesis of acetonides (9) and (10) which upon acid
treatment do not cyclize to the syringolides or secosyrins but
instead undergo 1,3-acyl migration to give the syributins.18
These results mirror those reported by other researchers5,11,12
and suggest that the syributins and secosyrins result from
degradation of the syringolides as shown in Scheme 2.
Results and Discussion
Acylation of the adducts (16) and (17) with either hex-
anoic or octanoic acid in the presence of dicyclohexyl-
carbodiimide and 4-dimethylaminopyridine gave the
butenolides (18) and (9) or (19) and (10) directly which were
now easily separable by silica gel flash chromatography. The
observed concomitant silyl group deprotection under mild
conditions suggests adducts (16) and (17) are indeed quite
labile. Acid treatment of the acetonides (9) and (10) then pro-
vided syributins 1 (5) and 2 (6) respectively which were
identical to the natural products in all respects (1H and 13C
n.m.r., [ꢁ]D, i.r., m.s.).5,10–12 Of all the acids tested,Amberlyst
Synthesis of Syributins 1 (5) and 2 (6)
The synthesis of acetonides (9) and (10) is shown in
Scheme 4. Treatment of the bromide (13) (synthesized in one
step from tetronic acid)16 with either t-butyldimethylsilyl or
triisopropylsilyl triflate and base provided the furans (14)16
and (15)17 as oils. Metal halogen exchange of (14) or (15)
with BuLi and addition of D-glyceraldehyde acetonide (12)19
provided the unstable furans (16) and (17) as a c. 1 : 1
mixture of isomers at C 1Ј. The yield for the addition reaction
using triisopropylsilyl furan (15) was significantly better

Synthesis of the Syributins
329
dropwise at 0°C. The reaction mixture was stirred at room temperature
for 1 h and light petroleum was added. The solution was then immedi-
ately washed with saturated aqueous NaHCO3, water, brine, then dried
(Na2SO4), filtered and concentrated. The crude furan was purified by
bulb-to-bulb distillation to yield the product (14) (4.00 g, 99%) as a
colourless oil, b.p. 70–90°C oven temp./0.1 mmHg (lit.16 70°C/0.07
mmHg). 1H n.m.r. ꢂ 0.24, s, 6H, Si(CH3)2; 0.96, s, 9H, C(CH3)3; 5.22,
d, J 1.0 Hz, 1H, H3; 6.84, d, J 1.0 Hz, 1H, H5. 13C n.m.r. ꢂ –4.9, 18.1,
25.4, 87.7, 100.4, 130.4.
15 ion exchange resin gave the best yields in both cases
(Table 1).
Table 1. Yields of syributins 1 (5) and 2 (6)
Conditions
2% HF/MeCN
Camphorsulfonic acid/MeOH
10% HCl/tetrahydrofuran
p-TsOH/MeOH
(5)
(6)
34%
51%
56%
81%
81%
—
—
51%
56%
81%
4-Bromo-2-(triisopropylsilyloxy)furan (15)
To a solution of 4-bromofuran-2(5H)-one (13) (1.70 g, 10.32 mmol)
in dry CH2Cl2 (14 ml) under argon and at 0°C was added freshly dis-
tilled triethylamine (2 ml, 14.40 mmol). After stirring for 1 min, triiso-
propylsilyl triflate (3.60 ml, 10.32 mmol) was added dropwise at 0°C.
The reaction mixture was stirred for 10 min, warmed up to room tem-
perature and stirred for a further 1.5 h, then diluted with petrol. The
aqueous phase was extracted with petrol and the combined organic frac-
tions were washed with saturated aqueous NaHCO3, water, brine, then
dried (Na2SO4), filtered and concentrated to give the crude furan which
was purified by bulb-to-bulb distillation to give the product (15) (3.14
g, 94%) as a colourless oil, b.p. 100–120°C oven temp./0.1 mmHg. 1H
n.m.r. ꢂ 1.06, d, J 7.0 Hz, 6H, SiCH(CH3)2; 1.23, sept, 1H, SiCH(CH3)3;
5.24, d, J 1.0 Hz, 1H, H3; 6.83, d, J 1.0 Hz, 1H, H5.
Amberlyst 15/MeOH
Formal Synthesis of Syringolide 1 (1)
Furan (17) was also converted into the known butenolide
(20) and its C 1Ј epimer by brief treatment with tetrabutyl-
ammonium fluoride at 0°C (Scheme 5). The physical and
spectroscopic data recorded for butenolide (20) were identi-
cal to those reported5 (1H and 13C n.m.r., [ꢁ]D, i.r., m.s.) and
the synthesis of this compound constitutes a formal total syn-
thesis of syringolide 1 (1) since Honda and coworkers con-
verted compound (20) into (1) by a five-step sequence.5
(1Ј S,2Ј R)-3-[2Ј,3Ј-(Isopropylidenedioxy)-1Ј-
(hexanoyloxy)propyl]but-2-en-4-olide (18) and (1Ј R,2Ј R)-3-[2Ј,3Ј-
(Isopropylidenedioxy)-1Ј-(hexanoyloxy)propyl]but-2-en-4-olide (9)
from t-Butyldimethylsilyl Compound (14)
To a solution of 4-bromo-2-(t-butyldimethylsilyloxy)furan (14)
(5.08 g, 22.26 mmol) in dry tetrahydrofuran (20 ml) was added BuLi
(10.70 ml, 26.75 mmol, 2.5 M) dropwise at –78°C. After stirring for 10
min at –78°C, freshly prepared and distilled 2,3-O-isopropylidene-D-
glyceraldehyde (12) (5.82 g, 44.72 mmol) in dry tetrahydrofuran (20
ml) was added by cannula. The mixture was stirred at –78°C for 1.5 h
then at 0°C for 40 min and quenched by the addition of ether and satu-
rated aqueous NaHCO3, and the aqueous layer was extracted with ether.
The combined organic fractions were washed with water, brine, then
dried, and the solvent removed under reduced pressure, the crude
product was purified by flash chromatography with 30% EtOAc/petrol
as eluent to yield furan (16) as a mixure of C 1Ј isomers (1.95 g, 27%)
which was used immediately in the next step.
Asolution of the alcohol (1.95 g, 5.94 mmol) and hexanoic acid (820
ꢃl, 6.53 mmol) in CH2Cl2 (15 ml) was stirred for 10 min and 4-di-
methylaminopyridine (72.5 mg, 0.59 mmol) was then added. The
mixture was then cooled to 0°C and treated with dicyclohexylcarbodi-
imide (1.35 g, 6.53 mmol) and stirred at 0°C for 30 min then at room
temperature for 1 h. The mixture was then diluted with petrol and fil-
tered through Celite and the filtrate was washed with 10% aqueous HCl,
saturated aqueous NaHCO3, water and brine, then dried (MgSO4) and
concentrated to give the crude butenolides. Purification by silica gel
chromatography with 30% EtOAc/petrol gave (18) (411 mg, 22%) as a
yellow oil, [ꢁ]2D3 +7.1 (c, 0.23 in CHCl3) (Found: C, 61.3; H, 7.3.
C16H24O6 requires C, 61.5; H, 7.7%). ꢄmax 2933, 2873, 1752 (CO), 1644,
1456, 1373, 1345, 1223, 1160, 1075, 1007, 885, 856 cm–1. 1H n.m.r. ꢂ
0.90, t, J 6.9 Hz, 3H, CH2CH3; 1.30, br m, 4H, 2×CH2; 1.35, s, 3H, CH3;
1.43, s, 3H, CH3; 1.64, br m, 2H, CH2; 2.38, t, J 7.5 Hz, 2H, COCH2;
3.84, dd, J 9.0, 4.5 Hz, 1H, H3aЈ; 4.14, dd, J 9.0, 6.0 Hz, 1H, H3bЈ; 4.37,
m, 1H, H2Ј; 4.87, dd, J 18.0, 1.8 Hz, 1H, H4a; 4.96, dd, J 18.0, 1.8 Hz,
1H, H 4b; 5.80, d, J 7.8 Hz, 1H, H1Ј; 6.01, q, J 1.5 Hz, 1H, H2. 13C
n.m.r. ꢂ 13.8, 22.2, 24.4, 24.9, 26.6, 31.1, 33.8, 66.7, 69.9, 71.7, 75.8,
110.7 (CMe2), 117.3 (C 2), 165.7 (C 3), 172.1 (C=O), 172.6 (C=O).
Further elution with 40% EtOAc/petrol gave the desired butenolide
(9) as a colourless oil (360 mg, 19%), [ꢁ]2D4 –18.6 (c, 0.42 in CHCl3),
lit.5 [ꢁ]2D6 –24.3 (c, 0.4 in CHCl3) (Found: C, 61.3; H, 7.8. Calc. for
C16H24O6: C, 61.5; H, 7.7%). ꢄmax 2956, 2931, 1776 (CO), 1741 (CO),
1641, 1453, 1369, 1344, 1220, 1154, 1114, 1069, 1040, 885, 852 cm–1.
1H n.m.r. ꢂ 0.90, t, J 6.6 Hz, 3H, CH2CH3; 1.25–1.33, br m, 4H, 2×CH2;
1.34, s, 3H, CH3; 1.44, s, 3H, CH3; 1.60, br m, 2H, CH2; 2.38, t, J 6.0
Hz, 2H, COCH2; 3.84, dd, J 9.0, 5.7 Hz, 1H, H3aЈ; 4.10, dd, J 9.0, 6.9
Conclusion
A short synthesis of both syributin 1 (5) and 2 (6) was
achieved from tetronic acid and D-glyceraldehyde acetonide
(12). In addition, a formal total synthesis of syringolide 1 (1)
was achieved; this involved the synthesis of the known
syringolide intermediate (20) from 2-silyloxyfuran (17).
Experimental
1H n.m.r. (300 MHz) and 13C n.m.r. (75.5 MHz) spectra were
recorded in (D)chloroform solution with chloroform as internal stan-
dard on a Varian Unity 300 instrument. Infrared spectra were recorded
on a Perkin–Elmer 938G infrared spectrophotometer. Low-resolution
mass spectra were determined on a JEOLAX-505H mass spectrometer.
High-resolution mass spectra were obtained on a Bruker 4.7T
BiOAPEX FTMS mass spectrometer. Microanalyses were carried out
at the University of Otago, Dunedin, New Zealand. Optical rotations
(deg cm2 g–1) were recorded for 1 ml solutions in a 10 cm microcell with
a Perkin–Elmer 141 polarimeter and a JASCO DIP-1000 digital
polarimeter. Analytical thin-layer chromatography was conducted on
aluminium-backed 2 mm thick silica gel 60 GF254 plates supplied by
Merck and chromatograms were visualized with a 20% w/w solution of
phosphomolybdic acid in ethanol. Flash chromatography was carried
out using Merck silica gel 60. Anhydrous tetrahydrofuran was distilled
from potassium metal and diethyl ether (ether) was distilled from
sodium metal. Petrol refers to petroleum spirits with b.p. 40–60°C. All
organic extracts were concentrated under reduced pressure.
4-Bromo-2-(t-butyldimethylsilyloxy)furan (14)
To a solution of 4-bromofuran-2(5H)-one (13) (2.40 g, 14.57 mmol)
and freshly distilled triethylamine (3.05 ml, 21.83 mmol) in dry CH2Cl2
(20 ml) was added t-butyldimethylsilyl triflate (4.34 ml, 18.92 mmol)

330
R. Di Florio and M. A. Rizzacasa
Hz, 1H, H 3bЈ; 4.37, m, 1H, H 2Ј; 4.83, dd, J 17.9, 1.5 Hz, 1H, H4a;
4.96, dd, J 18.0, 1.8 Hz, 1H, H 4b; 5.80, d, J 3.6 Hz, 1H, H 1Ј; 6.01, q, J
1.5 Hz, 1H, H2. 13C n.m.r. ꢂ 13.8, 22.2, 24.4, 24.8, 25.9, 31.2, 33.9,
65.3, 69.1, 71.7, 75.4, 110.4 (CMe2), 118.0 (C 2), 164.4 (C 3), 172.6
(2×C=O).
gave (18) (44 mg, 28%) and further elution with 40% EtOAc/petrol
gave (9) (45 mg, 29%), both as yellow oils.
Syributin 1 (5)
To a solution of the butenolide (9) (52.2 mg, 0.17 mmol) in dry
methanol (15 ml) was added Amberlyst 15 ion exchange resin (5.22 g).
The reaction mixture was left to stir at room temperature overnight,
then filtered through Celite and the filter cake was washed with
methanol. The methanol was removed under reduced pressure and the
residue was dissolved in ethyl acetate and the organic phase was
washed with saturated aqueous bicarbonate, water and brine and dried
(MgSO4). Removal of the solvent and purification of the crude product
by flash chromatography with 60% EtOAc/petrol as eluent gave
syributin 1 (5) as a pale yellow oil (37 mg, 81%), [ꢁ]2D4 +5.8 (c, 0.08 in
CHCl3), lit.11 [ꢁ]2D0 +6.0 (c, 0.8 in CHCl3), lit.5 [ꢁ]2D6 +6.8 (c, 0.5 in
CHCl3), lit.12 [ꢁ]2D0 +7.8 (c, 0.33 in CHCl3) (Found: MNa+ 295.1158.
Calc. for C13H20O6: MNa+ 295.1152). ꢄmax 3456 (OH), 2922, 2822,
2853, 1780 (CO), 1737 (CO), 1638, 1454, 1377, 1246, 1173, 1142,
1115, 1027, 900 cm–1. 1H n.m.r. ꢂ 0.90, t, J 6.6 Hz, 3H, CH2CH3; 1.31,
m, 4H, 2×CH2; 1.64, m, 2H, CH2; 2.36, t, J 7.6 Hz, 2H, COCH2CH2;
2.88, br s, 1H, OH; 3.05, br s, 1H, OH; 3.94, m, 1H, H4; 4.17, dd, J
11.7, 6.3 Hz, 1H, H5a; 4.34, dd, J 11.7, 5.1 Hz, 1H, H5b; 4.61, m, 1H,
H3; 4.89, dd, J 18.3, 1.8 Hz, 1H, H1a; 5.02, dd, J 18.3, 1.8 Hz, 1H, H1b;
6.08, q, J 1.8 Hz, 1H, H2Ј. 13C n.m.r. ꢂ 13.8, 22.2, 24.5, 31.2, 34.1, 64.7,
68.8, 71.5, 71.8, 116.6 (C 2Ј), 169.7 (C 2), 173.7 (C=O), 174.5 (C=O).
(1Ј S,2Ј R)-3-[2Ј,3Ј-(Isopropylidenedioxy)-1Ј-
(octanoyloxy)propyl]but-2-en-4-olide (19) and (1Ј R,2Ј R)-3-[2Ј,3Ј-
(Isopropylidenedioxy)-1Ј-(octanoyloxy)propyl]but-2-en-4-olide (10)
from t-Butyldimethylsilyl Compound (14)
A solution of the alcohol (16) (973 mg, 2.96 mmol) and octanoic
acid (854 ꢃl, 5.92 mmol) in CH2Cl2 (7.5 ml) was stirred for 15 min at
room temperature after which time 4-dimethylaminopyridine (36.2 mg,
0.30 mmol) was added. The mixture was then cooled to 0°C and treated
with dicylohexylcarbodiimide (672 mg, 3.25 mmol) and stirred at 0°C
for 30 min, then at room temperature for 1 h. The mixture was then
diluted with petrol and filtered through Celite and the filtrate was
washed with 10% aqueous HCl, saturated aqueous NaHCO3, water and
brine, then dried (MgSO4) and concentrated to give the crude buteno-
lides. Removal of the solvent and purification of the crude product by
flash chromatography with 40% EtOAc/petrol as eluent gave (19) as a
yellow oil (118 mg, 13%), [ꢁ]2D0 +1.63 (c, 1.37 in CHCl3) (Found: C,
63.4; H, 8.3. C18H28O6 requires C, 63.5; H, 8.3%). ꢄmax 2930, 2857,
1782 (CO), 1752 (CO), 1643, 1456, 1373, 1260, 1223, 1155, 1075,
1
1041, 886, 855 cm–1. H n.m.r. ꢂ 0.86, t, J 6.9 Hz, 3H, CH2CH3;
1.26–1.32, br m, 8H, 4×CH2; 1.41, s, 6H, C(CH3)2; 1.63, br m, 2H, CH2;
2.36, t, J 7.8 Hz, 2H, COCH2CH2; 3.81, dd, J 8.7, 4.5 Hz, 1H, H3aЈ;
4.10, dd, J 9.0, 6.7 Hz, 1H, H 3bЈ; 4.23, m, 1H, H 2Ј; 4.84, d, J 18.0 Hz,
1H, H 4a; 4.93, dd, J 18.0, 1.8 Hz, 1H, H4b; 5.41, d, J 8.1 Hz, 1H, H1Ј;
5.99, q, J 1.5 Hz, 1H, H 2. 13C n.m.r. ꢂ 13.9, 22.5, 24.8, 24.9, 26.6, 28.7,
29.0, 31.5, 33.9, 66.7, 70.0, 71.7, 75.9, 110.7 (CMe2), 117.35 (C 2),
165.7 (C 3), 172.1 (C=O), 172.6 (C=O).
Further elution with 50% EtOAc/petrol gave (10) (184 mg, 21%) as
a pale yellow oil, [ꢁ]2D1 –25.0 (c, 0.38 in CHCl3) (Found: C, 63.3; H, 8.3.
C18H28O6 requires C, 63.5; H, 8.3%). ꢄmax 2920, 1782 (CO), 1746 (CO),
1644, 1455, 1372, 1222, 1153, 1069, 851 cm–1. 1H n.m.r. ꢂ 0.87, t, J 7.2
Hz, 3H, CH2CH3; 1.26–1.35, br m, 8H, 4×CH2; 1.42, s, 6H, C(CH3)2;
1.62, br m, 2H, CH2; 2.38, t, J 6.9 Hz, 2H, COCH2CH2; 3.78, dd, J 9.0,
5.4 Hz, 1H, H 3aЈ; 4.06, dd, J 8.7, 6.9 Hz, 1H, H3bЈ; 4.36, m, 1H, H2Ј;
4.83, dd, J 18.0, 1.8 Hz, 1H, H 4a; 4.92, dd, J 18.0, 1.5 Hz, 1H, H 4b;
5.79, d, J 3.9 Hz, 1H, H 1Ј; 6.04, q, J 1.5 Hz, 1H, H 2. 13C n.m.r. ꢂ 13.9,
22.5, 24.8, 25.0, 25.9, 28.8, 29.0, 31.6, 44.0, 65.2, 69.0, 71.7, 75.4,
110.4 (CMe2), 118.0 (C 2), 164.4 (C 3), 172.6 (C=O).
Syributin 2 (6)
To a solution of the butenolide (10) (184 mg, 0.54 mmol) in dry
methanol (48 ml) was added Amberlyst 15 ion exchange resin (18.4 g).
The reaction mixture was left to stir at room temperature overnight,
then filtered through Celite and the filter cake was washed with
methanol. The methanol was removed under reduced pressure and the
residue was dissolved in EtOAc and the organic phase was washed with
saturated aqueous NaHCO3, water and brine and dried (MgSO4).
Removal of the solvent and purification of the crude product by flash
chromatography with 60% EtOAc/petrol as eluent gave syributin 2 (6)
(130 mg, 80%) as a pale yellow oil, [ꢁ]2D2 +4.3 (c, 0.32 in CHCl3), lit.12
[ꢁ]1D7 +5.9 (c, 0.18 in CHCl3) (Found: MNa+ 323.1456. Calc. for
C15H24O6: MNa+ 323.1464). ꢄmax 3414 (OH), 2926, 2856, 1780 (CO),
1742 (CO), 1682, 1640, 1454, 1378, 1262, 1168, 1111, 1066, 1027, 890
cm–1. 1H n.m.r. ꢂ 0.88, t, 3H, J 6.69 Hz, CH2CH3; 1.28, m, 8H, 4×CH2;
1.63, m, 2H, CH2; 2.36, t, J 7.5 Hz, 2H, COCH2CH2; 3.27, br s, 1H, OH;
3.45, br s, 1H, OH; 3.95, m, 1H, H4; 4.16, dd, J 11.7, 6.3 Hz, 1H, H5a;
4.30, dd, J 11.7, 5.1 Hz, 1H, H 5b; 4.62, m, 1H, H 3; 4.89, dd, J 18.3, 1.8
Hz, 1H, H 1a; 5.02, dd, J 18.3, 1.8 Hz, 1H, H1b; 6.07, q, J 1.8 Hz, 1H,
H2Ј. 13C n.m.r. ꢂ 14.0, 22.6, 24.8, 28.9, 29.0, 29.7, 31.6, 34.1, 64.7,
68.8, 71.5, 71.8, 116.7 (C 2Ј), 169.7 (C 2), 173.7 (C=O), 174.6 (C=O).
(1Ј S,2Ј R)-3-[2Ј,3Ј-(Isopropylidenedioxy)-1Ј-
(hexanoyloxy)propyl]but-2-en-4-olide (18) and (1Ј R,2Ј R)-3-[2Ј,3Ј-
(Isopropylidenedioxy)-1Ј-(hexanoyloxy)propyl]but-2-en-4-olide (9)
from Triisopropylsilyl Compound (15)
(1Ј S,2Ј R)-3-[1Ј-Hydroxy-2Ј,3Ј-(isopropylidenedioxy)propyl]but-2-
en-4-olide (21) and (1Ј R,2Ј R)-3-[1Ј-Hydroxy-2Ј,3Ј-(isopropylidene-
dioxy)propyl]but-2-en-4-olide (20)
To a solution of 4-bromo-2-(triisopropylsilyloxy)furan (2.50 g, 7.84
mmol) in dry ether (8 ml) was added t-butyllithium (9.20 ml, 15.68
mmol, 1.7 M) at –78°C, dropwise. The solution was stirred at –78°C for
1 min and freshly distilled 2,3-O-isopropylidene-D-glyceraldehyde
(1.02 g, 7.84 mmol) in ether (8 ml) was added by cannula at –78°C.
Stirring was continued at –78°C for 30 min, then ether and saturated
aqueous bicarbonate were added. The aqueous phase was extracted
with ether and the combined organic fractions were washed with water,
brine, dried with MgSO4, filtered and the solvent removed under
vacuum. Flash chromatography with 30% EtOAc/petrol as eluent gave
the alcohol (17) (1.23 g, 42%) which was used immediately.
To a stirred solution of (17) (183 mg, 0.49 mmol) in dry CH2Cl2 (3
ml) was added hexanoic acid (186 ꢃl, 1.48 mmol) and the solution was
allowed to stir for 15 min. 4-Dimethylaminopyridine (6.0 mg, 0.05
mmol) was then added and the mixture was cooled to 0°C and treated
with dicyclohexylcarbodiimide (113 mg, 0.65 mmol). After 30 min the
mixture was allowed to warm to room temperature and stirred over 2 h,
then diluted with petrol and filtered through Celite. The filtrate was
washed with 10% aqueous HCl, saturated aqueous NaHCO3, water,
brine, dried (MgSO4) and the solvent removed. Purification of the crude
product by flash chromatography with 30% EtOAc/petrol as eluent
To a solution of the addition product (17) (200 mg, 0.54 mmol) in
tetrahydrofuran (2 ml) at 0°C was added Bu4NF·3H2O (198 mg, 0.75
mmol) and the reaction mixture was stirred for 5 min, then diluted with
ethyl acetate and water and washed with water and brine, then dried
(Na2SO4). Removal of the solvent gave the crude product which was
purified by silica gel chromatography with 50% EtOAc/light petroleum
as eluent to provide the butenolides (20) and (21) as a mixture (64 mg,
55%). A portion of this mixture was separated by preparative t.l.c. with
60% EtOAc/petrol as eluent to give the pure butenolides (20) and (21)
as oils.
Data for (21), [ꢁ]2D0 –12.0 (c, 0.21 in CHCl3) (Found: MNa+
237.0732. C10H14O5 requires MNa+ 237.0739). ꢄmax 3435 (OH), 2919
(CH), 1740 (CO), 1630, 1453, 1371, 1253, 1216, 1142, 1067, 840 cm–1.
1H n.m.r. ꢂ 1.36, s, 3H, CH3; 1.45, s, 3H, CH3; 2.72, d, J 4.4 Hz, 1H,
OH; 3.99, dd, J 8.4, 5.2 Hz, 1H, H 3aЈ; 4.08, dd, J 8.8, 6.4 Hz, 1H, H3bЈ;
4.17, dd, J 11.6, 6.4 Hz, 1H, H2Ј; 4.60, br dd, J 4.4 Hz, 1H, H1Ј; 4.83,
ddd, J 18.4, 2.0, 1.6 Hz, 1H, H4a; 5.00, dd, J 18.0, 1.6 Hz, 1H, H4b;
6.08, q, J 1.6 Hz, 1H, H2. 13C n.m.r. 24.9, 26.6, 65.7, 69.3, 71.6, 77.0

Synthesis of the Syributins
331
6
7
(under CDCl3 peak), 110.3 (CMe2), 116.4 (C 2), 168.7 (C 3), 173.1
(C=O). Mass spectrum m/z 197 (M+–H2O, 15%), 215 (M++1, 20).
Data for (20), [ꢁ]2D5 –11.8 (c, 0.12 in CHCl3), lit.5 [ꢁ]2D5 –13.5 (c, 0.3
in CHCl3) (Found: MNa+ 237.0730. Calc. for C10H14O5: MNa+
237.0739). ꢄmax 3435 (OH), 2921 (CH), 1736 (CO), 1629, 1460, 1378,
1260, 1211, 1139, 1069, 853 cm–1. 1H n.m.r. ꢂ 1.38, s, 3H; 1.48, s, 3H;
2.60, d, J 4.8 Hz, 1H, OH; 3.93, dd, J 8.4, 5.4 Hz, 1H, H 3aЈ; 4.13, dd, J
8.4, 6.6 Hz, 1H, H3bЈ; 4.25, ddd, J 6.4, 5.6, 4.4 Hz, 1H, H 2Ј; 4.57, br
dd, J 4.8 Hz, 1H, H 1Ј; 4.89, dd, J 18.0, 2.0 Hz, 1H, H 4a; 5.01, dd, J
18.0, 2.0 Hz, 1H, H4b; 6.03, q, J 2.0 Hz, 1H, H2. 13C n.m.r. ꢂ 24.8, 26.4,
65.7, 69.2, 71.4, 77.0 (under CDCl3 peak), 110.5 (CMe2), 116.8 (C 2),
168.2 (C 3), 173.0 (C=O). Mass spectrum m/z 197 (M+–H2O, 22%), 215
(M++1, 18).
Zeng, C., Midland, S. L., Keen, N. T., and Sims, J. J., J. Org. Chem.,
1997, 62, 4780.
Ishihara, J., Sugimoto, T., and Murai, A., Tetrahedron, 1997, 53,
16029.
Yoda, H., Kawauchi, M., Takabe, K., and Hosoya, K., Heterocycles,
1997, 45, 1895.
Yu, P., Wang, Q.-G., Mak, T. C. W., and Wong, H. N. C.,
Tetrahedron, 1998, 54, 1783.
Midland, S. L., Keen, N. T., and Sims, J. J., J. Org. Chem., 1995, 60,
1118.
Yu, P., Yang, Y., Zhang, Z. Y., Mak, T. C. W., and Wong, H. N. C., J.
Org. Chem., 1997, 62, 6359.
Mukai, C., Moharram, S. M., Azukizawa, S., and Hanaoka, M., J.
Org. Chem., 1997, 62, 8095.
Carda, M., Castillo, E., Rodríguez, S., Falomir, E., and Marco, J. A.,
Tetrahedron Lett., 1998, 39, 8895.
8
9
10
11
12
13
14
15
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