Chiron approach for the formal synthesis of (+)-syributin 1

Article abstract of DOI:10.1016/j.tetasy.2010.07.006

A chiron approach for the formal synthesis of (+)-syributin 1 from d-mannitol has been described. The key steps are a Wittig reaction and RCM.

Full text of DOI:10.1016/j.tetasy.2010.07.006

Tetrahedron: Asymmetry 21 (2010) 2087–2091
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Tetrahedron: Asymmetry
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Chiron approach for the formal synthesis of (+)-syributin 1
*
D. Gautam , B. Venkateswara Rao
Organic Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A chiron approach for the formal synthesis of (+)-syributin 1 from
steps are a Wittig reaction and RCM.
D-mannitol has been described. The key
Received 25 May 2010
Accepted 5 July 2010
Available online 31 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
O
OH
O
O
H
Me(H2C)n
Some plant pathogens produce signal molecules (elicitors),
which are recognized specifically by resistant plants and enable
the plants to initiate active defense responses against these patho-
gens.1 In 1993, Sims et al.2 isolated syringolides 1 1 and 2 2 (Fig. 1)
from Pseudomonas syringae Pv. Tomato which are the first known
non-proteinaceous metabolites found to elicit hypersensitive
responses on soybean plants carrying the resistance gene Rpg4.3
Two years later, Sims et al.4 reported the isolation of four structur-
ally related metabolites from the same source, the secosyrins 1 4
and 2 5 and syributins 1 7 and 2 8. Although these compounds
are not active elicitors, they display biosynthetic interest as they
are co-produced with the syringolides and may provide clues as
to the nature of the genes involved in the hypersensitive response.
Yucel et al. reported the isolation of other analogs of these com-
pounds, syringolide 3 3, secosyrin 3 6, and syributin 3 9.5
The interesting properties of the syringolides triggered exten-
sive work regarding their biochemical evaluation in plant
research.6 The interesting structural features such as the spiro sys-
tem with a tertiary stereogenic center of the syringolides7 and
secosyrins8a,b,9 attracted the attention of many synthetic chemists.
Syributins have also been the target of many synthetic group-
s7d,k,n,o,8 as this is the simplest member of this class of compounds
and its synthetic approach can be utilized for the synthesis of other
compounds of the class. In continuation of our interest in the syn-
thesis of oxygenated heterocycles,10,11 we have already reported
the synthesis of (+)-secosyrin 1 4.9e Herein, we report the chiron
approach for the formal synthesis of (+)-syributin 1.
Me(H2C)n
O
O
O
O
HO
H
O
O
HO
1: syringolide1(n=4)
2: syringolide2 (n=6)
3: syringolide3 (n=2)
4: secosyrin1 (n=4)
5: secosyrin2 (n=6)
6: secosyrin3 (n=2)
O
O
HO
7: syributin1 (n=4)
8: syributin2 (n=6)
9: syributin3 (n=2)
O
(CH2)nMe
HO
O
Figure 1. Syringolides, secosyrins, and syributins.
ing material or from asymmetric dihydroxylation. Different strate-
gies have been adopted for the construction of the butenolide unit
of the syributins. In the majority of syntheses, the furan moiety is
converted to a butenolide. Other strategies include stereoselective
HWM reactions on a keto alcohol;7n dehydration of a lactone with
a tertiary alcohol,8c from butanolide using selenoxide chemistry,8b
using an intramolecular Wittig reaction7o and utilizing the Baylis
Hillmann and RCM reaction.8d Herein, we wish to present a chiron
Both achiral and chiral starting materials have been used for
the synthesis of syributins. From the achiral starting materials,
various furan derivatives were used. The chiral starting materials
utilized were isopropylidene
D
-glyceraldehydes,7k,8a,d diisopropyl
approach for the (+)-syributin 17 from D-mannitol.
D
-tartrate,7o,8a and -arabinose.7n,8c The chiral diol functionality
D
of syributins was obtained from the above-mentioned chiral start-
2. Results and discussion
The retrosynthetic analysis (Scheme 1) showed that 7 could be
obtained by acylation, and acetonide deprotection of butenolide
* Corresponding author. Tel.: +91 40 24035647; fax: +91 40 27193003.
E-mail address: gautamiict@gmail.com (D. Gautam).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.07.006

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D. Gautam, B. V. Rao / Tetrahedron: Asymmetry 21 (2010) 2087–2091
O
O
O
OH
O
O
O
O
O
Me(H2C)4
O
O
HO
O
O
O
OH
O
O
O
7
10
11
OH
OH
O
O
OH
O
OR
HO
O
O
O
O
HO
OH
O
O
D-mannitol 14
12
13
Scheme 1. Retrosynthetic analysis of syributin 1.
compound 10. Compound 10 could be obtained from lactone 11 by
selective acetonide deprotection, oxidation, and reduction of the
resulting aldehyde. Lactone 11 could be obtained by RCM of diole-
fin compound 12, which in turn was envisaged to obtain from
values.8b
CHCl3) (Scheme 3).
½
a 2D5
ꢀ
¼ þ10:5 (c 1.22, CHCl3) lit.8b
½
a 2D0
ꢀ
¼ þ12:2 (c 0.10,
3. Conclusion
ketone 13. The ketone 13 could be easily prepared from
14 (Scheme 1).
D-mannitol
In conclusion we have demonstrated a chiron approach for the
formal synthesis of (+)-syributin 1 7 utilizing a RCM strategy. This
strategy is useful in making related skeletons and analogs with
high enantiomeric purity.
The synthesis of 7 started from 15 which was readily obtained
by following the literature procedure from
D
-mannitol.11 The sec-
ondary hydroxy of 15 was selectively oxidized by using Bu2SnO
and bromine to 16.12 Ketone 16 was then used for one carbon
homologation under Wittig conditions. However, the reaction
was unsuccessful in giving compound 17 (Scheme 2).
4. Experimental
The primary hydroxyl in compound 16 was then protected as its
TBDPS ether to give 18. It was gratifying to note that the one car-
bon extension of 18 under Wittig reaction conditions was success-
ful to give 19. Removal of TBDPS in 19 with TBAF gave 17. The
hydroxyl group in 17 was treated with acryloyl chloride, Et3N,
and DMAP in CH2Cl2 to give diolefin compound 12. The diolefin
compound 12 was treated with Grubbs 1st generation catalyst to
cause RCM to give lactone 11. Selective isopropylidene deprotec-
tion of 11 was performed using a catalytic amount of HCl in MeOH
to afford 20, which upon treatment with NaIO4 followed by reduc-
tion of the resulting aldehyde using NaBH4 gave 10. Acylation of 10
with hexanoic anhydride gave ester 21 thus completing the formal
synthesis of (+)-syributin 1 7 since the conversion of 21 to 7 was
already reported in the literature.8b,8c The spectroscopic and phys-
ical properties of 21 are in good agreement with the reported
TLC was performed on Merck Kiesel Gel 60, F254 plates (layer
thickness 0.25 mm). Column chromatography was performed on sil-
ica gel (60–120 mesh) using ethyl acetate and hexane mixture as
eluent. Melting points were determined on a Fisher John’s melting
point apparatus and are uncorrected. IR spectra were recorded on
a Perkin–Elmer RX-1 FT-IR system. 1H NMR and 13C NMR spectra
were recorded using Varian Gemini-200 MHz or Bruker Avance-
300 MHz or Varian Inova-400 MHz or Varian Invova-500 MHz spec-
trometer. 1H NMR data are expressed as chemical shifts in ppm fol-
lowed by multiplicity (s-singlet; d-doublet; t-triplet; q-quartet; and
m-multiplet), number of proton(s), and coupling constant(s) J (Hz).
13C NMR chemical shifts are expressed in parts per million (ppm).
Optical rotations were measured with Horiba-SEPA-300 digital
polarimeter. Accurate mass measurement was performed on Q STAR
mass spectrometer (Applied Biosystems, USA).
OH
OH
O
OH
O
O
OH
a
OH
b
OH
HO
O
O
HO
O
OH
O
O
O
D-mannitol 14
15
16
O
OH
c
O
O
O
17
Scheme 2. Reagents and conditions: (a) Ref. 11; (b) Bu2SnO, Br2, CH2Cl2, 0 °C to rt, 1.5 h, 73%; (c) PPh3CH3I, KOtBu, THF.

D. Gautam, B. V. Rao / Tetrahedron: Asymmetry 21 (2010) 2087–2091
2089
O
O
O
O
O
OTBDPS
OTBDPS
a
b
OH
O
O
O
O
O
O
O
O
c
O
19
18
16
O
O
e
d
O
OH
O
O
O
O
O
O
O
O
12
17
O
O
O
O
g
f
O
O
O
O
HO
HO
O
O
HO
O
O
O
O
10
11
20
O
O
OH
O
h
i
O
H3C(HC)4
O
H3C(H2C)4
O
O
OH
O
O
7
21
Scheme 3. Reagents and conditions: (a) TBDPSCl, imidazole, CH2Cl2, rt, 3 h, 70%; (b) PPh3CH3I, KOtBu, THF, ꢁ20 °C to rt, 3 h, 75%; (c) TBAF, THF, rt, 2 h, 80%; (d) acryloyl
chloride, Et3N, CH2Cl2, 0 °C to rt, 2 h, 83%; (e) Grubbs 1st generation cat., CH2Cl2, 40 °C, 48 h, 70%; (f) MeOH, cat. HCl, rt, 4 h, 78%; (g) (i) NaIO4, MeOH, rt, 6 h, (ii) NaBH4, MeOH,
0 °C to rt, 1 h, 76% for two steps; (h) hexanoic anhydride, Et3N, DMAP, CH2Cl2, 0 °C to rt, 2.5 h, 85%; (i) Refs. 8b and c.
4.1. 2-Hydroxy-1-((4R,40R,5S)-2,2,20,20-tetramethyl-4,40-bi(1,3-
dioxolan)-5-yl)ethanone 16
ldiphenylsilylchloride (0.95 ml, 3.71 mmol) at room temperature
and stirred for 3 h. The solvent was removed and the residue was
taken in ethyl acetate (20 mL) and washed with water and brine.
The organic layer was separated, dried over anhydrous Na2SO4,
and evaporated. Purification by silica gel column chromatography
(hexane/ethyl acetate = 9:1) gave 18 (1.20 g, 70%) as a colorless
A solution of 15 (0.450 g, 1.72 mmol) and Bu2SnO (0.50 g,
2.0 mmol) in CH2Cl2 (4 mL) was stirred at 0 °C for 0.5 h, then bro-
mine (0.1 ml, 1.94 mmol), in CH2Cl2 (0.6 mL), was added. The con-
tents were stirred at 0 °C to rt for 1 h. The reaction mixture was
then concentrated under reduced pressure. The residue was puri-
fied by flash column chromatography on silica gel using hexane/
ethyl acetate (3:1) as the eluant to give 16 (0.325 g, 73%) as a syr-
upy liquid. 1H NMR (300 MHz, C6D6) d: 1.09 (s, 3H), 1.17 (s, 3H),
1.23 (s, 3H), 1.34 (s, 3H), 2.86 (t, J = 5.3 Hz, 1H), 3.78 (dd, J = 6.0,
8.3 Hz, 1H) 3.87 (dd, J = 4.9, 8.3 Hz, 1H), 3.92 (ddd, J = 4.9, 6.0,
6.4 Hz, 1H), 4.08 ((t, J = 6.0 Hz, 1H), 4.22 (dd, J = 5.3, 19.6 Hz, 1H),
4.22 (d, J = 6.0 Hz, 1H), 4.31 (dd, J = 5.3, 19.6 Hz, 1H); ESIMS (m/
z): 261 (M+H)+.
syrup. ½a 2D5
ꢀ
¼ ꢁ3:7 (c 1.0, CHCl3); IR mmax (Neat, cmꢁ1): 2928,
2856, 1740, 1376, 1214, 1070, 703; 1H NMR (300 MHz, CDCl3) d:
1.09 (s, 9H), 1.11 (s, 3H), 1.29 (s, 3H), 1.32 (s, 3H), 1.34 (s, 3H),
3.81–3.88 (m, 1H), 3.98–4.1 (m, 3H), 4.26 (d, J = 5.6 Hz, 1H), 4.53
(s, 2H), 7.3–7.43 (m, 6H), 7.62–7.67 (m, 4H); 13C NMR (75 MHz,
CDCl3) d: 19.3, 25.1, 25.9, 26.4, 26.7, 26.8, 66.4, 68.0, 76.2, 78.0,
80.2, 109.8, 111.3, 127.8, 129.9, 132.8, 132.9, 134.8, 135.6, 205.8;
ESIMS (m/z): 521 (M+Na)+; HRMS for (M+Na)+: calcd for
(C28H38O6NaSi) = 521.2335, found = 521.2345.
4.3. tert-Butyldiphenyl(2-((4S,40R,5R)-2,2,20,20-tetramethyl-4,40-
bi(1,3-dioxolan)-5-yl)allyloxy)silane 19
4.2. 2-(tert-Butyldiphenylsilyloxy)-1-((4R,40R,5S)-2,2,20,20-
tetramethyl-4,40-bi(1,3-dioxolan)-5-yl)ethanone 18
To a mixture of methyl triphenylphosphonium iodide (2.0 g,
4.95 mmol) and potassium tert-butoxide (0.40 g, 3.57 mmol) was
added dry THF (20 mL) and stirred at room temperature under
To a stirred solution of 16 (0.90 g, 3.46 mmol) in dry CH2Cl2
(50 mL) were added imidazole (0.470 g, 6.91 mmol) and tert-buty-

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D. Gautam, B. V. Rao / Tetrahedron: Asymmetry 21 (2010) 2087–2091
N2 for 4 h. Stirring was stopped and the solid was allowed to settle.
The clear supernatant orange-yellow liquid was then cannulated
into the solution of compound 18 (0.50 g, 1.00 mmol) in dry THF
(10 mL) at ꢁ20 °C. The reaction mixture was then slowly allowed
to attain room temperature. After 3 h the reaction was quenched
with crushed ice and the reaction mixture was diluted with ethyl
acetate. Organic portion was separated and dried over anhydrous
Na2SO4, filtered, and evaporated. The resulting syrup was purified
by silica gel column chromatography (hexane/ethyl acetate = 19:1)
4.6. 4-((4S,40R,5R)-2,2,20,20-Tetramethyl-4,40-bi(1,3-dioxolan)-5-
yl)furan-2(5H)-one 11
Olefin 12 (0.060 g, 0.192 mmol) was dissolved in dry CH2Cl2
(20 mL) after which Grubbs’ 1st generation catalyst (0.047 g,
0.057 mmol, 30 mol %) was added. The reaction mixture was stir-
red at 40 °C for 48 h. The reaction mixture was concentrated under
reduced pressure and the residue was purified by column chroma-
tography (hexane/ethyl acetate = 6:1) to afford compound 11
to give 19 (0.375 g, 75%) as a colorless syrupy liquid. ½a D25
ꢀ
¼ þ1:5 (c
(0.038 g, 70%) as a syrupy liquid. ½a D34
¼ ꢁ13:8 (c 1.05, CHCl3); IR
ꢀ
1.19, CHCl3); IR mmax (Neat, cmꢁ1): 3071, 2932, 2857, 1636, 1374,
1215, 1111, 1066, 703; 1H NMR (300 MHz, CDCl3) d: 1.07 (s, 9H),
1.25 (s, 3H), 1.26 (s, 3H), 1.31 (s, 3H),1.34 (s, 3H), 3.75–3.88 (m,
2H), 3.96–4.06 (m, 2H), 4.21, 4.28 (AB-q, J = 14.7 Hz, 2H), 4.35 (d,
J = 7.4 Hz, 1H) 5.30 (s, 1H) 5.45 (s, 1H), 7.30–7.43 (m, 6H),
7.62–7.70 (m, 4H); 13C NMR (75 MHz, CDCl3) d: 19.3, 25.2, 26.4,
26.8, 27.0, 29.7, 63.3, 66.8, 76.6, 80.2, 80.3, 109.2, 109.6, 112.4,
127.7, 129.7, 133.5, 135.5, 145.2; ESIMS (m/z): 519 (M+Na)+;
HRMS for (M+Na)+: calcd for (C28H38O6NaSi) = 519.2542, found =
519.2563.
mmax (Neat, cmꢁ1): 2988, 1751,1453, 1378, 1214, 1073, 846; 1H
NMR (300 MHz, CDCl3) d: 1.33 (s, 3H), 1.39 (s, 3H), 1.40 (s, 3H),
1.42 (s, 3H), 3.74 (dd, J = 7.2, 8.7 Hz, 1H), 3.90 (dd, J = 4.9, 8.7 Hz,
1H), 4.05 (ddd, J = 4.9, 6.0, 8.7 Hz, 1H), 4.17 (dd, J = 6.0, 8.7 Hz,
1H), 4.78 (ddd, J = 0.8, 1.9, 18.1 Hz, 1H), 4.83 (d, J = 7.2 Hz, 1H),
4.94 (dd, J = 1.9, 18.1 Hz, 1H), 6.12 (dd, J = 1.9, 3.8 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d: 24.9, 26.3, 26.4, 26.6, 67.9, 71.2, 77.0,
81.2, 110.0, 110.7, 116.7, 167.3, 173.1; ESIMS (m/z) 307 (M+Na)+;
HRMS for (M+Na)+: calcd for (C14H20O6Na) = 307.1157, found =
307.1167.
4.4. 2-((4S,40R,5R)-2,2,20,20-Tetramethyl-4,40-bi(1,3-dioxolan)-5-
yl)prop-2-en-1-ol 17
4.7. 4-((4R,5R)-5-((R)-1,2-Dihydroxyethyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)furan-2(5H)-one 20
To an ice-cooled solution of 19 (0.30 g, 0.60 mmol) in dry THF
(5 mL) was added 1 M solution of TBAF in THF (0.9 mL, 0.90 mmol)
and stirred for 2 h at room temperature. After completion of the
reaction, water was added to the reaction mixture and THF was re-
moved under vacuum. Then, the aqueous layer was extracted with
ethyl acetate (2 ꢂ 15 mL) and washed with saturated aqueous
NaHCO3 and brine. The combined organic layer was dried over
anhydrous Na2SO4 and concentrated. The residue was purified by
column chromatography (hexane/ethyl acetate = 8:2) to give 17
Compound 11 (0.320 g, 1.13 mmol) was dissolved in MeOH
(10 mL) and to it was added catalytic HCl at room temperature
and stirred for 4 h. Next, saturated NaHCO3 solution was added
and MeOH was removed under reduced pressure. The aqueous
layer was then extracted with ethyl acetate (2 ꢂ 15 mL) and
washed with saturated brine solution. The combined organic layer
was dried over anhydrous Na2SO4 and concentrated. The residue
was purified by column chromatography (hexane/ethyl ace-
tate = 2:3) to give 20 (0.215 g, 78%) as a colorless syrupy liquid.
(0.125 g, 80%) as a colorless syrup. ½a D25
ꢀ
¼ ꢁ11:5 (c 1.21, CHCl3);
½
a 2D5
ꢀ
¼ þ4:2 (c 0.8, MeOH); IR mmax (Neat, cmꢁ1): 3446, 2925,
IR mmax (Neat, cmꢁ1): 3451, 2988, 2934, 1456, 1375, 1215, 1157,
1066, 846; 1H NMR (300 MHz, CDCl3) d: 1.34 (s, 3H), 1.38 (s, 3H),
1.39 (s, 3H), 1.42 (s, 3H),, 2.41–2.54 (br s, 1H), 3.75–3.83 (m, 1H),
3.88–3.96 (m, 1H), 4.03–4.26 (m, 4H), 4.49 (d, J = 7.6 Hz, 1H),
5.23(s, 1H) 5.31 (s, 1H); 13C NMR (75 MHz, CDCl3) d: 25.2, 26.3,
26.8, 26.8, 63.9, 67.4, 76.9, 80.8, 81.0, 109.3, 109.9, 115.0, 145.4;
ESIMS (m/z): 281 (M+Na)+; HRMS for (M+Na)+: calcd for
(C13H22O5Na) = 281.1364, found = 281.1361.
1735, 1326, 1216, 1071, 760; 1H NMR (500 MHz, CDCl3) d: 1.41
(s, 3H), 1.45(s, 3H), 3.70 (dd, J = 5.4, 11.2 Hz, 1H), 3.76–3.81 (m,
1H), 3.87 (dd, J = 2.9, 11.2 Hz, 1H), 3.91 (dd, J = 7.3, 7.8 Hz, 1H),
4.87 (d, J = 18.5 Hz, 1H), 4.91 (d, J = 7.3 Hz, 1H), 5.00 (d,
J = 18.5 Hz, 1H), 6.16 (m, 1H); 13C NMR (75 MHz, CDCl3) d: 26.3,
26.6, 63.8, 71.9, 73.5, 76.5, 79.5, 110.7, 116.2, 169.4, 174.5; ESIMS
(m/z): 245(M+H)+, 267(M+Na)+; HRMS for (M+H)+: calcd for
(C11H17O6) = 245.1025, found = 245.1027.
4.5. 2-((4S,40R,5R)-2,2,20,20-Tetramethyl-4,40-bi(1,3-dioxolan)-5-
yl)allyl acrylate 12
4.8. 4-((4R,5R)-5-(Hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-
4-yl)furan-2(5H)-one 10
Acryloyl chloride (0.15 mL, 1.86 mmol) was slowly added to a
solution of 17 (0.380 g, 1.47 mmol), Et3N (0.3 mL, 2.15 mmol),
and DMAP (5 mg, ꢃ4 mol %) in CH2Cl2 (25 mL) at 0 °C under a
nitrogen atmosphere. The reaction mixture was stirred from 0 °C
to room temperature for 2 h. After completion, the reaction was
quenched with saturated NH4OH solution and then the aqueous
layer was extracted with CH2Cl2 (2 ꢂ 15 mL) and washed with sat-
urated brine solution. The combined organic layer was dried over
anhydrous Na2SO4 and concentrated. The residue was purified by
column chromatography (hexane/ethyl acetate = 19:1) to give es-
To a stirred solution of compound 20 (0.150 g, 0.61 mmol) in
MeOH (5 mL) were added NaIO4 (0.260 g, 1.22 mmol) and satu-
rated NaHCO3 solution (0.2 mL). Stirring was continued for 6 h, fil-
tered through
a pad of Na2SO4, washed with MeOH, and
concentrated under reduced pressure to give a crude aldehyde,
which was used as such for the next reaction immediately without
any purification. To an ice-cooled, stirred solution of crude alde-
hyde in MeOH (7 mL) was added NaBH4 (0.048 g, 1.27 mmol).
The reaction mixture was brought to room temperature and stirred
for 1 h. The reaction was quenched with saturated NH4Cl solution
and MeOH was removed under vacuum. The aqueous layer was ex-
tracted with ethyl acetate (2 ꢂ 10 mL) and washed with saturated
brine solution. The combined organic layer was dried over anhy-
drous Na2SO4 and concentrated. The residue was purified by col-
umn chromatography (hexane/ethyl acetate = 13:7 as eluant) to
ter 12 (0.380 g, 83%) as a syrupy liquid. ½a D25
¼ ꢁ16:5 (c 0.38,
ꢀ
CHCl3); IR mmax (Neat, cmꢁ1): 2988, 1728, 1375, 1214, 1068, 767;
1H NMR (300 MHz, CDCl3) d: 1.30 (s, 3H), 1.33–1.45 (m, 9H),
3.78–3.94 (m, 2H), 4.00–4.12 (m, 2H), 4.45 (d, J = 7.2 Hz, 1H)
4.71, 4.77 (AB-q, J = 13.8 Hz, 2H), 5.27(s, 1H) 5.40 (s, 1H), 5.83(d,
J = 10.4 Hz, 1H) 6.14(dd, J = 10.4, 17.2 Hz, 1H), 6.42(d, J = 17.2 Hz,
1H); 13C NMR (75 MHz, CDCl3) d: 25.2, 26.6, 26.8, 27.0, 63.8,
67.1, 76.7, 80.5, 80.6, 109.5, 109.8, 116.4, 128.3, 131.0, 141.0;
ESIMS (m/z): 335 (M++Na); HRMS for(M+Na)+: calcd for
(C16H24O6Na) = 335.1470, found = 335.1485.
yield 10 (0.10 g, 76%) as a syrupy liquid. [½a D25
¼ ꢁ5:8 (c 0.4,
ꢀ
CHCl3); IR mmax (Neat, cmꢁ1): 3447, 2953, 1742, 1303, 1142, 986,
688; 1H NMR (300 MHz, CDCl3) d: 1.42 (s, 3H), 1.45(s, 3H), 1.99
(br s, 1H), 3.72 (dd, J = 3.2, 11.9 Hz, 1H), 3.87 (dd, J = 4.2, 11.9 Hz,
1H), 3.94 (ddd, J = 3.2, 4.2, 8.0 Hz, 1H), 4.82 (ddd, J = 1.1, 2.0,

D. Gautam, B. V. Rao / Tetrahedron: Asymmetry 21 (2010) 2087–2091
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5. (a) Yucel, I.; Boyd, C.; Debnam, Q.; Keen, N. T. Mol. Plant-Microbe Interact. 1994,
7, 131; (b) Yucel, I.; Midland, S. L.; Sims, J. J.; Keen, N. T. Mol. Plant-Microb.
Interact. 1994, 7, 148; (c) Keen, N. T.; Midland, S. L.; Boyd, C.; Yucel, I.;
Tsurushima, T.; Lorang, J.; Sims, J. J.. In Advances in Molecular Genetics of Plant-
Microbe interactions; Daniels, M. J., Downie, J. A., Osburn, A. E., Eds.; Kluwer
Academic: Boston, MA, 1994; Vol. 3, pp 41–48.
17.9 Hz, 1H), 4.87(d, J = 8.0 Hz, 1H), 4.92 ((ddd, J = 0.6, 2.0, 17.9 Hz,
1H), 6.04(dd, J = 1.9, 3.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d: 26.4,
26.7, 61.3, 71.0, 74.2, 80.3, 110.6, 116.3, 167.1, 173.2; ESIMS (m/z):
237 (M+Na)+; HRMS for (M+Na)+: calcd for (C10H14O5Na) =
237.0738, found = 237.0744.
4.9. (10R,20R)-3-[30-(Hexanoyloxy)-10,20-(isopropylidenedioxy)-2-
buten-4-olide 21
6. Selected publications: (a) Atkinson, M. M.; Midland, S. L.; Sims, J. J.; Keen, N. T.
Plant Physiol. 1996, 112, 297; (b) Tsurushima, T.; Midland, S. L.; Zeng, C.-M.; Ji,
C.; Sims, J. J.; Keen, N. T. Phytochemistry 1996, 43, 1219; (c) Ji, C.; Okinaka, Y.;
Takeuchi, Y.; Tsurushima, T.; Buzzell, R. I.; Sims, J. J.; Midland, S. L.; Slaymaker,
D.; Yoshikawa, M.; Yamaoka, N.; Keen, N. T. Plant Cell 1997, 9, 1425; (d) Ji, C.;
Boyd, C.; Slaymaker, D.; Okinaka, Y.; Takeuchi, Y.; Midland, S. L.; Sims, J. J.;
Herman, E.; Keen, N. T. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 3306; (e)
Tsurushima, T.; Ji, C.; Okinaka, Y.; Takeuchi, Y.; Sims, J. J.; Midland, S. L.;
Yoshikawa, M.; Yamaoka, N.; Keen, N. T. Dev. Plant Pathol. 1998, 13, 139; (f)
Slaymaker, D. H.; Keen, N. T. Plant Sci. 2004, 166, 387.
7. (a) Kuwahara, S.; Moriguchi, M.; Miyagawa, K.; Konno, M.; Kodama, O.
Tetrahedron Lett. 1995, 36, 3201; (b) Kuwahara, S.; Moriguchi, M.; Miyagawa,
K.; Konno, M.; Kodama, O. Tetrahedron 1995, 51, 8809; (c) Wood, J. L.; Jeong, S.;
Salcedo, A.; Jenkins, J. J. Org. Chem. 1995, 60, 286; (d) Honda, T.; Mizutani, H.;
Kanai, K. J. Org Chem. 1996, 61, 9374; (e) Henschke, J. P.; Rickards, R. W.
Tetrahedron Lett. 1996, 37, 3557; (f) Ishihara, J.; Ugimoto, T.; Murai, A. Synlett
1996, 335; (g) Zeng, C.-M.; Midland, S. L.; Keen, N. T.; Sims, J. J. J. Org. Chem.
1997, 62, 4780; (h) Yoda, H.; Kawauchi, M.; Takabe, K.; Ken, H. Heterocycles
1997, 45, 1895; (i) Ishihara, J.; Sugimoto, T.; Murai, A. Tetrahedron 1997, 53,
16029; (j) Yu, P.; Wang, Q.-G.; Mak, T. C. W.; Wong, H. N. C. Tetrahedron 1998,
54, 1783; (k) Di Florio, R.; Rizzacasa, M. A. Austr. J. Chem. 2000, 53, 327; (l)
Chenevert, R.; Dasser, M. Can. J. Chem. 2000, 78, 275; (m) Chenevert, R.; Dasser,
M. J. Org. Chem. 2000, 65, 4529; (n) Varvogli, A.-A. C.; Karagiannis, I. N.;
Koumbis, A. E. Tetrahedron 2009, 65, 1048; (o) Villalabos, M. N.; Wood, J. L.;
Jeong, S.; Benson, C. L.; Zeman, S. M.; McCarthy, C.; Weiss, M. M. Tetrahedron
2009, 65, 8091.
8. (a) Yu, P.; Yang, Y.; Zhang, Z. Y.; Mak, T. C. W.; Wong, H. N. C. J. Org. Chem. 1997,
62, 6359; (b) Mukai, C.; Moharram, S. M.; Azukizawa, S.; Hanaoka, M. J. Org.
Chem. 1997, 62, 8095; (c) Yoda, H.; Kawauchi, M.; Takabe, K.; Hosoya, K.
Heterocycles 1997, 45, 1903; (d) Krishna, P. R.; Narsingam, M.; Kannan, V.
Tetrahedron Lett. 2004, 45, 4773; (e) Wong, H. N. C. Pure Appl. Chem. 1996, 68,
335.
9. (a) Mukai, C.; Moharram, S. M.; Hanaoka, M. Tetrahedron Lett. 1997, 38, 2511;
(b) Carda, M.; Castillo, E.; Rodriguez, S.; Falomir, E.; Alberto Marco, J.
Tetrahedron Lett. 1998, 39, 8895; (c) Donohoe, T. J.; Fisher, J. W.; Edwards, P.
J. Org. Lett. 2004, 6, 465; (d) Koumbis, A. E.; Varvogli, A.-A. C. Synlett 2006, 3340;
(e) Gautam, D.; Rao, B. V. Tetrahedron Lett. 2009, 50, 1693.
Hexanoic anhydride (0.33 mL, 1.43 mmol) was slowly added to
a solution of 10 (0.10 g, 0.467 mmol), Et3N (0.2 mL, 1.43 mmol),
and DMAP (5 mg, ꢃ4 mol %) in THF (12 mL) at 0 °C under a nitro-
gen atmosphere. The reaction mixture was stirred at 0 °C for
30 min, then warmed to room temperature, and stirred for a fur-
ther 2 h. After completion of the reaction, water was added to
the reaction mixture and THF was removed under vacuum. Then
the aqueous layer was extracted with ethyl acetate (2 ꢂ 10 mL)
and washed with saturated aqueous NaHCO3 and brine. The com-
bined organic layer was dried over anhydrous Na2SO4 and concen-
trated. The residue was purified by column chromatography
(hexane/ethyl acetate = 5:1) to give ester 21 (0.124 g, 85%) as a col-
orless liquid; ½a D25
ꢀ
¼ þ10:5 (c 1.22, CHCl3), lit.8b
½
a 2D0
ꢀ
¼ þ12:2 (c
0.10, CHCl3); IR mmax (Neat, cmꢁ1): 2927, 1781, 1748, 1377, 1241,
1166, 1095, 863; 1H NMR (200 MHz, CDCl3) d: 0.90 (t, J = 6.6 Hz,
3H), 1.22–1.39 (m, 4H), 1.44 (s, 3H), 1.47(s, 3H), 1.54–1.74 (m,
2H), 2.36 (t, J = 7.4, 2H), 4.10 (ddd, J = 4.7, 4.7, 8.2 Hz, 1H), 4.26
(dd, J = 4.7, 12.1 Hz, 1H), 4.34 (dd, J = 4.7, 12.1 Hz, 1H), 4.73 (d,
J = 8.2 Hz, 1H), 4.85 (ddd, J = 0.8, 2.0, 18.0 Hz, 1H), 4.97 (dd,
J = 2.0, 18.0 Hz, 1H), 6.11(dd, J = 2.0, 3.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d: 13.7, 22.1, 24.3, 26.3, 26.5, 31.1, 33.8, 62.5,
70.6, 74.4, 77.9, 110.9, 116.7, 165.8, 172.6, 173.2; ESIMS (m/z):
335 (M+Na)+; HRMS for (M+Na)+: calcd for (C16H24O6Na) =
335.1470, found = 335.1477.
Acknowledgments
D. Gautam thanks the CSIR-New Delhi for a research fellowship.
The authors also thank Dr. J. S. Yadav, Dr. A. C. Kunwar, and Dr. T. K.
Chakraborty for their help and encouragement. They also thank
DST (SR/SI/OC-14/2007), New Delhi, for financial assistance.
10. (a) Ramu, E.; Rao, B. V. Tetrahedron: Asymmetry 2008, 19, 1820; (b) Gautam, D.;
Kumar, D. N.; Rao, B. V. Tetrahedron: Asymmetry 2006, 17, 819; (c) Ramu, E.;
Bhaskar, G.; Rao, B. V.; Ramanjaneyulu, G. S. Tetrahedron Lett. 2006, 47, 3401;
(d) Naveen Kumar, D.; Sudhakar, N.; Rao, B. V.; Kishore, K. H.; Murty, U. S.
Tetrahedron Lett. 2006, 47, 771; (e) Kumar, A. R.; Sudhakar, N.; Rao, B. V.;
Raghunandhan, N.; Venkatesh, A.; Sarangapani, M. Bioorg. Med. Chem. Lett.
2005, 15, 2085; (f) Sudhakar, N.; Kumar, A. R.; Prabhakar, A.; Jagadeesh, B.; Rao,
B. V. Tetrahedron Lett. 2005, 46, 325; (g) Naveen Kumar, D.; Rao, B. V.;
Ramajaneyulu, G. S. Tetrahedron: Asymmetry 2005, 16, 1611; (h) Naveen
Kumar, D.; Rao, B. V. Tetrahedron Lett. 2004, 45, 2227.
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