Total synthesis of the proposed structures of eushearilide

Article abstract of DOI:10.3987/COM-13-S(S)79

Total synthesis of (3R,16Z,20E,23S)- and (3R,16Z,20E,23R)-eushearilide was accomplished in 15 steps, respectively. Using either enantiomer of one of the four building blocks to assemble the phosphonium salt for the latter Wittig reaction, two diastereomers of eushearilide were prepared. Shiina macrolactonization (2-methyl-6-nitrobenzoic anhydride) was a key step in production of the 24-membered lactone in high yield.

Full text of DOI:10.3987/COM-13-S(S)79

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HETEROCYCLES, Vol. 88, No. 2, 2014, pp. 1175 - 1189. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 2nd July, 2013, Accepted, 9th September, 2013, Published online, 18th September, 2013
DOI: 10.3987/COM-13-S(S)79
TOTAL SYNTHESIS OF THE PROPOSED STRUCTURES OF
EUSHEARILIDE
Takayasu Yamauchi,*,a Jun-ichi Takidaira,a Kenya Okamoto,a
Takaya Sugiura,a Hiroki Horikoshi,a Shintaro Kudo,a Shigeru Sasaki,a Noriko
Mizushima,b and Kimio Higashiyamaa
aInstitute of Medicinal Chemistry, Hoshi University, Ebara, Shinagawa, Tokyo
b
142-8501, Japan and Yokohama College of Pharmacy, Yokohama 245-0066,
Japan; E-mail; yamauchi@hoshi.ac.jp
Abstract – Total synthesis of (3R,16Z,20E,23S)- and (3R,16Z,20E,23R)-
eushearilide was accomplished in 15 steps, respectively. Using either enantiomer of
one of the four building blocks to assemble the phosphonium salt for the latter
Wittig reaction, two diastereomers of eushearilide were prepared. Shiina
macrolactonization (2-methyl-6-nitrobenzoic anhydride) was a key step in
production of the 24-membered lactone in high yield.
INTRODUCTION
Eushearilide (1), which was isolated from Eupenicillium shearii by Hosoe in 2006, shows broad-spectrum
antifungal activity against various fungi and yeasts including the human pathogens Aspergillus fumigatus,
Trichophyton sp. and Candida sp.1 Its planar structure was elucidated by a combination of 1H, 13C and 31P
NMR, IR and MS spectroscopy. It is a novel 24-membered macrolide with two asymmetric carbons and
two non-conjugated double bonds, and a choline attached to a phosphate diester at the C3 hydroxyl group
(Figure 1). This structure is quite different from that of well-known antifungal drugs such as amphotericin
B, terbinafine hydrochloride, and isoconazole. Eushearilide is expected to be a promising antifungal drug.
Because the absolute configuration at C3 and C23 in 1 has not been clarified, we attempted to synthesize
two diastereomers with different chirality at C23, and determine the correct structure and stereochemistry
of the natural product by an extensive spectroscopic study.
Dedicated to Dr. Victor Snieckus, Professor of Queen’s University, on the occasion of his 77th birthday.

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RESULTS AND DISCUSSION
Our initial retrosynthetic analysis for (3R,16Z,20E,23S)- and (3R,16Z,20E,23R)-1 is shown in Scheme 1.
We attempted to optimize access to a key intermediate of 1 by a convergent synthesis. Esterification of
3-hydroxy-lactone 2 was expected to produce the choline phosphate ester chain in 1. Macrolactonization of
seco acid 3 by an efficient condensation reagent would be the key step to produce the desired macrolide
core 2. The (16Z)-substrate 3 for macrolactonization would be prepared by a Wittig reaction of aldehyde 5
with phosphonium salt 4. In this manner, coupling of two components for total synthesis of eushearilide
using the Wittig reaction was envisaged. Phosphonium salt 4 was envisaged to result from alkylation of
lithiated acetylene 6 to propylene oxide 7. Aldehyde 5 would be obtained by Wittig reaction of long chain
hydroxyphosphonium salt 8 and aldehyde prepared by oxidation of alcohol 9. Finally, the chiral center in
alcohol 9 was to be established from L-malic acid. The other eushearilide isomer with a 3R,16Z,20E
configuration, that is, (3R,16Z,20E,23R)-1 was to be obtained in a completely analogous fashion,
employing the enantiomer of building blocks (R)-7.
Synthesis of the phosphonium salts (S)-4 and (R)-4 was investigated for their use as precursors in the Wittig
reaction (Scheme 2). Regioselective addition of the known acetylene 62 with enantiopure propylene oxide
(7) (S>99 % ee, and R>99 % ee), which was prepared from racemic propylene oxide by hydrolytic kinetic
resolution using Jacobsen’s reagent with excellent enantioselectivity,3 produced the expected secondary
alcohol 10 as a single enantiomer.4 Subsequent desilylation of 10 under acidic conditions, followed by
Birch reduction of the resulting diol 11 afforded (E)-olefin 12 as a single diastereomer.5 Regioselective
bromination of diol 12 with CBr4 and PPh3 proceeded smoothly producing the desired bromide 13 in high
yield. As the last step, protection of alcohol 13 with TBDPSOTf6 followed by treatment with PPh3
produced the phosphonium salt (S)- and (R)-4, respectively.7

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Scheme 1. Retrosynthesis of eushearilide (1)
Scheme 2. Synthesis of phosphonium salts (S)- and (R)-4

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Scheme 3 outlines the synthesis of aldehyde 5. L-Malic acid is an inexpensive, commercially available
compound that is an appropriate starting material for synthesis of 1. In the synthesis, chiral center on
alcohol 9 derived from malic acid will remain at the C-3 position of the natural product. The known alcohol
9 was prepared from L-malic acid in high yield in two steps.8 Dess–Martin periodinane (DMP) oxidation of
the primary alcohol 9 was followed by the standard Wittig reaction with known hydroxyphosphonium
bromide, which was prepared from commercially available dodecane-1,12-diol in two steps.9 These steps
produced the expected alcohol 14 in low yield because of an unstable aldehyde intermediate. The reaction
yield was increased to 51 % by optimizing the reaction conditions and handling. Treatment of 14 with
Pd-fibroin in a H2 atmosphere (1 atm) and subsequent DMP oxidation produced the desired aldehyde 5.
Scheme 3. Synthesis of aldehyde 5
After successful synthesis of the enantiomeric phosphonium salts (S)-4 and (R)-4, synthesis of the two
diastereomers of 1 was attempted. Synthesis of (3R,16Z,20E,23S)- and (3R,16Z,20E,23R)-1 is depicted in
Scheme 4. First, successive Wittig reaction of aldehyde 5 with phosphonium bromide 4 led to the formation
of the long chain (16Z)-diene 15 as a single diastereomer. Regioselective reduction of benzylidene acetal 15
with DIBAL proceeded successfully to form the 3-benzyloxy-alcohol 16.10 Conversion of 16 by Swern and
Pinnick oxidations gave carboxylic acid 17 in excellent yield.11 Deprotection of the TBDPS group with
TBAF provided seco acid 3. The conventional Yamaguchi reagent (2,4,6-trichlorobenzoyl chloride)12 and
Shiina reagent (2-methyl-6-nitrobenzoic anhydride)13 were compared for the macrolactonization. In highly
dilute conditions, each condensation of (23S)-3 gave the requisite macrolide (23S)-18 as the sole product in
68% (Yamaguchi) or 79% (Shiina) yield. Compared to the Shiina reaction, the Yamaguchi reaction required
a higher temperature (reflux in toluene vs. room temperature). Treatment of benzyl ether 18 with TiCl4
provided -hydroxy-lactone 2.14 Finally, alcohol 2 was successfully converted to (3R,16Z,20E,23S)- and
(3R,16Z,20E,23R)-1 in two steps by phosphate esterification with ethylene chlorophosphate under basic
conditions, followed by cleavage of the dioxyphospholane ring with trimethylamine.15 Although the
spectroscopic properties of the synthetic diastereomers of 1 were similar, they were not completely
identical to those of the proposed natural product 1. In particular, 13C NMR spectrum showed the chemical

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shifts of C14–18 at both synthetic compound 1 moved slightly upfield as compared with that of natural
product (Table 1). It has been known as the common phenomenon attributed to p orbital compression.
Therefore, we speculate that the geometry at C16 and C20 of the natural product is trans (E) and trans (E).
In conclusion, this is the first report of a total synthesis of the two diastereomers (3R,16Z,20E,23S)- and
(3R,16Z,20E,23R)-1 via coupling of four components to form the macrolide core. The Shiina reaction was
highly efficient for macrolactonization of the 24-membered macrolide. Synthesis of derivatives of 1 is
important for structural research for development of antifungal drugs.
Scheme 4. Completion of total synthesis of (3R,16Z,20E,23S)- and (3R,16Z,20E,23R)-eushearilide (1)

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EXPERIMENTAL
All melting points were measured with a Yanagimoto Micro melting point apparatus without collection. IR
spectra were recorded on a JASCO FT/IR-200 spectrophotometer. 1H and 13C NMR spectra were obtained
on a Bruker AVIII-400 instrument, and chemical sifts are reported in ppm on the -scale from internal
Me4Si. MS spectra were measured with a JEOL JMS D-600 and JMS T-100LP spectrometer by using the
chemical ionization (CI) with isobutene, the electron impact (EI) methods, and ElectroSpray Ionization
(ESI) methods. Elemental analyses were performed on a Perkin-Elmer 240-B instrument. Optical rotation
were taken with a JASCO-DIP-370 polarimeter at rt. Shibata Glass Tube Oven GTO-350RD was used as
distillation apparatus. Column chromatography was performed on Silica gel 60 (100−210 m, Kanto
Chemical Co., Inc.), Chromatorex NH (100−200 mesh, Fuji Silysia Chemical LTD), and Sephadex LH−20
(GE Healthcare Bio−Sciences AB). HPLC analysis was performed on a Shimazu LC-20AD. Chiralpac OD
column was purchased from Daicel Chemical Industry. The reaction solvents were prepared as the
following. HMPA was distilled over sodium metal. Acetonitrile and DMSO were distilled over calcium
hydride. Hexane was distilled over sodium hydride. Anhydrous THF, DCM, and toluene were purchased
from Wako Pure Chemical Industries and Kanto Chemical.
(S)-8-(tert-Butyldimethylsilyloxy)oct-4-yn-2-ol ((S)-10). To a solution of 6 (30 mmol, 6.0 g) in THF (70
mL) was added n-BuLi (1.6 M in THF, 33 mmol, 20 mL) dropwise under N2 atmosphere at –78 °C and
stirred for 1 h at –78 °C. After BF3•Et2O (3 mL) was added, the reaction mixture was stirred for 10 min. The
solution of (S)-propylene oxide (7) (33 mmol, 1.9 g) in THF (15 mL) was added dropwise at –78 °C, and
stirred for additional 2 h at –78 °C. The reaction mixture was quenched with saturated aqueous NH4Cl, and
extracted with AcOEt. The combined organic layer was washed with brine, dried over anhydrous sodium
sulfate, filtrated, and evaporated under reduced pressure. The crude product was purified by column
chromatography with silica gel (hexane / AcOEt = 4: 1) to afford (S)-10 (6.7 g, 86%). []D27 +7.51 (c 1.00,
CHCl3). 1H NMR (400 MHz, CDCl3) : 3.93–3.87 (1H, m), 3.69 (2H, t, J = 6.1 Hz), 2.40–2.24 (4H, m),
1.99 (1H, d, J = 4.0 Hz), 1.73–1.67 (2H, m), 1.24 (3H, d, J = 6.2 Hz), 0.90 (9H, s), 0.06 (6H, s). 13C NMR

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(100 MHz, CDCl3) : 82.7, 76.2, 66.5, 61.6, 32.0, 29.4, 25.9, 22.2, 18.3, 15.1. IR (film) cm-1: 3460, 2960,
2930, 2900, 2860. MS (ESI+) m/z: 279 (M+Na+, base peak). HRMS (ESI+) m/z: Found 279.1776 (Calcd for
C14H28NaO2Si (M+Na+) 279.1756). (R)-10, []D23 –7.71 (c 1.53, CHCl3).
(S)-Oct-4-yne-1,7-diol (S)-11. To a solution of (S)-10 (33 mmol, 8.5 g) in THF (120 mL) was added 1%
HCl (120 mL) at rt and stirred for 3 h. The reaction mixture was alkalized with saturated aqueous sodium
hydrogen carbonate and extracted with AcOEt. The combined organic layer was washed with brine, dried
over anhydrous sodium sulfate, filtrated, and evaporated under reduced pressure. The crude product was
purified by column chromatography with silica gel (CHCl3 / MeOH = 15: 1) to afford (S)-11 (3.7 g, 79%).
[]D29 +16.0 (c 1.01, CHCl3). 1H NMR (400 MHz, CDCl3) : 3.91 (1H, sext, J = 5.7 Hz), 3.74 (2H, t, J = 6.0
Hz), 2.59 (1H, br), 2.46 (1H, br), 2.39–2.24 (4H, m), 1.74 (2H, quin, J = 6.2 Hz), 1.24 (3H, d, J = 6.0 Hz).
13C NMR (100 MHz, CDCl3) : 82.3, 77.0, 66.5, 61.9, 31.4, 29.3, 22.3, 15.5. IR (film) cm-1: 3350, 2970,
2930, 2880. MS (ESI+) m/z: 165 (M+Na+, base peak). HRMS (ESI+) m/z: Found 165.0900 (Calcd for
C8H14NaO2 (M+Na+) 165.0892). (R)-11, []D25 –16.0 (c 1.00, CHCl3).
(S,E)-Oct-4-ene-1,7-diol (S,E)-12. To a solution of (S)-11 (26 mmol, 3.7 g) in THF (40 mL) was added
liquid NH3 (150 mL) and Na metal at –78 °C under N2 atmosphere and stirred for 8 h at –78 °C. After
NH4Cl was added slowly, the reaction mixture was stirred for additional 14 h at rt and extracted with Et2O.
The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtrated, and
evaporated under reduced pressure. The crude product was purified by column chromatography with silica
gel (CHCl3 / MeOH = 15: 1) to afford (S,E)-12 (3.0 g, 78%). []D28 +10.9 (c 1.00, CHCl3). 1H NMR (400
MHz, CDCl3) : 5.61–5.43 (2H, m), 3.84–3.76 (1H, m), 3.66 (2H, t, J = 6.4 Hz), 2.24–2.06 (4H, m), 1.72
(2H, br), 1.66 (2H, quin, J = 6.8 Hz), 1.19 (3H, d, J = 6.2 Hz). 13C-NMR (100 MHz, CDCl3) : 133.5, 126.5,
67.2, 62.1, 42.3, 32.0, 29.2, 22.6. IR (film) cm-1: 3340, 2965, 2930, 2880, 1650. MS (CI) m/z: 145 (M+H+),
27
69 (base peak). HRMS (CI) m/z: Found 145.1231 (Calcd for C8H17O2 (M+H+) 145.1228). (R,E)-12, []D
–10.7 (c 1.00, CHCl3).
(S,E)-8-Bromooct-4-en-2-ol (S,E)-13. To a solution of (S,E)-12 (2.7 mmol, 400 mg) in DCM (20 mL) was
added a solution of CBr4 (3.6 mmol, 1.2 g) in DCM (5 mL) and PPh3 (3.7 mmol, 1.0 g) in DCM (5 mL)
under N2 atmosphere at 0 °C. The reaction mixture was stirred for 30 min at 0 °C, filtered through silica gel,
and evaporated under reduced pressure. The crude product was purified by column chromatography with
silica gel (hexane / AcOEt = 4: 1) to afford (S,E)-13 (540 mg, 95%). []D25 +7.51 (c 1.00, CHCl3). 1H NMR
(400 MHz, CDCl3) : 5.55–5.45 (2H, m), 3.85–3.77 (1H, m), 3.41 (2H, t, J = 6.7 Hz), 2.24–2.08 (4H, m),
1.93 (2H, quin, J = 6.9 Hz), 1.68 (1H, br), 1.19 (3H, d, J = 6.2 Hz). 13C NMR (100 MHz, CDCl3) : 131.7,
127.6, 67.1, 42.3, 33.1, 32.0, 30.8, 22.6. IR (film) cm-1: 3420, 2960, 2930, 2840, 1640. MS (ESI+) m/z: 230
(M+Na+), 119 (base peak). HRMS (ESI+) m/z: Found 229.0204 (Calcd for C8H15BrNaO (M+Na+)

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229.0202). (R,E)-13, []D29 –6.94 (c 1.00, CHCl3).
(S,E)-[7-(tert-Butyldiphenylsilyloxy)oct-4-enyl]triphenylphosphonium bromide (S,E)-4. To a solution
of TBDPSOTf (3.2 mmol, 1.2 g) in DCM (4 mL) was added a solution of (S,E)-13 (1.3 mmol, 270 mg) in
DCM (3 mL) and 2,6-lutidine (4.0 mmol, 0.5 mL) at 0 °C under N2 atmosphere. After being stirred for 2 h
at 0 °C, the reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate and
extracted with CHCl3. The combined organic layer was washed with saturated aqueous NH4Cl, dried over
anhydrous sodium sulfate, filtrated, and evaporated under reduced pressure. The crude product was purified
by column chromatography with silica gel (hexane
/
AcOEt
=
15: 1) to afford
(S,E)-(8-bromooct-4-en-2-yloxy)tert-butyldiphenylsilane (570 mg, 97%). []D25 –20.9 (c 1.00, CHCl3). 1H
NMR (400 MHz, CDCl3) : 7.67–7.66 (4H, m), 7.44–7.35 (6H, m), 5.41 (1H, dtt, J = 1.1, 7.0, 15.3 Hz),
5.28 (1H, dtt, J = 1.2, 6.6, 15.3 Hz), 3.85 (1H, sext, J = 6.0 Hz), 3.37 (2H, t, J = 6.8 Hz), 2.19–2.05 (4H, m),
1.86 (2H, quin, J = 6.8 Hz), 1.05 (9H, s), 1.05 (3H, d, J = 6.0 Hz). 13C NMR (100 MHz, CDCl3) : 135.9,
135.8, 134.7, 134.5, 130.4, 129.5, 129.4, 128.2, 127.5, 127.4, 69.5, 42.6, 33.3, 32.3, 30.9, 28.8, 27.0, 22.9,
19.2, 18.7. IR (film) cm-1: 3070, 3050, 2960, 2930, 2895, 2800, 1590. MS (CI) m/z: 445 (M+H+), 283 (base
peak). HRMS (CI) m/z: Found 445.1579 (Calcd for C24H34OSiBr (M+H+) 445.1562). (R,E)-compound.
[]D29 +20.4 (c 1.00, CHCl3). A solution of (S,E)-(8-bromooct-4-en-2-yloxy)-tert-butyldiphenylsilane (4.0
mmol, 1.8 g) and PPh3 (20 mmol, 5.3 g) in acetonitrile (80 mL) was refluxed for 48 h. After being cooled at
rt, the resulting mixture was evaporated acetonitrile with hexane several times under reduced pressure, and
recrystallized from Et2O to afford (S,E)-4 (2.4 g, 84%). []D25 –14.54 (c 1.02, CHCl3). 1H NMR (400 MHz,
CDCl3) : 7.85–7.76 (9H, m), 7.70–7.62(10H, m), 7.42–7.31 (6H, m), 5.36 (1H, dt, J = 7.0, 15.3 Hz), 5.23
(1H, dt, J = 6.6, 15.3 Hz), 3.85–3.76 (3H, m), 2.32 (2H, dt, J = 7.0, 7.1 Hz), 2.15–2.02 (2H, m), 1.71–1.61
(2H, m), 1.00–0.98 (12H, m). 13C NMR (100 MHz, CDCl3) : 135.6, 134.9 (d, J = 2.9 Hz), 134.5, 134.2,
133.5 (d, J = 10.1 Hz), 130.4 (d, J = 12.5 Hz), 130.3, 129.3, 128.8, 127.3, 118.1 (d, J = 85.9 Hz), 69.2, 42.5,
32.9, 32.7, 26.8, 22.7, 22.3, 21.7, 19.0. IR (KBr) cm-1: 3070, 3050, 2960, 2930, 2890, 2860, 2790, 1590. MS
(ESI+) m/z: 627 (M–Br+, base peak). HRMS (ESI+) m/z: Found 627.3212 (Calcd for C42H48OPSi (M–Br+)
627.3211). (R,E)-4, []D29 +15.0 (c 1.00, CHCl3).
(Z)-13-[(4S)-2-Phenyl-1,3-dioxan-4-yl]tridec-12-en-1-ol 14. To a solution of 9 (7.7 mmol, 1.5 g) in DCM
(15 mL) was added pyridine (11 mmol, 0.9 mL) and DMP (10 mmol, 4.3 g) at rt under Ar atmosphere. After
being stirred for 90 min, the reaction mixture was filtered and evaporated under reduced pressure. The
residue was purified by column chromatography with silica gel (hexane / AcOEt = 1: 1) to afford aldehyde
(990 mg). To a solution of (12-hydroxydodecyl)triphenylphosphonium bromide (8) (6.7 mmol, 3.5 g) in
THF (50 mL) was added t-BuOK (1.0 M in THF, 15 mmol, 15 mL) dropwise at –50 °C under N2
atmosphere. After being stirred for 1.5h, a solution of aldehyde (990 mg) in THF (10 mL) was dropwise

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added at –50 °C. The reaction mixture was stirred for additional 2 h at rt, quenched with H2O, and extracted
with Et2O. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate,
filtrated, and evaporated under reduced pressure. The crude product was purified by column
25
chromatography with silica gel (hexane / AcOEt = 4: 1) to afford 14 (1.4 g, 51%). []D +63.9 (c 0.60,
CHCl3). 1H NMR (400 MHz, CDCl3) : 7.51–7.49 (2H, m), 7.37–7.31 (3H, m), 5.58 (1H, s), 5.56–5.47 (2H,
m), 4.68 (1H, ddd, J = 2.5, 7.0, 11.2 Hz), 4.28 (1H, dd, J = 3.8, 11.5 Hz), 4.02 (1H, dt, J = 2.5, 11.5 Hz), 3.62
13
(2H, t, J = 6.6 Hz), 2.18–2.07 (2H, m), 2.01–1.91 (1H, m), 1.57–1.47 (3H, m), 1.44–1.27 (18H, m). C
NMR (100 MHz, CDCl3) : 138.6, 133.0, 129.3, 128.7, 128.1, 126.1, 101.2, 73.6, 66.9, 62.9, 32.7, 31.5,
29.5, 29.4, 29.2, 27.9, 25.7. IR (film) cm-1: 3300, 3200, 3040, 3070, 3090, 2920, 2850. MS (EI) m/z: 360
(M+), 106 (base peak). HRMS (EI) m/z: Found 360.2669 (Calcd for C23H36O3 (M+) 360.2664).
13-[(4R)-2-Phenyl-1,3-dioxan-4-yl]tridecanal 5. A solution of 14 (1.4 mmol, 500 mg) and Pd fibroin (50
mg) in AcOEt (14 mL) was stirred at rt for 24 h under H2 atmosphere (1 atm). The reaction mixture was
filtered with celite and was concentrated under reduced pressure. The crude product was purified by
column chromatography with silica gel (hexane
/
AcOEt
=
4: 1) to afford
27
1
13-[(4R)-2-phenyl-1,3-dioxan-4-yl]tridecan-1-ol (490mg, 97%). []D +16.2 (c 0.60, CHCl3). H NMR
(400 MHz, CDCl3) : 7.50–7.48 (2H, m), 7.37–7.31 (3H, m), 5.50 (1H, s), 4.23 (1H, dd, J = 4.0, 11.4 Hz),
3.95 (1H, dt, J = 2.6, 12.2 Hz), 3.84–3.77 (1H, m), 3.60 (2H, t, J = 6.6 Hz), 1.84–1.73 (1H, m), 1.72–1.62
(1H, m) 1.56–1.43 (4H, m), 1.39–1.24 (20H, m). 13C NMR (100 MHz, CDCl3) : 138.9, 128.6, 128.2, 126.0,
101.1, 77.3, 67.1, 63.1, 36.0, 31.3, 29.6, 29.4, 25.7, 25.0. IR (film) cm-1: 3420, 3360, 2920, 2850. MS (EI)
m/z: 362 (M+, base peak). HRMS (EI) m/z: Found 362.2836 (Calcd for C23H38O3 (M+) 362.2821). To a
solution of 13-[(4R)-2-phenyl-1,3-dioxan-4-yl]tridecan-1-ol (1.4 mmol, 500 mg) in DCM (30 mL) was
added pyridine (1.9 mmol, 0.2 mL) and DMP (1.8 mmol, 760 mg) at rt under Ar atmosphere. After being
stirred for 1 h, the reaction mixture was quenched with aqueous sodium carbonate and sodium thiosulfate
and extracted with CHCl3. The combined organic layer was washed with brine, dried over anhydrous
sodium sulfate, filtrated, and evaporated under reduced pressure. The crude product was purified by column
chromatography with silica gel (hexane / AcOEt = 6: 1) to afford 5 (440 mg, 89%). []D27 +17.3 (c 1.00,
CHCl3). 1H NMR (400 MHz, CDCl3) : 9.74 (1H, s), 7.50–7.47 (2H, m), 7.37–7.25 (3H, m), 5.49 (1H, s),
4.25 (1H, dd, J = 4.4, 11.4 Hz), 3.94 (1H, dd, J = 2.5, 12.1 Hz), 3.83–3.77 (1H, m), 2.40 (2H, dt, J = 1.3, 7.4
Hz), 1.83–1.73 (1H, m), 1.71–1.52 (3H, m), 1.51–1.41 (2H, m), 1.38–1.23 (18H, m). 13C NMR (100 MHz,
CDCl3) : 202.6, 138.8, 128.3, 127.9, 125.8, 100.9, 77.1, 66.9, 43.7, 35.9, 31.2, 29.4, 29.2, 28.9, 24.8, 21.8.
IR (film) cm-1: 3420, 2930, 2860, 2720, 1720. MS (ESI+) m/z: 383 (M+Na+). HRMS (ESI+) m/z: Found
383.2562 (Calcd for C23H36NaO3 (M+Na+) 383.2580).
tert-Butyldiphenyl[(2S,4E,8Z)-21-{(4R)-2-phenyl-1,3-dioxan-4-yl}henicosa-4,8-dien-2-yloxy]silane

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(23S)-15. To a solution of (S)-4 (1.3 mmol, 920 mg) in THF (30 mL) was added n-BuLi (1.6 M in THF, 1.6
mmol, 1 mL) dropwise at –50 °C under N2 atmosphere. After being stirred for 1 h at –50 °C, a solution of 5
(1.0 mmol, 360 mg) in THF (10 mL) was added dropwise at –50 °C. The reaction mixture was stirred for
additional 2 h at rt, quenched with H2O, and extracted with Et2O. The combined organic layer was washed
with brine, dried over anhydrous sodium sulfate, filtrated, and evaporated under reduced pressure. The
crude product was purified by column chromatography with silica gel (hexane / AcOEt = 15: 1) to afford
(23S)-15 (660 mg, 93%). []D23 –3.60 (c 0.30, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.69–7.66 (4H, m),
7.51–7.48 (2H, m), 7.43–7.31 (9H, m), 5.50 (1H, s), 5.36–5.33 (4H, m), 4.26 (1H, ddd, J = 1.2, 5.0, 11.3
Hz), 3.95 (1H, ddd, J = 2.6, 11.5, 12.2 Hz), 3.86–3.78 (2H, m), 2.19–1.96 (8H, m), 1.87–1.66 (2H, m),
1.57–1.22 (24H, m), 1.05–1.03 (12H, m). 13C NMR (100 MHz, CDCl3) : 138.9, 135.9, 134.8, 134.5, 132.3,
130.2, 129.4 129.1, 128.6, 128.2, 127.4, 126.7, 126.0, 101.1, 77.3, 69.6, 67.1, 42.8, 36.0, 32.8, 31.3, 29.7,
29.6, 29.5, 29.3, 27.6, 27.2, 27.0, 25.0, 22.9, 19.2. IR (film) cm-1: 3070, 2930, 2855, 1560, 1530. MS (EI)
m/z: 708 (M+), 190 (base peak). HRMS (EI) m/z: Found 708.4940 (Calcd for C47H68O3Si (M+) 708.4938).
(23R)-15 69%, []D20 +20.2 (c 1.11, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.69–7.66 (4H, m), 7.51–7.48
(2H, m), 7.43–7.31 (9H, m), 5.50 (1H, s), 5.36–5.33 (4H, m), 4.26 (1H, ddd, J = 1.3, 4.9, 11.3 Hz), 3.95 (1H,
dd, J = 2.3, 11.9 Hz), 3.88–3.78 (2H, m), 2.28–1.92 (8H, m), 1.85–1.74 (1H, m), 1.71–1.65 (1H, m),
1.56–1.43 (3H, m), 1.39–1.24 (20H, m), 1.05–1.03 (12H, m). 13C NMR (100 MHz, CDCl3) : 138.9, 135.9,
135.8, 134.5, 132.3, 130.2, 129.4, 129.1, 128.6, 128.2, 127.4, 126.7, 126.0, 101.1, 77.0, 69.6, 67.1, 42.8,
36.0, 32.8, 32.6, 32.5, 31.6, 31.3, 29.7, 29.6, 29.3, 29.2, 27.3, 27.2, 27.0, 25.0, 22.9, 22.6, 19.2, 14.1. IR
(film) cm-1: 3070, 3040, 3000, 2960, 2920, 2850, 1590. MS (ESI+) m/z: 731 (M+Na+). HRMS (ESI+) m/z:
Found 731.4835 (Calcd for C47H68NaO3Si (M+Na+) 731.4835).
(3R,16Z,20E,23S)-3-Benzyloxy-23-(tert-butyldiphenylsilyloxy)tetracosa-16,20-dien-1-ol (23S)-16. To
a solution of (23S)-15 (0.5 mmol, 330 mg) in toluene (30 mL) was added DIBAL (1.0 M in hexane, 7.1
mmol, 7.1 mL) dropwise at –40 °C under N2 atmosphere. After being stirred for 6 h at –40 °C, the reaction
mixture was quenched with H2O and extracted with Et2O. The combined organic layer was washed with
brine, dried over anhydrous sodium sulfate, filtrated, and evaporated under reduced pressure. The crude
product was purified by column chromatography with silica gel (hexane / AcOEt = 4: 1) to afford (23S)-16
(310 mg, 94%). []D26 –25.4 (c 1.20, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.70–7.66 (4H, m), 7.43–7.25
(11H, m), 5.36–5.33 (4H, m), 4.60 (1H, d, J = 11.4 Hz), 4.48 (1H, d, J = 11.4 Hz), 3.85–3.73 (3H, m),
3.66–3.61 (1H, m), 2.42 (1H, br), 2.15–1.97 (8H, m), 1.83–1.53 (4H, m), 1.38–1.24 (18H, m), 1.05–1.03
(12H, m). 13C NMR (100 MHz, CDCl3) : 138.4, 135.9, 135.8, 134.8, 134.5, 132.3, 130.2, 129.4, 129.4,
128.4, 127.8, 127.7, 127.4, 126.7, 78.7, 70.9, 69.9, 60.8, 42.7, 35.8, 33.4, 32.8, 29.8, 29.6, 29.3, 27.3, 27.2,
27.0, 25.1, 22.9, 19.2. IR (film) cm-1: 3400, 3070, 2930, 2860, 1750, 1560, 1530. MS (ESI+) m/z: 711

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1185
(M+H+), 387 (base peak). HRMS (ESI+) m/z: Found 711.5193 (Calcd for C47H71O3Si (M+H+) 711.5173).
(23R)-16 83%, []D27 –2.2 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.70–7.66 (4H, m), 7.43–7.27
(11H, m), 5.39–5.31 (4H, m), 4.60 (1H, d, J = 11.5 Hz), 4.48 (1H, d, J = 11.5 Hz), 3.88–3.70 (3H, m),
3.67–3.61 (1H, m), 2.42 (1H, br), 2.20–1.93 (8H, m), 1.86–1.49 (4H,m), 1.37–1.26 (18H, m), 1.05–1.03
(12H, m). 13C NMR (100 MHz, CDCl3) : 138.4, 135.9, 135.8, 134.8, 134.5, 132.3, 130.2, 129.4, 129.1,
128.4, 127.8, 127.7, 127.4, 126.7, 78.7, 70.9, 69.6, 42.7, 35,8, 33.4, 32.8, 29.8, 29.7, 29.6, 29.3, 27.3, 27.2,
27.0, 25.1, 22.9, 19.2. IR (film) cm-1: 3450, 3070, 2930, 2860, 1650. MS (ESI+) m/z: 733 (M+Na+), 387
(base peak). HRMS (ESI+) m/z: Found 733.4985 (Calcd for C47H70NaO3Si (M+Na+) 733.4992).
(3R,16Z,20E,23S)-3-Benzyloxy-23-(tert-butyldiphenylsilyloxy)tetracosa-16,20-dienoic acid (23S)-17.
To a solution of oxalyl chloride (1.9 mmol, 0.2 mL) in DCM (3 mL) was added a solution of DMSO (3.9
mmol, 0.3 mL) in DCM (3 mL) dropwise at –78 °C under N2 atmosphere. After being stirred for 30 min, the
resulting mixture was added (23S)-16 (0.4 mmol, 310 mg) in DCM (3 mL) and stirred for 1 h at –78 °C.
Et3N (2.2 mmol, 220 mg) was added and the whole mixture was warmed to rt, stirred for additional 30 min,
quenched with H2O, and extracted with CHCl3. The combined organic layer was dried over anhydrous
sodium sulfate, filtrated, and evaporated under reduced pressure. The residue was dissolved in THF (15
mL) and poured into a solution of NaClO2 and sulfamic acid in water. After being stirred for 15 min, the
reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate and extracted with
AcOEt. The combined organic layer was dried over anhydrous sodium sulfate, filtrated, and evaporated
under reduced pressure. The crude product was purified by column chromatography with silica gel (hexane
34
1
/ AcOEt = 4: 1) to afford (23S)-17 (270 mg, 85%). []D –61.7 (c 1.00, CHCl3). H NMR (400 MHz,
CDCl3) : 7.70–7.66 (4H, m), 7.43–7.26 (11H, m), 5.39–5.30 (4H, m), 4.57 (2H, s), 3.88–3.82 (2H, m),
2.62 (1H, dd, J = 6.9, 15.5 Hz), 2.58 (1H, dd, J = 5.2, 15.5 Hz), 2.19–1.97 (8H, m), 1.70–1.51 (2H, m),
1.38–1.03 (20H, m), 0.89–0.88 (12H, m). 13C NMR (100 MHz, CDCl3) : 175.8, 138.0, 135.9, 135.9, 134.8,
134.5, 132.3, 130.2, 129.4, 129.1, 128.4, 127.8, 127.7, 127.4, 126.7, 75.7, 71.5, 69.6, 42.8, 39.3, 34.1, 32.8,
29.7, 29.6, 29.3, 27.3, 27.2, 27.0, 25.1, 22.9, 19.2. IR (film) cm-1: 2930, 2855, 1710, 1560, 1520. MS (ESI+)
m/z: 725 (M+H+), 509 (base peak). HRMS (ESI+) m/z: Found 725.5000 (Calcd for C47H69O4Si (M+H+)
725.4965). (23R)-17 76%, []D29 +10.6 (c 0.8, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.70–7.66 (4H, m),
7.43–7.26 (11H, m), 5.39–5.30 (4H, m), 4.57 (2H, s), 3.88–3.82 (2H, m), 2.62 (1H, dd, J = 6.9, 15.5 Hz),
2.58 (1H, dd, J = 5.2, 15.5 Hz), 2.19–1.97 (8H, m), 1.70–1.51 (2H, m), 1.38–1.03 (20H, m), 0.89–0.88 (12H,
m). 13C NMR (100 MHz, CDCl3) : 177.2, 138.2, 135.8, 134.7, 132.2, 130.2, 129.4, 129.3, 129.0, 128.3,
127.8, 127.6, 127.4, 127.3, 126.7, 75.7, 71.5, 69.6, 42.7, 396, 34.2, 32.7, 29.7, 29.6, 29.5, 29.3, 27.4, 27.2,
27.1, 25.1, 22.8, 19.2. IR (film) cm-1: 2920, 2860, 1710. MS (ESI+) m/z: 747 (M+Na+), 509 (base peak).
HRMS (ESI+) m/z: Found 747.4831 (Calcd for C47H68NaO4Si (M+Na+) 747.4785).

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HETEROCYCLES, Vol. 88, No. 2, 2014
(3R,16Z,20E,23S)-3-Benzyloxy-23-hydroxytetracosa-16,20-dienoic acid (23S)-3. To a solution of
(23S)-17 (1.1 mmol, 820 mg) in THF (30 mL) was added TBAF (1.0 M in THF, 10 mmol, 10 mL) dropwise
at 0 °C under Ar atmosphere. After being stirred for 48 h, the reaction mixture was quenched with saturated
aqueous NH4Cl and extracted with AcOEt. The combined organic layer was dried over anhydrous sodium
sulfate, filtrated, and evaporated under reduced pressure. The crude product was purified by column
chromatography with silica gel (hexane / AcOEt = 4: 1) to afford (23S)-3 (440 mg, 79%). []D26 –0.30 (c
1.00, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.34–7.28 (5H, m), 5.57–5.30 (4H, m), 4.57 (2H, s), 3.87 (1H,
quin, J = 6.0 Hz), 3.83–3.75 (1H, m), 2.62 (2H, dd, J = 6.9, 15.5 Hz), 2.56 (2H, dd, J = 5.2, 15.5 Hz),
2.23–1.96 (8H, m), 1.71–1.52 (2H, m), 1.28–1.26 (20H, m), 1.19 (3H, d, J = 6.2 Hz). 13C NMR (100 MHz,
CDCl3) : 175.0, 138.3, 133.8, 130.4, 128.8, 128.2, 127.7, 127.5, 126.2, 75.9, 71.4, 67.8, 67.1, 42.4, 39.5,
34.2, 32.6, 29.6, 29.5, 29.2, 29.0, 27.2, 27.0, 25.5, 25.1, 22.4. IR (film) cm-1: 3520, 2930, 2860, 1650. MS
(ESI+) m/z: 509 (M+Na+), 468 (base peak). HRMS (ESI+) m/z: Found 509.3612 (Calcd for C31H50NaO4
(M+Na+) 509.3607). (23R)-3 66%, []D26 –2.20 (c 0.50, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.38–7.27
(5H, m), 5.59–5.51 (1H, m), 5.46–5.30 (3H, m), 4.57 (2H, s), 3.87 (1H, quin, J = 6.1 Hz), 3.81–3.73 (1H,
m), 2.63 (2H, dd, J = 6.7, 15.8 Hz), 2.56 (2H, dd, J = 5.4, 15.8 Hz), 2.24–2.17 (1H, m), 2.14–1.94 (7H, m),
1.71–1.52 (2H, m), 1.43–1.26 (20H, m), 1.19 (3H, d, J = 6.3 Hz). 13C NMR (100 MHz, CDCl3) : 175.1,
137.9, 134.1, 130.5, 128.8, 128.4, 127.8, 126.2, 75.7, 71.5, 67.1, 42.4, 39.1, 32.7, 29.6, 29.5, 29.3, 27.2,
27.0, 25.0, 22.5. IR (film) cm-1: 3420, 2920, 2860, 1710. MS (ESI+) m/z: 509 (M+Na+), 468 (base peak).
HRMS (ESI+) m/z: Found 509.3599 (Calcd for C31H50NaO4 (M+Na+) 509.3607).
(3R,16Z,20E,23S)-3-Benzyloxytetracosa-16,20-dien-23-olide (23S)-18. To a solution of MNBA (0.01
mmol, 33 mg) and DMAP (0.22 mmol, 27 mg) in DCM (33 mL) was added a solution of (23S)-3 (0.07
mmol, 36 mg) in THF (46 mL) with syringe pump for 9 h at rt under N2 atmosphere. After being stirred for
additional 1 h, the reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate and
extracted with CHCl3. The combined organic layer was dried over anhydrous sodium sulfate, filtrated, and
evaporated under reduced pressure. The crude product was purified by column chromatography with silica
gel (hexane / AcOEt = 20: 1) to afford (23S)-18 (27 mg, 79%). []D27 –6.39 (c 1.20, CHCl3). 1H NMR (400
MHz, CDCl3) : 7.34–7.27 (5H, m), 5.52–5.31 (4H, m), 4.98–4.90 (1H, m), 4.56 (1H, d, J = 11.4 Hz), 4.52
(1H, d, J = 11.4 Hz), 3.89–3.83 (1H, m), 2.65 (1H, dd, J = 5.9, 14.8 Hz), 2.43 (1H, dd, J = 7.0, 14.8 Hz),
2.23 (2H, dt, J = 5.5, 6.2 Hz), 2.10–1.99 (6H, m), 1.57 (2H, m), 1.41–1.24 (20H, m), 1.21 (3H, d, J = 6.3 Hz).
13C NMR (100 MHz, CDCl3) : 171.3, 138.6, 133.4, 130.4, 129.1, 128.3, 127.8, 127.6, 125.2, 76.0, 71.3,
70.6, 39.9, 39.1, 33.9, 32.8, 29.0, 28.6, 28.4, 28.2, 27.3, 26.7, 24.4, 19.5. IR (film) cm-1: 2920, 2860, 1730.
MS (EI) m/z: 468 (M+), 91 (base peak). HRMS (EI) m/z: Found 468.3629 (Calcd for C31H48O3 (M+)
468.3603). (23R)-18 67%, []D22 +5.26 (c 1.40, CHCl3). 1H NMR (400 MHz, CDCl3) : 7.34–7.27 (5H, m),

HETEROCYCLES, Vol. 88, No. 2, 2014
1187
5.48 (1H, dt, J = 6.2, 15.3 Hz) 5.40–5.30 (3H, m), 4.97–4.89 (1H, m), 4.58 (1H, d, J = 11.5 Hz), 4.51 (1H, d,
J = 11.5 Hz), 3.86–3.80 (1H, m), 2.65 (1H, dd, J = 5.5, 13.9 Hz), 2.44 (1H, dd, J = 7.3, 14.2 Hz), 2.24 (2H,
sext, J = 7.2 Hz), 2.12–1.96 (6H, m), 1.61–1.53 (2H, m), 1.44–1.25 (20H, m), 1.20 (3H, d, J = 6.6 Hz). 13C
NMR (100 MHz, CDCl3) : 170.9, 138.5, 133.5, 130.4, 129.1, 128.3, 127.7, 127.5, 125.0, 7.58, 71.1, 70.6,
40.1, 39.0, 33.7, 32.7, 29.0, 28.6, 28.5, 28.4, 28.3, 27.2, 26.7, 24.2, 19.3. IR (film) cm-1: 2920, 2860, 1730.
MS (ESI+) m/z: 468 (M+Na+). HRMS (ESI+) m/z: Found 491.3500 (Calcd for C31H47NaO3 (M+Na+)
491.3501).
(3R,16Z,20E,23S)-3-Hydroxytetracosa-16,20-dien-23-olide (23S)-2. To a solution of (23S)-18 (0.07
mmol, 33 mg) and 2-methyl-2-butene (3.5 mmol, 245 mg) in DCM (15 mL) was added dropwise a solution
of TiCl4 (0.35 mmol, 60 mg) in DCM (1 mL) at 0 °C under Ar atmosphere. After being stirred for 15 min,
the reaction mixture was quenched with H2O and extracted with CHCl3. The combined organic layer was
dried over anhydrous sodium sulfate, filtrated, and evaporated under reduced pressure. The crude product
was purified by column chromatography with silica gel (hexane / AcOEt = 4: 1) to afford (23S)-2 (28 mg,
99%). []D30 –28.1 (c 0.70, CHCl3). 1H NMR (400 MHz, CDCl3) : 5.54–5.31 (4H, m), 5.04–4.96 (1H, m),
3.98–3.95 (1H, m), 2.87 (1H, br), 2.49 (1H, dd, J = 3.6, 16.0 Hz), 2.40 (1H, dd, J = 8.4, 16.0 Hz), 2.33–2.19
(2H, m), 2.10–2.00 (6H, m), 1.59–1.28 (22H, m), 1.24 (3H, d, J = 6.3 Hz). 13C NMR (100MHz, CDCl3) :
172.4, 133.5, 130.3, 128.9, 125.1, 70.7, 67.9, 41.5, 39.0, 35.8, 32.7, 29.2, 28.4, 28.3, 28.1, 28.03, 28.0, 27.8,
27.1, 26.9, 24.5, 19.6. IR (film) cm-1: 3440, 2920, 2860, 1720, 1650. MS (ESI+) m/z: 379 (M+H+), 401
(base peak, M+Na+). HRMS (ESI+) m/z: Found 379.3212 (Calcd for C24H43O3 (M+H+) 379.3210). (23R)-2
24
1
83%, []D +10.8 (c 0.87, CHCl3). H NMR (400 MHz, CDCl3) : 5.50 (1H, dt, J = 6.0, 15.3 Hz),
5.42–5.32 (3H, m), 5.04–4.96 (1H, m), 3.95–3.94 (1H, m), 2.91 (1H, br), 2.51 (1H, dd, J = 4.4, 15.8 Hz),
2.43 (1H, dd, J = 7.5, 15.8 Hz), 2.35–2.19 (2H, m), 2.13–1.97 (6H, m), 1.55–1.28 (22H, m), 1.24 (3H, d, J
= 6.3 Hz). 13C NMR (100 MHz, CDCl3) : 172.3, 133.7, 130.6, 129.0, 124.9, 70.8, 68.2, 41.2, 39.0, 36.0,
33.7, 29.1, 28.6, 28.4, 28.3, 28.1, 28.0, 27.9, 27.8, 27.1, 26.9, 24.5, 19.6. IR (film) cm-1: 3440, 2920, 2860,
1730. MS (ESI+) m/z: 401 (base peak, M+Na+). HRMS (ESI+) m/z: Found 401.3041 (Calcd for
C24H42NaO3 (M+Na+) 401.3032).
(3R,16Z,20E,23S)-Eushearilide (23S)-1 To a solution of (23S)-2 (0.1 mmol, 40 mg) in toluene (1 mL) was
added a solution of 2-chloro-2-oxo-1,3,2- dioxaphosphorane (5.3 mmol, 750 mg) in toluene (1 mL) at 0 °C
under N2 atmosphere. After being stirred for 15 min, Et3N (2.1 mmol, 210 mg) was added to the reaction
mixture, stirred for additional 18 h, quenched with H2O, and extracted with AcOEt. The combined organic
layer was dried over anhydrous sodium sulfate, filtrated, and evaporated under reduced pressure. The
residue was dissolved in a (2 mL) and liquid Me3N (2 mL) was added. After the reaction mixture was stirred
for 18 h at 70 °C with sealed tube, and evaporated under reduced pressure. The residue was filtered with

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HETEROCYCLES, Vol. 88, No. 2, 2014
amino silica gel (CHCl3 / hexane = 5: 1 to CHCl3 / MeOH = 3: 1) and purified by column chromatography
with SephadexTM LH-20 to afford (23S)-1 (26 mg, 52%). []D –12.0 (c 0.34, MeOH). 1H NMR (400 MHz,
CD3OD) : 5.50 (1H, dt, J = 6.5, 15.2 Hz), 5.42–5.31 (3H, m), 4.92–4.85 (1H, m), 4.58–4.49 (1H, m),
4.29–4.23 (2H, m), 3.64–3.61 (2H, m), 3.22 (9H, s), 2.82 (1H, dd, J = 4.7, 15.0 Hz), 2.51 (1H, dd, J = 8.3,
15.0 Hz), 2.31–2.20 (2H, m), 2.14–1.98 (6H, m), 1.68–1.62 (2H, m), 1.43–1.28 (20H, m), 1.20 (3H, d, J =
6.3 Hz). 13C NMR (100 MHz, CD3OD) : 172.0, 134.7, 131.3, 130.2, 126.5, 74.1 (d, J = 6.0 Hz), 72.0, 67.6,
60.3 (d, J = 5.0 Hz), 54.7, 41.6 (d, J = 3.3 Hz), 40.2, 36.1 (d, J = 5.1 Hz), 33.9, 30.0, 29.8, 29.7, 29.6, 29.4,
29.2, 28.4, 27.5, 25.4, 19.8. IR (film) cm-1: 3380, 2920, 2860, 1720, 1650. MS (ESI+) m/z: 544 (M+H+),
304 (base peak). HRMS (ESI+) m/z: Found 544.3793 (Calcd for C29H55NO6P (M+H+) 544.3767). (23R)-1
35%, []D21 –1.79 (c 0.39, MeOH). 1H NMR (400 MHz, CD3OD) : 5.56–5.47 (1H, m), 5.43–5.31 (3H, m),
4.92–4.86 (1H, m), 4.58–4.50 (1H, m), 4.28–4.22 (2H, m), 3.64–3.61 (2H, m), 3.21 (9H, s), 2.82 (1H, dd, J
= 4.6, 14.4 Hz), 2.53 (1H, dd, J = 8.5, 14.4 Hz), 2.34–2.19 (2H, m), 2.15–1.98 (6H, m), 1.68–1.61 (2H, m),
1.50–1.40 (20H, m), 1.20 (3H, d, J = 6.3 Hz). 13C NMR (100 MHz, CD3OD) : 171.8, 134.8, 131.3, 130.3,
126.4, 74.1 (d, J = 6.0 Hz), 72.3, 67.5, 60.3 (d, J = 5.0 Hz), 54.7, 42.1 (d, J = 3.3 Hz), 40.1, 36.1 (d, J = 5.1
Hz), 33.8, 30.0, 29.9, 29.8, 29.7, 29.4, 29.2, 28.4, 27.5, 25.4, 19.7. IR (film) cm-1: 3380, 2920, 2860, 1720.
MS (ESI+) m/z: 544 (M+H+), 304 (base peak). HRMS (ESI+) m/z: Found 544.3785 (Calcd for C29H55NO6P
(M+H+) 544.3767).
ACKNOWLEDGEMENTS
We thank Dr. Ken-ichi Kawai and Dr. Tomoo Hosoe for their assistance with the spectral analysis of
eushearilide. This work was supported in part by the Science Research Promotion Fund from the Promotion
and Mutual Aid Corporation for Private Schools of Japan.
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