Synthesis and stereochemistry of musacins isolated from Streptomyces griseoviridis (FH-S 1832)

Article abstract of DOI:10.1039/b415759c

Musacins E (1a), B₁, (2a) and B₂ (3a) have been synthesized starting from D-erythronolactone, L-tartaric acid and (S)-malic acid. The absolute stereochemistry of musacins was unambiguously established by this synthesis.

Full text of DOI:10.1039/b415759c

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A R T I C L E
Synthesis and stereochemistry of musacins isolated from
Streptomyces griseoviridis (FH-S 1832)
Toshihiko Ueki and Takamasa Kinoshita*
Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi-ku,
Osaka, 558-8585, Japan
Received 11th October 2004, Accepted 24th November 2004
First published as an Advance Article on the web 14th December 2004
Musacins E (1a), B1 (2a) and B2 (3a) have been synthesized starting from D-erythronolactone, L-tartaric acid and
(S)-malic acid. The absolute stereochemistry of musacins was unambiguously established by this synthesis.
1a (unit A), corresponding to compounds 12a and 12b, which
were prepared from D-erythronolactone and L-tartaric acid,
respectively (Scheme 1).
Introduction
New secondary metabolites of musacins A to F, which are highly
functionalized c-butyrolactones including a conjugated hydroxy
enone, have been isolated1 from Streptomyces griseoviridis (FH-
S 1832). The geometry of the double bonds was proposed
to be trans by spectroscopic analysis; however, the relative
and absolute configuration at the four stereogenic centers of
musacins B1 (2a) and B2 (3a) was not determined. An analogous
butyrolactone, lactone II, closely related to 2a and 3a has also
been reported.2 It is reported that the methyl ester (musacin
C) of the ring-opened c-lactone from musacin B1/B2 exhibits
anthelminthic and weak antiviral activities against adenoviruses,
HSV-1 and HSV-2, and the influenza virus. Thus, it is important
to clarify the stereostructure for exploring structure–activity
relationships among musacins. We describe herein the synthesis
and structure of musacins E, B1 and B2. Our synthetic plan is
briefly illustrated in Fig. 1.
The requisite acid 13a (a-series) was synthesized as shown in
Scheme 1. The protected ester 5 was obtained from the lactone
4 [prepared from D-erythronolactone] by successive alkaline
hydrolysis, silyl protection and esterification with diazomethane.
Diisobutylaluminium hydride reduction of 5 afforded the alde-
hyde 7a in 92% yield. The Takai reaction3 of 7a gave the trans
olefin 8a in good yield as a single product. Cyclohexylidene
protection was superior to acetonide protection in this coupling
reaction. Deprotection of the silyl group in 8a with tetrabutylam-
monium fluoride afforded the alcohol 9a, which was converted
to the aldehyde 10a by the Swern oxidation. The trans a,b-
unsaturated ester 11a was obtained in 93% yield as a single
product by the Horner–Wadsworth–Emmons reaction.4 After
alkaline hydrolysis of 11a, the selective reduction of the acid 12a
with sodium borohydride5 gave 13a in 87% yield.
Another isomer 13b (b-series) was synthesized from L-tartaric
acid. The alcohol 6 was obtained by the selective silyl protection
of the known diol6 which was derived from L-tartaric acid. The
aldehyde 7b obtained from 6 by the Dess–Martin oxidation was
also converted to 13b by a subsequent series of reactions in the
same manner.
Synthesis of 1a
Acid-catalyzed hydrolysis of 13a and 13b in hot 1,4-dioxane with
concentrated hydrochloric acid gave the c-lactone 1a and 1b in 79
and 68% yield, respectively (Scheme 2). The compound 1a was
found to be identical with the natural product1 by comparing
1
the optical rotation, MS, H and 13C NMR spectra with those
reported, while the physical data of 1b were all different except
the MS. Epimerization of the hydroxyl group in 1b by the
Mitsunobu reaction7 afforded 1c in 74% yield. Compound 1c
was identical with 1a in all respects except for the sign of specific
optical rotation.
Synthesis of 2a and 3a
Coupling reaction of the acid 12a with the known lactone 14a8
[prepared from (S)-malic acid] provided separable compounds
15a (47%) and 15b (22%). The stereochemistries of these
compound were confirmed by 1H NMR analysis and NOE
experiments (Fig. 2). The signals of H-2 appeared at d 4.48
(J = 8.8 Hz) in 15a and d 4.62 (J = 7.9 Hz) in 15b. A smaller
NOE (0.3%) in 15a and a larger NOE (3.5%) in 15b were
observed. From these results, 15a and 15b are presumed to be
2,3-trans and 2,3-cis isomers, respectively. On treatment of 15a
Fig. 1
Results and discussion
Synthesis of the acid unit A
We have assumed that musacin E is the intramolecular ester of
the 4,5-dihydroxyocta-6-enoic acid moiety of musacin B1/B2,
in which esterification takes place with 4-OH to result in
a c-lactone. First, it is necessary to establish the absolute
stereochemistry of the dihydroxyl group at the 4,5-position in
◦
or 15b with acetic acid in tetrahydrofuran at 80 C to remove
the cyclohexylidene and tetrahydropyranyl protection, the final
products 2a and 2b were obtained, respectively, in satisfactory
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2
2 9 5
©

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Scheme 1 Reagents, conditions and yields: (i) cyclohexanone, p-TsOH, toluene, reflux, 80%; (ii) (a) KOH, THF, H2O, rt; (b) TBDMSCl, DMF,
imidazole, rt; (c) diazomethane, ether, 76% (3 steps); (iii) DIBAL, CH2Cl2, −78 ◦C, 92%; (iv) ref. 5; (v) NaH, TBDMSCl, THF, rt, 89%; (vi)
Dess–Martin periodinane, CH2Cl2, 92%; (vii) CrCl2, CH3CHI2, THF, rt, 85%; (viii) TBAF, THF, rt, 100% for 8a, 97% for 8b; (ix) (a) (COCl)2,
DMSO, Et3N, CH2Cl2, −78 ◦C; (b) NaH, (EtO)2P(O)CH2CO2Et, THF, rt, 93% for 11a, 91% for 11b (2 steps); (x) KOH, EtOH, H2O, rt, 97% for 12a,
93% for 12b; (xi) NaBH4, EtOH, 40 ◦C, 87% for 13a, 98% for 13b.
Direct synthesis of 2a and 3a by the rearrangement reaction
We have observed8 the interesting rearrangement via intramolec-
ular double esterification of the 3-oxymethyl anion, generated
from 2,3-trans-3-silyloxymethyl-1ꢀ-ketoalkyl-4-butanolides, as
shown in Scheme 4. It is assumed that both the compounds
15a and 17a are able to be concurrently synthesized from 21
by using this reaction. The key compound 21 was prepared
from 11a by way of four steps (Scheme 5). The alcohol 19
obtained from 11a by diisobutylaluminium hydride reduction
was transformed into the aldehyde 20 by the Dess–Martin
Scheme 2 Reagents, conditions and yields: (i) HCl, 1,4-dioxane, 50 ◦C,
68% for 1a, 79% for 1a; (ii) (a) Ph3P, diethyl azodicarboxylate, benzoic
acid, THF, rt, 94%; (b) KOH, EtOH, H2O, rt, 79%.
oxidation. Alkylation of 20 with the lactone 14c8 and subsequent
oxidation afforded the ketone 21 in 81% yield. The treatment of
21 with tetrabutylammonium fluoride, as expected, provided 15a
(26%) and 17a (17%), along with 14a,b and 13a. It is probable
that the thermodynamically stable trans isomer 15a generated
predominantly in the final protonation stage and the low yield
of 15a and 17a resulted in hydrolysis of the products to give 13a
and 14a,b.
Conclusion
In conclusion, we have achieved the stereoselective synthesis
of musacins from D-erythronolactone and (S)-malic acid, and
determined their absolute configurations. The biological activ-
ities of compounds related to musacins are currently under
investigation and will be reported in due course.
Fig. 2 Coupling constants (J2,3) and NOEs of 15a, 15b and 21a.
Experimental
yield. Isomers 2c and 2d were synthesized from 12b and 14a, and
compounds 3a and 3b were also derived from 12a and 14b8 in the
same manner. The compounds 2a and 3b have similar H and
For general experimental procedures see ref. 8.
1
13C NMR spectra, as do 2b and 3a. This is most noticeable
in the C2–C3 coupling constants, because they have similar
stereochemistry on the lactone ring. Of the twelve compounds
(2a–d, 3a,b, 16a–d and 18a,b) synthesized as shown in Scheme 3,
2a and 18a (the triacetate of 3a) correspond to the reported
compounds, because the NMR and the specific rotations are the
closest match (see Experimental section). From these results,
the absolute configuration of musacin B1 (2a) and B2 (3a) were
determined as 2S,3R,4ꢀR,5ꢀS and 2R,3R,4ꢀR,5ꢀS, respectively.
2,3-O-Cyclohexylidene-a-D-erythronolactone 4
A mixture of a-D-erythronolactone (1.0 g, 8.47 mmol), cyclo-
hexanone (1.14 cm3, 11.0 mmol) and p-toluenesulfonic acid
(100 mg) in toluene (50 cm3) was refluxed for 15 h. After cooling
the mixture was poured into saturated aqueous NaHCO3, and
extracted with ether. The combined organic layers were washed
with brine, dried and concentrated. The residue was purified by
chromatography (hexane–ethyl acetate, 2 : 1) to give 4 (1.35 g,
2 9 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2

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Scheme 3 Reagents and conditions: (i) DCC, DMAP, camphorsulfonic acid, CH2Cl2, rt; (ii) AcOH, THF, 80 ◦C; (iii) Ac2O, pyridine, rt.
◦
80%) as a colorless needles; mp: 79–80 C (ethyl acetate); [a]D21
−106.6 (c 1.03, CHCl3); mmax(nujol)/cm−1 1773, 1456, 1371, 1184,
1113, 1061, 990 and 929; dH (300 MHz, CDCl3): 4.87 (1H, dd, J
3.7 and 5.7), 4.75 (1H, d, J 5.5), 4.48 (1H, d, J 11.1), 4.40 (1H,
dd, J 3.7 and 11.1), 1.57–1.67 (8H, m) and 1.40–1.42 (2H, m);
dC (75 MHz, CDCl3): 174.2 (s), 114.7 (s), 75.0 (d), 74.3 (d), 70.3
(t), 36.3 (t), 35.0 (t), 24.7 (t), 23.8 (t) and 23.6 (t); [Found: M+,
198.0895. C10H14O4 requires M, 198.0892].
Methyl (2R,3R)-4-(tert-butyldimethylsilyloxy)-2,3-O-
cyclohexylidenebutanoate 5
To a solution of 4 (527 mg, 2.66 mmol) in THF (5 cm3) was
added 50% aqueous KOH (2 cm3). After stirring for 45 min at
Scheme 4 Intramolecular double esterification of the 3-oxymethyl
anion.
room temperature, the mixture was concentrated to dryness. To
3
˚
the residue in DMF (20 cm ) was added 4 A molecular sieves
(5 g), imidazole (1.09 g, 16.0 mmol) and tert-butyldimethylsilyl
chloride (1.2 g, 8.0 mmol), and the mixture was stirred for 45 min
Scheme 5 Reagents, conditions and yields: (i) DIBAL, THF, −78 ◦C, 72%; (ii) Dess–Martin periodinane, CH2Cl2, 84%; (iii) (a) LDA, HMPA, THF,
−78 ◦C; (b) Dess–Martin periodinane, CH2Cl2, 81% (2 steps); (iv) TBAF, THF, 0 ◦C.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2
2 9 7

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at room temperature. The reaction mixture was quenched with
water and extracted with ether. After acidification (pH 4) of the
water layer with 3 M aqueous phosphoric acid, the aqueous
layer was extracted with ether. The combined organic layer was
washed with water, after esterification with diazomethane, dried
and concentrated. The residue was purified by chromatography
(hexane–ethyl acetate, 5 : 1) to give 5 (699 mg, 76%) as a colorless
oil; [a]2D2 −2.5 (c 0.89 CHCl3); mmax(film)/cm−1 2936, 2857, 1767,
1369, 1253, 1204 and 1107; dH (300 MHz, CDCl3): 4.63 (1H, d,
J 7.1), 4.38 (1H, dt, J 5.0 and 7.1), 3.78 (1H, dd, J 5.3 and 11.0),
3.73 (3H, s), 3.69 (1H, dd, J 4.7 and 11.0), 1.79–1.83 (2H, m),
1.58–1.67 (6H, m), 1.40–1.43 (2H, m), 0.88 (9H, s), 0.06 (3H, s)
and 0.05 (s, 3H); dC (75 MHz, CDCl3): 170.1 (s), 111.2 (s), 77.9
(d), 74.8 (d), 61.7 (t), 51.9 (q), 36.6 (t), 34.8 (t), 25.8 (q), 25.1 (t),
24.0 (t), 23.7 (t), 18.3 (s), −5.37 (q) and −5.43 (q); [Found: M+,
344.2043. C17H32O5Si requires M, 344.2019].
and −5.43 (q); [Found: M+, 326.2251. C18H34O3Si requires M,
326.2277].
(2S,3S,4E)-1-(tert-Butyldimethylsilyloxy)-2,3-O-
cyclohexylidene-4-hexene 8b
Dess–Martin periodinane (1.76 g, 4.14 mmol) was added to a
solution of 6 (655 mg, 2.07 mmol) in dichloromethane (40 cm3).
After stirring at room temperature for 2 h, the mixture was
diluted with ether and quenched by addition of saturated
aqueous NaHCO3 (20 cm3) and saturated aqueous sodium
thiosulfate (20 cm3). After dissolution of the precipitate that
was formed, the mixture was washed with aqueous NaHCO3
and water, dried and evaporated. The residue was purified by
chromatography to afford 7b as a pale yellow oil; dH (300 MHz,
CDCl3): 9.76 (1H, d, J 1.7), 4.31 (1H, dd, J 1.7 and 7.0), 4.12 (1H,
dt, J 4.6 and 7.0), 3.79 (2H, d, J 4.4), 1.61–1.62 (8H, m), 1.40–
1.43 (2H, m), 0.90 (9H, s) and 0.08 (6H, s); dC (75 MHz, CDCl3):
201.1 (d), 112.1 (s), 81.7 (d), 77.2 (d), 63.1 (t), 36.4 (t), 35.8 (t),
25.8 (q), 24.9 (t), 23.8 (t), 23.7 (t), 18.3 (s), −5.4 (q) and −5.5 (q).
The aldehyde 7b was treated with chromium(II) chloride
and 1,1-diiodoethene as described above to give 8b in 72%
yield (2 steps) as a colorless oil; [a]2D9 −7.7 (c 1.33, CHCl3);
mmax(film)/cm−1 2936, 2859, 1448, 1166, 1103, 1045 and 966; dH
(400 MHz, CDCl3): 5.79 (1H, qd, J 6.6 and 15.2), 5.47 (1H, dd,
J 7.6 and 15.2), 4.25 (1H, t, J 7.6), 3.63–3.80 (3H, m), 1.71 (3H,
d, J 6.6), 1.61–1.63 (8H, m), 1.38–1.40 (2H, m), 0.89 (9H, s) and
0.06 (6H, s); dC (100 MHz, CDCl3): 130.7 (d), 128.9 (d), 109.2
(s), 80.9 (d), 78.8 (d), 62.7 (t), 36.7 (t), 36.4 (t), 25.8 (q), 25.2
(t), 23.9 (t), 23.8 (t), 18.3 (s), 17.8 (q), −5.3 (q) and −5.4 (q);
[Found: M+, 326.2268. C18H34O3Si requires M, 326.2277].
(2S,3S)-4-(tert-Butyldimethylsilyloxy)-2,3-O-
cyclohexylidenebutan-1-ol 6
To a suspension of sodium hydride (60% dispersion in mineral
oil; 852 mg, 21.3 mmol) in THF (50 cm3) was added 2,3-O-
cyclohexylidene-L-threitol6 (2.15 g, 10.6 mmol) at 0 ◦C, and the
mixture was stirred for 45 min. Tert-butyldimethylsilyl chloride
(1.6 g, 10.6 mmol) was added to the mixture, and the reaction
mixture was stirred overnight. After quenching with water the
mixture was extracted with ether, washed with water, dried
and concentrated. The residue was purified by chromatography
(hexane–ethyl acetate, 8 : 1) to give 6 (2.98 g, 89%) as a colorless
oil; [a]2D7 +8.4 (c 0.86, CHCl3); dH (300 MHz, CDCl3): 3.98 (1H,
t, J 7.0), 3.84–3.91 (2H, m), 3.62–3.80 (3H, m), 1.57–1.62 (8H,
m), 1.38–1.40 (2H, m), 0.90 (9H, s) and 0.09 (6H, s); dC (75 MHz,
CDCl3): 109.6 (s), 79.8 (d), 77.7 (d), 63.9 (t), 62.9 (t), 36.6 (t),
36.5 (t), 25.8 (q), 25.1 (t), 23.9 (t), 23.8 (t), 18.3 (s) and −5.5 (q);
[Found: M+, 316.2053. C16H32O4Si requires M, 316.2070].
(2R,3S,4E)- and (2S,3S,4E)-2,3-O-cyclohexylidene-4-
hexen-1-ol 9a and 9b
To a solution of 8a (233 mg, 0.71 mmol) in THF (15 cm3)
was added tetra-n-butylammonium fluoride (1.0 M in THF,
2.1 cm3, 2.1 mmol) at 0 ◦C, and the mixture was stirred for
1 h at room temperature. The reaction mixture was quenched
with aqueous NH4Cl, and extracted with ether. The extract
was washed with water and brine, dried and concentrated. The
residue was purified by chromatography (hexane–ethyl acetate,
5 : 1) to give 9a (151 mg, 100%) as a colorless oil; [a]2D0 +34.8
(c 1.56, CHCl3); mmax(film)/cm−1 3424, 2936, 2859, 1448, 1364,
1283, 1166, 1041 and 971; dH (300 MHz, CDCl3): 5.84 (1H, qd,
J 6.5 and 15.2), 5.51 (1H, qdd, J 1.5, 8.2 and 15.2), 4.61 (1H,
dd, J 7.9 and 8.2), 4.20 (1H, ddd, J 5.8, 7.9 and 12.0), 3.58 (2H,
br s), 2.04 (1H, br s, OH), 1.74 (3H, dd, J 1.5 and 6.5), 1.60–1.64
(8H, m) and 1.39–1.40 (2H, m); dC (75 MHz, CDCl3): 131.6 (d),
125.7 (d), 109.1 (s), 77.82 (d), 77.80 (d), 62.2 (t), 37.6 (t), 34.6 (t),
25.1 (t), 23.6 (t) and 17.8 (q); [Found: M+, 212.1425. C12H20O3
requires M, 212.1412].
Compound 9b was obtained from 8b in 97% yield as a colorless
oil; [a]2D8 −19.2 (c 0.64, CHCl3); mmax(film)/cm−1 3481, 2936, 2861,
1450, 1365, 1281, 1166, 1105 and 1044; dH (400 MHz, CDCl3):
5.84 (1H, qd, J 6.4 and 15.4), 5.46 (1H, qdd, J 1.3, 8.3 and 15.4),
4.27 (1H, t, J 8.3), 3.80–3.85 (1H, m), 3.74–3.78 (1H, m), 3.56
(1H, ddd, J 3.7, 8.3 and 12.0), 1.92 (1H, dd, J 4.6 and 8.3), 1.73
(3H, dd, J 1.3 and 6.6), 1.61–1.68 (8H, m) and 1.38–1.40 (2H,
m); dC (100 MHz, CDCl3): 131.9 (d), 128.1 (d), 109.4 (s), 80.5
(d), 77.8 (d), 60.8 (t), 36.7 (t), 36.5 (t), 25.1 (t), 23.80 (t), 23.76
(t) and 17.8 (q); [Found: M+, 212.1387. C12H20O3 requires M,
212.1412].
(2R,3S,4E)-1-(tert-Butyldimethylsilyloxy)-2,3-O-
cyclohexylidene-4-hexene 8a
To a solution of 5 (618 mg, 1.79 mmol) in dichloromethane
(16 cm3) was added diisobutyl aluminium hydride (1.5 M in
◦
toluene, 1.32 cm3, 1.98 mmol) at −78 C, and the mixture was
stirred for 1 h. The reaction mixture was quenched by addition of
water, and the precipitated inorganic material was removed by
filtration through Celite. The filtrate was washed with water,
dried and concentrated to give aldehyde 7a: dH (300 MHz,
CDCl3): 9.68 (1H, d, J 2.2), 4.49 (1H, dd, J 2.2 and 6.9), 4.41
(1H, ddd, J 2.8, 3.8 and 6.9), 3.80 (1H, dd, J 3.8 and 11.3), 3.69
(1H, dd, J 2.8 and 11.3), 1.54–1.80 (8H, m), 1.40–1.43 (2H, m),
0.88 (9H, s), 0.05 (3H, s) and 0.04 (3H, s); dC (75 MHz, CDCl3):
200.5 (d), 111.3 (s), 80.5 (d), 79.4 (d), 60.6 (t), 36.5 (t), 34.5 (t),
25.7 (q), 25.0 (t), 23.9 (t), 23.7 (t), 18.1 (s), −5.5 (q) and −5.7 (q).
This was used without further purification in the following step.
To a suspension of chromium(II) chloride (1.33 g, 10.8 mmol)
in◦THF (20 cm3) under a nitrogen atmosphere in the dark at
0 C was added a solution of 7a and 1,1-diiodoethene (0.36 cm3,
3.59 mmol) in THF (5 cm3) in one portion. After stirring for
17 h at room temperature, water (20 cm3) was added and the
mixture was extracted with ether. The combined organic phase
was washed with saturated aqueous NaHCO3 and brine, dried
and concentrated. The residue was purified by chromatography
(hexane–ethyl acetate, 30 : 1) to give 8a (496 mg, 85%, 2 steps) as
a colorless oil; [a]D20 −1.04 (c 0.94, CHCl3); mmax(film)/cm−1 2935,
2857, 1251, 1098 and 967; dH (300 MHz, CDCl3): 5.77 (1H, dqd,
J 1.0, 6.4 and 15.2), 5.51 (1H, qdd, J 1.3, 8.3 and 15.2), 4.56
(1H, dd, J 6.8 and 7.7), 4.13 (1H, dd, J 6.2 and 12.2), 3.63 (1H,
dd, J 6.3 and 10.4), 3.59 (1H, dd, J 5.7 and 10.4), 1.72 (3H, dd, J
1.3 and 6.4), 1.57–1.62 (8H, m), 1.35–1.39 (2H, m), 0.88 (9H, s),
0.06 (3H, s) and 0.05 (3H, s); dC (75 MHz, CDCl3): 130.1 (d),
126.7 (d), 108.7 (s), 78.3 (d), 78.1 (d), 62.4 (t), 37.8 (t), 34.8 (t),
25.8 (q), 25.2 (t), 24.1 (t), 23.8 (t), 18.2 (s), 17.9 (q), −5.38 (q)
Ethyl (4R,5S,2E,6E)- and (4S,5S,2E,6E)-4,5-O-
cyclohexylidene-2,6-octadienoate 11a and 11b
A stirred solution of oxalyl chloride (0.1 cm3, 1.14 mmol) in
dichloromethane (15 cm3) was cooled to −78 ◦C, then a solution
of DMSO (0.16 cm3, 2.19 mmol) in dichloromethane (1 cm3) was
added dropwise and stirring was continued for 5 min. Next, a
2 9 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2

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solution of 9a (185.6 mg, 0.88 mmol) in dichloromethane (2 cm3)
was added drop◦wise over 5 min and the resultant slurry stirred
for 1 h at −78 C. After this period, triethylamine (0.61 cm3,
4.38 mmol) was added and the resultant slurry stirred for an
additional 5 min at −78 ◦C. The mixture was warmed to room
temperature over 5 min, and water was added. The mixture
was extracted with dichloromethane, washed with water, dried
and concentrated to give crude aldehyde 10a as a pale yellow oil,
which was used without further purification in the following step.
Ethyl diethylphosphonoacetate (0.26 cm3, 1.31 mmol) was
added dropwise to a suspension of sodium hydride (60%
dispersion in mineral oil; 52.5 mg, 1.31 mmol) in THF (15 cm3) at
0 ◦C, and the mixture was allowed to warm to room temperature
with stirring for 30 min. The aldehyde 10a was added to
the reaction mixture at 0 ◦C and stirred for 35 min. After
dilution with ether, the mixture was washed with water, dried
and concentrated. The residue was purified by chromatography
(hexane–ethyl acetate, 15 : 1) to give 11a (227 mg, 93%, 2 steps)
as a colorless oil; [a]1D9 +27.9 (c 1.40, CHCl3); mmax(film)/cm−1
2936, 2857, 1724, 1448, 1367, 1305, 1269, 1165 and 1034; dH
(300 MHz, CDCl3): 6.81 (1H, dd, J 5.3 and 15.6), 6.07 (1H, dd,
J 1.5 and 15.6), 5.82 (1H, qd, J 6.4 and 15.2), 5.35 (1H, qdd, J
1.5, 8.0 and 15.2), 4.70 (1H, ddd, J 1.5, 6.3 and 7.0), 4.66 (1H,
dd, J 7.0 and 8.3), 4.21 (2H, q, J 7.1), 1.72 (3H, dd, J 1.5 and
6.4), 1.60–1.63 (8H, m), 1.41–1.43 (2H, m) and 1.30 (3H, t, J
7.1); dC (75 MHz, CDCl3): 166.1 (s), 144.4 (d), 131.9 (d), 126.3
(d), 122.4 (d), 109.8 (s), 79.3 (d), 71.1 (d), 60.4 (t), 37.6 (t), 34.8
(t), 25.1 (t), 24.0 (t), 23.7 (t), 17.8 (q) and 14.2 (q); [Found: M+,
280.1677. C16H24O4 requires M, 280.1675].
(4R,5S,6E)- and (4S,5S,6E)-4,5-O-Cyclohexylidene-6-octenoic
acid 13a and 13b
To a solution of 12a (19.2 mg, 0.076 mmol) in ethanol (2 cm3)
was added sodium borohydride (10.4 mg, 0.25 mmol), and the
◦
mixture was stirred at 40 C for 15 h. A small amount of 1 M
hydrochloric acid was, with cooling, added to decompose excess
sodium borohydride, and the mixture was extracted with ether.
The extract was washed with water, dried and concentrated. The
residue was purified by chromatography to give 13a (16.9 mg,
87%) as a colorless oil; [a]2D9 +20.1 (c 0.73, CHCl3); dH (300 MHz,
CDCl3): 5.79 (1H, qd, J 6.4 and 15.2), 5.46 (1H, qdd, J 1.5, 8.4
and 15.2), 4.51 (1H, dd, J 6.1 and 8.4), 4.09 (1H, ddd, J 4.7,
6.1 and 9.3), 2.39–2.61 (2H, m), 1.68–1.79 (2H, m), 1.73 (3H,
dd, J 1.5 and 6.4), 1.58–1.65 (8H, m) and 1.38–1.40 (2H, m); dC
(100 MHz, CDCl3): 179.1 (s), 131.0 (d), 126.6 (d), 108.8 (s), 79.0
(d), 76.8 (d), 38.1 (t), 35.1 (t), 30.7 (t), 26.1 (t), 25.1 (t), 24.1 (t),
23.8 (t) and 17.9 (q); [Found: M+, 254.1512. C14H22O4 requires
M, 254.1518].
Compound 13b was obtained from 12b in 98% yield as a
colorless oil; [a]D31 −19.4 (c 1.34, CHCl3); mmax(film)/cm−1 2935,
2862, 2669, 1711, 1448, 1364 and 1113; dH (400 MHz, CDCl3):
5.82 (1H, qd, J 6.6 and 15.4), 5.42 (1H, qdd, J 1.5, 8.0 and
15.4), 3.98 (1H, dd, J 8.0 and 8.3), 3.66 (1H, dt, J 3.6 and 8.3),
2.44–2.62 (2H, m), 1.89–1.98 (1H, m), 1.77–1.84 (1H, m), 1.73
(3H, dd, J 1.5 and 6.6), 1.59–1.61 (8H, m) and 1.36–1.40 (2H,
m); dC (100 MHz, CDCl3): 179.1 (s), 131.1 (d), 126.6 (d), 109.1
(s), 81.9 (d), 78.9 (d), 36.7 (t), 36.5 (t), 30.6 (t), 26.1 (t), 25.1 (t),
24.1 (t), 23.8 (t) and 17.9 (q); [Found: M+, 254.1514. C14H22O4
requires M, 254.1518].
Compound 11b was obtained from 9b in 91% yield as a pale
yellow oil; [a]3D0 −17.1 (c 0.92, CHCl3); dH (400 MHz, CDCl3):
6.85 (1H, dd, J 5.1 and 15.6), 6.12 (1H, dd, J 1.5 and 15.6),
5.84 (1H, qd, J 6.6 and 15.4), 5.47 (1H, qdd, J 1.5, 8.0 and
15.4), 4.21 (2H, q, J 7.1), 4.19–4.23 (1H, m), 4.09 (1H, t, J 8.2),
1.74 (3H, dd, J 1.5 and 6.6), 1.61–1.69 (8H, m), 1.39–1.41 (2H,
m) and 1.30 (3H, t, J 7.1); dC (100 MHz, CDCl3): 166.0 (s),
143.4 (d), 132.4 (d), 126.7 (d), 122.4 (d), 110.1 (s), 81.6 (d), 79.5
(d), 60.5 (t), 36.6 (t), 36.2 (t), 25.0 (t), 23.8 (t), 23.7 (t), 17.8
(q) and 14.2 (q); [Found: M+, 280.1681. C16H24O4 requires M,
280.1675].
(4R)-4-[(1ꢀS,2ꢀE)-1ꢀ-Hydroxy-2ꢀ-butenyl]-4-butanolide 1a
(musacin E) and (4S)-4-[(1ꢀS,2ꢀE)-1ꢀ-hydroxy-2ꢀ-butenyl]-
4-butanolide 1b
To a solution of 13a (15.5 mg, 0.06 mmol) in 1,4-dioxane (3 cm3)
was added concentrated hydrochloric acid (0.5 cm3), and the
mixture was stirred at 50 ◦C for 12 h. The reaction mixture
was diluted with water, and extracted with ether. The extract
was washed with water, dried and concentrated. The resultant
oil was purified by chromatography (hexane–ethyl acetate, 2 :
1) to give 1a (7.5 mg, 79%) as a colorless oil; [a]2D1 +10.9 (c
0.10, CHCl3); {ref. 1 [a]D20 +10.8 (c 0.3, CHCl3)}; dH (300 MHz,
CDCl3): 5.87 (1H, dqd, J 1.0, 6.6 and 15.4 Hz), 5.44 (1H, qdd, J
1.7, 6.6 and 15.4), 4.50 (1H, dt, J 3.1 and 7.3), 4.37–4.44 (1H, m),
2.49–2.61 (2H, m), 2.15–2.25 (2H, m), 1.94 (1H, d, J 3.6, OH)
and 1.74 (3H, ddd, J 1.0, 1.5 and 6.6); dC (100 MHz, CDCl3):
177.4 (s), 130.4 (d), 127.4 (d), 82.3 (d), 72.8 (d), 28.5 (t), 21.3 (t)
and 17.9 (q); [Found: (M + H)+, 157.0837. C8H13O3 requires M,
157.0865].
Compound 1b was obtained from 13b in 68% yield as a
colorless oil; [a]2D8 +35.2 (c 0.20, CHCl3); dH (300 MHz, CDCl3):
5.86 (1H, dqd, J 1.0, 6.6 and 15.4), 5.52 (1H, qdd, J 1.7, 6.3
and 15.4), 4.44 (1H, dt, J 5.4 and 7.1), 4.09 (1H, br t, J 6.4),
2.50–2.61 (2H, m), 2.05–2.26 (2H, m) and 1.74 (3H, dd, J 1.0
and 6.3); dC (75 MHz, CDCl3): 177.1 (s), 130.8 (d), 127.9 (d),
82.7 (d), 74.9 (d), 28.4 (t), 23.7 (t) and 17.8 (t); [Found: (M +
H)+, 157.0837. C8H13O3 requires M, 157.0865].
(4R,5S,2E,6E)- and (4S,5S,2E,6E)-4,5-O-cyclohexylidene-2,6-
octadienoic acid 12a and 12b
To a solution of 11a (38.1 mg, 0.14 mmol) in ethanol (3 cm3) was
added 50% aqueous KOH (0.04 cm3), and the mixture was stirred
for 45 min at room temperature. After removal of ethanol, water
was added and acidified (pH 4) with 3 M aqueous phosphoric
acid. The aqueous solution was extracted with ether, and the
extract was dried and concentrated. The residue was purified
by chromatography (hexane–ethyl acetate, 2 : 1) to give 12a
(33.4 mg, 97%) as a white wax; [a]2D0 +33.1 (c 1.43, CHCl3); dH
(300 MHz, CDCl3): 6.92 (1H, dd, J 5.1 and 15.6), 6.09 (1H, dd,
J 1.5 and 15.6), 5.83 (1H, qd, J 6.6 and 15.0), 5.33 (1H, qdd, J
1.7 Hz, 8.2 and 15.0), 4.74 (1H, ddd, J 1.5, 5.1 and 6.8), 4.68 (1H,
dd, J 6.8 and 8.2), 1.72 (3H, dd, J 1.7 and 6.6), 1.59–1.69 (8H,
m) and 1.41–1.43 (2H, m); dC (75 MHz, CDCl3): 171.3 (s), 147.2
(d), 132.0 (d), 126.1 (d), 121.6 (d), 110.0 (s), 79.3 (d), 76.9 (d),
37.5 (t), 34.7 (t), 25.0 (t), 24.0 (t), 23.7 (t) and 17.8 (q); [Found:
(M − H)+, 251.1270. C14H19O4 requires M, 251.1283].
(4S)-4-[(1ꢀR,2ꢀE)-1ꢀ-Hydroxy-2ꢀ-butenyl]-4-butanolide 1c
Compound 12b was obtained from 11b in 93% yield as a
white wax; [a]2D9 −22.4 (c 1.63, CHCl3); dH (400 MHz, CDCl3):
6.97 (1H, dd, J 4.9 and 15.6), 6.15 (1H, dd, J 1.0 and 15.6), 5.85
(1H, qd, J 6.6 and 15.4), 5.48 (1H, qdd, J 1.7, 8.0 and 15.4),
4.25 (1H, ddd, J 1.7, 4.9 and 8.4), 4.10 (1H, t, J 8.4), 1.75 (3H,
dd, J 1.7 and 6.6), 1.63–1.70 (8H, m) and 1.41–1.44 (2H, m);
dC (100 MHz, CDCl3): 171.3 (s), 146.3 (d), 132.7 (d), 126.6 (d),
121.4 (d), 110.4 (s), 81.5 (d), 79.3 (d), 36.6 (t), 36.2 (t), 25.0 (t),
23.8 (t), 23.7 (t) and 17.8 (q); [Found: M+, 252.1349. C14H20O4
requires M, 252.1362].
To a mixture of 1b (16 mg, 0.10 mmol), triphenylphosphine
(54 mg, 0.21 mmol), benzoic acid (25 mg, 0.21 mmol) in
THF (7 cm3) was added diethyl azodicarboxylate (0.02 cm3,
0.21 mmol) in THF (2 cm3), and the mixture was stirred for
23 h at room temperature. After concentration the resultant oil
was purified by chromatography (hexane–ethyl acetate, 3 : 1) to
give the benzoate (24.5 mg, 94%) as a colorless oil; [a]3D0 +24.6
(c 1.40, CHCl3); dH (300 MHz, CDCl3): 8.01–8.04 (2H, m), 7.41–
7.60 (3H, m), 5.99 (1H, dq, J 6.6 and 15.0), 5.63 (1H, dd, J 3.3
and 7.6), 5.54 (1H, ddq, J 1.5, 7.6 and 15.0 Hz), 4.74 (1H, ddd,
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2
2 9 9

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J 0.9, 3.5 and 6.8), 2.48–2.68 (2H, m), 2.16–2.42 (2H, m) and
1.76 (3H, dd, J 1.5 and 6.6); dC (100 MHz, CDCl3): 176.7 (s),
165.4 (s), 133.6 (s), 133.2 (d), 129.6 (d), 128.4 (d), 128.1 (d), 123.3
(d), 80.3 (d), 75.5 (d), 27.9 (t), 22.8 (t) and 18.0 (q); [Found: M+,
260.1031. C15H16O4 requires M, 260.1049].
Hydrolysis of the benzoate with KOH in ethanol–water gave
1c (12.6 mg, 79%) as a colorless oil; [a]2D7 −13.0 (c 0.28, CHCl3);
dH (300 MHz, CDCl3): 5.87 (1H, dqd, J 1.1, 6.6 and 15.4), 5.44
(1H, qdd, J 1.7, 6.6 and 15.4), 4.48–4.51 (1H, m), 4.37–4.41 (1H,
m), 2.53–2.56 (2H, m), 2.18–2.22 (2H, m) and 1.74 (3H, ddd, J
0.9, 1.5 and 6.6); dC (75 MHz, CDCl3): 177.4 (s), 130.4 (d), 127.4
(d), 82.3 (d), 72.8 (d), 28.5 (t), 21.3 (t) and 17.9 (q); [Found: (M +
H)+, 157.0837. C8H13O3 requires M, 157.0865].
(d), 110.3 (s), 97.9 (d), 81.5 (d), 79.3 (d), 70.8 (d), 67.0 (t), 62.5
(t), 62.0 (t), 41.7 (d), 36.6 (t), 36.2 (t), 30.0 (t), 25.1 (t), 25.0 (t),
23.75 (t), 23.69 (t), 19.0 (t) and 17.8 (q); [Found: M+, 450.2248.
C24H34O8 requires M, 450.2254].
15d: 28% yield (colorless oil); dH (400 MHz, CDCl3): 6.86 (1H,
dd, J 5.1 and 15.6), 6.11 (1H, dd, J 1.5, and 15.6), 5.85 (1H, qd,
J 6.6 and 15.4), 5.47 (1H, qdd, J 1.5, 8.0 and 15.4), 5.09 (1H,
d, J 6.8), 4.62 (1H, d, J 7.8), 4.47 (1H, dd, J 4.6 and 11.4),
4.30–4.39 (3H, m), 4.19–4.23 (1H, m), 4.09 (1H, dd, J 7.6 and
8.6), 3.79–3.84 (1H, m), 3.55–3.57 (1H, m), 2.95–3.02 (1H, m),
1.75 (3H, dd, J 1.5 and 6.6), 1.62–1.69 (14H, m) and 1.40–1.41
(2H, m); dC (100 MHz, CDCl3): 174.2 (s), 165.6 (s), 144.6 (d),
132.4 (d), 126.6 (d), 121.4 (d), 110.2 (s), 98.0 (d), 81.5 (d), 79.4
(d), 69.3 (d), 67.6 (t), 62.7 (t), 61.1 (t), 38.8 (d), 36.6 (t), 36.1 (t),
29.9 (t), 25.1 (t), 24.9 (t), 23.7 (t), 23.6 (t), 19.0 (t) and 17.8 (q);
[Found: M+, 450.2248. C24H34O8 requires M, 450.2254].
General procedure for coupling of 12 with 14
To a mixture of 148 (38.3 mg, 0.18 mmol) and the carboxylic acid
12 (50.3 mg, 0.20 mmol) in dichloromethane (20 cm3) were added
4-dimethylaminopyridine (68.7 mg, 0.56 mmol), camphorsul-
fonic acid (10 mg), and 1,3-dicyclohexylcarbodiimide (116.0 mg,
0.56 mmol) at 0 ◦C. After stirring for 19 h at room temperature,
the mixture was concentrated. The residue (an isomeric mixture)
was separated by chromatography (hexane–ethyl acetate, 4 : 1)
to give 15 or 17.
General procedure for acid hydrolysis of THP and
cyclohexylidene groups
A solution of 15 or 17 (17.8 mg, 0.04 mmol) in acetic acid (2 cm3),
THF (1 cm3), and water (0.5 cm3) was stirred at 80 ◦C. After
stirring for 4 h the mixture was concentrated. The residue was
purified by chromatography on silica gel (10 g) with ethyl acetate
to give 2 or 3.
(2S,3R)- and (2S,3S)-3-[(4ꢀR,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-O-
Cyclohexylidene-1ꢀ-oxooct-2ꢀ,6ꢀ-dienyoxylmethyl]-2-
tetrahydropyranyloxy-4-butanolide 15a and 15b
(2S,3R)-4ꢀ,5ꢀ-Dihydroxy-1ꢀ-oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-
hydroxy-4-butanolide 2a (musacin B1) and (2S,3S)-3-
[(4ꢀR,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-dihydroxy-1ꢀ-oxooct-2ꢀ,6ꢀ-
dienyloxymethyl]-2-hydroxy-4-butanolide 2b
These compounds were obtained from 12a and 14a.
15a: 47% yield (colorless oil); [a]2D2 −64.5 (c 0.75, CHCl3); dH
(300 MHz, CDCl3): 6.85 (1H, dd, J 4.9 and 15.5), 6.09 (1H, dd,
J 1.1 and 15.5), 5.83 (1H, qd, J 6.5 and 15.2 Hz), 5.32 (1H, qdd,
J 1.5, 8.2 and 15.2), 5.16–5.18 (1H, m), 4.73 (1H, dd, J 1.1 and
7.0), 4.67 (1H, dd, J 7.0 and 8.3), 4.48 (1H, d, J 8.8), 4.43 (1H,
dd, J 4.1 and 11.7), 4.32 (1H, dd, J 6.4 and 11.7), 4.28 (1H, d, J
9.3), 4.07 (1H, dd, J 9.3 and 9.4), 3.51–3.58 (1H, m), 3.17 (1H,
m), 2.87–2.99 (1H, m), 1.72 (3H, dd, J 1.5 and 6.5), 1.57–1.83
(14H, m) and 1.40–1.45 (2H, m); dC (75 MHz, CDCl3): 174.6 (s),
165.6 (s), 146.1 (d), 132.0 (d), 126.2 (d), 121.1 (d), 110.0 (s), 97.9
(d), 79.2 (d), 76.9 (d), 70.7 (d), 67.1 (t), 62.6 (t), 61.9 (t), 41.7
(d), 37.6 (t), 34.7 (t), 30.1 (t), 25.2 (t), 25.0 (t), 24.0 (t), 23.7 (t),
19.0 (t) and 17.8 (q); [Found: M+, 450.2248. C24H34O8 requires
M, 450.2254].
Compound 2a was obtained from 15a in 72% yield as a colorless
oil; [a]2D6 −17.0 (c 0.36, MeOH); {ref. 1 [a]1D7 −10.1 (c 0.4,
MeOH)}; dH (500 MHz, CD3OD): 7.08 (1H, dd, J 4.5 and 15.5),
6.09 (1H, dd, J 1.5 and 15.5), 5.74 (1H, dqd, J 1.0, 6.5 and 15.5),
5.53 (1H, qdd, J 1.5, 7.5 and 15.5), 4.44 (1H, dd, J 8.0 and 9.0),
4.41 (1H, dd, J 4.0 and 11.5), 4.32 (1H, d, J 10.0), 4.30 (1H, dd,
J 6.5 and 11.5), 4.14 (1H, ddd, J 1.5, 4.5 and 5.5), 4.06 (1H, dd,
J 9.5 and 10.0), 3.98 (1H, dd, J 5.5 and 7.5), 2.76–2.79 (1H, m)
and 1.71 (3H, dd, J 1.5 and 6.5); dC (75 MHz, CD3OD): 178.5
(s), 167.6 (s), 150.3 (d), 131.4 (d), 129.6 (d), 121.6 (d), 76.4 (d),
75.1 (d), 69.9 (d), 68.1 (t), 63.3 (t), 44.9 (d) and 18.0 (q); [Found:
(M − H)+, 285.0970. C13H17O7 requires M, 285.0974].
Compound 2b was obtained from 15b in 60% yield as a
colorless oil; [a]21 +51.8 (c 0.34, MeOH); dH (500 MHz, CD3OD):
7.02 (1H, dd, J D5.0 and 15.5), 6.03 (1H, dd, J 2.0 and 15.5), 5.74
(1H, qd, J 6.5 and 15.5), 5.54 (1H, qdd, J 1.5, 7.0 and 15.5),
4.63 (1H, d, J 8.0), 4.40 (1H, dd, J 6.0 and 9.5), 4.37 (1H, dd,
J 4.0 and 11.5), 4.29 (1H, dd, J 2.0 and 9.5), 4.24 (1H, dd, J
5.5 and 11.5), 4.14 (1H, ddd, J 2.0, 5.0 and 6.5), 3.98 (1H, dd,
J 6.5 and 7.0), 2.90–2.93 (1H, m) and 1.71 (3H, dd, J 1.5 and
6.5); dC (75 MHz, CD3OD): 178.8 (s), 167.7 (s), 150.1 (d), 131.3
(d), 129.6 (d), 121.7 (d), 76.4 (d), 75.2 (d), 69.1 (d), 68.3 (t), 62.5
(t), 40.5 (d) and 18.0 (q); [Found: (M − H)+, 285.0965. C13H17O7
requires M, 285.0974].
15b: 22% yield (colorless oil); [a]2D3 −6.7 (c 0.5, CHCl3); dH
(300 MHz, CDCl3): 6.83 (1H, dd, J 5.0 and 15.6), 6.09 (1H, dd,
J 0.9 and 15.6), 5.83 (1H, qd, J 6.6 and 15.0), 5.33 (1H, dd, J
7.5 and 15.0), 5.11 (1H, m), 4.66–4.73 (2H, m), 4.62 (1H, d, J
7.9), 4.48 (1H, dd, J 4.6 and 11.6), 4.27–4.39 (3H, m), 3.78–3.85
(1H, m), 3.53–3.60 (1H, m), 2.94–3.04 (1H, m), 1.73 (3H, d, J
6.6), 1.57–1.80 (14H, m) and 1.41–1.42 (2H, m); dC (75 MHz,
CDCl3): 174.7 (s), 166.1 (s), 146.1 (d), 132.4 (d), 126.6 (d), 121.9
(d), 110.3 (s), 98.4 (d), 79.7 (d), 77.4 (d), 69.7 (d), 68.0 (t), 63.1
(t), 61.5 (t), 39.2 (d), 38.0 (t), 35.2 (t), 30.4 (t), 25.6 (t), 25.5 (t),
24.4 (t), 24.1 (t), 19.4 (t) and 18.2 (q); [Found: M+, 450.2235.
C24H34O8 requires M, 450.2254].
(2S,3R)- and (2S,3S)-3-[(4ꢀS,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-Dihydroxy-1ꢀ-
oxooct-2ꢀ,6ꢀ-dienyloxy-methyl]-2-hydroxy-4-butanolide 2c and
2d
(2S,3R)- and (2S,3S)-3-[(4ꢀS,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-O–
Cyclohexylidene-1ꢀ-oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-
tetrahydropyranyloxy-4-butanolide 15c and 15d
Compound 2c was obtained from 15c in 72% yield as a colorless
oil; [a]2D8 −70.0 (c 0.39, MeOH); dH (400 MHz, CD3OD): 7.02
(1H, dd, J 4.4 and 15.6), 6.09 (1H, dd, J 1.7 and 15.6), 5.74 (1H,
qd, J 6.4 and 15.4), 5.48 (1H, qdd, J 1.5, 7.3 and 15.4), 4.44
(1H, dd, J 8.3 and 8.8), 4.40 (1H, dd, J 4.4 and 11.5), 4.31 (1H,
d, J 11.2), 4.30 (1H, dd, J 6.1 and 11.2), 4.17 (1H, ddd, J 1.7,
4.4 and 5.9), 4.06 (1H, dd, J 9.3 and 10.0), 3.96 (1H, dd, J 5.9
and 7.4), 2.76–2.79 (1H, m) and 1.70 (3H, dd, J 1.5 and 6.4);
dC (100 MHz, CD3OD): 178.5 (s), 167.6 (s), 150.2 (d), 131.1 (d),
130.1 (d), 121.5 (d), 76.4 (d), 75.1 (d), 69.9 (d), 68.1 (t), 63.3 (t),
44.9 (d) and 18.0 (q); [Found: (M − H)+, 285.0965. C13H17O7
requires M, 285.0974].
These compounds were obtained from 12b and 14a.
15c: 43% yield (colorless oil); dH (400 MHz, CDCl3): 6.90 (1H,
dd, J 4.6 and 15.6), 6.15 (1H, dd, J 1.7 and 15.6), 5.85 (1H, qd,
J 6.6 and 15.4), 5.47 (1H, qdd, J 1.7, 8.0 and 15.4), 5.15–5.18
(1H, m), 4.47 (1H, dd, J 8.3 and 9.0), 4.424 (1H, d, J 9.5), 4.416
(1H, dd, J 4.0 and 11.5), 4.33 (1H, dd, J 6.6 and 11.5), 4.23 (1H,
ddd, J 1.7, 4.9 and 8.6), 4.05–4.13 (2H, m), 3.78–3.84 (1H, m),
3.52–3.56 (1H, m), 2.88–2.98 (1H, m), 1.75 (3H, dd, J 1.7 and
6.6), 1.60–1.69 (14H, m) and 1.41–1.43 (2H, m); dC (100 MHz,
CDCl3): 174.5 (s), 165.6 (s), 140.5 (d), 132.6 (d), 126.6 (d), 121.0
3 0 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2

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Compound 2d was obtained from 15d in 61% yield as a
colorless oil; [a]2D8 +5.6 (c 0.28, MeOH); dH (400 MHz, CD3OD):
6.97 (1H, dd, J 4.4 and 15.6), 6.04 (1H, dd, J 1.7 and 15.6), 5.74
(1H, qd, J 6.6 and 15.4), 5.49 (1H, qdd, J 1.5, 7.3 and 15.4),
4.62 (1H, d, J 8.1), 4.40 (1H, dd, J 6.4 and 9.8), 4.36 (1H, dd, J
3.9 and 11.2), 4.29 (1H, dd, J 2.2 and 9.8), 4.25 (1H, dd, J 5.6
and 11.2), 4.13 (1H, ddd, J 1.7, 4.4 and 6.1), 3.94 (1H, dd, J 6.1
and 7.4), 2.90–2.94 (1H, m) and 1.71 (3H, dd, J 1.5 and 6.6);
dC (100 MHz, CD3OD): 178.8 (s), 167.7 (s), 150.0 (d), 131.1 (d),
130.1 (d), 121.7 (d), 76.4 (d), 75.2 (d), 69.1 (d), 68.3 (t), 62.5 (t),
40.5 (d) and 18.0 (q); [Found: (M − H)+, 285.0969. C13H17O7
requires M, 285.0974].
and 1.73 (3H, dd, J 0.9 and 6.5); [Found: (M + H)+, 413.1445.
C19H25O10 requires M, 413.1449].
(2R,3R)- and (2R,3S)-3-[(4ꢀR,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-O-
Cyclohexylidene-1ꢀ-oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-
tetrahydropyranyl-4-butanolide 17a and 17b
These compounds were obtained from 12a and 14b.
17a: 39% yield (colorless oil); [a]2D3 +55.5 (c 1.40, CHCl3). dH
(300 MHz, CDCl3): 6.82 (1H, dd, J 5.0 and 15.6), 6.07 (1H, dd,
J 1.5 and 15.6), 5.82 (1H, qd, J 6.6 and 15.0), 5.34 (1H, qdd, J
1.5, 8.1 and 15.2), 5.10–5.12 (1H, m), 4.72 (1H, ddd, J 1.5, 5.0
and 6.8), 4.68 (1H, d, J 8.0), 4.63 (1H, d, J 7.8), 4.48 (1H, dd,
J 4.4 and 11.3), 4.37 (1H, dd, J 6.0 and 9.4), 4.27–4.33 (2H, m),
3.78–3.85 (2H, m), 3.53–3.60 (1H, m), 2.94–3.04 (1H, m), 1.72
(3H, dd, J 1.5 and 6.6), 1.57–1.67 (14H, m) and 1.41–1.42 (2H,
m); dC (75 MHz, CDCl3): 174.3 (s), 165.6 (s), 145.7 (d), 131.9 (d),
126.2 (d), 121.4 (d), 109.9 (s), 98.1 (d), 79.2 (d), 77.0 (d), 69.3 (d),
67.6 (t), 62.7 (t), 61.1 (t), 38.8 (d), 37.5 (t), 34.7 (t), 30.0 (t), 25.1
(t), 25.0 (t), 24.0 (t), 23.7 (t), 19.0 (t) and 17.8 (q); [Found: M+,
450.2251. C24H34O8 requires M, 450.2254].
General procedure for acetylation of triols 2 and 3
To a solution of 2 or 3 (10.9 mg, 0.038 mmol) in acetic anhydride
(1 cm3) and pyridine (1.5 cm3) was stirred at room temperature.
After stirring for 6 h the mixture was concentrated. The residue
was purified by chromatography on silica gel (10 g) with hexane–
ethyl acetate (1 : 1) to give 16 or 18.
17b: 49% yield (colorless oil); [a]2D4 +124.4 (c 0.80, CHCl3). dH
(300 MHz, CDCl3): 6.85 (1H, dd, J 4.7 and 15.7), 6.09 (1H, dd,
J 1.4 and 15.7), 5.83 (1H, qd, J 6.6 and 15.2), 5.32 (1H, qdd, J
1.5, 8.1 and 15.2), 5.16–5.18 (1H, m), 4.74 (1H, ddd, J 1.7, 4.5
and 6.6), 4.68 (1H, dd, J 7.1 and 8.0), 4.48 (1H, d, J 8.4), 4.43
(1H, d, J 9.3), 4.42 (1H, dd, J 4.3 and 11.8), 4.34 (1H, dd, J
6.2 and 11.8), 4.08 (1H, dd, J 9.3 and 9.5), 3.52–3.58 (2H, m),
2.87–3.00 (1H, m), 1.72 (3H, dd, J 1.5 and 6.6), 1.59–1.68 (14H,
m) and 1.41–1.43 (2H, m); dC (75 MHz, CDCl3): 174.6 (s), 165.6
(s), 146.1 (d), 132.0 (d), 126.2 (d), 121.0 (d), 110.0 (s), 97.9 (d),
79.2 (d), 76.9 (d), 70.7 (d), 67.0 (t), 62.5 (t), 61.9 (t), 41.7 (d),
37.6 (t), 34.7 (t), 30.6 (t), 25.2 (t), 25.0 (t), 24.0 (t), 23.7 (t), 19.0
(t) and 17.8 (q); [Found: M+, 450.2245. C24H34O8 requires M,
450.2254].
(2S,3R)- and (2S,3S)-3-[(4ꢀR,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-Diacetoxy-1ꢀ-
oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-acetoxy-4-butanolide 16a and
16b
Compound 16a was obtained from 2a in 78% yield as a colorless
oil; [a]2D2 −34.2 (c 0.21, CHCl3); dH (300 MHz, CD3OD): 6.89
(1H, dd, J 5.3 and 15.8), 6.01 (1H, dd, J 1.7 and 15.8), 5.86 (1H,
qd, J 6.4 and 15.2), 5.80–5.86 (1H, m), 5.57 (1H, ddd, J 1.6, 3.7
and 5.2), 5.44 (1H, d, J 9.5), 5.40–5.43 (1H, m), 4.54 (1H, dd, J
8.8 and 9.0), 4.38 (1H, dd, J 4.4 and 11.7), 4.30 (1H, dd, J 5.9
and 11.7), 4.14 (1H, dd, J 9.3 and 9.5), 3.00–3.03 (1H, m), 2.19
(3H, s), 2.13 (3H, s), 2.07 (3H, s) and 1.73 (3H, dd, J 1.0 and
6.4); dC (75 MHz, CDCl3): 171.5 (s), 169.9 (s), 169.7 (s), 169.6
(s), 165.0 (s), 142.5 (d), 133.1 (d), 123.8 (d), 122.5 (d), 74.2 (d),
72.9 (d), 68.8 (d), 66.8 (t), 61.8 (t), 41.0 (d), 21.0 (q), 20.8 (q),
20.5 (q) and 17.9 (q); [Found: (M + H)+, 413.1438. C19H25O10
requires M, 413.1449].
Compound 16b was obtained from 2b in 60% yield as a
colorless oil; [a]2D3 +73.1 (c 0.20, CHCl3); dH (300 MHz, CDCl3):
6.86 (1H, dd, J 5.3 and 15.8), 5.98 (1H, dd, J 1.6 and 15.8),
5.80–5.90 (2H, m), 5.63 (1H, d, J 8.2), 5.56 (1H, ddd, J 1.6, 3.7
and 5.3), 5.42 (1H, dd, J 3.3 and 6.8), 4.47 (1H, dd, J 5.7 and
9.7), 4.40 (1H, dd, J 1.7 and 9.7), 4.30 (1H, dd, J 4.4 and 11.7),
4.21 (1H, dd, J 5.5 and 11.7), 3.12–3.16 (1H, m), 2.20 (3H, s),
2.12 (3H, s), 2.07 (3H, s) and 1.74 (3H, dd, J 1.1 and 6.8); dC
(75 MHz, CDCl3): 171.3 (s), 169.9 (s), 169.7 (s), 169.6 (s), 165.0
(s), 142.4 (d), 133.0 (d), 123.9 (d), 122.5 (d), 74.2 (d), 72.8 (d),
67.6 (d), 67.5 (t), 61.1 (t), 37.2 (d), 21.0 (q), 20.8 (q), 20.4 (q)
and 17.8 (q); [Found: (M + H)+, 413.1455. C19H25O10 requires
M, 413.1449].
(2R,3R)-4ꢀ,5ꢀ-Dihydroxy-1ꢀ-oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-
hydroxy-4-butanolide 3a (musacin B2) and (2R,3S)-3-
[(4ꢀR,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-dihydroxy-1ꢀ-oxooct-2ꢀ,6ꢀ-
dienyloxymethyl]-2-hydroxy-4-butanolide 3b
Compound 3a was obtained from 17a in 57% yield as a colorless
oil; [a]2D4 −23.8 (c 0.51, MeOH). dH (300 MHz, CD3OD): 7.02
(1H, dd, J 4.4 and 15.8), 6.03 (1H, dd, J 1.7 and 15.8), 5.74 (1H,
qd, J 6.4 and 15.2), 5.53 (1H, qdd, J 1.1, 6.8 and 15.2), 4.62 (1H,
d, J 8.1), 4.41 (1H, dd, J 6.3 and 9.5), 4.37 (1H, dd, J 3.8 and
11.7), 4.29 (1H, dd, J 1.8 and 9.5), 4.24 (1H, dd, J 5.7 and 11.7),
4.14 (1H, ddd, J 1.7, 5.0 and 6.6), 3.99 (1H, dd, J 5.5 and 6.8),
2.89–2.97 (1H, m) and 1.71 (3H, d, J 6.4); dC (75 MHz, CD3OD):
178.8 (s), 167.7 (s), 150.1 (d), 131.3 (d), 129.6 (d), 121.7 (d), 76.4
(d), 75.2 (d), 69.1 (d), 68.3 (t), 62.5 (t), 40.5 (d) and 18.0 (q);
[Found: (M − H)+, 285.0968. C13H17O7 requires M, 285.0974].
Compound 3b was obtained from 17b in 50% yield as a
colorless oil; [a]24 +66.8 (c 0.26, MeOH); dH (500 MHz, CD3OD):
7.08 (1H, dd, J D4.5 and 15.5), 6.09 (1H, dd, J 2.0 and 15.5), 5.74
(1H, qd, J 6.5 and 15.5), 5.53 (1H, qdd, J 1.5, 7.5 and 15.5),
4.44 (1H, dd, J 8.0 and 9.0), 4.41 (1H, dd, J 4.0 and 11.5), 4.32
(1H, d, J 9.8), 4.30 (1H, dd, J 6.5 and 11.5), 4.14 (1H, ddd, J
2.0, 4.5 and 5.5), 4.06 (1H, dd, J 9.5 and 9.8), 3.98 (1H, dd, J
6.0 and 7.5), 2.75–2.80 (1H, m) and 1.71 (3H, dd, J 1.5 and 6.5);
dC (75 MHz, CD3OD): 178.5 (s), 167.6 (s), 150.3 (d), 131.5 (d),
129.6 (d), 121.6 (d), 76.4 (d), 75.1 (d), 69.9 (d), 68.2 (t), 63.3 (t),
45.0 (d) and 18.0 (q); [Found: (M − H)+, 285.0965. C13H17O7
requires M, 285.0974].
(2S,3R)- and (2S,3S)-3-[(4ꢀS,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-Diacetoxy-1ꢀ-
oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-acetoxy-4-butanolide 16c and
16d
Compound 16c was obtained from 2c in 83% yield as a colorless
oil; dH (300 MHz, CDCl3): 6.87 (1H, dd, J 5.1 and 15.8), 5.99
(1H, dd, J 1.7 and 15.8), 5.85–5.87 (2H, m), 5.52–5.56 (1H, m),
5.42 (1H, d, J 9.5), 5.36–5.38 (1H, m), 4.53 (1H, t, J 9.2), 4.38
(1H, dd, J 4.6 and 11.7), 4.29 (1H, dd, J 6.2 and 11.7), 4.13
(1H, t, J 9.5), 3.29–3.31 (1H, m), 2.19 (3H, s), 2.14 (3H, s), 2.07
(3H, s) and 1.72 (3H, d, J 6.4); [Found: (M + H)+, 413.1451.
C19H25O10 requires M, 413.1449].
Compound 16d was obtained from 2d in 79% yield as a
colorless oil; [a]2D9 +49.7 (c 0.45, CHCl3); dH (300 MHz, CDCl3):
6.83 (1H, dd, J 5.0 and 15.8), 5.95 (1H, dd, J 1.7 and 15.8),
5.85–5.86 (1H, m), 5.62 (1H, d, J 8.3), 5.51–5.54 (1H, m), 5.37–
5.40 (1H, m), 4.46 (1H, dd, J 6.0 and 9.9), 4.38 (1H, dd, J 1.5
and 9.9), 4.30 (1H, dd, J 4.2 and 11.7), 4.19 (1H, dd, J 5.7 and
11.7), 3.12–3.16 (1H, m), 2.20 (3H, s), 2.13 (3H, s), 2.08 (3H, s)
(2R,3R)- and (2R,3S)-3-[(4ꢀR,5ꢀS,2ꢀE,6ꢀE)-4ꢀ,5ꢀ-Diacetoxy-1ꢀ-
oxooct-2ꢀ,6ꢀ-dienyloxymethyl]-2-acetoxy-4-butanolide 18a and
18b
Compound 18a was obtained from 3a in 91% yield as a colorless
oil; [a]2D3 −43.1 (c 0.34, CHCl3); {ref. 1 [a]D20 −45.5 (c 0.4, CHCl3)};
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 9 5 – 3 0 2
3 0 1

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dH (300 MHz, CDCl3): 6.85 (1H, dd, J 5.1 and 15.8), 5.97 (1H,
dd, J 1.6 and 15.8), 5.85–5.88 (1H, m), 5.63 (1H, d, J 8.2), 5.54
(1H, ddd, J 1.6, 3.5 and 5.0), 5.41–5.42 (1H, m), 4.47 (1H, dd,
J 1.6,3.5 and 5.0), 5.41–5.42 (1H, m), 4.47 (1H, dd, J 6.1 and
9.9), 4.39 (1H, dd, J 1.5 and 9.9), 4.32 (1H, dd, J 4.2 and 11.7),
4.19 (1H, dd, J 5.7 and 11.7), 3.12–3.18 (1H, m), 2.20 (3H, s),
2.12 (3H, s), 2.08 (3H, s) and 1.73 (3H, dd, J 0.9 and 6.4); dC
(75 MHz, CDCl3): 171.4 (s), 169.9 (s), 169.7 (s), 169.6 (s), 165.0
(s), 142.4 (d), 133.0 (d), 123.9 (d), 122.4 (d), 74.2 (d), 72.8 (d),
67.54 (d), 67.47 (t), 61.1 (t), 37.3 (d), 21.0 (q), 20.8 (q), 20.4 (q)
and 17.8 (q); [Found: (M + H)+, 413.1435. C19H25O10 requires
M, 413.1449].
Compound 18b was obtained from 3b in 100% yield as a
colorless oil; [a]2D4 +61.8 (c 0.22, CHCl3); dH (300 MHz, CD3OD):
6.89 (1H, dd, J 5.3 and 15.8), 6.02 (1H, dd, J 1.6 and 15.8), 5.80–
5.86 (2H, m), 5.56 (1H, ddd, J 1.6, 3.5 and 5.1), 5.44 (1H, d, J
9.5), 5.40–5.42 (1H, m), 4.54 (1H, dd, J 8.4 and 9.2), 4.39 (1H,
dd, J 4.6 and 11.9), 4.30 (1H, dd, J 6.1 and 11.9), 4.14 (1H, dd,
J 9.3 and 9.5), 3.00–3.04 (1H, m), 2.19 (3H, s), 2.13 (3H, s), 2.07
(3H, s) and 1.73 (3H, dd, J 0.9 and 6.4); dC (75 MHz, CDCl3):
171.5 (s), 169.9 (s), 169.7 (s), 169.6 (s), 165.0 (s), 142.5 (d), 133.0
(d), 123.8 (d), 122.5 (d), 74.2 (d), 72.8 (d), 68.8 (d), 66.8 (t), 61.8
(t), 41.0 (d), 21.0 (q), 20.8 (q), 20.5 (q) and 17.9 (q); [Found:
(M + H)+, 413.1439. C19H25O10 requires M, 413.1449].
at −78 ◦C for 1.5 h. The reaction mixture was quenched by
◦
addition of saturated aqueous NH4Cl (2 cm3) at −78 C, and
extracted with ethyl acetate. The extract was washed with water
and brine, dried, and concentrated under reduced pressure. The
residue was purified by chromatography (hexane–ethyl acetate,
20 : 1) to give an oil. This oil was stirred with Dess–Martin
periodinane (586 mg, 1.38 mmol) in dichloromethane (15 cm3)
at 0 ◦C for 1 h. The reaction mixture was quenched by addition
of saturated aqueous NaHCO3 (10 cm3) and saturated aqueous
sodium thiosulfate (10 cm3). After removal of the precipitate, the
filtrate was extracted with dichloromethane. The organic layer
was washed with water and brine, dried, and concentrated under
reduced pressure. The residue was purified by chromatography
(hexane–ethyl acetate, 10 : 1) to give 21 (314.8 mg, 81%) as a
colorless oil; [a]2D2 +27.6 (c, 1.57, CHCl3); dH (300 MHz, CDCl3):
6.90 (1H, dd, J 3.3 and 15.4), 6.83 (1H, d, J 15.4), 5.81 (1H, qd,
J 6.4 and 15.0), 5.31 (1H, ddd, J 1.7, 8.4 and 15.0), 5.18–5.20
(1H, m), 4.90 (1H, dd, J 2.6 and 6.8), 4.75 (2H, dd, J 3.4 and
6.8), 4.67 (1H, dd, J 7.3 and 8.1), 4.39 (1H, dd, J 7.7 and 8.1),
4.19 (1H, dd, J 3.3 and 9.3), 3.84–3.94 (1H, m), 3.65 (1H, dd,
J 8.4 and 9.9), 3.45–3.47 (1H, m), 3.18–3.19 (1H, m), 1.71 (3H,
dd, J 1.7 and 6.4), 1.54–1.68 (8H, m), 1.41–1.43 (2H, m), 0.85
(9H, s) and 0.03 (6H, s); dC (75 MHz, CDCl3): 190.5 (s), 171.9
(s), 144.7 (d), 131.9 (d), 126.5 (d), 124.1 (d), 109.7 (s), 97.4 (d),
83.9 (s), 79.2 (d), 77.2 (d), 68.1 (t), 64.2 (t), 58.2 (t), 48.8 (d), 37.6
(t), 34.7 (t), 30.6 (t), 25.7 (q), 25.0 (t), 24.7 (t), 23.9 (t), 23.6 (t),
20.4 (t), 18.1 (s), 17.8 (q), −5.7 (q) and −5.8 (q); [Found: M+,
564.3106. C30H48O8Si requires M, 564.3118].
(4R,5S,2E,6E)-4,5-O-Cyclohexylidene-2,6-octadien-1-ol 19
The ester 11a was treated as in the synthesis of the aldehyde 7a to
give 19 in 72% yield as a colorless oil; [a]2D1 +18.4 (c 1.09, CHCl3);
dH (300 MHz, CDCl3): 5.89 (1H, dt, J 5.1 and 15.4), 5.75 (1H,
qd, J 6.4 and 15.2), 5.66 (1H, dd, J 7.5 and 15.4), 5.41 (1H, qdd,
J 1.5, 7.9 and 15.2), 4.58 (1H, dd, J 6.4 and 8.4), 4.55 (1H, dd,
J 6.4 and 8.0), 4.16 (2H, d, J 5.1), 1.72 (3H, dd, J 1.5 and 6.4),
1.57–1.68 (8H, m) and 1.38–1.43 (2H, m); dC (75 MHz, CDCl3):
133.2 (d), 130.8 (d), 127.4 (d), 126.9 (d), 109.1 (s), 79.3 (d), 78.5
(d), 62.7 (t), 37.8 (t), 34.9 (t), 25.0 (t), 24.0 (t), 23.7 (t) and 17.8
(q); [Found: M+, 238.1560. C14H22O3 requires M, 238.1569].
Synthesis of 15a and 17a by the rearrangement reaction
To a solution of 21 (40.7 mg, 0.072 mmol) in THF (7 cm3)
was added tetra-n-butylammonium fluoride (1.0 M in THF,
0.14 cm3, 0.14 mmol) at 0 ◦C under nitrogen, and the mixture was
stirred for 20 min at 0 ◦C. The reaction mixture was quenched
with acetic acid (0.2 cm3) and aqueous NH4Cl, and extracted
with ether. The extract was washed with water and brine, dried
and concentrated. The residue was purified by chromatography
(hexane–ethyl acetate, 2 : 1) to give 15a (8.4 mg, 26%), 17a
(5.4 mg, 17%), 14a and 14b (6.2 mg) and 13a (7.7 mg).
(4R,5S,2E,6E)-4,5-O-Cyclohexylidene-2,6-octadienal 20
The diol 19 was treated as in the synthesis of the aldehyde 7b
to give 20 in 84% yield as a colorless oil; [a]2D6 +74.5 (c 2.17,
CHCl3); dH (300 MHz, CDCl3): 9.60 (1H, d, J 8.0), 6.69 (1H,
dd, J 5.1 and 15.6), 6.34 (1H, ddd, J 1.5, 7.9 and 15.6), 5.85 (1H,
qd, J 6.5 and 15.2), 5.33 (1H, qdd, J 1.7, 8.4 and 15.2), 4.83
(1H, ddd, J 1.5, 5.1 and 7.3), 4.72 (1H, dd, J 7.3 and 8.2), 1.73
(3H, dd, J 1.6 and 6.5), 1.56–1.67 (8H, m) and 1.40–1.45 (2H,
m); dC (75 MHz, CDCl3): 193.0 (d), 153.1 (d), 132.7 (d), 132.0
(d), 126.0 (d), 110.1 (s), 79.2 (d), 77.0 (d), 37.5 (t), 34.7 (t), 25.0
(t), 24.0 (t), 23.9 (t), 23.6 (t) and 17.7 (q); [Found: M+, 236.1401.
C14H20O3 requires M, 236.1412].
Acknowledgements
T. Ueki thanks Osaka City University for the OCU Grant for
Graduate Course Students.
References
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(2R,3S,4ꢀS,5ꢀR,2ꢀE,6ꢀE)-2-(4ꢀ, 5ꢀ-O-Cyclohexylidene-2ꢀ,
6ꢀ-octadienoyl)-2-tetrahydropyranyloxy-3-(tert-
butyldimethylsilyloxymethyl)-4-butanolide 21
To a solution of LDA, prepared from diisopropylamine
(0.34 cm3, 2.43 mmol) in THF (10 cm3) and n-butyllithum
(1.6 M in hexane, 1.50 cm3, 2.43 mmol), was added a solution
of th◦e lactone 14c8 (322 mg, 0.98 mmol) in THF (1 cm3) at
−78 C, and the mixture was stirred for 45 min. The aldehyde
19 (163 mg, 0.69 mmol) and hexamethylphosphoric triamide
(0.25 cm3) in THF (1 cm3) was added over 5 min, and stirred
5 S. B. Kadin, J. Org. Chem., 1966, 31, 620.
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