Enantioselective total synthesis of marine natural products untenone A and plakevulin A

Article abstract of DOI:10.1055/s-2005-863742

An enantioselective total synthesis of untenone A and plakevulin A has been achieved. Construction of a cyclopentene derivative, the key intermediate in this synthesis, was carried out by using a ruthenium-catalyzed ring-closing metathesis reaction of a d

Full text of DOI:10.1055/s-2005-863742

LETTER
793
Enantioselective Total Synthesis of Marine Natural Products Untenone A and
Plakevulin A
Enantioselective
T
i
otal Sy
r
nthesis o
o
f
M
arine
N
a
t
tural Pr
a
oducts ke Mizutani, Masayuki Watanabe, Toshio Honda*
Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
Fax +81(3)54985791; E-mail: honda@hoshi.ac.jp
Received 7 January 2005
CO2Me
CO2Me
OH
CH3
Abstract: An enantioselective total synthesis of untenone A and
OH
plakevulin A has been achieved. Construction of a cyclopentene
derivative, the key intermediate in this synthesis, was carried out by
using a ruthenium-catalyzed ring-closing metathesis reaction of a
divinyl compound, prepared from octadecanal in several steps in-
cluding the Sharpless asymmetric epoxidation to generate a chiral
quaternary carbon center.
O
HO
CH3
15
15
untenone A (1)
plakevulin A (2)
CO2Me
OH
CH3
O
Key words: natural product, total synthesis, DNA polymerase in-
hibitor, Sharpless asymmetric epoxidation, ring-closing metathesis
O
H3C
O
15
proposed structure of plakevulin A (3)
Untenone A (1), isolated from the Okinawan marine
sponge, Plakortis sp., in 1993,1 is known to exhibit an
inhibitory activity against mammalian DNA polymerases
Figure 1 Structure of untenone A and plakevulin A
a and b.2 Owing to its interesting biological activity, construction of cyloalkene ring systems. We also assumed
several synthetic approaches toward 1 have been reported that the stereochemistry at the C-1 and C-5 positions in 5
to date.2,3 Plakevulin A (2) was also isolated from the could be controlled at the later stage of this synthesis.
Okinawan Plakortis sponge (SS-973) and inhibits DNA Thus, the introduction of chirality at the tetra-substituted
polymerases.4 Although the levulinyl ester 3 was initially carbon center would be a crucial step in this synthesis. To
reported as the structure of plakevulin A, it has recently generate the desired stereochemistry, we adopted a similar
been revised to 2 by Kobayashi’s group (Figure 1).5 Here- synthetic strategy to our previous work,7 in which the
in, we describe the enantioselective syntheses of untenone Sharpless asymmetric epoxidation8 of an allyl alcohol and
A and plakevulin A by employing ring-closing metathesis subsequent regioselective ring-opening reaction of a
as a key reaction.
chiral epoxide with a nucleophile were exploited as key
reactions.
The retrosynthetic analysis for untenone A and plakevulin
A is outlined in Scheme 1, where construction of a cyclo- Thus, the requisite starting material was prepared as fol-
pentene skeleton of 1 and 2 would be envisaged via ring- lows. Octadecanal 6 was converted into a,b-unsaturated
closing metathesis6 of a divinyl compound 5, since RCM aldehyde 7 by using the Eschenmoser salt in CH2Cl2,9
has been recognized to be a powerful synthetic tool for which on reduction with sodium borohydride in the
CO2Me
OR
CO2Me
OR
RCM
untenone A
and
plakevulin A
HO
HO
5
CH3
15
CH3
15
4
1
4
5
O
Sharpless AE
H3C
H3C
H3C
CHO
15
15
15
OH
OH
octadecanal
Scheme 1 Retrosynthetic route for untenone A and plakevulin A
SYNLETT 2005, No. 5, pp 0793–0796
2
1.
0
3.
2
0
0
5
Advanced online publication: 09.03.2005
DOI: 10.1055/s-2005-863742; Art ID: U00905ST
© Georg Thieme Verlag Stuttgart · New York

794
H. Mizutani et al.
LETTER
presence of cerium(III) chloride in methanol10 afforded
the allyl alcohol 8 in 80% yield from 6. The Sharpless
asymmetric epoxidation reaction of 8 with L-(+)-diiso-
propyl tartrate as a chiral source gave the corresponding
epoxy alcohol 9 in 94% yield, whose optical purity was
determined as 97% ee based on the HPLC analysis of its
p-nitrobenzoate using the chiral stationary phase
(CHIRALCEL OD, Daicel Chemical Industries). Treat-
ment of 9 with Dess–Martin periodinane11 in CH2Cl2 fol-
lowed by Wittig methylenation of the resulting epoxy
aldehyde 10 furnished the corresponding vinyl epoxide 11
in 75% yield in two steps. Regioselective cyanation reac-
tion of epoxide 11 was accomplished by treatment with
potassium cyanide and ammonium chloride to give the
cyanide 1212 which, on protection of the tert-alcohol with
TMSCl, provided the silyl ether 13 in quantitative yield
(Scheme 2).
CO2R
OTMS
CO2Me
OTMS
CH3
15
HO
i
H3C
13
15
14 R=H
15 R=Me
16
ii
Scheme 3 Reagents and conditions: (i) 3 M aq NaOH, 30% H2O2,
EtOH, 45 °C; (ii) catalytic amount of p-TsOH, MeOH, reflux (62%
for two steps)
in THF provided an unseparable 1:1 diastereomeric mix-
ture of the allyl alcohol 1813 in 82% yield. The ring-clos-
ing metathesis reaction of 18 was achieved by using 1
mol% of Grubbs’ 2nd generation ruthenium catalyst {tri-
cyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-
dihydroimidazol-2-ylidene][benzylidene]ruthenium(IV)
dichloride} in CH2CH2 at room temperature to afford the
desired cyclopentene 1914 in quantitative yield. Oxidation
of an allylic alcohol in 19 with manganese oxide gave the
cyclopentenone 20,15 which is the known key intermedi-
ate for the synthesis of untenone A, in 99% yield. Accord-
ing to the reported reaction conditions,3d compound 20
was subjected to methoxycarbonylation with LDA and
methyl cyanocarbonate in the presence of HMPA in THF
to give b-ketoester 21 in 68% yield as a 5:1 diastereomeric
mixture. Deprotection of the TMS group and epimeriza-
tion at the C-5 position of 21 with Dowex 50W-8 and MS
4 Å in MeOH–THF (1:1) at room temperature furnished
untenone A as a 10:1 diastereomeric mixture. After re-
crystallization of the mixture from hexane, pure untenone
A16 was obtained as a white solid, whose spectroscopic
data including specific optical rotation and melting point
H3C
H3C
H3C
H
OH
H
H3C
H
i
ii
15
15
O
O
6
7
iii
iv
O
H3C
OH
15
15
8
9
v
O
vi
O
H3C
15
15
O
11
10
CN
CN
OH
vii
{[a]D26 –79.7 (c 1.0, CHCl3), mp 63–65 °C; lit.3d [a]D
27
OTMS
H3C
H3C
–73.3 (c 1.2, CHCl3), mp 62–64 °C} were identical to
15
15
those reported in the literature.
12
13
In order to accomplish the synthesis of plakevulin A, dia-
stereoselective 1,2-reduction of a,b-unsaturated ketone
would be required. Although we attempted a direct forma-
tion of 2 by using 1,2-reduction of untenone A under var-
ious reaction conditions such as tetramethylammonium
triacetoxyborohydride in MeCN,17 hydrogenation with a
catalytic amount of RuCl2(PPh3)3 and ethylene diamine in
isopropanol,18 none of the desired product was isolated.
Finally, untenone A was treated with DIBALH in the
presence of zinc bromide in THF to give the b-oriented al-
lyl alcohol 2219 in 50% yield. The Mitsunobu reaction of
22, followed by hydrolysis of the corresponding benzoate
under alkaline conditions afforded plakevulin A (2)20 in
66% yield in two steps (Scheme 5). Although the spectro-
scopic data of the synthesized compound were identical
to those reported in the literature,5 the specific optical ro-
+
Scheme 2 Reagents and conditions: (i) CH2=N(CH3)2 I–, CH2Cl2,
r.t. (82%); (ii) NaBH4, CeCl3·7H2O, MeOH–CHCl3 (20:1), 0 °C to r.t.
(97%); (iii) Ti(Oi-Pr)4, L-DIPT, TBHP, CHCl3, –20 °C (94%); (iv)
Dess–Martin periodinane, CH2Cl2, r.t. (94%); (v) CH3PPh3 Br+, n-
BuLi, THF, –78 °C to r.t. (80%); (vi) KCN, NH4Cl, THF–MeOH–
H2O (5:4:1), 80 °C (98%); (vii) TMSCl, imidazole, DMF, r.t. (99%)
–
To prepare the divinyl compound 5, a key compound for
the ruthenium-catalyzed ring-closing metathesis reaction,
hydrolysis of the cyanide 13 under alkaline reaction
conditions followed by methylation of the resulting car-
boxylic acid 14 was carried out to give the methyl ester 15
in 62% in two steps. Although aldol reaction of 15 with
acrolein under various reaction conditions was attempted
to obtain the diene 16, none of the desired product was
generated (Scheme 3).
22
tation and melting point21 {[a]D +24.1 (c 0.6, CHCl3),
Therefore, we were obliged to change the synthetic route
to untenone A through the reported key intermediate 20 as
shown in Scheme 4. The cyanide 13 was treated with
DIBALH in CH2Cl2 to give the aldehyde 17 in 94% yield,
which on further treatment with vinylmagnesium bromide
mp 74–75 °C} obtained here were different from the
reported values {lit.4 [a]D25 +19 (c 2.0, CHCl3)}, since the
original data were reported for the mixture of 2 and
levulinic acid in a ratio of 1:1.
Synlett 2005, No. 5, 793–796 © Thieme Stuttgart · New York

LETTER
Enantioselective Total Synthesis of Marine Natural Products
(3) Synthesis of ( )-untenone A, see: (a) Takeda, K.;
795
CHO
Nakayama, I.; Yoshii, E. Synlett 1994, 178. (b) Al-Busafi,
S.; Whitehead, R. C. Tetrahedron Lett. 2000, 41, 3467.
(c) Kuhn, C.; Skaltsounis, L.; Monneret, C.; Florent, J.-C.
Eur. J. Org. Chem. 2003, 2585. (d) Chiral synthesis of
untenone A, see: Asami, M.; Ishizaki, T.; Inoue, S.
Tetrahedron Lett. 1995, 36, 1893. (e) Miyaoka, H.;
Watanuki, T.; Saka, Y.; Yamada, Y. Tetrahedron 1995, 51,
8749.
OTMS
CH3
15
OTMS
HO
i
ii
H3C
13
15
17
18
OTMS
CH3
15
OTMS
CH3
15
iii
HO
O
(4) Tsuda, M.; Endo, T.; Perpelescu, M.; Yoshida, S.;
Watanabe, K.; Fromont, J.; Mikami, Y.; Kobayashi, J.
Tetrahedron 2003, 59, 1137.
iv
19
(5) Saito, F.; Takeuchi, R.; Kamino, T.; Kuramochi, K.;
Sugawara, F.; Sakaguchi, K.; Kobayashi, S.; Tsuda, M.;
Kobayashi, J. Tetrahedron Lett. 2004, 45, 8069.
(6) For recent reviews on metathesis, see: (a) Grubbs, R. H.;
Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446.
(b) Schrock, R. R. Tetrahedron 1999, 55, 8141.
20
CO2Me
OTMS
CH3
15
CO2Me
OH
vi
v
O
O
CH3
15
(c) Fürstner, A. Angew. Chem. Int. Ed. 2000, 39, 3013.
(d) Trunka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18. (e) Hoveyda, A. H.; Schrock, R. R. Chem.–Eur. J. 2001,
7, 945. (f) Schrock, R. R.; Hoveyda, A. H. Angew. Chem.
Int. Ed. 2003, 42, 4592. (g) Schrock, R. R. J. Mol. Catal. A:
Chem. 2004, 213, 21. (h) Schmidt, B. Eur. J. Org. Chem.
2004, 1865. (i) Grubbs, R. H. Tetrahedron 2004, 60, 7117.
(7) Mizutani, H.; Watanabe, M.; Honda, T. Tetrahedron 2002,
58, 8929.
(–)-untenone A
21
Scheme 4 Reagents and conditions: (i) DIBALH, CH2Cl2, –40 °C
(94%); (ii) vinylmagnesium bromide (1 M THF solution), THF, 0 °C
(82%); (iii) Grubbs’ 2nd generation Ru catalyst, CH2Cl2, r.t. (99%);
(iv) MnO2, CH2Cl2, r.t. (99%); (v) LDA, methyl cyanocarbonate,
HMPA, THF, –70 °C to –42 °C (68%); (vi) Dowex 50W-8, MS 4 Å,
MeOH–THF (1:1), r.t. (60%)
(8) (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980,
102, 5974. (b) For reviews on Sharpless asymmetric
epoxidation, see: Finn, M. G.; Sharpless, K. B. In On the
Mechanism of Asymmetric Epoxidation with Titanium-
Tartrate Catalysts. Asymmetric Synthesis, Vol. 5; Morrison,
J. D., Ed.; Academic Press: Tokyo, 1985, 247–308.
(c) Pfenninger, A. Synthesis 1986, 89. (d) Shum, W. P.;
Cannarsa, M. J. Chirality in Industry II: Developments in the
Commercial Manufacture and Applications of Optically
Active Compounds; Collins, A. N.; Sheldrake, G. N.;
Crosby, J., Eds.; John Wiley & Sons: New York, 1997, 363.
(9) Schreiber, J.; Maag, H.; Hashimoto, N.; Eschenmoser, A.
Angew. Chem., Int. Ed. Engl. 1971, 10, 330.
CO2Me
i
OH
ii, iii
HO
untenone A
plakevulin A
CH3
15
22
Scheme 5 Reagents and conditions: (i) DIBALH, ZnBr2, THF,
–50 °C (50%); (ii) 40% DEAD in toluene, PPh3, p-bromobenzoic
acid, THF, r.t. (72%); (iii) K2CO3, MeOH–THF (1:1), r.t., (92%)
(10) (a) Luche, J.-L. J. Am. Chem. Soc. 1978, 100, 2226.
(b) Gemel, A. L.; Luche, J.-L. J. Am. Chem. Soc. 1981, 103,
5454.
In summary, we have succeeded in the enantioselective
synthesis of untenone A and plakevulin A by employing
the RCM reaction to construct the basic cyclopentene ring
system and the Sharpless asymmetric epoxidation reac-
tion to generate the chiral quaternary carbon center. This
synthetic strategy would be applicable to the synthesis of
its related derivatives in optically pure forms.
(11) (a) Dess, B. D.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(b) Dess, B. D.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277.
(12) Chini, M.; Crotti, P.; Favero, L.; Macchia, F. Tetrahedron
Lett. 1991, 32, 4775.
(13) Preparation and Spectroscopic Data of Compound 18.
To a stirred solution of aldehyde 17 (844 mg, 2.13 mmol) in
THF (11.0 mL) was added a solution of vinylmagnesium
bromide in THF (2.98 mL, 2.98 mmol) at –20 °C under
argon, and the mixture was allowed to stir for 1 h. After
quenching by addition of sat. aq NH4Cl, the mixture was
extracted with EtOAc. The organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The
residue was purified by silica gel column chromatography
(n-hexane–EtOAc, 40:1) to give 18 (737 mg, 82%) as a
colorless oil. 1H NMR (CDCl3): d = 0.14 and 0.17 (each 3 H,
each s), 0.87 (3 H, t, J = 6.7 Hz), 1.19–1.33 (28 H, br m),
1.60–1.79 (4 H, m), 3.93 and 4.13 (each 0.5 H, each s), 4.32–
Acknowledgment
This work was supported in part by a grant from the Ministry of
Education, Culture, Sports, Science and Technology of Japan.
References
(1) (a) Ishibashi, M.; Takeuchi, S.; Kobayashi, J. Tetrahedron
Lett. 1993, 34, 3749. (b) Kobayashi, J. Kagaku To Seibutsu
1993, 31, 659.
(2) Saito, F.; Takeuchi, R.; Kamino, T.; Kuramochi, K.;
Sugawara, F.; Sakaguchi, K.; Kobayashi, S. Bioorg. Med.
Chem. Lett. 2004, 14, 1975.
4.48 (1 H, m), 5.01–5.30 (4 H, m), 5.73–6.00 (2 H, m). 13
C
NMR (CDCl3): d = 2.47, 2.48, 14.0, 22.6, 24.0, 24.5, 29.3,
29.5, 29.5, 29.6, 30.0, 30.1, 31.9, 40.0, 42.2, 44.2, 45.5, 69.4,
69.7, 79.1, 80.8, 113.4, 113.5, 113.8, 114.0, 140.8, 141.0,
141.9, 143.6. IR (thin film): 3510, 2925, 2855, 1676, 1644,
1468, 1413, 1252, 1144, 1048, 922, 842, 755 cm–1. HRMS:
Synlett 2005, No. 5, 793–796 © Thieme Stuttgart · New York

796
H. Mizutani et al.
LETTER
m/z calcd for C26H52O2Si: 424.3736; found: 424.3755. Anal.
Calcd for C26H52O2Si: C, 73.52; H, 12.34. Found: C, 73.50;
H, 12.27.
mmol) at –50 °C under argon, and the resulting mixture was
allowed to stir for 2 h. After quenching by addition of sat.
NH4Cl aq, the mixture was filtrated through a Celite pad, and
then the filtrate was concentrated under reduced pressure.
The residue was purified by silica gel column
(14) Preparation and Spectroscopic Data of Compound 19.
To a stirred solution of compound 18 (100 mg, 0.24 mmol)
in CH2Cl2 (23.5 mL) was added Grubbs’ 2nd generation
ruthenium catalyst (2.00 mg, 2.36 mmol) at r.t., and the
mixture was allowed to stir for 45 min. After removal of the
solvent, the residue was purified by silica gel column
chromatography (n-hexane–EtOAc, 7:1) to give 19 (92.9
mg, 99%) as a white solid; mp 31.5–33 °C. 1H NMR
(CDCl3): d = 0.06 and 0.12 (each 4.5 H, each t, J = 3.3 Hz),
0.87 (3 H, t, J = 6.7 Hz), 1.19–1.65 (30 H, br m), 1.72–1.73
and 1.78 (each 0.5 H, each m), 2.32 (0.5 H, dd, J = 7.09, 14.2
Hz), 2.45 (0.5 H, dd, J = 7.0, 13.6 Hz), 4.61 (0.5 H, m), 4.96
(0.5 H, m), 5.83–5.91 (2 H, m). 13C NMR (CDCl3): d = 2.1,
2.4, 14.1, 22.7, 24.3, 24.4, 29.3, 29.7, 30.0, 30.0, 31.9, 42.4,
43.4, 48.8, 49.6, 75.3, 76.1, 86.1, 87.3, 134.1,135.1, 140.3,
140.3. IR (thin film): 3320, 2920, 2855, 1468, 1360, 1250,
1105, 1050, 960, 880, 840, 755 cm–1. HRMS: m/z calcd for
C24H48O2Si: 396.3424; found: 396.3410. Anal. Calcd for
C24H48O2Si: C, 72.66; H, 12.20. Found: C, 72.76; H, 12.03.
(15) Preparation of Compound 20.
chromatography (n-hexane–EtOAc, 4:1) to give compound
22
22 (15.1 mg, 50%) as colorless needles; mp 70–71 °C. [a]D
–54.6 (c 0.90, CHCl3). 1H NMR (CDCl3): d = 0.88 (3 H, t,
J = 6.6 Hz), 1.22–1.33 (28 H, br m), 1.60–1.78 (2 H, m),
2.99 (1 H, d, J = 6.1 Hz), 3.04 (1 H, d, J = 8.2 Hz), 3.50 (1
H, s), 3.80 (3 H, s), 4.82 (2 H, ddd, J = 2.4, 5.8, 8.2 Hz), 6.04
(1 H, d, J = 5.8 Hz), 6.09 (1 H, dd, J = 2.4, 5.8 Hz). 13C NMR
(CDCl3): d = 14.1, 22.7, 24.4, 29.3, 29.5, 29.6, 29.6, 29.7,
29.9, 31.9, 39.3, 52.0, 55.0, 75.8, 83.9, 134.7, 140.0, 172.9.
IR (thin film): 3527, 3462, 2916, 2848, 1720, 1464, 1396,
1366, 1240, 1176, 1096, 1049, 1030, 970, 924, 800, 781
cm–1. HRMS: m/z calcd for C23H42O4: 382.3083; found:
382.3085. Anal. Calcd for C23H42O4: C, 72.21; H, 11.07.
Found: C, 72.70; H, 11.20.
(20) Preparation and Spectroscopic Data of p-Bromo-
benzoate of 22 and (+)-Plakevulin A (2).
To a solution of compound 22 (37.0 mg, 0.10 mmol) in THF
(2.0 mL) were added PPh3 (107 mg, 0.41 mmol), 40%
DEAD in toluene solution (0.16 mL, 0.42 mmol) and p-
bromobenzoic acid (70.1 mg, 0.35 mmol) at r.t. under argon,
and the resulting mixture was allowed to stir for 6 h. After
quenching by addition of sat. NaHCO3 aq, the mixture was
extracted with EtOAc. The organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The
residue was purified by silica gel column chromatography
(n-hexane–EtOAc, 5:1) to give p-bromobenzoate (39.4 mg,
72%) as a white solid; mp 59–62 °C. [a]D20 +89.9 (c 0.60,
CHCl3). 1H NMR (CDCl3): d = 0.88 (3 H, t, J = 6.6 Hz),
1.16–1.46 (28 H, br m), 1.82–1.88 (2 H, m), 2.32 (1 H, s),
3.11 (1 H, d, J = 4.3 Hz), 3.79 (3 H, s), 5.99–6.06 (2 H, m),
6.27 (1 H, m), 7.58 (2 H, dd, J = 1.8, 6.8 Hz), 7.87 (2 H, dd,
J = 1.8, 6.8 Hz). 13C NMR (CDCl3): d = 14.1, 22.7, 24.2,
29.3, 29.6, 29.6, 29.7, 29.9, 31.9, 40.8, 52.3, 57.9, 81.2, 85.4,
128.3, 128.7, 131.2, 131.3, 131.7, 140.2, 165.4, 171.7. IR
(thin film): 3486, 2924, 2852, 1724, 1590, 1268, 1172, 1114,
1100, 1012, 758 cm–1. HRMS: m/z [M + 1] calcd for
C30H46O5Br: 565.2528; found: 565.2534. Anal. Calcd for
C30H45O5Br: C, 63.71; H, 8.02. Found: C, 63.81; H, 8.03.
To a mixed solution of the p-bromobenzoate of 22 (45.0 mg,
0.08 mmol) in MeOH–THF (1:1, 1.0 mL) was added K2CO3
at r.t., and the mixture was allowed to stir for 1.5 h. After
quenching by addition of sat. NH4Cl aq, the resulting
mixture was extracted with EtOAc. The organic layer was
washed with brine, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by silica gel column
chromatography (n-hexane–EtOAc, 2:1) to give (+)-pla-
kevulin A (2, 28.0 mg, 92%) as colorless needles; mp 74–75
°C. [a]D22 +24.1 (c 0.60, CHCl3). 1H NMR (CDCl3): d = 0.88
(3 H, t, J = 6.7 Hz), 1.19–1.38 (28 H, br m), 1.75–1.86 (2 H,
m), 2.02 (1 H, d, J = 14.7 Hz), 2.45 (1 H, s), 2.83 (1 H, d,
J = 5.3 Hz), 3.79 (3 H, s), 5.30–5.38 (1 H, m), 5.84 (1 H, dd,
J = 1.6, 5.7 Hz), 5.94 (1 H, dd, J = 1.8, 5.7 Hz). 13C NMR
(CDCl3): d = 14.1, 22.7, 24.5, 29.4, 29.6, 29.7, 29.9, 31.9,
40.6, 52.1, 60.5, 78.2, 84.9, 135.7, 137.0, 172.6. IR (thin
film): 3430, 2916, 2848, 1728, 1464, 1436, 1380, 1366,
1265, 1198, 1085, 994, 862, 786, 722 cm–1. HRMS: m/z
[M + 1] calcd for C23H43O4: 383.3161; found: 383.3138.
Anal. Calcd for C23H42O4: C, 72.21; H, 11.07. Found: C,
71.96; H, 10.95.
A mixed suspension of compound 19 (386 mg, 0.97 mmol)
and MnO2 (3.86 g, 44.4 mmol) in CH2Cl2 was stirred for
11.5 h at r.t. After filtration of the mixture through a Celite
pad, the filtrate was concentrated under reduced pressure.
The residue was purified by silica gel column
chromatography (n-hexane–EtOAc, 40:1) to give 20 (379
mg, 99%) as a white solid; mp 32.5–34.0 °C. [a]D25 –14.9 (c
1.00, CHCl3). 1H NMR (CDCl3): d = 0.10 (9 H, s), 0.87 (3 H,
t, J = 6.6 Hz), 1.18–1.35 (28 H, br m), 1.58–1.74 (2 H, m),
2.48 (2 H, s), 6.09 (1 H, d, J = 5.6 Hz), 7.43 (1 H, d, J = 5.8
Hz). 13C NMR (CDCl3): d = 2.14, 14.1, 22.7, 24.3, 29.4,
29.5, 29.5, 29.7, 29.8, 31.9, 41.9, 49.6, 81.3, 132.8, 166.8,
206.9. IR (thin film): 2924, 2854, 1726, 1464, 1252, 1200,
1078, 840 cm–1. HRMS: m/z calcd for C24H46O2Si:
394.3267; found: 394.3253. Anal. Calcd for C24H46O2Si: C,
73.03; H, 11.75. Found: C, 72.90; H, 11.86.
(16) Preparation and Spectroscopic Data of (–)-Untenone A
(1).
To a mixed solution of compound 21 (195 mg, 0.43 mmol)
in MeOH–THF (5:1, 6 mL) were added Dowex 50W-X8
(1.95 g) and MS 4 Å (975 mg) at r.t. and the resulting
mixture was allowed to stir for 5 h. After filtration through a
Celite pad, the filtrate was concentrated under reduced
pressure. The residue was purified by silica gel column
chromatography (n-hexane–EtOAc, 6:1) to give (–)-unte-
none A (1, 102 mg, 62%) as a white solid; mp 63–65 °C.
[a]D26 –79.7 (c 1.00, CHCl3). 1H NMR (CDCl3): d = 0.88 (3
H, t, J = 6.5 Hz), 1.22–1.33 (28 H, m), 1.64–1.88 (2 H, m),
3.47 (1 H, s), 3.61 (1 H, s), 3.80 (3 H, s), 6.11 (1 H, d, J = 5.6
Hz), 7.52 (1 H, d, J = 5.6 Hz). 13C NMR (CDCl3): d = 14.1,
22.7, 23.8, 29.3, 29.4, 29.5, 29.6, 29.7, 31.9, 40.3, 52.9, 60.8,
79.9, 132.3, 167.0, 169.0, 199.9. IR (thin film): 3480, 2918,
2850, 1742, 1736, 1708, 1468, 1436, 1320, 1218, 1156, 770
cm–1. HRMS: m/z calcd for C23H40O4: 380.2926; found:
380.2924. Anal. Calcd for C23H40O4: C, 72.59; H, 10.59.
Found: C, 72.60; H, 10.74.
(17) Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem.
Soc. 1988, 110, 3560.
(18) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem.
Soc. 1995, 117, 10417.
(19) Preparation and Spectroscopic Data of Compound 22.
To a mixed solution of (–)-untenone A(1) (30.0 mg, 0.08
mmol) and ZnBr2 (17.8 mg, 0.08 mmol) in THF (1.0 mL)
was added 0.97 M DIBALH in hexane (0.21 mL, 0.20
(21) The melting point of optically active 2 has not been reported
in the literature.
Synlett 2005, No. 5, 793–796 © Thieme Stuttgart · New York