An efficient access to aspermytin A and oblongolide C through an intramolecular nitrile oxide-alkene [3+2] cycloaddition

Article abstract of DOI:10.1055/s-0032-1317693

The second generation synthesis of (+)-aspermytin A and the first total synthesis of (-)-oblongolide C have been accomplished employing an intramolecular nitrile oxide-alkene [3+2] cycloaddition as the key step. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317693

LETTER
▌61
lAettner Efficient Access to Aspermytin A and Oblongolide C through an Intra-
molecular Nitrile Oxide–Alkene [3+2] Cycloaddition
Efficient Access to Aspermytin A and Oblongolide C
Atsushi Inoue,a Makoto Kanematsu,a Seiji Mori,b Masahiro Yoshida,a Kozo Shishido*a
a
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
E-mail: shishido@ph.tokushima-u.ac.jp
b
Department of Chemistry, Faculty of Science, Ibaraki University, Bunkyo, Mito 310-8512, Japan
Received: 15.10.2012; Accepted after revision: 05.11.2012
the tricyclic isoxazoline 5, constructed diastereoselective-
ly through the INOC of the nitrile oxide 6, which could be
derived from (–)-citronellal (7, Scheme 1).
Abstract: The second generation synthesis of (+)-aspermytin A
and the first total synthesis of (–)-oblongolide C have been accom-
plished employing an intramolecular nitrile oxide–alkene [3+2] cy-
cloaddition as the key step.
O
H
OH
O
H
Key words: total synthesis, enantioselectivity, cycloaddition,
aspermytin A, nitrile oxide
O
4
OH
OH
Aspermytin A (1)1 has been isolated from a marine-de-
rived fungus of the genus Aspergillus sp. by Tsukamoto et
al. The key structural features of the molecule are the
functionalized trans-octahydronaphthalene skeleton and
the four contiguous stereogenic centers on the ring, two of
which are quaternary carbons. Aspermytin A showed sig-
nificant neurotrophic effects on rat pheochromocytoma
(PC-12) cells at a concentration of 50 μM and could be a
potential lead for the development of anti-Alzheimer che-
motherapeutic agents. In our previous paper, we reported
the first enantioselective total synthesis of (+)-aspermytin
A (1) via an intramolecular Diels–Alder reaction as the
key step, in which the synthesis was accomplished in
9.7% overall yield for 24 steps.2 However, further evalu-
ation of the biological activities of the natural product and
its congeners necessitated the development of a much
more efficient synthetic route. Herein we describe the sec-
ond generation synthesis of (+)-1, which has been
achieved efficiently, employing as the key step a highly
diastereoselective intramolecular nitrile oxide–alkene
[3+2] cycloaddition reaction (INOC)3 for the construction
of the C4 quaternary carbon stereogenic center. In addi-
tion, the first enantioselective total synthesis of oblon-
golide C (2), which was isolated from the endophytic
fungus Phomopsis sp. and shown to exhibit antimicrobial
activities against some kinds of bacteria and fungi,4 has
been accomplished, starting from an intermediate used in
the synthesis of 1 (Figure 1).
H
H
aspermytin A (1)
oblongolide C (2)
Figure 1 Structures of aspermytin A and oblongolide C
2
OH
CHO
3 steps2
(70%)
H
H
H
H
O
O
4
1
3
4
O
N
O–
+
N
H
H
H
CHO
H
5
6
7
Scheme 1 Retrosynthetic analysis
Reduction of 8, prepared from 7 (3 steps, 89%) according
to a published method,5 with lithium aluminum hydride
gave the alcohol 9, which was converted to the cyanide 11
via the tosylate 10. Reduction with diisobutylaluminum
hydride followed by reaction of the resulting aldehyde
with hydroxylamine hydrochloride and sodium acetate
provided the oxime 12. With the precursor of nitrile oxide
6 in hand, we then examined the key conversion. Treat-
ment of 12 with a 7% aqueous solution of NaOCl in
dichloromethane6 at room temperature for 24 hours pro-
vided, via the [3+2] cycloaddition of 6, the isoxazoline 57
in 67% yield as a single product (method A). When the
reaction was conducted in toluene,8 isoxazoline 5 was
obtained in higher yield (81%) in a shorter period of time
(6 h, method B). Alternatively, for the sake of compari-
son, the INOC using a nitroalkane9 was examined. Thus,
Swern oxidation of 9 gave the aldehyde 13, which was
converted into the one-carbon elongated nitroalkane 14 by
a sequential addition of nitromethane, acetylation, and re-
Our synthetic strategy is outlined in Scheme 1. Since
aspermytin A (1) has been synthesized uneventfully from
the aldehyde 3 via a three-step sequence,2 we decided to
prepare 3. Our idea was to prepare the quaternary stereo-
genic center at C4 and the enone moiety in 3 from 4 by ox-
idation. The β-hydroxyketone 4 would be derived from
SYNLETT 2013, 24, 0061–0064
Advanced online publication: 04.12.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317693; Art ID: ST-2012-U0888-L
© Georg Thieme Verlag Stuttgart · New York

62
A. Inoue et al.
LETTER
duction with sodium borohydride.3g,10 Upon exposure to mosphere of hydrogen to give the β-hydroxy ketone 4 in
phenyl isocyanate and triethylamine in benzene at room 87% yield. Attempted direct conversion of 4 to 3 employ-
temperature to reflux, the starting 14 was recovered com- ing IBX (at 80 °C, 48 h) resulted in decomposition. When
pletely whereas when p-chlorophenyl isocyanate11 and tri- the reaction was conducted with the IBX·MPO (4-meth-
ethylamine in benzene at room temperature were used, the oxypyridine-N-oxide) complex,17a the corresponding keto
isoxazoline 5 was produced in 84% yield diastereoselec- aldehyde was obtained quantitatively; however, oxidation
tively (method C). The reaction using ethyl chlorofor- to the enone did not occur. Therefore, we decided to try a
mate, triethylamine, and 4-DMAP in chloroform at room stepwise conversion.17b
temperature12 provided 5 in a comparable yield of 81%
(method D, Scheme 2).13
H
3 steps5
a–c
7
CO2Me
H
8
H
H
H
H
f
d, e
N
R
OH
12
9: R = OH
10: R = OTs
11: R = CN
O
N
H
H
5
Figure 2 Two transition structures for INOC; atomic distances in
angstroms (underlined) at the B3LYP/6-31G(d) level
H
H
H
g
i
h
9
CHO
NO2
Thus, treatment of 4 with TMSOTf and triethylamine in
dichloromethane at 0 °C gave the silyl enol ether 15,
which was sequentially reacted with IBX·MPO and IBX18
in a mixture of DMSO and dichloromethane at room tem-
perature to give the key intermediate 319 in 58% yield for
the two steps. The synthetic 3 was spectroscopically iden-
tical to the authentic material2 which has been synthesized
in our laboratories. Finally, it was converted, via the keto
alcohol 16, into (+)-aspermytin A (1)20 in three steps2
thereby completing the second-generation total synthesis
(Scheme 3).
H
13
14
Scheme 2 Reagents and conditions: (a) LiAlH4, Et2O, r.t., 2 h; (b) p-
TsCl, Et3N, 4-DMAP, CH2Cl2, r.t., 1 h; (c) KCN, KI, DMSO, H2O, 60
°C, 12 h, 89% (3 steps); (d) DIBAL-H, CH2Cl2, –78 °C, 2 h; (e)
NH2OH·HCl, NaOAc, MeOH, r.t., 15 min, quant. (2 steps); (f) meth-
od A: 7% NaOCl (aq), CH2Cl2, r.t., 24 h, 67%; method B: 7% NaOCl
(aq), toluene, r.t., 6 h, 81%; (g) (COCl)2, DMSO, Et3N, CH2Cl2, –78
°C to 0 °C, 1 h; (h) MeNO2, KF, 18-crown-6 then Ac2O, 4-DMAP
then NaBH4, THF, r.t., 14 h, 57% (3 steps from 8); (i) method C: 4-
ClC6H4NCO, Et3N, benzene, r.t., 3 h, 84%; method D: ClCO2Et,
Et3N, 4-DMAP, CHCl3, r.t., 16 h, 81%.
OTMS
The stereochemistry of 5 was confirmed by NOE experi-
ments as shown in Scheme 2, and the preferential forma-
tion was supported by theoretical calculations3h,14 of the
transition-state energy for the two conformers shown in
Figure 2. Thus, with the aid of B3LYP-D(PCM)/6-
311+G(d)//B3LYP/6-31G(d) calculations,15 the transition
state 6-T1 leading to the formation of 5 was found to be
more stable in Gibbs energy than 6-T2, which leads to the
C4 epimer 5′, by 20.9 kJ/mol. The forming B-ring in 6-T1
adopts a twist-chair conformation, while in 6-T2 it as-
sumes a twist-boat conformation. The higher stability of
H
OTMS
a
b
c
5
4
3
H
15
O
H
d, e
f
(+)-1
OH
H
16
6-T1 is due to the more steric hindrance in 6-T2 [shorter Scheme 3 Reagents and conditions: (a) H2, Raney Ni (W2),
(MeO)3B, MeOH, CH2Cl2, H2O, r.t., 1 h, 87%; (b) TMSOTf, Et3N,
CH2Cl2, 0 °C, 0.5 h; (c) IBX·MPO then IBX, DMSO, CH2Cl2, r.t., 10
h, 58% (2 steps); (d) MeLi, THF, –78 °C, 1 h, 80%; (e) TPAP, NMO,
distance between the two hydrogen atoms in 6-T2 (2.22 Å
than the sum of the van der Waals radii (2.4 Å), Figure 2].
The isoxazoline 5 was then treated with trimethyl borate
4 Å MS, CH2Cl2, r.t., 1 h, 92%; (f) LDA, {1H-benzo[d][1,2,3]triazol-
1-yl}methanol, THF, –78 °C, 2 h, 95%.
and Raney nickel (W2) in aqueous methanol16 under an at-
Synlett 2013, 24, 61–64
© Georg Thieme Verlag Stuttgart · New York

LETTER
Efficient Access to Aspermytin A and Oblongolide C
63
We next turned our attention to the synthesis of oblon-
golide C (2) starting from 3. For this synthesis, the con-
struction of a quaternary stereogenic center at C13 with
the R configuration by a diastereoselective introduction of
one extra carbon was necessary. Pinnick oxidation of 3
provided the carboxylic acid 17, which was treated with
the benzyloxymethyl anion,21 generated in situ from (ben-
zyloxymethyl)tri-n-butylstannane and n-butyllithium, in
THF at –78 °C, to give the hydroxyl carboxylic acid 1922
as a single diastereomer in 74% yield for the two steps.
The configuration at the newly generated quaternary ste-
reogenic center was established by NOE experiments as
shown in Scheme 4. The highly diastereoselective forma-
tion of the requisite 19 can be explained by taking into ac-
count the chelated transition state 18, in which the
benzyloxymethyllithium would coordinate to the carbox-
ylic acid and the C13 carbonyl oxygens. Finally, 19 was
treated with lithium in liquid ammonia in THF at –40 °C
to produce, via debenzylation followed by spontaneous
lactonization, (–)-oblongolide C (2),23 the spectroscopic
properties and optical rotation of which are completely
identical with those reported for the natural material
(Scheme 4).4
Acknowledgment
This work was supported financially by a Grant-in-Aid for the Pro-
gram for Promotion of Basic and Applied Research for Innovation
in the Bio-oriented Industry (BRAIN). S. M. acknowledges finan-
cial support by a grant (No. 23105507; molecular activation) for
Scientific Research on Priority Areas from MEXT of Japan. The ge-
nerous allotment of computation time from the Research Center for
Computational Science (RCCS), the National Institutes of Natural
Sciences, Japan, is also gratefully acknowledged. We thank the Ta-
kasago International Co. for the generous gift of citronellal.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
References and Notes
(1) Tsukamoto, S.; Miura, S.; Yamashita, Y.; Ohta, T. Bioorg.
Med. Chem. Lett. 2004, 14, 417.
(2) Inoue, A.; Kanematsu, M.; Yoshida, M.; Shishido, K.
Tetrahedron Lett. 2010, 51, 3966.
(3) Our reports on natural products synthesis using INOC, see:
(a) Shishido, K.; Tokunaga, Y.; Omachi, N.; Hiroya, K.;
Fukumoto, K.; Kametani, T. J. Chem. Soc., Chem. Commun.
1989, 1093. (b) Shishido, K.; Tokunaga, Y.; Omachi, N.;
Hiroya, K.; Fukumoto, K.; Kametani, T. J. Chem. Soc.,
Perkin Trans. 1 1990, 2481. (c) Shishido, K.; Umimoto, K.;
Shibuya, M. Heterocycles 1990, 31, 597. (d) Shishido, K.;
Irie, O.; Shibuya, M. Tetrahedron Lett. 1992, 33, 4589.
(e) Shishido, K.; Umimoto, K.; Takata, T.; Irie, O.; Shibuya,
M. Heterocycles 1993, 36, 345. (f) Shishido, K.; Umimoto,
K.; Ouchi, M.; Irie, O.; Omodani, T.; Shibuya, M. J. Chem.
Res., Synop. 1993, 58. (g) Shishido, K.; Takata, T.;
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(h) Omodani, T.; Shishido, K. J. Chem. Soc., Chem.
Commun. 1994, 2781. (i) Irie, O.; Fujiwara, Y.; Nemoto, H.;
Shishido, K. Tetrahedron Lett. 1996, 37, 9229. (j) Sasaki,
H.; Yokoe, H.; Shindo, M.; Yoshida, M.; Shishido, K.
Heterocycles 2009, 77, 773.
CO2H
H
n-Bu3SnCH2OBn
n-BuLi, THF
NaOCl, NaH2PO4
2-methylbut-2-ene
O
13
3
t-BuOH, THF
–78 °C, 2 h
H2O, r.t., 2 h
74% (2 steps)
H
17
Bn
CO2H
O
O
H
Li
O
Li, liq. NH3
OBn
O
H
2
OH
THF, –40 °C
2 h, 82%
H
H
H
19
18
(4) Dai, J.; Krohn, K.; Gehle, D.; Kock, I.; Flörke, U.; Aust, H.-
J.; Draeger, S.; Schulz, B.; Rheinheimer, J. Eur. J. Org.
Chem. 2005, 4009.
(5) (a) Tietze, L. F.; Beifuss, U.; Antel, J.; Sheldrick, G. M.
Angew. Chem., Int. Ed. Engl. 1988, 27, 703. (b) Tietze, L. F.;
Beifuss, U. Synthesis 1988, 359. (c) Tietze, L. F.; Beifuss, U.
Org. Synth. 1993, 71, 167.
OBn
H
CO2H
OH
H
H
H
H
Scheme 4 Synthesis of (–)-oblongolide C
(6) Lee, G. A. Synthesis 1982, 508.
(7) Analytical Data for 5
23
Colorless needles, mp 94.5–94.8 °C (Et2O–hexane); [α]D
In summary, the second-generation enantiocontrolled to-
tal synthesis of (+)-aspermytin A (1) has been achieved in
a highly efficient manner in 15 steps from (–)-citronellal
(7) with an overall yield of 19% (in the oxime route; cf.2
in 9.7% overall for 24 steps from 7) employing a highly
diastereoselective INOC for the construction of the C4
quaternary carbon stereogenic center as the key step. In
addition, the first enantioselective total synthesis of ob-
longolide C (2) has been completed from the key interme-
+22.6 (c 1.22, CHCl3). IR (KBr): 2920, 1713, 1494, 1455,
1377, 946, 846 cm–1. 1H NMR (400 MHz, CDCl3): δ = 4.11
(d, J = 7.6 Hz, 1 H), 3.91 (d, J = 7.6 Hz, 1 H), 2.62 (ddd, J =
14.8, 4.8, 2.0 Hz, 1 H), 2.21 (dt, J = 14.0, 5.6 Hz, 1 H), 1.82–
1.88 (dddd, J = 12.8, 5.6, 5.2, 1.6 Hz, 1 H), 1.72–1.76 (m, 2
H), 1.28 (dq, J = 12.4, 3.2 Hz, 1 H), 1.23–1.34 (m, 3 H), 1.13
(s, 3 H), 1.09–1.20 (m, 2 H), 0.87–0.96 (m, 1 H), 0.89 (d, J
= 6.4 Hz, 3 H), 0.67 (q, J = 12.4 Hz, 1 H). 13C NMR (100
MHz, CDCl3): δ = 164.4 (C), 80.8 (CH2), 54.2 (C), 51.3
(CH), 42.1 (CH2), 36.0 (CH), 34.5 (CH2), 33.5 (CH2), 32.1
(CH), 27.7 (CH2), 22.3 (CH3), 21.9 (CH2), 17.1 (CH3). ESI-
HRMS: m/z calcd for C13H21NONa [M + Na]+: 230.1521;
found: 230.1519.
diate
3
via the chelation-controlled, highly
diastereoselective addition of benzyloxymethyllithium.
The synthetic route developed here is general, efficient,
and flexible and could be applied not only to the syntheses
of other oblongolides4 but could also be used for assem-
bling a library of compounds for biological evaluations.
(8) Yun, H.; Paek, S.-M.; Jung, J.-W.; Kim, N.-J.; Kim, S.-H.;
Suh, Y.-G. Chem. Commun. 2009, 2463.
(9) Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82,
5339.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 61–64

64
A. Inoue et al.
LETTER
(10) Wollenberg, R. H.; Miller, S. J. Tetrahedron Lett. 1978, 19,
3219.
(11) Kozikowski, A. P.; Stein, P. D. J. Am. Chem. Soc. 1982, 104,
4023.
(12) Shimizu, T.; Hayashi, Y.; Shibafuchi, H.; Teramura, K. Bull.
Chem. Soc. Jpn. 1986, 59, 2827.
(13) The yields of the isoxazoline 5 from the literature known 8
via the oxime 12 and the nitroalkane 13 were 72% (6 steps)
and 48% (4 steps), respectively.
(14) For theoretical studies on the intra- and intermolecular nitrile
oxide–alkene [3+2] cycloadditions, see: (a) Brown, F. K.;
Singh, U. C.; Kollman, P. A.; Raimondi, L.; Houk, K. N.;
Bock, C. W. J. Org. Chem. 1992, 57, 4862. (b) Kim, D.; Lee,
J.; Shim, P. J.; Lim, J. I.; Doi, T.; Kim, S. J. Org. Chem.
2002, 67, 772. (c) Namboothiri, I. N. N.; Rastogi, N.;
Ganguly, B.; Mobin, S. M.; Cojocaru, M. Tetrahedron 2004,
60, 1453. (d) Luft, J. A. R.; Meleson, K.; Houk, K. N. Org.
Lett. 2007, 9, 555.
exchangeable, 1 H), 5.93 (brs, OH, D2O exchangeable, 1 H),
5.70 (dd, J = 10.0, 2.8 Hz, 1 H), 5.37 (dd, J = 10.0 Hz, 1.6
Hz, 1 H), 4.29 (br s, 2 H), 3.64 (dt, J = 17.6 Hz, 6.4 Hz, 1 H),
3.04 (dt, J = 17.6, 6.0 Hz, 1 H), 2.07 (dt, J = 10.4, 2.0 Hz, 1
H), 1.74–1.84 (m, 2 H), 1.63–1.68 (m, 2 H), 1.54 (s, 3 H),
1.49 (s, 3 H), 1.30–1.42 (m, 1 H), 1.04 (dq, J = 12.4, 2.8 Hz,
1 H), 0.98 (dq, J = 2.4, 12.4 Hz, 1 H), 0.84 (d, J = 6.4 Hz, 3
H), 0.78 (q, J = 12.4 Hz, 1 H). 13C NMR (100 MHz, C5D5N):
δ = 214.1 (C), 135.5 (CH), 129.6 (CH), 73.3 (C), 57.8 (CH2),
57.7 (C), 45.8 (CH2), 43.8 (CH), 42.1 (CH2), 38.9 (CH), 35.9
(CH2), 33.6 (CH), 28.7 (CH3), 28.0 (CH2), 22.7 (CH3), 12.8
(CH3). ESI-HRMS: m/z calcd for C16H27O3 [M + H] +:
267.1960; found: 267.1966.
(21) (a) Still, W. C. J. Am. Chem. Soc. 1978, 100, 1481.
(b) Fernández-Megía, E.; Ley, S. V. Synlett 2000, 455.
(c) Yoshimura, T.; Yakushiji, F.; Kondo, S.; Wu, X.;
Shindo, M.; Shishido, K. Org. Lett. 2006, 8, 475.
(22) Analytical Data for 19
(15) For computational methodology, see Supporting
Information.
Colorless oil. [α]D29 +61.2 (c 2.81, CHCl3). IR (neat): 3541–
2552 (v. broad), 3027, 2921, 2867, 1696, 1454, 1120, 1096,
735, 698 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.34–12.5
(br, 1 H), 7.23–7.38 (m, 5 H), 5.52 (d, J = 10.4 Hz, 1 H), 5.28
(dd, J = 10.4, 2.4 Hz, 1 H), 4.57 (d, J = 12.0 Hz, 1 H), 4.40
(d, J = 12.0 Hz, 1 H), 3.67 (d, J = 9.2 Hz, 1 H), 3.29 (d, J =
9.6 Hz, 1 H), 2.73–2.99 (br, OH, D2O exchangeable, 1 H),
1.73–1.84 (m, 2 H), 1.59–1.69 (m, 3 H), 1.37–1.52 (m, 1 H),
1.19 (s, 3 H), 0.99 (q, J = 10.8 Hz, 1 H), 0.94–1.07 (m, 1 H),
0.88 (d, J = 6.4 Hz, 3 H), 0.75 (q, J = 12.0 Hz, 1 H). 13C NMR
(100 MHz, CDCl3): δ = 181.2 (C), 137.6 (C), 134.0 (CH),
128.6 (CH), 128.3 (2 × CH), 127.5 (CH), 127.2 (2 × CH),
75.3 (C), 73.0 (CH2), 73.0 (CH2), 51.3 (C), 43.7 (CH), 41.3
(CH2), 38.3 (CH), 35.3 (CH2), 33.2 (CH), 27.5 (CH2), 22.3
(CH3), 12.4 (CH3). ESI-HRMS: m/z calcd for C21H29O4 [M
+ H]+: 345.2066; found: 345.2070.
(16) Curran, D. P. J. Am. Chem. Soc. 1982, 104, 4024.
(17) (a) Nicolaou, K. C.; Montagnon, T.; Baran, P. S. Angew.
Chem. Int. Ed. 2002, 41, 993. (b) Nicolaou, K. C.; Gray, D.
L. F.; Montagnon, T.; Harrison, S. T. Angew. Chem. Int. Ed.
2002, 41, 996.
(18) The corresponding aldehyde was initially obtained by the
reaction with IBX·MPO and the requisite enone 3 was
generated by the subsequent addition of IBX in a one-pot
process.
(19) Analytical Data for 3
Colorless needles, mp 62.5–63.3 °C (hexane) (lit.2 62.3–62.6
°C). [α]D29 –107 (c 1.74, CHCl3) {lit.2 [α]D22 –103 (c 0.91,
CHCl3)}. IR (KBr): 2934, 2839, 2734, 1733, 1660 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 9.52 (s, 1 H), 6.75 (dd, J =
10.0, 1.6 Hz, 1 H), 5.97 (dd, J = 10.0, 2.8 Hz, 1 H), 2.27 (tdd,
J = 11.2, 2.8, 2.8 Hz, 1 H), 2.09 (ddd, J = 11.6, 10.8, 3.2 Hz,
1 H), 2.01 (ddd, J = 13.2, 3.2, 3.2 Hz, 1 H), 1.75–1.82 (m, 1
H), 1.47–1.64 (m, 1 H), 1.35 (dq, J = 13.2, 4.0 Hz, 1 H), 1.27
(dtd, J = 12.4, 12.0, 3.6 Hz, 1 H), 1.19 (s, 3 H), 0.97 (d, J =
6.8 Hz, 3 H), 0.94–1.07 (m, 2 H). 13C NMR (100 MHz,
CDCl3): δ = 200.5 (CH), 200.4 (C), 155.1 (CH), 127.1 (CH),
60.5 (C), 43.3 (CH), 40.2 (CH2), 37.1 (CH), 34.0 (CH2), 32.9
(CH), 26.0 (CH2), 22.2 (CH3), 11.0 (CH3). ESI-HRMS: m/z
calcd for C13H18O2Na [M + Na]+: 229.1204; found:
229.1198.
(23) Analytical Data for Oblongolide C (2)
Colorless needles, mp 104–105 °C (Et2O–hexane) (lit.4
amorphous powder). [α]D27 –194 (c 1.11, CH2Cl2) {lit.4
[α]D25 –184 (c 0.20, CH2Cl2). IR (KBr): 3398, 2950, 2921,
1740, 1237, 1122, 1021, 767, 733 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 5.65 (d, J = 10.0 Hz, 1 H), 5.55 (dd, J = 10.0, 2.4
Hz, 1 H), 4.26 (s, 2 H), 2.00 (t, J = 10.8 Hz, 1 H), 1.76 (s,
OH, D2O exchangeable, 1 H), 1.76–1.88 (m, 3 H), 1.42–1.50
(m, 2 H), 1.26–1.36 (m, 1 H), 1.14 (s, 3 H), 0.91 (d, J = 6.4
Hz, 3 H), 0.85–0.95 (m, 1 H), 0.77 (q, J = 12.0 Hz, 1 H). 13
C
NMR (100 MHz, CDCl3): δ = 178.9 (C), 135.7 (CH), 125.6
(CH), 78.8 (C), 76.9 (CH2), 49.4 (C), 43.8 (CH), 41.1 (CH2),
36.3 (CH), 34.7 (CH2), 32.8 (CH), 25.8 (CH2), 22.2 (CH3),
8.9 (CH3). ESI-HRMS: m/z calcd for C14H20O3Na [M +
Na]+: 259.1310; found: 259.1304.
(20) Analytical Data for Aspermytin A (1)
Colorless needles, mp 122–123 °C (hexane). [α]D28 +7.64 (c
0.97, CHCl3) {lit.1 [α]D25 +1.2 (c 0.102, CHCl3)}. IR (KBr):
3501, 2946, 2910, 1686, 1659, 1374, 1342, 1073, 1042 cm–
1. 1H NMR (400 MHz, C5D5N): δ = 6.44 (s, OH, D2O
Synlett 2013, 24, 61–64
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