Asymmetric total synthesis of botcinic acid and its derivatives: synthetic revision of the structure of botcinolides

Article abstract of DOI:10.1016/j.tetlet.2008.08.108

The stereoselective total syntheses of botcinic acid, botcinic acid methyl ester, 3-O-acetylbotcinic acid methyl ester, botcineric acid, and botcinin E were achieved. The structures of these compounds have been unequivocally determined through their total

Full text of DOI:10.1016/j.tetlet.2008.08.108

Tetrahedron Letters 49 (2008) 6514–6517
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Tetrahedron Letters
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Asymmetric total synthesis of botcinic acid and its derivatives:
synthetic revision of the structure of botcinolides
*
Hiroki Fukui, Seiichi Hitomi, Ryo-suke Suzuki, Tatsuhiko Ikeda, Yuma Umezaki, Keisuke Tsuji, Isamu Shiina
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The stereoselective total syntheses of botcinic acid, botcinic acid methyl ester, 3-O-acetylbotcinic acid
methyl ester, botcineric acid, and botcinin E were achieved. The structures of these compounds have been
unequivocally determined through their total synthesis, and they are identified with the revised struc-
tures of botcinolide, 4-O-methylbotcinolide, 3-O-acetyl-5-O-methylbotcinolide, homobotcinolide, and
2-epibotcinolide, respectively.
Received 7 August 2008
Revised 26 August 2008
Accepted 29 August 2008
Available online 3 September 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Total synthesis
Botcinin
Botcinic acid
Botcinolide
Structural revision
Botcinolide (1) was isolated from the culture broth of Botrytis
cinerea as a significant phytotoxic metabolite in 1993 by Cutler
et al.1a The relative configuration of 1 was suggested on the basis
of the spectroscopic analysis using COSY, TOCSY, HETCORR, HMBC,
and NOESY.1b In 1996, Collado et al. isolated other metabolites
from B. cinerea (strain UCA 992) related to 1, which were called
4-O-methylbotcinolide (2), 3-O-acetyl-5-O-methylbotcinolide (3),
2-epibotcinolide (5), and 3-O-acetyl-2-epibotcinolide (6).1c In the
same year, homobotcinolide (4) was also isolated from B. cinerea
by Cutler, and the structure of 4 was assigned by its elemental
analysis, IR spectra, and comparison of the 13C NMR and partial
botcinolide (4) should be revised to those of 3-O-acetylbotcinic
acid methyl ester (9) and botcineric acid (10), respectively, based
on the studies of the chemical conversion of the botcinic acid
derivatives and comparison of their spectroscopic data. Further-
more, they reported that the structure of 2-epibotcinolide (5)
might be the same as that of 11 because the NMR data of 5 and
11 are almost identical; however, there are four exceptional reso-
nances in the NMR spectra, which should be clarified by advanced
investigations in order to determine the exact structure of 5.
Recently, we have established a method for the synthesis of the
proposed structure of 2-epibotcinolide (5) by the stereoselective
aldol reactions and rapid lactonization using MNBA.3 We
1H NMR spectroscopic data of
4
with those of 1.1d Other
botcinolide derivatives were also isolated by Collado’s group and
similar nine-membered ring structures were proposed as shown
in Figure 1.1e,f
4
1
2
3
5
6
R6O
R5O
nBu nBu nBu nHex nBu nBu
CH3 CH3
R1
R2
R3
R4
R5
OH
R1
O
O
H
H
H
H
5
After one decade, Nakajima et al. obtained metabolites 7, 11,
and 12 from the culture filtrate of a different strain of B. cinerea
(strain AEM 211), and some of them showed antifungal activity
against Magnaporthe grisea, a pathogen of the rice blast disease.2a
Nakajima first named them botcinic acid (7), botcinin E (11), and
botcinin A (12), and later reported that the structure of botcinolide
(1) should be revised to that of 7, the structure of 4-O-methyl-
botcinolide (2) should be revised to that of botcinic acid methyl
ester (8), and the structure of 3-O-acetyl-2-epibotcinolide (6)
should be revised to that of 12.2b They also expected that the
structures of 3-O-acetyl-5-O-methylbotcinolide (3) and homo-
7
CH3 CH3 CH3 CH3
H
H
H
H
H
Ac
H
R4O
R3
R2
3
O
O
H
CH3
H
H
H
H
Ac
H
CH3
H
H
H
O
R6
H
O
OH
10
7
8
9
3'
7
HO
3
R1
nBu nBu nBu nHex
R1
R2
R3
4'
2'
R3O
H
H
H
Ac
H
H
O
CH3 CH3
O
R2O
OH
H
O
O
1
3
O
11 12
Ac
nBu
H
R
O
O
RO
* Corresponding author. Tel.: +81 3 5228 8263; fax: +81 3 3260 5609.
E-mail address: shiina@rs.kagu.tus.ac.jp (I. Shiina).
Figure 1. Structure match-up between botcinolides and botcinic acid derivatives.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.108

H. Fukui et al. / Tetrahedron Letters 49 (2008) 6514–6517
6515
concluded that the reported nine-membered ring structures of
2-epibotcinolide (5) and other related compounds are extremely
doubtful based on the detailed comparison of the 1H NMR spec-
trum of the synthetic intermediates with natural products. In this
Letter, we report the total synthesis of the botcinic acid analogues
(7–10) and botcinin E (11), which have updated the proposed
structures of botcinolides in order to show the true forms of these
natural products.
The retrosynthetic analyses of botcinic acid and its derivatives
are described as shown in Scheme 1. Botcinin E (11) could be
prepared from botcinic acid (7) via lactonization under acidic
conditions.4 Botcinic acid consists of the highly substituted tetra-
hydropyran moiety 13 and the side chain parts 14. The latter moi-
ety 14 has already been synthesized by our group as reported in
the previous Letter.5 The basic skeleton 13 could be synthesized
from the 1,3-diol 15, which might be constructed from the epoxide
16 by regioselective methylation. This epoxide could be prepared
from the allylic alcohol 17 by Katsuki-Sharpless asymmetric epox-
idation, and 17 might be obtained from the tetrahydropyran deriv-
ative 18 by a one-carbon elongation. We have already established
an effective method for the synthesis of the key intermediate 18 by
utilizing the asymmetric aldol and 6-endo ring closure reactions.5
The synthetic routes to produce botcinic acid (7), botcinin E
(11), and botcineric acid (10) are depicted in Scheme 2. First, the
protection of 185 followed by ozonolysis of 19 afforded the corre-
sponding aldehyde 20. Olefination of the aldehyde 20 and succes-
sive reduction of the coupling product 21 yielded the allylic alcohol
22. After deprotecting the TES group in 22, the asymmetric epoxi-
dation of 236 was carried out and the desired epoxy alcohol 24 was
obtained as a single diastereomer. Chakraborty reported the facile
methylation of the epoxy diol 24 to form 25 using lithium dimeth-
ylcuprate,7 however, our attempted epoxy ring-opening reaction of
24 using the cuprate reagent gave not only the desired 1,3-diol 25,
but also the undesired 1,2-diol 26 as a major product via the Payne
rearrangement. On the other hand, the methylation of 27, which
was generated from 24 by protection, regioselectively proceeded
and the desired compound 28 was exclusively produced. After pro-
tection of 28 and removal of the PMB group in 29, the side chain
OH
nBu
OH
nBu
H
O
O
O
HO
HO
O
O
HO
O
O
O
Botcinin E (11)
Botcinic acid (7)
HO
O
RO
OH
TBSO
HO
+
RO
R
O
14a: R=nBu
O
13
O
RO
14b: R=nHex
RO
OR
RO
OR
HO
HO
HO
O
O
O
15
OR
16
O
HO
RO
HO
OPMB
O
17
18
Scheme 1. Retrosynthesis of botcinic acid analogues.
TESO
OPMB
TESO
EtOOC
OPMB
TESO
OPMB
HO
OPMB
TESO
OHC
OPMB
v
i
ii
iii
iv
18
HO
HO
O
O
O
O
O
20
19
21
22
23
HO
OPMB
HO
HO
OPMB
HO
HO
OPMB
vi
vii
+
HO
HO
O
O
O
O
24
26
25
HO
viii
TESO
TESO
OH
TESO
O
OPMB
TESO
OPMB
TESO
OPMB
xii
14a/14b
ix
x
xi
TESO
xv
TESO
TESO
TESO
O
O
O
O
O
30
27
28
29
HO
TESO
TESO
TBSO
TBSO
TBSO
TBSO
TESO
O
TESO
HOOC
O
TESO
O
O
O
xiii
xiv
R
R
R
R
HO
O
O
TESO
O
O
O
O
OHC
TESO
34a: R=nBu
31a/b
HO
32a/b
33a/b
TESO
O
HO
TESO
34b: R=nHex
OH
OH
nBu
OH
nBu
H
O
O
O
HO
HO
O
xvi
xviii
nHex
34a
34b
O
O
O
HOOC
O
O
HOOC
O
HO
HO
Botcinic acid (7)
Botcinin E (11)
Botcineric acid (10)
xvii
Scheme 2. Reagents and conditions: (i) TESOTf, DMAP, Py, rt, 1 h, quant.; (ii) O3, CH2Cl2/MeOH (10:1), ꢀ78 °C, 35 min, then PPh3, ꢀ78 °C for 45 min and 0 °C for 1.5 h, 96%;
(iii) Ph3P@CHCOOEt, toluene, reflux, 20 h, quant.; (iv) DIBAL-H, CH2Cl2, 0 °C, 1.5 h, 95%; (v) TBAF, THF, rt, 2 h, 95%; (vi) Ti(OiPr)4, (–)-DIPT, TBHP, MS 3 Å, CH2Cl2, 0 °C, 1.5 h,
93%; (vii) Me2CuLiꢁLiI, Et2O, ꢀ20 °C to rt, 13.5 h, 43% of 25, 50% of 26; (viii) TESCl, imidazole, DMF, rt, 12 h, quant.; (ix) Me2CuLiꢁLiCN, Et2O, ꢀ30 °C, 2.5 h, 84%; (x) TESOTf,
DMAP, Py, rt, 22 h, quant.; (xi) DDQ, CH2Cl2/phosphate buffer (pH 7) (5:1), rt, 1.5 h, 65%; (xii) (a) 14a, MNBA, Et3N, DMAP, CH2Cl2, rt, 12 h, 91% of 31a; (b) 14b, MNBA, Et3N,
DMAP, CH2Cl2, rt, 14 h, 93% of 31b; (xiii) (a) PPTS, CH2Cl2/MeOH (1:1), ꢀ25 °C, 3 h, 94% of 32a; (b) PPTS, CH2Cl2/MeOH (1:1), ꢀ25 °C, 1 h, 90% of 32b; (xiv) (a) TPAP, NMO, MS
4 Å, CH2Cl2, 0 °C, 1 h, 81% of 33a; (b) TPAP, NMO, MS 4 Å, CH2Cl2, 0 °C, 1 h, 88% of 33b; (xv) (a) 33a, NaClO2, NaH2PO4, 2-methyl-2-butene, tBuOH/H2O (3.4:1), rt, 22 h; (b) 33b,
NaClO2, NaH2PO4, 2-methyl-2-butene, tBuOH/H2O (3.4:1), rt, 15 h; (xvi) TsOH, THF/H2O (10:1), rt, 2 days, 56% of 7 and 37% of 11 from 33a (two steps); (xvii) TsOH, THF, rt,
23 h, 82%; (xviii) TsOH, THF/H2O (10:1), rt, 24 h, 73% of 10 from 33b (two steps).

6516
H. Fukui et al. / Tetrahedron Letters 49 (2008) 6514–6517
TBSO
TBSO
TESO
MeOOC
O
TESO
MeOOC
O
iii
i
nBu
nBu
33a
O
O
O
O
DPTC
O
O
O
35
36
HO
AcO
S
ii
iv
N
O
O
N
DPTC
OH
nBu
OH
nBu
HO
HO
O
HO
O
3'
MeOOC
MeOOC
O
AcO
Botcinic acid methyl ester (8)
3-O-Acetylbotcinic acid methyl ester (9)
Scheme 3. Reagents and conditions: (i) (a) NaClO2, NaH2PO4, 2-methyl-2-butene, tBuOH/H2O (3.4:1), rt, 18.5 h; (b) TMSCHN2, MeOH, rt, 10 min, quant. (two steps); (ii) HFꢁPy,
THF/Py (2:1), rt, 20 min. 74%; (iii) AcOH, DPTC, DMAP, neat, 65 °C, 40 h, 35% of 36 and 57% of the recovered 35; (iv) HFꢁPy, THF/Py (2:1), rt, 11 h, 50%.
parts 14a/b5 were added to the alcohol 30 by the MNBA-promoted
coupling reaction.8 The site-selective deprotection of a TES group
in the coupling products 31a/b was realized, and the resulting pri-
mary alcohols 32a/b were oxidized to form the corresponding
aldehydes 33a/b, which were further converted into carboxylic
acids 34a/b under Pinnick’s conditions. Finally, deprotection of
the TES groups afforded botcinic acid (7)9 and botcinin E (11)10
from 34a, and also botcineric acid (10)11 from 34b. It was also
confirmed that the acid-catalyzed lactonization of 7 smoothly
proceeded to afford 11 at room temperature.
natural product assumed to be 3-O-acetyl-5-O-methylbotcinolide
(3) should be revised to that of 3-O-acetylbotcinic acid methyl
ester (9).
The structure of homobotcinolide (4) also had to be revised to
that of botcineric acid (10) because the structure of 4 was
conjectured by the homological analysis of the spectroscopic data
of botcinolide (1), whose structure has been revised to botcinic
acid (7). Actually, the 13C NMR data of the synthetic botcineric acid
(10) in CD3OD were identical to those of the reported homobotcin-
olide (4).1d
The syntheses of botcinic acid methyl ester (8) and 3-O-acetyl-
botcinic acid methyl ester (9) are described in Scheme 3. Oxida-
tion of 33a and successive treatment of the resulting carboxylic
acid 34a with TMS diazomethane afforded the corresponding
methyl ester 35. Deprotection of the TES and TBS groups in 35 gave
botcinic acid methyl ester (8)12 in good yield. Preparation of an-
other metabolite 9 was also attempted by acetylation of the 3-hy-
droxyl group in 35, but it was revealed that the coupling required
very strict conditions. When the acetylation of 35 was performed
by conventional methods, such as Ac2O/DMAP in pyridine or
AcCl/Et3N in dichloromethane, no coupling product was generated
at all. We found that only the protocol using O,O-di(2-pyridyl) thio-
carbonate (DPTC)13 was effective for introducing the acetyl group
into 35, and the desired 36 was successfully obtained in the
presence of DPTC/DMAP. Finally, cleavage of the silyl groups in
36 provided 3-O-acetylbotcinic acid methyl ester (9).14
In summary, we achieved the first asymmetric total syntheses
of botcinic acid (7), botcinic acid methyl ester (8), 3-O-acetylbotci-
nic acid methyl ester (9), botcineric acid (10), and botcinin E (11).
The previous synthetic studies3,5 and the present report on the
synthesis of 7, 8, and 11 confirmed that the structures of
botcinolides (1, 2, and 5) are incorrect and should be revised to
those of 7, 8, and 11. Extensive examinations including a detailed
comparison of the spectroscopic data of 3-O-acetylbotcinic acid
methyl ester (9) and botcineric acid (10) with those of other
reported botcinolides concluded that the true forms of the natural
compounds assumed to be 3-O-acetyl-5-O-methylbotcinolide (3)
and homobotcinolide (4) are unambiguously identified as having
the structures of 9 and 10, respectively.
Acknowledgments
As described above, the asymmetric total syntheses of botcinic
acid (7), botcinic acid methyl ester (8), 3-O-acetylbotcinic acid
methyl ester (9), botcineric acid (10), and botcinin E (11) were suc-
cessfully achieved. The 1H and 13C NMR data of the synthetic 7, 8,
and 11 are in good agreement with those of the isolated com-
pounds2 in the same solvent, and the values of the optical rotations
of the synthetic 7 and 11 were similar to those of the natural prod-
ucts. These results strongly support the fact that the structures of
botcinic acid (7), its methyl ester (8), and botcinin E (11) proposed
by Nakajima et al. are absolutely correct.
The authors appreciate Prof. Nakajima (Tottori Univ.) to share
the spectral data for botcinic acid and botcinin E. The authors
thank the Central Glass Co., Ltd (Japan) for kindly providing trifluo-
romethanesulfonic acid as a bulk sample. This study was par-
tially supported by a Research Grant from the Center for Green
Photo-Science and Technology, and Grants-in-Aid for Scientific Re-
search from the Ministry of Education, Science, Sports and Culture,
Japan.
References and notes
The 1H and 13C NMR data of the synthetic 3-O-acetylbotcinic
acid methyl ester (9) in CDCl3 were almost identical to those of
the isolated 3-O-acetyl-5-O-methylbotcinolide (3)1c except for
one chemical shift in the 1H NMR spectra. The resonance at dH
6.70 ppm (H-30)15 in the reported data seems to correspond to
the resonance at dH 6.99 ppm (H-30) in our data, however, we have
assumed that the chemical shift at dH 6.70 ppm in the former paper
might be incorrectly typed because the resonances of the protons
for H-30 of the other botcinolides are observed in the range from
dH 6.97 to 7.04 ppm. Furthermore, Collado reported that ‘The 1H
NMR spectrum of 3 was very similar to that of botcinolide (1)
except for the presence of two new signals at dH 3.64 (3H, s) and
2.22 (3H, s)’, therefore, it is determined that the structure of the
1. (a) Cutler, H. G.; Jacyno, J. M.; Harwood, J. S.; Dulik, D.; Goodrich, P. D.; Roberts,
R. G. Biosci. Biotechnol. Biochem. 1993, 57, 1980–1982; (b) Jacyno, J. M.;
Harwood, J. S.; Cutler, H. G.; Dulik, D. M. Tetrahedron 1994, 50, 11585–11592;
(c) Collado, I. G.; Aleu, J.; Hernandez-Galan, R.; Hanson, J. R. Phytochemistry
1996, 42, 1621–1624; (d) Cutler, H. G.; Parker, S. R.; Ross, S. A.; Crumley, F. G.;
Schreiner, P. R. Biosci. Biotechnol. Biochem. 1996, 60, 656–658; (e) Reino, J. L.;
´
´
´
´
Hernandez-Galan, R.; Duran-Patron, R.; Collado, I. G. J. Phytopathol. 2004, 152,
563–566; (f) Reino, J. L.; Dura´n-Patro´n, R. M.; Daoubi, M.; Collado, I. G.;
´
´
Hernandez-Galan, R. J. Org. Chem. 2006, 71, 562–565.
2. (a) Tani, H.; Koshino, H.; Sakuno, E.; Nakajima, H. J. Nat. Prod. 2005, 68, 1768–
1772; (b) Tani, H.; Koshino, H.; Sakuno, E.; Cutler, H. G.; Nakajima, H. J. Nat.
Prod. 2006, 69, 722–725.
3. Shiina, I.; Takasuna, Y.; Suzuki, R.; Oshiumi, H.; Komiyama, Y.; Hitomi, S.; Fukui,
H. Org. Lett. 2006, 8, 5279–5282.
4. Private communication with Dr. Nakajima.

H. Fukui et al. / Tetrahedron Letters 49 (2008) 6514–6517
6517
5. Fukui, H.; Shiina, I. Org. Lett. 2008, 10, 3153–3156.
6. Another method for the synthesis of 23 has been reported: see Ref. 7.
7. Chakraborty, T. K.; Goswami, R. K. Tetrahedron Lett. 2007, 48, 6463–6465.
8. Shiina, I.; Kubota, M.; Oshiumi, H.; Hashizume, M. J. Org. Chem. 2004, 69, 1822–
1830.
3H), 1.23 (s, 3H), 0.99 (d, J = 6.1 Hz, 3H), 0.97 (d, J = 6.4 Hz, 3H), 0.90 (d,
J = 7.0 Hz, 3H); 13C NMR (CD3OD): d 180.8,* 167.7, 153.6, 120.2, 80.0, 78.5, 78.0,
72.5, 71.6, 69.3, 39.9, 39.3, 37.5, 32.9, 30.3, 26.4, 23.6, 18.3, 17.8, 15.0, 14.7,
*
14.4; HR MS: calcd for C22H38O8Na (M+Na+) 458.2459, found 458.2448. This
resonance was observed as a cross peak in HMBC spectrum.
9. Compound 7: ½a D21
ꢂ
ꢀ17.9 (c 0.42, EtOH) [lit2b
½
a 2D5
ꢂ
ꢀ14 (c 0.35, EtOH)]; IR (neat):
12. Compound 8: ½a D21
ꢀ22.9 (c 0.70, EtOH); IR (neat): 3437, 2932, 2874, 1715,
ꢂ
3411, 2931, 1706, 1655 cmꢀ1
;
1H NMR (CD3OD): d 6.98 (dd, J = 15.5, 5.0 Hz,
1653 cmꢀ1 1H NMR (CDCl3): d 6.99 (dd, J = 15.5, 4.5 Hz, 1H), 6.05 (dd, J = 15.5,
;
1H), 6.02 (dd, J = 15.5, 1.8 Hz, 1H), 4.33 (dd, J = 10.5, 10.0 Hz, 1H), 4.26–4.22 (m,
1H), 3.77 (d, J = 11.1 Hz, 1H), 3.60 (dq, J = 10.0, 6.3 Hz, 1H), 3.56 (br s, 1H), 2.75–
2.71 (m, 1H), 1.91–1.83 (m, 1H), 1.61–1.53 (m, 2H), 1.49–1.28 (m, 4H), 1.32 (d,
J = 7.0 Hz, 3H), 1.22 (s, 3H), 0.99 (d, J = 6.3 Hz, 3H), 0.97 (d, J = 7.0 Hz, 3H), 0.92
(t, J = 7.0 Hz, 3H); 13C NMR (CD3OD): d 180.3, 167.7, 153.6, 120.2, 80.0, 78.5,
77.7, 72.4, 71.6, 69.3, 39.7, 39.3, 37.3, 28.7, 23.6, 18.1, 17.5, 14.9, 14.7, 14.3; HR
MS: calcd for C20H34O8Na (M + Na+) 425.2146, found 425.2147.
2.0 Hz, 1H), 4.40 (dd, J = 10.7, 9.8 Hz, 1H), 4.35–4.31 (m, 1H), 3.90 (dd, J = 11.0,
5.6 Hz, 1H), 3.71 (d, J = 11.1 Hz, 1H), 3.65 (s, 3H), 3.59–3.53 (m, 2H), 2.78 (dq,
J = 2.1, 7.2 Hz, 1H), 2.15 (d, J = 5.6 Hz, 1H), 1.88 (ddq, J = 11.0, 10.7, 6.4 Hz, 1H),
1.64 (d, J = 4.5 Hz, 1H), 1.64–1.57 (m, 2H), 1.46-1.32 (m, 4H), 1.36 (d, J = 7.2 Hz,
3H), 1.24 (s, 3H), 1.01 (d, J = 6.4 Hz, 3H), 0.98 (d, J = 6.0 Hz, 3H), 0.91 (t,
J = 7.0 Hz, 3H);1H NMR (C6D6): d 7.11 (dd, J = 16.1, 4.3 Hz, 1H), 6.24 (dd,
J = 16.1, 1.2 Hz, 1H), 4.78 (dd, J = 10.4, 9.7 Hz, 1H), 4.05–4.01 (m, 1H), 3.94 (d,
J = 10.4 Hz, 1H), 3.87–3.81 (m, 1H), 3.61 (dq, J = 9.7, 6.3 Hz, 1H), 3.56 (d,
J = 11,3 Hz, 1H), 3.34 (s, 3H), 2.74 (q, J = 6.8 Hz, 1H), 1.99–1.93 (m, 1H), 1.84 (br
s, 1H), 1.36 (d, J = 6.8 Hz, 1H), 1.28–1.20 (m, 2H), 1.24 (d, J = 4.3 Hz, 1H), 1.16–
1.12 (m, 4H), 1.16 (s, 3H), 1.14 (d, J = 6.3 Hz, 3H), 1.13 (d, J = 6.1 Hz, 3H), 0.83 (t,
J = 7.0 Hz, 3H); 13C NMR (CDCl3): d 176.7, 165.9, 151.1, 119.5, 78.6, 77.0, 76.7,
71.8, 71.2, 68.0, 51.4, 38.0, 37.8, 36.4, 27.4, 22.5, 18.1, 17.0, 14.4, 14.0, 13.9; 13C
NMR (C6D6): d 176.6, 165.9, 151.9, 119.6, 79.1, 77.3, 77.0, 71.6, 70.9, 68.4, 51.0,
38.4, 38.2, 36.5, 27.6, 22.8, 18.4, 17.2, 14.4, 14.3, 14.1; HR MS: calcd for
C21H36O8Na (M+Na+) 439.2308, found 439.2307.
10. Compound 11: ½a D30
ꢂ
ꢀ88.9 (c 0.38, EtOH), [lit2b a 2D5
½ ꢂ ꢀ69 (c 0.23, EtOH)]; IR
(neat): 3445, 2934, 2874, 1730 cmꢀ1 1H NMR (CDCl3): d 7.02 (dd, J = 15.5,
;
4.5 Hz, 1H), 6.07 (dd, J = 15.5, 1.5 Hz, 1H), 4.53 (dd, J = 11.0, 9.5 Hz, 1H), 4.37–
4.32 (m, 1H), 4.15 (dd, J = 9.2, 3.8 Hz, 1H), 3.73 (dq, J = 9.5, 6.0 Hz, 1H), 3.70 (d,
J = 10.8 Hz, 1H), 3.06 (dq, J = 9.2, 7.0 Hz, 1H), 2.18 (ddq, J = 11.0, 10.8, 6.0 Hz,
1H), 1.98 (d, J = 3.8 Hz, 1H), 1.68 (d, J = 4.0 Hz, 1H), 1.63–1.55 (m, 2H), 1.48–
1.33 (m, 4H), 1.28 (d, J = 7.0 Hz, 3H), 1.28 (s, 3H), 1.12 (d, J = 6.0 Hz, 3H), 1.06 (d,
J = 6.0 Hz, 3H), 0.92 (t, J = 6.0 Hz, 3H); 1H NMR (CD3OD): d 7.02 (dd, J = 15.5,
5.0 Hz, 1H), 6.05 (dd, J = 15.5, 1.5 Hz, 1H), 4.50 (dd, J = 11.0, 9.5 Hz, 1H), 4.26–
4.22 (m, 1H), 4.08 (d, J = 9.3 Hz, 1H), 3.94 (d, J = 11.0 Hz, 1H), 3.78 (dq, J = 9.5,
6.0 Hz, 1H), 3.20 (dq, J = 9.3, 7.0 Hz, 1H), 2.25–2.17 (m, 1H), 1.62–1.49 (m, 2H),
1.40–1.26 (m, 4H), 1.17 (s, 3H), 1.14 (d, J = 7.0 Hz, 1H), 1.07 (d, J = 6.0 Hz, 1H),
0.97 (d, J = 6.0 Hz, 3H), 0.92 (t, J = 6.0 Hz, 3H);13C NMR (CDCl3): d 174.0, 165.8,
151.8, 119.1, 78.4, 77.2, 76.2, 74.0, 71.1, 68.4, 38.3, 36.4, 35.6, 27.4, 22.5, 18.2,
13.9, 13.7, 11.0, 10.3; 13C NMR (CD3OD): d 177.4, 167.6, 154.1, 119.8, 79.6, 78.1,
77.9, 75.0, 71.5, 69.5, 39.5, 37.2, 36.8, 28.7, 23.6, 18.6, 14.3, 14.0, 11.6, 10.5; HR
MS: calcd for C20H32O7Na (M+Na+) 407.2040, found 407.2034.
13. Saitoh, K.; Shiina, I.; Mukaiyama, T. Chem. Lett 1998, 679–680.
14. Compound 9: ½a D22
ꢀ14.7 (c 1.20, EtOH); IR (neat): 3477, 2935, 1723, 1254,
ꢂ
1167 cmꢀ1 1H NMR (CDCl3): d 6.99 (dd, J = 15.5, 4.5 Hz, 1H), 6.05 (dd, J = 15.5,
;
1.5 Hz, 1H), 4.98 (d, J = 3.8 Hz, 1H), 4.40 (dd, J = 10.5, 9.8 Hz, 1H), 4.35–4.30 (m,
1H), 3.66 (s, 3H), 3.57 (dq, J = 9.8, 6.0 Hz, 1H), 3.10 (dd, J = 10.5, 4.5 Hz, 1H),
3.01 (dd, J = 3.8, 6.8 Hz, 1H), 2.99 (d, J = 4.5 Hz, 1H), 2.23 (s, 3H), 1.91 (ddq,
J = 10.5, 10.5, 6.3 Hz, 1H), 1.64–1.54 (m, 2H), 1.40–1.31 (m, 4H), 1.34 (s, 3H),
1.22 (d, J = 6.8 Hz, 3H), 1.03 (d, J = 6.0 Hz, 3H), 0.99 (d, J = 6.3 Hz, 3H), 0.91 (t,
J = 7.0 Hz, 3H); 13C NMR (CDCl3): d 174.0, 172.9, 165.9, 151.0, 119.5, 78.3, 77.9,
76.6, 72.1, 71.2, 68.1, 51.5, 38.8, 37.0, 36.4, 27.4, 22.5, 20.9, 18.0, 16.1, 14.9,
14.3, 13.9; HR MS: calcd for C23H38O9Na (M+Na+) 481.2408, found 481.2379.
15. The proton positions in parentheses are numbered according to the botcinin
skeleton nomenclature by Nakajima.
11. Compound 10: ½a D30
ꢂ
ꢀ7.9 (c 0.90, EtOH); IR (neat): 3418, 2929, 1716, 1462,
1273, 1166, 1107 cmꢀ1
;
1H NMR (CD3OD): d 6.97 (dd, J = 15.6, 4.9 Hz, 1H), 6.02
(dd, J = 15.6, 1.5 Hz, 1H), 4.33 (dd, J = 10.4, 10.1 Hz, 1H), 4.25–4.22 (m, 1 H),
3.76 (d, J = 10.4 Hz, 1H), 3.63–3.57 (m, 1H), 3.53 (br s, 1H), 2.76–2.67 (m, 1H),
1.91–1.83 (m, 1H), 1.60–1.49 (m, 2H), 1.40–1.28 (m, 8H), 1.32 (d, J = 6.6 Hz,