Synthesis of the DE-ring of goniodomin A and prediction of its natural relative stereochemistry

Article abstract of DOI:10.1016/j.tetlet.2007.11.084

Goniodomin A (1) was first isolated from Alexandrium hiranoi as a stereochemically unidentified antifungal agent in 1987 by Murakami. In this study, two stereoisomeric series of non-macrocyclic and macrocyclic DE-ring model compounds of 1 were synthesized

Full text of DOI:10.1016/j.tetlet.2007.11.084

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 233–237
Synthesis of the DE-ring of goniodomin A and prediction of its
natural relative stereochemistry
a
a,
a
Takahiro Katagiri , Kenshu Fujiwara *, Hidetoshi Kawai a,b, Takanori Suzuki
a
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan
PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan
b
Received 30 October 2007; revised 14 November 2007; accepted 15 November 2007
Available online 21 November 2007
Abstract
Goniodomin A (1) was first isolated from Alexandrium hiranoi as a stereochemically unidentified antifungal agent in 1987 by Mura-
kami. In this study, two stereoisomeric series of non-macrocyclic and macrocyclic DE-ring model compounds of 1 were synthesized, and
the natural relative stereochemistry of the DE-ring was predicted by NMR comparison of 1 with these model compounds.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Goniodomin A; Polyether macrolide; Ireland–Claisen rearrangement; NMR analysis; Natural product synthesis
Goniodomin A (1, Fig. 1), isolated first from dinoflagel-
late Alexandrium hiranoi as an antifungal agent by Mura-
kami1 and later from A. monilatium by Moeller and co-
workers,2 possesses remarkable bioactivity toward actin
organization.3–5 Although the unique planar structure of
its stereochemistry has not yet been clarified. Lack of
stereochemical information for 1 arrests further biological
studies to elucidate the mechanism of its action. Therefore,
we have launched a program for the determination of the
full absolute configuration of 1 by total synthesis. Previ-
ously, we confirmed the natural relative stereochemistry
of the A- and F-rings of 1 by NMR comparison of 1 and
synthetic A- and F-ring model compounds having unam-
biguous stereochemistry.6 We next focus our attention on
the stereochemistry of the DE-ring of 1. We describe herein
the synthesis of DE-ring model compounds with and with-
out a macrocyclic ring and the prediction of the natural rel-
ative stereochemistry of the DE-ring by NMR comparison
of 1 and these model compounds.
First, we deduced the cis-configuration of the D-ring
and the trans-configuration of the E-ring from Murakami’s
NMR data of 1 showing the presence of an NOE interac-
tion between H16 and H20 and the absence of an NOE
between H21 and H24.1a,b Therefore, two possible configu-
rations, 1a and 1b (Fig. 2), for the stereochemical relation-
ship between the D- and E-rings were derived. We next
planned to synthesize DE-ring models 2a and 2b (Fig. 3),
corresponding to 1a and 1b, respectively, to elucidate
the correct stereochemistry of the D- and E-rings by
1, featuring
a 32-membered macrolactone including
5- and 6-membered cyclic ethers, a spirocyclic acetal, and a
6-membered cyclic hemiacetal, was determined by Murakami,
OH
21
20
E
O
D
OH
24
26
O
27
16
5
15
C
HO
O
A
O
6
2
11O
B
7
1
31
O
H
H
OH
Me
32
O
9
O
33
F
Me
36
34
Me
Goniodomin A (1)
Fig. 1.
*
Corresponding author. Tel.: +81 11 706 2701; fax: +81 11 706 4924.
E-mail address: fjwkn@sci.hokudai.ac.jp (K. Fujiwara).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.084

234
T. Katagiri et al. / Tetrahedron Letters 49 (2008) 233–237
JH20-H21 = 9.4 Hz
OH
TBSO
TBSO
O
a, b, c
81%
d, e
f
O
20
21
E
D
24
16
O
76%
91%
PMBO
O
H
H
PMBO
PMBO
7
R'
H
R H
6
8
NOE
no NOE
OH
O
OH
cis
trans
TBSO
g, h
80%
i, j, k, l
20
Partial relative stereochemistry of the D- and E-rings of 1
O
PMBO
10
O
PMBO
11
deduced from Murakami's NMR data
H
H
H
H
54%
HO
TBSO
PMBO
9
2021
20 21
E
E
D
D
24
24
TBSO
TBSO
16
16
O
O
O
O
HH
HH
R'
R'
O
m, e
81%
n
g, h
H
H
or
R H
R H
7
(16S*,20R*,21R*,24R*)
(16R*,20S*,21R*,24R*)
85%
82%
PMBO
OH
PMBO
OH
1a
1b
12
13
Two possible relative stereostructures for the DE-ring of 1
OH
o, p, j, k, l
37%
20
Fig. 2.
O
PMBO
O
H
H
H
H
HO
TBSO
PMBO
14
15
20 21
20 21
E
E
D
H
D
H
Scheme 1. Reagents and conditions: (a) allylmagnesium bromide, CuCN,
THF, ꢀ20 °C; (b) TBSOTf, 2,6-lutidine, CH2Cl2, 23 °C; (c) OsO4, NMO,
THF–H2O (2:1), 23 °C, then NaIO4; (d) (PhO)2P(O)CH2CO2Et, NaH,
THF, ꢀ78 °C, then 7, ꢀ78!ꢀ20 °C; (e) DIBAH, Et2O, ꢀ78 °C; (f)
TBHP, (ꢀ)-DET, Ti(Oi-Pr)4, MS4A, CH2Cl2, ꢀ25 °C; (g) TBAF, THF;
(h) CSA, CH2Cl2, 0 °C; (i) PivCl, pyridine, CH2Cl2, 0 °C, then TBSOTf,
0 °C; (j) DIBAH, CH2Cl2, ꢀ78 °C; (k) DMPI, CH2Cl2, 23 °C; (l)
Ph3PCH3Br, NHMDS, 23 °C, then aldehyde, ꢀ78! 23°C; (m)
Ph3PCHCO2Et, benzene, 23 °C; (n) TBHP, (+)-DET, Ti(Oi-Pr)4,
MS4A, CH2Cl2, ꢀ25 °C; (o) PivCl, pyridine, DMAP, CH2Cl2, 0 °C; (p)
TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C.
O
O
O
25
O
25
HH
HH
H
H
15
15
15
15
PMBO
PMBO
OH
OH
2a
2b
20 21
20 21
E
E
D
H
D
H
O
O
O
O
25
25
HH
HH
H
H
O
O
O
O
n
n
O
O
O
O
3a: n = 6
4a: n = 4
5a: n = 2
3b: n = 6
4b: n = 4
5b: n = 2
give 9 (91%). After the TBS group was removed from 9,
the resulting dihydroxy epoxide was cyclized with CSA to
afford 10 (80%), which was transformed to 11 (54%) by a
four-step process [(i) one-pot selective protection of the pri-
mary and secondary hydroxy groups, (ii) detachment of the
Piv group, (iii) Dess–Martin oxidation,9 and (iv) Wittig
methylenation]. Intermediate E-ring 15 for 2b was also syn-
thesized from 7 via trans-epoxide 13. After conversion of 7
to E-allyl alcohol 12 (81%) via Wittig reaction followed by
DIBAH reduction, 13 was prepared by asymmetric epoxi-
dation using (+)-DET (85%).8 Transformation of 13 to
15 (overall yield 30%) was performed similarly to that of
9 to 11.
Next, DE-ring models 2a and 2b were synthesized from
11 and 15, respectively, via a process which included Ire-
land–Claisen rearrangement and ring-closing olefin
metathesis (RCM) (Scheme 2).10 Deprotection of 11
followed by reaction with bromoacetic acid afforded 16,
which was subjected to condensation with (S)-17 and sub-
sequent partial hydrogenation to give 18 (67% from 11).
Treatment of 18 with LHMDS in the presence of
MeSiCl311 at ꢀ78 °C followed by warming to ambient tem-
perature induced the Ireland–Claisen rearrangement, and
19 was isolated (93%) after methylation with diazomethane.
Diene 19 was transformed to 2a through RCM with
Fig. 3.
comparison of the JH20–H21 values of 1 and the models.
Unfortunately, both the models synthesized had consider-
ably different values of JH20–H21 (2a: 5.9 Hz, 2b: 6.6 Hz)
from that of 1 (9.4 Hz),1a,b and the relative stereochemistry
of the DE-ring could not be established (as described
below). Since this failure is likely caused by the lack of a
macrocyclic ring in the models, we transformed 2a and
2b to the corresponding macrocyclic compounds 3–5a
and 3–5b (Fig. 3) for a more precise evaluation of the rel-
ative stereochemistry at C20 and C21 of 1.
In the synthesis of 2a and 2b, we first undertook the con-
struction of the E-ring by intramolecular 5-exo opening of
a 24-hydroxy-20,21-epoxide to establish the configurations
at C20 and C21 (Scheme 1). Therefore, intermediate E-ring
11 for 2a was synthesized from cis-epoxide 9, prepared
from 6. Epoxide 6 was initially converted to 7 (81%) by
allylation, TBS-protection, and oxidative cleavage of the
alkene part. Modified Horner–Wadsworth–Emmons reac-
tion7 of 7 followed by DIBAH reduction selectively pro-
duced Z-allyl alcohol 8 (76%), which was then epoxidized
by the Katsuki–Sharpless procedure8 using (ꢀ)-DET to

T. Katagiri et al. / Tetrahedron Letters 49 (2008) 233–237
235
Me
OPMB
a
O
n
H O
67%
O
HH
HO
OTBDPS
H
a, b
c, d
OH
Me
O
H
2a
OTBDPS
n
11
O
O
O
CO2H
O
HH
HH
O
O
H
H
PMBO
PMBO
O
(4 steps)
22: n = 6
23: n = 4
24a: n = 6 (98% from 2a)
25a: n = 4 (89% from 2a)
16
(S)-17
18
Me
3a
69%,
JH20-H21
= 5.9 Hz
20 21
b, c, d
e
f
2 steps
4a
O
O
n
e, f
g, h
O
O
HH
HH
H
H
O
O
HH
O
O
H
H
HH
OH
OH
CO2H
H
H
62%,
2 steps
93%
80%
H
O
H
O
CHO
O
PMBO
PMBO
n
OH
OMe
19
2a
Me
O
O
26a: n = 6 (67%)
27a: n = 4 (58%)
28a: n = 6
29a: n = 4
Me
a, b, c, d, e, f
3b (50% from 2b)
4b (9% from 2b)
H O
22 / 23
a, b, i, d
OH
e, f
2b
O
15
O
O
O
O
HH
HH
H
H
Scheme 3. Reagents and conditions: (a) 2a or 2b, DCC, DMAP, CH2Cl2,
23 °C; (b) TBAF, THF, 23 °C; (c) DMPI, CH2Cl2, 23 °C; (d) DDQ,
CH2Cl2–H2O (10:1), 23 °C; (e) NaClO2, NaH2PO4, 2-methyl-2-butene,
t-BuOH–H2O (3.5:1), 23 °C; (f) 2,4,6-trichlorobenzoyl chloride, Et3N,
23 °C, then DMAP, toluene (5 mM of substrate), 60 °C.
93%
90%
O
H
PMBO
PMBO
Me
OMe
(R)-17
20
21
JH20-H21
= 6.6 Hz
20 21
g, h
O
O
HH
H
81%
H
OH
verted to 3a (69%) by Pinnick oxidation13 and Yamaguchi
lactonization.14 Macrocyclic models 3b, 4a, and 4b were
similarly obtained in 50% (from 2b), 32% (from 2a), and
9% overall yield (from 2b), respectively.
PMBO
2b
Scheme 2. Reagents and conditions: (a) TBAF, THF, 23 °C; (b) NaH,
t-BuOK, bromoacetic acid, THF, 23 °C; (c) (S)-17, EDCIÆHCl, DMAP,
CH2Cl2, 23 °C; (d) H2, Lindlar cat., EtOH-0.5% quinoline in hexane
(10:1.3, v/v); (e) LHMDS, MeSiCl3, THF, ꢀ78 °C, then 23 °C; (f) CH2N2,
Et2O, 0 °C; (g) (H2IMes)(PCy3)Cl2RuCHPh, CH2Cl2 (3 mM of substrate),
23 °C; (h) LiAlH4, Et2O, ꢀ20 °C; (i) (R)-17, EDCIÆHCl, DMAP, CH2Cl2,
23 °C.
Since 16-membered cyclic models 5a,b could not be pre-
pared from 2a,b by the above route, we employed their
alternative synthesis from 19 and 21 (Scheme 4).15 Ester
19 was first reduced with LiAlH4, and the resulting alcohol
was converted to 31a (75%) via esterification with 30 and
TBDPS deprotection. Dess–Martin oxidation9 of 31a
followed by PMB deprotection and Pinnick oxidation13 gave
32a, which was lactonized by Yamaguchi’s method14 to
produce 33a (67% from 31a). Diene 33a was cyclized with
second-generation Grubbs’ catalyst12 to furnish 5a (53%).
Model 5b was also synthesized from 21 in the same way
(overall 28%). Since 5a and 5b were obtained as crystals,
their stereochemistry was confirmed by X-ray crystallo-
graphic analysis (Fig. 4).16
The JH20–H21 values of models 2–5a,b are listed in Table
1. While the JH20–H21 values of non-macrocyclic models
2a,b are both around 6 Hz, each JH20–H21 of the a-series
macrocyclic models is clearly larger (5.4–7.5 Hz) than that
of the corresponding b-series model (2.6–3.6 Hz). There-
fore, the JH20–H21 values of a-series models replicated that
of 1 better than the b-series models. It is also notable that,
as the ring size of the models decreased, the difference of
JH20–H21 between a- and b-series models increased and
the discrepancy of JH20–H21 between an a-series model
and 1 was reduced.17
second-generation Grubbs’ catalyst12 followed by reduc-
tion of the ester group (80%). Model 2b was synthesized
from 15 via the same process as above except that (R)-17
was employed in the condensation step (overall yield 68%).
Both model compounds 2a and 2b showed an NOE
enhancement between H16 and H20 and an absence of
NOE between H21 and H24 in accordance with the
reported data of 1. However, both the models also dis-
played different values of JH20–H21 (2a: 5.9 Hz, 2b:
6.6 Hz) from that of 1, and the relative stereochemistry
of the DE-ring of 1 could not be confirmed at this stage.
This disappointing result was attributed to the absence of
a macrocyclic ring in the models. Therefore, macrocyclic
models 3–5a,b were synthesized for more precise stereo-
chemical assessment of the DE-ring of 1.
DE-ring models 2a and 2b were successfully transformed
to the corresponding macrocyclic models 3–4a and 3–4b
through a common six-step process illustrated in Scheme
3. For example, DE-ring model 2a was initially condensed
with carboxylic acid 22 (98%), and the resulting ester 24a
was subjected to a process including removal of the TBDPS
group, Dess–Martin oxidation,9 and PMB deprotection to
produce hydroxyaldehyde 26a (67%), which was then con-
In the following paragraphs, we discuss the effect of the
relative stereochemistry of the macrocyclic models on the
3
size of JH20–H21 values. Because a measured value of JH–H
in a flexible molecule results from a population weighted

236
T. Katagiri et al. / Tetrahedron Letters 49 (2008) 233–237
There are three basic conformers around the C20–C21
Me
bond in each DE-ring model, namely, two H20,H21-gauche
and one H20,H21-anti conformers.18 From the ORTEP
diagrams (Fig. 4), it is clear that the conformation of
macrocyclic model 5a in the crystal form assumes an
H20,H21-anti relationship, and that of 5b takes on an
H20,H21-gauche relationship. The conformational prefer-
ence is attributed to the distance between C15 and C25.
When the dicarboxylate chain is of limited length, the
a, b, c
O
n
d, e, f
O
O
HH
19
H
H
OPMB
TBDPSO
HO
75%
O
OH
O
30
31a: n = 2
Me
Me
˚
C15–C25 distance is kept to a minimum (6.982 A in 5a
˚
and 6.101 A in 5b). On the other hand, conformers with
a longer C15–C25 distance would be energetically unfavor-
able in such a situation. Therefore, an H20,H21-gauche
conformer of 5a and an H20,H21-anti-conformer of 5b,
g
h
O
O
HH
O
O
O
HH
5a
H
H
H
H
OH
CO2H
67%
(4 steps)
53%
O
O
O
˚
n
n
in which the estimated C15–C25 distances are 8.27 A and
O
˚
O
8.08 A, respectively, would constitute only negligible frac-
33a: n = 2
32a: n = 2
tions of the total conformer population.19
The measured JH20–H21 values in each of 1, non-macro-
cyclic models 2a,b, and macrocyclic models 3–5a,b result
from a population weighted average of JH20–H21 values
for all conformers around the C20–C21 bond in each com-
pound. It is predicted from the Karplus relationship20 that
the JH20-H21 value of the H20,H21-gauche conformer is
small (0–3 Hz) and that of the H20,H21-anti conformer is
large (7–10 Hz).21,22 Hence, the negligible contribution of
the H20,H21-gauche conformer of the a-series macrocyclic
models would make the observed JH20–H21 value large,
while the minor population of the H20,H21-anti conformer
of the b-series models would reduce the observed JH20–H21
value. The observed medium values of JH20–H21 of 2a and
2b are attributed to a relatively uniform population distri-
bution of the three basic conformers. Thus, it is reasonable
to assume that the relative stereochemistry of macrocyclic
DE-ring models is reflected in the size of their JH20–H21
values.
a, b, c, d, e, f, g, h
28%
21
5b
Scheme 4. Reagents and conditions: (a) LiAlH4, Et2O, ꢀ20 °C; (b) 30,
DCC, DMAP, CH2Cl2, 23 °C; (c) TBAF, THF, 23 °C; (d) DMPI, CH2Cl2,
23 °C; (e) DDQ, CH2Cl2–H2O (20:1), 23 °C; (f) NaClO2, NaH2PO4,
2-methyl-2-butene, t-BuOH–H2O (3.5:1); (g) 2,4,6-trichlorobenzoyl
chloride, Et3N, 23 °C, then DMAP, toluene (5 mM of substrate), 60 °C;
(h) (H2IMes)(PCy3)Cl2RuCHPh, CH2Cl2, reflux.
Goniodomin A (1) has a large JH20–H21 value (9.4 Hz).
This suggests a high incidence of an H20,H21-anti con-
former due to the restricted C20–C21 bond rotation, even
though the DE-ring of 1 is connected with a long chain
(at least 15 atoms) between C15 and C25. This is not sur-
prising, because the chain is inflexible. It includes only eight
rotatable bonds and several rigid parts [an oxane (A-ring),
a spirocyclic acetal (BC-ring), an ester group, and a cis
double bond (C29@C30)]. Therefore, the chain would keep
the distance between C15 and C25 to a minimum, and the
DE-ring would adopt the H20,H21-anti conformer, which
shows a large JH20–H21, with high occurrence. From consid-
eration of the macrocyclic models, it is clear that the
H20,H21-anti conformer of the DE-ring with a shorter
C15–C25 distance would be included in a compound that
has the a-series stereochemistry (1a). Thus, it is predicted
that the relative stereochemistry of the DE-ring of 1 is the
same as that of the a-series models (Fig. 5).
Fig. 4. ORTEP diagrams of 5a and 5b.
Table 1
a-Series JH20–H21
2a: 5.9 Hza
b-Series JH20–H21
2b: 6.6 Hzb
Non-macrocyclic models
Macrocyclic models
n = 6
3a: 5.4 Hzc
4a: 6.1 Hzd
5a: 7.5 Hzb
9.4 Hzb
3b: 3.6 Hzb
4b: 3.3 Hza
5b: 2.6 Hzb
n = 4
n = 2
Goniodomin A (1)
a
In CDCl3.
In C6D6.
In CD3CN.
In C5ND5.
b
c
d
In conclusion, two stereoisomeric series of non-macro-
cyclic and macrocyclic DE-ring model compounds of
goniodomin A (1) were synthesized, and the natural rela-
tive stereochemistry of the DE-ring (1a) was predicted by
3
average of JH–H values over all conformers, difference of
the stereoisomeric macrocyclic models in conformer popu-
lation ratio should be considered.

T. Katagiri et al. / Tetrahedron Letters 49 (2008) 233–237
237
5. Abe, M.; Inoue, D.; Matsunaga, K.; Ohizumi, Y.; Ueda, H.; Asano,
T.; Murakami, M.; Sato, Y. J. Cell. Physiol. 2002, 190, 109.
6. Fujiwara, K.; Naka, J.; Katagiri, T.; Sato, D.; Kawai, H.; Suzuki, T.
Bull. Chem. Soc. Jpn. 2007, 80, 1173.
7. Ando, K.; Oishi, T.; Hirama, M.; Ohno, H.; Ibuka, T. J. Org. Chem.
2000, 65, 4745.
8. Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974.
9. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
10. Burke, S. D.; Ng, R. A.; Morrison, J. A.; Alberti, M. J. J. Org. Chem.
1998, 63, 3160.
From This Work
20 21
OH
E
D
25
OH
OH
O
O
HH
H
H
15
HO
O
C
A
O
6
O
B
1
31
O
H
H
O
9
Me
O
F
Me
11. Because the use of Me3SiCl according to the standard procedure gave
36
Me
a
significant amount of a by-product due to the [2,3]-Wittig
1
rearrangement, MeSiCl3 was used to suppress the side reaction.
12. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
953.
Fig. 5. Predicted partial relative stereochemistry of 1.
13. Bal, B. S.; Childers, W. E., Jr.; Pinnick, H. W. Tetrahedron 1981, 37,
2091.
14. Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull.
Chem. Soc. Jpn. 1979, 52, 1989.
15. Although the precursor secoic acids for 5a,b having an intact DE-ring
could be synthesized from 2a and 2b, the final macrocyclization step
gave only oligomeric side products.
NMR comparison of 1 with these model compounds.
Further studies toward determination of the full absolute
configuration of 1 by total synthesis are in progress in this
laboratory.
16. Crystal data of 5a: C17H24O6, M 324.37, orthorhombic P212121 (No.
˚
˚
˚
Acknowledgments
19), a = 5.140(1) A, b = 16.891(4) A, c = 18.332(5) A, V =
1591.7(7) A , Dc (Z = 4) = 1.354 g/cm3, T = 153 K, l = 1.02 cmꢀ1
.
3
˚
The final R value is 0.034 for 2436 independent reflections with
I > 2rI and 209 parameters. Crystal data of 5b: C17H24O6, M 324.37,
We are grateful to Professor Makoto Sasaki and Profes-
sor Masato Oikawa (Graduate School of Life Sciences,
Tohoku University) for helpful discussions. We also thank
Mr. Kenji Watanabe and Dr. Eri Fukushi (GC–MS and
NMR Laboratory, Graduate School of Agriculture,
Hokkaido University) for the measurements of mass spec-
tra. This work was supported by a Global COE Program
(Project No. B01: Catalysis as the Basis for Innovation in
Materials Science) and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science, and Technology of Japanese Government.
˚
˚
orthorhombic P212121 (No. 19), a = 5.249(3) A, b = 9.302(5) A,
3
c = 34.16(2) A, V = 1667.7(1) A , Dc (Z = 4) = 1.292 g/cm3, T =
153 K, l = 0.97 cmꢀ1. The final R value is 0.068 for 951 independent
reflections with I > 3rI and 209 parameters. Crystallographic data
(excluding structure factors) of 5a and 5b have been deposited with
the Cambridge Crystallographic Data Center as supplementary
publication numbers CCDC 664790 and 664791, respectively. Copies
of the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 0 1223 336033,
e-mail: deposit@ccdc.cam.ac.uk, or web: http://www.ccdc.cam.ac.
uk/].
˚
˚
17. There is still a slight discrepancy between the JH20–H21 values of model
5a (7.5 Hz) and 1 (9.4 Hz). The discrepancy may be attributable to the
difference in the rigidity between the simple dicarboxylate chain of the
model and the complex chain of 1 which includes several inflexible
parts, such as an oxane and a spirocyclic acetal.
18. The terms ‘H20,H21-gauche’ and ‘H20,H21-anti’ are used for conve-
nience. ‘H20,H21-gauche’ and ‘H20,H21-anti’ indicate that the
conformational relationship between H20 and H21 is gauche or anti,
respectively.
References and notes
1. (a) Murakami, M.; Makabe, K.; Yamaguchi, K.; Konosu, S.;
Wa¨lchli, M. R. Tetrahedron Lett. 1988, 29, 1149; (b) Murakami,
M.; Makabe, K.; Yamaguchi, K.; Konosu, S.; Wa¨lchli, M. R.
Abstracts of Papers, 28th Symposium on the Chemistry of Natural
Products; Sendai; Organizing Committee of the 28th Symposium on
19. The C15–C25 distances of the H20,H21-gauche conformer of 5a and
the H20,H21-anti conformer of 5b were estimated from simple
Chem3D models based on the X-ray coordinates of 5a and 5b. Each
model conformer was obtained as follows: the dicarboxylate chain
was removed from each coordinate, and the C20–C21 bond was
simply rotated until the desired conformer was given. The remaining
H20,H21-gauche conformers of 5a and 5b are expected to exist with
relatively high conformer population due to the relatively short
C15–C25 distances approximated (6.79 A in 5a and 6.99 A in 5b).
20. Karplus, M. J. Chem. Phys. 1959, 30, 11.
21. Haasnoot, C. A. G.; De Leeuw, F. A. A. M.; Altona, C. Tetrahedron
1980, 36, 2783–2792.
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Murakami, M.; Okita, Y.; Matsuda, H.; Okino, T.; Yamaguchi, K.
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Murakami, M.; Yamaguchi, K. Toxicon 1989, 27, 269.
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3. (a) Furukawa, K.-I.; Sakai, K.; Watanabe, S.; Maruyama, K.;
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268, 26026; (b) Yasuda, M.; Nakatani, K.; Matsunaga, K.; Muraka-
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(c) Matsunaga, K.; Nakatani, K.; Murakami, M.; Yamaguchi, K.;
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