Synthesis and relative stereochemistry of the A-and F-rings of goniodomin A

Article abstract of DOI:10.1246/bcsj.80.1173

The synthesis of the A-and F-rings of goniodomin A (1), which is a stereochemically unidentified antifungal agent isolated from dinoflagellate Alexandrium hiranoi, was performed to determine of the relative stereochemistry of these parts. The relative stereochemistry of the A-and F-rings was first deduced from Murakami's NMR data, and model compounds corresponding to these parts were then synthesized. The synthetic A-ring model, of which the structure was established by X-ray crystallographic analysis, showed good agreement with the natural A-ring on the basis of J and NOE behavior in the H NMR spectroscopy. The chemical shifts in ¹H and ^l3CNMR specta and J _32-OH-H33 of the synthetic F-ring model having a 33S,34R configuration also agreed with those of the F-ring of 1. Thus, the relative stereochemistry of the A-and F-rings of 1 was elucidated.

Full text of DOI:10.1246/bcsj.80.1173

Ó 2007 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 80, No. 6, 1173–1186 (2007) 1173
Synthesis and Relative Stereochemistry
of the A- and F-Rings of Goniodomin A
ꢀ
Hidetoshi Kawai, and Takanori Suzuki
Kenshu Fujiwara, Jota Naka, Takahiro Katagiri, Daisuke Sato,
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810
Received November 24, 2006; E-mail: fjwkn@sci.hokudai.ac.jp
The synthesis of the A- and F-rings of goniodomin A (1), which is a stereochemically unidentified antifungal agent
isolated from dinoflagellate Alexandrium hiranoi, was performed to determine of the relative stereochemistry of these
parts. The relative stereochemistry of the A- and F-rings was first deduced from Murakami’s NMR data, and model com-
pounds corresponding to these parts were then synthesized. The synthetic A-ring model, of which the structure was es-
tablished by X-ray crystallographic analysis, showed good agreement with the natural A-ring on the basis of J and NOE
1
1
behavior in the H NMR spectroscopy. The chemical shifts in H and 13C NMR specta and J32-OH{H33 of the synthetic
F-ring model having a 33S,34R configuration also agreed with those of the F-ring of 1. Thus, the relative stereochemistry
of the A- and F-rings of 1 was elucidated.
Goniodomin A (1, Fig. 1) was first isolated from dinoflagel-
late Alexandrium hiranoi as an antifungal agent by Murakami
et al. in 1988.1 It has been found to have diverse bioactivity,
such as modulation of actomyosin ATPase activities,2 increas-
ing the filamentous actin content of human astronoma cells,3
and antiangiogenic activity via inhibition of actin reorganiza-
tion in endothelial cells.4 Very recently, Moeller and co-work-
ers have also isolated 1 as a cytotoxin from Alexandrium
monilatium.5 Although the unique planar structure of 1 fea-
tured by a 32-membered macrolactone including 5- and 6-
membered cyclic ethers (the A-, D-, and E-rings), a spirocyclic
acetal (the BC-ring part), and a 6-membered cyclic hemiacetal
(the F-ring part) has been reported, the stereochemistry of 1
has not been determined. Since the complex structure and
the remarkable bioactivities of 1 attracted our interest, we
started the total synthesis in order to determine the absolute
stereochemistry of 1. Here, stereochemical prediction, synthe-
sis, and determination of the relative stereochemistry of the
A- and F-rings of 1 are reported as a part of our program.
sis of 1 and reported large JH5{H6 (8.6 Hz) and NOE between
H2 and H6 in its A-ring, the relative stereochemistry of the
A-ring has been deduced as 2 in Fig. 2, where the relationship
of the substituents at C2 and C6 is cis and that of the substitu-
ents at C5 and C6 is trans. In order to confirm the deduced
stereostructure, we undertook comparison of the NMR data
of 1 with that of synthetic A-ring model 3 possessing the same
relative stereochemistry as 2. The synthetic strategy for A-ring
model 3 is shown in Scheme 1. In order to avoid undesired mi-
gration of the double bond from the ꢀ-position of the ester
group to the ꢁ-position, it was planned to prepare ester 3 from
4 by oxidative diol fission at the last stage of the synthesis,
and tetrahydropyran 4 should be made from 5 through 6-exo
epoxide ring-opening.
The synthesis of 3, starting from known epoxide 6
(87%ee),6 is illustrated in Scheme 2. Epoxide 6 was treated
with 4-methoxybenzyl alcohol and Ti(OiPr)4 to give 7 (60%),7
which was transformed into epoxide 8 through tosylation of
H
H
HO
R
HO
TBDPSO
Results and Discussion
5
6
JH5-H6
8.6 Hz
=
A
2
1
O
OMe
Synthesis and Relative Stereochemistry of the A-Ring
Part of 1. Since Murakami performed extensive NMR analy-
O
R
O
H
NOE
H
H
H
O
O
2
Synthetic
A-Ring Model 3
(A-Ring of 1)
OH
21
E
O
D
20
OH
Fig. 2.
24
2
26
O
27
16
15
5
HO
O
Oxidative
Diol
Fission
6-exo
Epoxide
Opening
C
A
11O
B
7
1
31
O
TBSO
TBSO
6
O
OH
OH
Me
32
O
O
3
9
O
33
O
OH
OTBDPS
HO
F
Me
OTBDPS OH
36
34
Me
Goniodomin A (1)
4
5
Fig. 1.
Scheme 1.
Published on the web June 13, 2007; doi:10.1246/bcsj.80.1173

1174 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
O
TBSO
RO
OH
HO
a
c
e
a
b, c
d
OH
OH
O
15
O
O
OR
OTBDPS
OPMB
OPMB
OTBDPS
OTBDPS OH
OTBDPS
OTBDPS
OH
19: R=PMB
20: R=H
21: R=TBS
22: R=H
b
d
6
7
8
R1O
TBSO
TBDPSO
X
H
HO
g
i
HO
TBDPSO
R2
5
6
f, g
2
OPMB
OPMB
TBDPSO
OMe
O
O
CHO
9: R1=H, R2=TMS
12: X=SnBu3
13: X=I
H
H
e
f
h
10: R1=H, R2=H
O
OTBDPS
no NOE
11: R1=TBS, R2=H
J
H5-H6 = 9.4 Hz
23
24
HO
Scheme 3. (a) TBHP, (ꢂ)-DET, Ti(Oi-Pr)4, MS4A, CH2Cl2,
ꢂ25 ꢁC, 33 h, 98%; (b) DDQ, CH2Cl2–H2O (10:1), 0 ꢁC,
1 h, 82%; (c) CSA, CH2Cl2, ꢂ20 ꢁC, 30 min, 90%; (d)
OH
TBSO
TBSO
j
k
pyridine HF, MeCN, 0 ꢁC, 1.5 h, 61%; (e) NaIO4, MeOH–
OPMB
OPMB
OTBDPS
ꢃ
OTBDPS
H2O (2:1), 25 ꢁC, 15 min; (f) NaClO2, NaH2PO4 2H2O,
ꢃ
2-methyl-2-butene, t-BuOH–H2O (3.5:1), 25 ꢁC, 40 min;
14
15
(g) CH2N2, THF, 0 ꢁC, 15 min, 64% for 3 steps.
OTBS
RO
HO
OH
13 (62%). Iodide 13 was coupled with 2-propynyl alcohol by
Sonogashira reaction10 to give 14, which was reduced with
Red-AlÒ to (E)-allyl alcohol 15 (80%). Katsuki–Sharpless
asymmetric epoxidation of 15 using (+)-DET (diethyl tartrate)
stereoselectively yielded almost optically pure 16 (94%),11
which was transformed into diol 5 with DDQ (2,3-dichloro-
5,6-dicyano-1,4-benzoquinone) (93%). Treatment of 5 with
CSA (camphor-10-sulfonic acid) successfully gave 6-endo cy-
clized product 4 (60%). Removal of TBS (42%) followed by
oxidative cleavage of the diol part afforded aldehyde 18, which
was converted to methyl ester 3 (colorless needles, mp 118.0–
118.3 ꢁC) through oxidation with NaClO2 and methylation
with CH2N2 (71% for 3 steps).12 Stereochemistry of 3 was es-
tablished by X-ray crystallographic analysis, and a large JH5{H6
value (9.5 Hz) was observed. In addition, the presence of NOE
between H2 and H6 was similar to that observed in natural 1.
The C2 epimer (24) of 3 was also synthesized from 15
through a 7-step process including Katsuki–Sharpless asym-
metric epoxidation with (ꢂ)-DET (Scheme 3). Although epi-
mer 24 had a large JH5{H6 value (9.4 Hz), no NOE was present
between H2 and H6, which was different from 1.
Thus, two A-ring models 3 and 24 were stereoselectively
synthesized, and the stereochemistry of 3 was unambiguously
confirmed by X-ray crystallographic analysis. Although the de-
viations in the NMR chemical shifts and coupling constants
from the reported values of 1 (Table 1) were similar for both
compounds, the relative stereochemistry of the A-ring part of
1 was judged to be identical with that of 3 on the basis of
the presence of NOE between H2 and H6 in both 1 and 3 as
well as the absence of NOE between H2 and H6 in 24.
Synthesis and Relative Stereochemistry of the F-Ring
Part of 1. The presence of two methyl groups at C33 and
C34 in the F-ring (25) of 1 has been reported by Murakami et
al. (Fig. 3).1a,b However, it has been unclear whether the stereo-
chemical relationship of the groups is trans (26) or cis (27).
The stereochemistry of C32 has not been determined, and
we could only speculate that the hydroxy group at C32 has
an axial position in the chair conformation of the F-ring on
the basis of the anomeric effect. Therefore, we undertook the
m
o
O
O
O
CHO
OR
OTBDPS
16: R=PMB
5: R=H
OTBDPS OH
OTBDPS
OH
4: R=TBS
17: R=H
18
l
n
H
HO
5
6
p, q
2
OMe
O
H
H
TBDPSO
H5-H6 = 9.5 Hz
O
NOE
J
3
ORTEP diagram of 3
Scheme 2. Reagents and conditions: (a) PMBOH, Ti(O-
i-Pr)4, toluene, reflux, 1.5 h, 60%; (b) TsCl, pyridine,
CH2Cl2, 0 ꢁC, 11 h; (c) K2CO3, MeOH, 25 ꢁC, 1 h, 64%
from 7; (d) ethynyltrimethylsilane, BuLi, Et2O BF3, THF,
ꢃ
ꢂ78 ꢁC, 35 min, ꢄ100%; (e) K2CO3, MeOH, 25 ꢁC, 1 h,
88%; (f) TBSOTf, 2,6-lutidine, CH2Cl2, 25 ꢁC, 30 min,
86%; (g) LDA, Bu3SnH, THF, ꢂ40 ꢁC, 30 min, then
CuCN, 11, ꢂ78 ꢁC, 55 min, then MeOH, ꢂ78 ! 0 ꢁC,
20 min; (h) I2, Et2O, 25 ꢁC, 15 min, 62% from 11; (i) 2-pro-
pynyl alcohol, [PdCl2(PPh3)2], PPh3, CuI, BuNH2, ben-
zene, 25 ꢁC, 2 h, 96%; (j) Red-AlÒ, Et2O, ꢂ25 ꢁC, 1 h, 83%
from 13; (k) TBHP, (+)-DET, Ti(Oi-Pr)4, MS4A, CH2Cl2,
ꢂ25 ꢁC, 27 h, 94%; (l) DDQ, CH2Cl2–H2O (20:1), 0 ꢁC,
50 min, 94%; (m) CSA, CH2Cl2, 0 ꢁC, 10 min, 60%; (n)
pyridine HF, MeCN, 0 ꢁC, 1.5 h, 42%; (o) NaIO4, MeOH–
ꢃ
H2O (2:1), 25 ꢁC, 15 min; (p) NaClO2, NaH2PO4 2H2O,
ꢃ
2-methyl-2-butene, t-BuOH–H2O (3.5:1), 25 ꢁC, 30 min;
(q) CH2N2, THF, 0 ꢁC, 10 min, 71% from 17.
the primary alcohol followed by basic treatment (64%). Substi-
tution with ethynyltrimethylsilane8 and the subsequent remov-
al of the TMS (Me3Si) group afforded 10 (88%). After protec-
tion of alcohol 10 as a TBS (t-BuMe2Si) ether (86%), the re-
sulting acetylene 11 was converted with a higher order tin cup-
rate reagent to vinyltin 12,9 which reacted with I2 to produce

K. Fujiwara et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007) 1175
Table 1. Comparison of Selected NMR Data of 1, 3, and 24
O
BnO
HO
O
BnO
O
Bn
Me
R1
1H NMR (C6D6)
13C NMR (CDCl3)
N
O
Position
33
33
Me
R1
Me
R1
ꢂ(1)
ꢂ(3)
/ppm
ꢂ(24)
/ppm
ꢂ(1)
ꢂ(3) ꢂ(24)
O
/ppma)
/ppma) /ppm /ppm
34
RO
RO
R2
R2
R2
1
2
3
168.1 169.2 170.8
76.2
28: R1=Me, R2=H
30: R1=Me, R2=H
32: R1=Me, R2=H
4.309
4.34
4.58
78.7 75.0
139.7 139.2 139.0
112.1 111.9 115.5
29: R1=H, R2=Me
31: R1=H, R2=Me
33: R1=H, R2=Me
3=CHa 4.779
3=CHb 5.002
4a
4b
5
5-OH
6
7
4.74
4.80
2.03
2.57
3.70
2.17
3.27
4.78
4.79
2.38
2.56
3.78
2.47
4.28
Me
Me
2.331
2.820
4.133
4.455
3.683
40.7
70.2
40.3 37.8
71.2 70.8
OHC
34
Me
34
HO
Me
TBSO
(S)-(-)-Citronellol (35)
80.2
73.1
78.7 77.2
66.7 66.5
5.133 3.95/3.98 4.00/4.12
Scheme 4.
J(1)
/Hza)
J(3)
/Hz
J(24)
/Hz
Bn
O
Me
JH4a{H5
JH4b{H5
10.5
5.3
JH4a{H4b 13.3
JH5{H6 8.6
9.5
5.5
13.0
9.5
11.4
5.1
13.0
19.4
O
N
Me
b
ref. 17
R
35
O
Bn
NH
37
O
TBSO
34: R=H
O
d
TBSO
a
38
36: R=OH
a) Data from Ref. 1a.
O
Bn
Me
Me
Me
R
R
R
O
O
N
Me
HO
O
H
HO
HO
O
Me
33
34
Me
Me
Me
Me
e, f
c
32
O
O
HO
33
34
33
34
F
BnO SnBu3
36
Me
TBSO
TBSO
H
41
39
40
JH33-H34 = 5.1 Hz
(33S*,34R*)
(33S*,34S*)
25
26
27
BnO
Me
(F-ring of 1)
Me
Fig. 3.
g, h
HO
28
TBSO
BnO
HO
BnO
42
HO
O
Me
Me
32
32
O
33
34
33
34
Scheme 5. Reagents and conditions: (a) NaClO2, NaH2PO4
ꢃ
36
36
2H2O, 2-methyl-2-butene, t-BuOH–H2O (3.5:1), 25 ꢁC,
30 min, 93%; (b) PivCl, Et3N, CH2Cl2, 0 ꢁC, 30 min,
then 37, LiCl, THF–CH2Cl2 (1:1), 25 ꢁC, 9 h, 76%; (c)
NHMDS, THF, ꢂ78 ꢁC, 30 min, then MeI, ꢂ78 ꢁC, 33 h,
88%; (d) LiAlH4, THF, 0 ꢁC, 10 min, 67%; (e) TPAP
(cat.), NMO, MS4A, CH2Cl2, 25 ꢁC, 20 min; (f) 41, BuLi,
THF, ꢂ78 ꢁC, 30 min, then aldehyde, ꢂ78 ꢁC, 30 min,
66% from 40; (g) DMPI, CH2Cl2, 25 ꢁC, 6 h; (h) Bu4NF,
THF, 25 ꢁC, 40 min, 81% from 42.
Me
Me
(33S,34R)
(33S,34S)
28
29
Fig. 4.
synthesis of F-ring models 28 and 29 having trans (33S,34R)
and cis (33S,34S) relationships, respectively, in order to deter-
mine the relative configuration of the F-ring of 1 by compari-
son of the NMR data of 1 and that of the models (Fig. 4).
As shown in Scheme 4, it was planned to synthesize the cy-
clic hemiacetals 28 and 29 from the corresponding keto alco-
hols 30 and 31 at the last stage of the synthesis. In both cycli-
zation reactions, the anomeric effect was expected to manage
the hydroxy group at C32 to have an axial position as specu-
lated above. Ketones 30 and 31 can be prepared from the cor-
responding 32 and 33, of which the methyl group at C33 can
be introduced by using the Evans method.13 In order to estab-
lish the stereochemistry at C34, we envisioned the use of 34,
preparable from (S)-(ꢂ)-citronellol (35) by the Lee proce-
dure,14 as a common intermediate for 32 and 33. Because of
the potential symmetry of 34, its 34R configuration should
be inverted facilely to 34S configuration by a four-step reduc-
tion/protection/deprotection/oxidation process.
The synthesis of 28 is depicted in Scheme 5. According to
the Lee procedure,14 (S)-(ꢂ)-citronellol (35) was first convert-
15
ed to 34. Aldehyde 34 was oxidized with NaClO2 to afford
36 (93%), which was condensed with (S)-4-benzyl-2-oxazoli-
dinone 37 by the Ho method to provide 38 (76%).16 Treatment
of 38 with NHMDS (sodium hexamethyldisilazanide) followed
by the reaction with MeI selectively produced 39 in good yield
(88%). The chiral auxiliary of 39 was reductively removed

1176 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
R1O
Me
HO
Me
Me
NOEs
HO
BnO
33 H
32
O
36
a
f
d, e
H
O
34
34Me
H
Me
32
33
OH
BnO
R2O
PMBO
H
H
34
Me
O
36 H
43 R1=H, R2=TBS
45
NOEs
b, c
44 R1=PMB, R2=H
28
29
JH33-H34 = 10.6 Hz
JH33-H34 = 4.0 Hz
Bn
Bn
Me
Fig. 5.
O
N
Me
g
O
N
Me
h
between H36a and H34, which suggested that all of C32-
OH, H34, and H36ax had axial positions at the same side of
the chair-shaped oxane ring. The large (10.6 Hz) coupling con-
stant between H33 and H34 (JH33{H34) in 28 indicated an anti-
diaxial relationship between H33 and H34. Accordingly, it was
confirmed that F-ring model 28 had two equatorial methyl
groups at C33 and C34, an equatorial benzyloxymethyl group
at C32, and an axial hydroxy group at C32. On the other hand,
model 29 displayed NOEs between H36a and H34 and be-
tween H34 and the proton of C32-OH, which explained the
chair conformation of the oxane ring of 29 having axial
C32-OH, H34, and H36a. Since the value of JH33{H34 was
small (4.0 Hz), it was suggested that H33 had an equatorial po-
sition. Thus, the presence of an axial methyl group at C33, an
equatorial methyl group at C34, an equatorial benzyloxymeth-
yl group at C32, and an axial hydroxy group at C32 in 29 was
confirmed. It is notable that both hydroxy groups of 28 and 29
had axial positions as expected.
O
O
O
O
PMBO
PMBO
46
47
Me
BnO
Me
Me
Me
k, l
i, j
HO
HO
29
PMBO
PMBO
48
49
Scheme 6. Reagents and conditions: (a) LiAlH4, THF,
25 ꢁC, 30 min; (b) NaH, PMBCl, Bu4NI, DMF, 25 ꢁC,
18 h; (c) Bu4NF, THF, 25 ꢁC, 30 min, 100% from 34; (d)
TPAP (cat.), NMO, MS4A, CH2Cl2, 25 ꢁC, 20 min; (e)
NaClO2, NaH2PO4 2H2O, 2-methyl-2-butene, t-BuOH–
ꢃ
H2O (3.5:1), 25 ꢁC, 30 min, 79% from 44; (f) PivCl, Et3N,
CH2Cl2, 0 ꢁC, 30 min, then 37, LiCl, THF–CH2Cl2 (1:1),
25 ꢁC, 3 h, 68%; (g) NHMDS, THF, ꢂ78 ꢁC, 30 min, then
MeI, ꢂ78 ꢁC, 33 h, 53%; (h) LiAlH4, THF, 0 ꢁC, 30 min,
80%; (i) TPAP (cat.), NMO, MS4A, CH2Cl2, 25 ꢁC, 20
min; (j) 41, BuLi, THF, ꢂ78 ꢁC, 30 min, then aldehyde,
ꢂ78 ꢁC, 30 min, 48% from 48; (k) DMPI, CH2Cl2, 25
ꢁC, 2 h; (l) DDQ, CH2Cl2–H2O (20:1), 25 ꢁC, 1.5 h, 82%
from 49.
Next, the NMR data of 28 and 29 were compared with the
reported data of 1 (Table 2).1a,b The 1H and 13C chemical
shifts of 1 were in agreement with those of trans-dimethyl
model 28. The deviation of the chemical shifts of 28 and 29
from those of 1 is shown in Fig. 6, and the similarity in the
stereostructures of 28 and the F-ring of 1 is clearly seen.19
On the other hand, the reported JH33{H34 of 1 (5.1 Hz) agreed
with that of 29 (4.0 Hz) rather than that of 28 (10.6 Hz). How-
ever, other reported J values of 1 were almost identical with
those of 28. Especially, the long-range coupling between
H33 and the proton of C32-OH (4J32-OH{H33) was observed
(1.0 Hz) in both 1 and 28, but not in 29. 4J coupling is typically
observed when four successive bonds lie in the same plane and
form a W-shaped conformation. Although in both 28 and 29,
the four successive bonds H–O–C32–C33–H33 are in the same
plane, only in 28 can they be arranged in a W-shaped confor-
(67%) to yield 40, which was transformed into 42 (66% for
two steps) through TPAP (tetrapropylammonium perruthenate)
oxidation17 and the subsequent reaction with benzyloxymeth-
yllithium derived from 41. The Dess–Martin oxidation18 of
42, followed by desilylation, afforded 28 as a single product
(81% for two steps).
Next, another F-ring model 29 was synthesized from 34
(Scheme 6). The stereochemistry at C34 was successfully in-
verted as follows. Reduction of 34 with LiAlH4 followed by
a conventional PMB-protection/desilylation process (PMB:
4-methoxybenzyl) gave 44 (100% for three steps), which
was oxidized to 45 on treatment with TPAP17 followed by
4
mation. Accordingly, the presence of clear J32-OH{H33 in both
1 and 28 strongly suggested the same relative stereochemistry
at C32 and C33 of 1 as that of 28. Thus, it was concluded that
the relative stereochemistry of the F-ring of 1, including the
anomeric C32 position, was identical to that of 28.
15
NaClO2 (79% for two steps). Then, the carboxylic acid 45
was condensed with 37 to afford 46 (68%). Stereoselective
methylation of 46 in accordance with the Evans procedure
(53%),13 and its subsequent reduction afforded 48 (80%). After
alcohol 48 was oxidized to the corresponding aldehyde, it
was reacted with benzyloxymethyllithium, prepared from 41,
to give 49 (48% for two steps), which was then oxidized, fol-
lowed by removal of PMB, to produce 29 stereoselectively
(82% for two steps).
The stereochemistry of the two F-ring models 28 and 29 was
confirmed by 1H NMR analysis in C6D6 (Fig. 5). Model 28
showed NOEs between one of the protons at C36 (H36a)
and the proton of the hydroxy group at C32 (C32-OH) and
In conclusion, the synthesis of the A- and F-ring parts of
goniodomin A (1), a stereochemically unidentified antifungal
agent isolated from dinoflagellate Alexandrium hiranoi,1a,b
was performed to determine of the relative stereochemistry
of these parts. The relative stereochemistry of the A- and F-
rings was first deduced from Murakami’s NMR data,1a,b and
model compounds corresponding to these rings were then syn-
thesized. A-ring model 3, of which the structure was deter-
mined by X-ray crystallographic analysis, showed good agree-
ment with the natural A-ring on the basis of its J values and the
1
NOE behavior in H NMR spectroscopy. The chemical shifts

K. Fujiwara et al.
Table 2. Comparison of Selected NMR Data of 1, 28, and 29
Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007) 1177
1H NMR (C6D6)
1H NMR (CDCl3)
Position
Position
ꢂ(1)/ppma)
ꢂ(28)/ppm
ꢂ(29)/ppm
ꢂ(1)/ppmb)
ꢂ(28)/ppm
ꢂ(29)/ppm
31
32-OH
33
33-Me
34
34-Me
35a
35b
36a
36b
5.962
2.979
1.329
0.984
1.664
0.740
3.34/3.41
2.83
1.14
0.94
1.72
3.27/3.45
3.47
1.63
0.66
2.48
0.75
0.96
1.33
3.60
31
32-OH
33
33-Me
34
34-Me
35a
35b
36a
36b
5.714
2.773
1.240
0.920
1.720
0.910
1.280
1.490
3.650
3.910
3.40/3.52
2.93
1.23
0.92
1.70
0.90
1.36
1.52
3.66
3.31/3.53
3.50
1.64
0.76
2.36
0.87
1.22
1.46
3.66
0.79
1.170
1.23
3.560
3.902
3.57
3.98
4.03
3.97
3.97
1H NMR (C6D6)
13C NMR (CDCl3)
Position
Position
J(1)/Hza)
J(28)/Hz
J(29)/Hz
ꢂ(1)/ppma)
ꢂ(28)/ppm
ꢂ(29)/ppm
32-OH–H33
H33–33Me
H33–H34
H34–34Me
H36a–H36b
1.0
6.5
5.1
6.5
1.0
6.6
10.6
6.6
0.0
7.1
4.0
7.0
31
32
33
33-Me
34
34-Me
35
36
73.5
97.5
40.9
12.7
30.8
20.0
34.2
60.6
73.9
97.3
41.7
13.5
31.1
20.3
34.4
60.5
74.9
97.1
38.9
6.8
27.1
19.0
27.7
61.1
11.0
11.0
11.0
a) Data from Ref. 1a. b) Data from Ref. 1b.
(a) Deviation of the chemical shifts of 28 from the reported values of GDA.
OH
E
O
D
O
OH
5
HO
O
C
A
6
O
2
1
O
O
B
H
H
OH
Me
32
O
O
33
F
Me
36
34
Me
Goniodomin A (1)
Fig. 7.
(b) Deviation of the chemical shifts of 29 from the reported values of GDA.
Experimental
General Methods. All reactions involving air- or moisture-
sensitive reagents were carried out in an anhydrous solvent system
under an argon atmosphere in oven-dried glassware capped with
septa, and sensitive liquids and solutions were transferred by using
syringe- or cannula-techniques, unless otherwise noted. All com-
mercially available reagents including anhydrous solvents, such
as dichloromethane, ether, and N,N-dimethylformamide (DMF),
were used without further purification with the following excep-
tions: tetrahydrofuran (THF) was distilled from sodium diphenyl-
ketyl under argon and benzene was distilled from CaH2 prior to
use. Normal reagent-grade solvents were used for flash chroma-
tography and extraction. Special reagent-grade solvents were used
for high-pressure liquid chromatography (HPLC). All reactions
were monitored by thin-layer chromatography (TLC) with pre-
coated silica gel (SiO2) plates (Merck, silica gel 60 F254). Plates
were visualized by ultraviolet light and by treatment with acidic
anisaldehyde or phosphomolybdic acid stain, followed by heating.
For flash chromatography was utilized SiO2 (YMC, SIL-60-400/
230W). HPLC was run with a JASCO Intelligent HPLC Pump
Fig. 6.
in 1H and 13C NMR and J32-OH{H33 of F-ring model 28, having
a 33S,34R configuration, also coincided with those of the
F-ring of 1. Thus, the relative stereochemistry of the A- and
F-rings of 1 was elucidated as shown in Fig. 7. Further studies
toward the total synthesis of 1 are currently under way in this
laboratory.

1178 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
PU-986, equipped with a JASCO Intelligent UV/VIS Detector
UV-975 and a YMC-Pack SIL-06 (250 ꢅ 10 or 20 mm I.D.)
HPLC column. Melting points were measured on Yanagimoto mi-
cro-melting apparatus without calibration. Optical rotations were
recorded on a JASCO P-1020 digital polarimeter. Infrared (IR)
spectra were measured on a JEOL JIR-WINSPEC100 infrared
spectrometer. 1H and 13C NMR spectra were recorded on JEOL
JNM-AL300 spectrometer (1H at 300 MHz, 13C at 75 MHz).
1H NMR spectra are reported as chemical shifts (ꢂ) in parts-
per-million (ppm) referenced to tetramethylsilane (0.00 ppm) in
CDCl3 or C6HD5 (7.15 ppm) in C6D6. Splitting patterns were
designated as ‘‘s, d, t, q, m, and br’’ indicating ‘‘singlet, doublet,
triplet, quartet, multiplet, and broad,’’ respectively. J values are
reported in Hertz (Hz). 13C NMR spectra are reported as chemical
shifts (ꢂ) in ppm referenced to 13CDCl3 (77.0 ppm) in CDCl3 or
13C12C5D6 (128.0 ppm) in C6D6. High-resolution mass spectra
(HR-MS) were measured on a JEOL JMS-600H mass spectrome-
ter under electron impact ionization (EI) condition, a JEOL
AX500 mass spectrometer under EI condition, and a JEOL JMS-
SX102A mass spectrometer under field desorption ionization (FD)
condition.
(1H, d, J ¼ 11:3 Hz), 6.83 (2H, d, J ¼ 8:6 Hz), 7.15 (2H, d,
J ¼ 8:6 Hz), 7.35–7.49 (6H, m), 7.64–7.70 (4H, m); 13C NMR
(75 MHz, CDCl3) ꢂ 18.9 (C), 26.6 (CH3 ꢅ 3), 55.0 (CH3), 63.3
(CH2), 63.6 (CH2), 72.0 (CH), 72.2 (CH), 79.4 (CH), 113.6
(CH ꢅ 2), 127.6 (CH ꢅ 4), 129.3 (CH ꢅ 2), 129.7 (CH ꢅ 2), 130.0
(C), 132.7 (C), 132.8 (C), 135.4 (CH ꢅ 4), 159.1 (C); LR-FDMS,
m=z 481 (63.5%, ½M þ Hꢆþ), 121 (bp, [C8H9O]þ); HR-FDMS,
calcd for C28H37O5Si ½M þ Hꢆþ: 481.2411, found: 481.2428.
(2S,3R)-4-(t-Butyldiphenylsilyloxy)-1,2-epoxy-3-(4-methoxy-
benzyloxy)butane (8). To a solution of 7 (11.21 g, 23.32 mmol)
in CH2Cl2 (200 mL) were added pyridine (21 mL, 260 mmol) and
TsCl (Ts: 4-toluenesulfonyl) (4.891 g, 25.7 mmol) at 0 ꢁC, and the
mixture was stirred for 3 h. Then, TsCl (4.891 g, 25.7 mmol) was
added, and the mixture was stirred for 11 h. Then, TsCl (1.70 g,
8.91 mmol) was added. After the mixture was stirred for 2 h, the
reaction was quenched with H2O. The mixture was extracted with
ether (ꢅ3), and the combined organic layers were washed with
brine, dried over anhydrous MgSO4, filtered, and concentrated un-
der reduced pressure. The residue was dissolved in MeOH
(250 mL), and K2CO3 (9.259 g, 70.0 mmol) was added to the solu-
tion at 0 ꢁC. Then, the mixture was warmed to 25 ꢁC and stirred
for 1 h. The reaction was quenched with H2O, and the mixture
was extracted with ether (ꢅ3). The combined organic layers were
washed with brine, dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified
by silica-gel chromatography (150 g, hexane/EtOAc = 10) to
give 8 (6.939 g, 64% from 7).
X-ray Measurement. Crystal data of 3: C25H32O5Si, Mr ¼
440:61, colorless block, 0:20 ꢅ 10:00 ꢅ 0:05 mm3, monoclinic
˚
˚
˚
P21 (No. 4), a ¼ 9:350ð4Þ A, b ¼ 9:597ð4Þ A, c ¼ 14:130ð7Þ A,
ꢀ ¼ 108:039ð2Þꢁ, V ¼ 1205:6ð10Þ A , Dcalcd ðZ ¼ 2Þ ¼ 1:214
3
˚
g cmꢂ3. A total of 2850 unique data (2ꢃmax ¼ 54:9ꢁ) were mea-
sured at T ¼ 153 K by a Rigaku/MSC Mercury CCD apparatus
17
˚
(Mo Kꢁ radiation, ꢄ ¼ 0:71069 A). Numerical absorption correc-
8: a colorless oil; ½ꢁꢆD ¼ ꢂ10:0 (c 0.855, CHCl3); IR (neat)
tion was applied (ꢅ ¼ 1:29 cmꢂ1). The structure was solved by
direct methods and refined by using the full-matrix least-squares
method of F with anisotropic temperature factors for non-hydro-
gen atoms. Hydrogen atoms were included but not refined. The
final R and Rw values were 0.069 and 0.107, respectively, for
2808 reflections with I > 3ꢆI and 280 parameters. Crystallo-
graphic data of 3 have been deposited with the Cambridge Crys-
tallographic Data Center as supplementary publication numbers
CCDC 632022. Copies of the data can be obtained, free of charge,
via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Center, 12, Union Road, Cam-
bridge, CB2 1EZ, UK; fax: +44 1223 336033; E-mail: deposit@
ccdc.cam.ac.uk).
ꢇmax 3074, 3052, 3000, 2960, 2934, 2900, 2861, 2838, 1614,
1590, 1516, 1473, 1460, 1429, 1303, 1250, 1173, 1114, 1038,
1
824, 743, 703 cmꢂ1; H NMR (300 MHz, CDCl3) ꢂ 1.06 (9H, s),
2.72 (1H, dd, J ¼ 2:9, 5.4 Hz), 2.74 (1H, dd, J ¼ 3:9, 5.4 Hz),
3.12 (1H, ddd, J ¼ 2:9, 3.9, 4.5 Hz), 3.46 (1H, brq, J ¼ 5:0 Hz),
3.76–3.84 (2H, m), 3.80 (3H, s), 4.51 (1H, d, J ¼ 11:5 Hz), 4.54
(1H, d, J ¼ 11:5 Hz), 6.84 (2H, d, J ¼ 8:7 Hz), 7.22 (2H, d, J ¼
8:7 Hz), 7.32–7.46 (6H, m), 7.65–7.71 (4H, m); 13C NMR (75
MHz, CDCl3) ꢂ 19.1 (C), 26.7 (CH3 ꢅ 3), 44.8 (CH2), 51.3 (CH),
55.0 (CH3), 64.4 (CH2), 72.1 (CH2), 77.9 (CH), 113.6 (CH ꢅ 2),
127.6 (CH ꢅ 4), 129.1 (CH ꢅ 2), 129.6 (CH ꢅ 2), 130.4 (C),
133.2 (C ꢅ 2), 135.5 (CH ꢅ 4), 159.0 (C); LR-EIMS, m=z 405
(0.4%, ½M ꢂ t-Buꢆþ), 121 (bp, [C8H9O]þ); HR-EIMS, calcd for
C24H25O4Si ½M ꢂ t-Buꢆþ: 405.1522, found: 405.1517.
(2S,3R)-4-(t-Butyldiphenylsilyloxy)-3-(4-methoxybenzyloxy)-
butane-1,2-diol (7).
A mixture of 4-methoxybenzyl alcohol
(2S,3R)-1-(t-Butyldiphenylsilyloxy)-2-(4-methoxybenzyloxy)-
(120 mL, 962 mmol) and Ti(Oi-Pr)4 (52 mL, 175 mL) was heated
at 100 ꢁC under reduced pressure for 100 min and then was cooled
to 25 ꢁC. To the resulting Ti(OPMB)4 (PMB: 4-methoxybenzyl)
was added a solution of 6 (29.3 g, 85.6 mmol) in toluene
(90 mL), and the mixture was stirred and refluxed for 90 min. Af-
ter the mixture was cooled to ambient temperature, 10% aqueous
DL-tartaric acid (80 mL) was added, and the mixture was stirred
for 35 min. Then, EtOAc (500 mL) and NaF (43.8 g) were added,
and the resulting mixture was stirred for 30 min. The mixture was
filtered through a celite pad, and the pad was washed with EtOAc
several times. The combined filtrates were condensed under re-
duced pressure, and the residue was purified by silica-gel chroma-
tography (600 g, hexane/EtOAc = 3) to give 7 (24.7 g, 60%).
hex-5-yn-3-ol (10).
(8.5 mL, 60.1 mmol) in THF (150 mL) was added BuLi (38 mL,
To a solution of ethynyltrimethylsilane
1.58 M in hexane, 60.0 mmol) at ꢂ78 ꢁC, and the mixture was stir-
red for 15 min. Then, Et2O BF3 (7.6 mL, 60.0 mmol) was added at
ꢃ
ꢂ78 ꢁC, and the mixture was stirred for 30 min. A solution of 8
(6.935 g, 14.99 mmol) in THF (20 mL) was then added, and the
mixture was stirred for 35 min. The reaction was quenched with
saturated aqueous NH4Cl, and the mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under re-
duced pressure. The residue was roughly purified by silica-gel
chromatography (80 g, hexane/EtOAc = 5). The resulting impure
(2S,3R)-1-(t-butyldiphenylsilyloxy)-2-(4-methoxybenzyloxy)-6-
trimethylsilyl-hex-5-yn-3-ol (9) was dissolved in MeOH (150
mL), and K2CO3 (6.125 g, 45.0 mmol) was added to the solution
at 25 ꢁC. After the mixture was stirred for 1 h, the reaction was
quenched with H2O. The mixture was extracted with ether (ꢅ3),
and the combined organic layers were washed with brine, dried
over anhydrous MgSO4, filtered, and concentrated under reduced
17
7: a colorless oil; ½ꢁꢆD ¼ ꢂ14:8 (c 0.950, CHCl3); IR (neat)
ꢇ
max 3423, 3071, 3050, 3000, 2950, 2930, 2890, 2857, 1612, 1588,
1514, 1470, 1463, 1428, 1302, 1248, 1173, 1112, 1040, 823, 743,
702 cmꢂ1; 1H NMR (300 MHz, CDCl3) ꢂ 1.06 (9H, s), 2.22 (1H, t,
J ¼ 6:3 Hz), 2.96 (1H, d, J ¼ 5:5 Hz), 3.59 (1H, q, J ¼ 5:5 Hz),
3.63–3.90 (5H, m), 3.79 (3H, s), 4.36 (1H, d, J ¼ 11:3 Hz), 4.50

K. Fujiwara et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007) 1179
pressure. The residue was purified by silica-gel chromatography
(60 g, hexane/EtOAc = 5) to give 10 (6.417 g, 88% from 8).
rated aqueous NH4Cl/conc. NH4OH = 9), and the mixture was
extracted with ether (ꢅ3). The combined organic layers were
washed with brine, dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was roughly pu-
rified by silica-gel chromatography (150 g, hexane/benzene = 4).
The resulting impure (4S,5R)-4-(t-butyldimethylsilyloxy)-6-(t-
butyldiphenylsilyloxy)-5-(4-methoxybenzyloxy)-2-(tributylstan-
nyl)-1-hexene (12) was dissolved in ether (20 mL), and iodine was
added portionwise to the stirred solution at 25 ꢁC until the solution
turned yellow. After the mixture was stirred for 15 min, the reac-
tion was quenched with saturated aqueous Na2SO3, and the mix-
ture was extracted with ether (ꢅ3). The combined organic layers
were washed with brine, dried over anhydrous MgSO4, filtered,
and concentrated under reduced pressure. The residue was purified
by silica-gel chromatography (50 g, hexane/benzene = 2.5) to
give 13 (752 mg, 62% from 11).
17
10: a colorless oil; ½ꢁꢆD ¼ ꢂ23:69 (c 0.640, CHCl3); IR (neat)
ꢇ
max 3485, 3312, 3075, 3050, 3010, 3000, 2950, 2931, 2890, 2850,
2120, 1614, 1589, 1514, 1472, 1460, 1429, 1391, 1362, 1303,
1248, 1173, 1112, 1075, 1040, 1010, 930, 823, 742, 702 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ 1.06 (9H, s), 2.03 (1H, t, J ¼ 2:6
Hz), 2.50 (1H, ddd, J ¼ 2:6, 6.4, 16.5 Hz), 2.55 (1H, ddd, J ¼ 2:6,
5.0, 16.5 Hz), 2.78 (1H, d, J ¼ 5:0 Hz), 3.56 (1H, td, J ¼ 5:0,
6.4 Hz), 3.80 (3H, s), 3.86 (2H, d, J ¼ 5:0 Hz), 3.97 (1H, tt, J ¼
5:0, 6.4 Hz), 4.42 (1H, d, J ¼ 11:1 Hz), 4.55 (1H, d, J ¼ 11:1 Hz),
6.84 (2H, d, J ¼ 8:7 Hz), 7.19 (2H, d, J ¼ 8:7 Hz), 7.34–7.48 (6H,
m), 7.66–7.71 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ 19.1 (C),
23.2 (CH2), 26.8 (CH3 ꢅ 3), 55.2 (CH3), 63.7 (CH2), 70.4 (CH),
70.6 (CH), 72.4 (CH2), 80.0 (CH), 81.0 (C), 113.7 (CH ꢅ 2),
127.7 (CH ꢅ 4), 129.4 (CH ꢅ 4), 129.8 (CH ꢅ 2), 130.2 (C),
132.8 (C), 132.9 (C), 135.6 (CH ꢅ 4), 159.2 (C); LR-EIMS, m=z
431 (0.11%, ½M ꢂ t-Buꢆþ), 121 (bp, [C8H9O]þ); HR-EIMS, calcd
for C26H27O4Si ½M ꢂ t-Buꢆþ: 431.1679, found: 431.1641.
(2S,3R)-3-(t-Butyldimethylsilyloxy)-1-(t-butyldiphenylsilyl-
oxy)-2-(4-methoxybenzyloxy)-5-hexyne (11). To a stirred solu-
tion of 10 (1.00 g, 2.046 mmol) and 2,6-lutidine (1.0 mL, 8.6
mmol) in CH2Cl2 (20 mL) was added TBSOTf (TBS: t-BuMe2Si,
Tf: CF3SO2) (0.9 mL, 3.9 mmol) at 0 ꢁC. The mixture was warmed
to 25 ꢁC and stirred for 30 min. The reaction was quenched with
saturated aqueous NH4Cl, and the mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by silica-gel chroma-
tography (50 g, hexane/EtOAc = 20) to give 11 (1.066 g, 86%
from 8).
19
13: a colorless oil; ½ꢁꢆD ¼ 0:46 (c 0.385, CHCl3); IR (neat)
ꢇmax 3070, 3049, 3030, 2950, 2928, 2890, 2855, 1610, 1585,
1513, 1470, 1460, 1430, 1390, 1360, 1300, 1249, 1170, 1140,
1112, 1040, 1005, 940, 845, 825, 810, 780, 740, 701, 678 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ 0.05 (3H, s), 0.11 (3H, s), 0.85
(9H, s), 1.06 (9H, s), 2.51–2.67 (2H, m), 3.57–3.70 (3H, m), 3.79
(3H, s), 4.22 (1H, ddd, J ¼ 2:0, 4.6, 7.0 Hz), 4.54 (1H, d, J ¼ 11:4
Hz), 4.64 (1H, d, J ¼ 11:4 Hz), 5.72 (1H, d, J ¼ 1:0 Hz), 6.04
(1H, d, J ¼ 1:0 Hz), 6.83 (2H, d, J ¼ 8:7 Hz), 7.22 (2H, d, J ¼
8:7 Hz), 7.30–7.45 (6H, m), 7.63–7.70 (4H, m); 13C NMR (75
MHz, CDCl3) ꢂ ꢂ4:1 (CH3 ꢅ 2), 18.1 (C), 19.1 (C), 26.0
(CH3 ꢅ 3), 26.8 (CH3 ꢅ 3), 48.8 (CH2), 55.2 (CH3), 63.5 (CH2),
71.6 (CH), 72.7 (CH2), 82.5 (CH), 109.3 (C), 113.6 (CH ꢅ 2),
127.7 (CH ꢅ 4), 128.4 (CH2), 129.2 (CH ꢅ 2), 129.6 (CH),
129.7 (CH), 130.9 (C), 133.3 (C ꢅ 2), 135.6 (CH ꢅ 2), 135.7
(CH ꢅ 2), 159.0 (C); LR-EIMS, m=z 673 (0.5%, ½M ꢂ t-Buꢆþ),
121 (bp, [C8H9O]þ); HR-EIMS, calcd for C32H42O4Si2I ½M ꢂ
t-Buꢆþ: 673.1666, found: 673.1677.
17
11: a colorless oil; ½ꢁꢆD ¼ ꢂ8:73 (c 1.005, CHCl3); IR (neat)
ꢇ
max 3310, 3072, 3049, 2999, 2950, 2929, 2890, 2857, 2120, 1613,
1588, 1514, 1472, 1460, 1428, 1390, 1361, 1302, 1248, 1173,
1113, 1038, 1006, 928, 824, 778, 740, 701, 620, 615 cmꢂ1
;
(6S,7R)-6-(t-Butyldimethylsilyloxy)-8-(t-butyldiphenylsilyl-
oxy)-7-(4-methoxybenzyloxy)-4-methyleneoct-2-yn-1-ol (14).
To a stirred solution of [PdCl2(PPh3)2] (730.7 mg, 1.041 mmol),
CuI (317.2 mg, 1.666 mmol), and PPh3 (546.1 mg, 2.082 mmol)
in benzene (50 mL) were added a solution of 2-propynyl alcohol
(2.4 mL, 41.6 mmol) and 13 (7.3578 g, 10.411 mmol) in benzene
(50 mL) and BuNH2 (4.1 mL, 41.6 mmol) at 25 ꢁC, and the result-
ing solution was stirred for 2 h. The reaction was quenched with
saturated aqueous NH4Cl, and the mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was roughly purified by silica-gel
chromatography (500 g, hexane/benzene = 2) to give 14 (6.590 g,
96%).
1H NMR (300 MHz, CDCl3) ꢂ ꢂ0:04 (3H, s), 0.07 (3H, s), 0.83
(9H, s), 1.06 (9H, s), 1.96 (1H, t, J ¼ 2:6 Hz), 2.40 (1H, ddd,
J ¼ 2:6, 4.9, 17.1 Hz), 2.54 (1H, ddd, J ¼ 2:6, 5.5, 17.1 Hz),
3.67–3.78 (2H, m), 3.80 (3H, s), 3.80–3.88 (1H, m), 3.95 (1H, brq,
J ¼ 5:0 Hz), 4.59 (1H, d, J ¼ 11:0 Hz), 4.67 (1H, d, J ¼ 11:0 Hz),
6.84 (2H, d, J ¼ 8:6 Hz), 7.24 (2H, d, J ¼ 8:6 Hz), 7.30–7.45 (6H,
m), 7.65–7.70 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ4:7 (CH3),
ꢂ4:6 (CH3), 18.0 (C), 19.2 (C), 23.6 (CH2), 25.8 (CH3 ꢅ 3), 26.9
(CH3 ꢅ 3), 55.2 (CH3), 64.3 (CH2), 70.0 (CH), 71.0 (CH), 73.2
(CH2), 81.8 (CH), 81.9 (C), 113.7 (CH ꢅ 2), 127.7 (CH ꢅ 4),
129.4 (CH ꢅ 2), 129.6 (CH ꢅ 2), 131.1 (C), 133.4 (C), 133.5
(C), 135.6 (CH ꢅ 2), 135.7 (CH ꢅ 2), 159.1 (C); LR-EIMS, m=z
602 (0.06%, [M]þ), 121 (bp, [C8H9O]þ); HR-EIMS, calcd for
C36H50O4Si2 ½Mꢆþ: 602.3248, found: 602.3248.
16
14: a colorless oil; ½ꢁꢆD ¼ 11:9 (c 0.545, CHCl3); IR (neat)
(4S,5R)-4-(t-Butyldimethylsilyloxy)-6-(t-butyldiphenylsilyl-
oxy)-2-iodo-5-(4-methoxybenzyloxy)-1-hexene (13). To a solu-
tion of i-Pr2NH (1.9 mL, 13.46 mmol) in THF (20 mL) was added
BuLi (8.2 mL, 1.58 M in hexane, 12.96 mmol) at 0 ꢁC, and the
solution was stirred for 20 min. After the solution was cooled to
ꢂ40 ꢁC, Bu3SnH (3.4 mL, 12.83 mmol) was added, and the mix-
ture was stirred for 30 min. Then, the mixture was cooled to
ꢂ78 ꢁC, CuCN (594 mg, 6.632 mmol) was added. After the mix-
ture was stirred for 15 min, a solution of 11 (1.0 g, 1.659 mmol)
in THF (8 mL) was added, and the mixture was stirred for
40 min. Then, MeOH (5.4 mL, 133 mmol) was added, and the
mixture was allowed to warm to 0 ꢁC for 20 min. The reaction
was quenched with an aqueous solution of NH4Cl/NH4OH (satu-
ꢇmax 3418, 3090, 3072, 3050, 3000, 2950, 2930, 2890, 2857, 1612,
1585, 1514, 1472, 1460, 1428, 1390, 1360, 1300, 1249, 1170,
1112, 1040, 1005, 940, 905, 827, 780, 740, 702 cmꢂ1 1H NMR
;
(300 MHz, CDCl3) ꢂ 0.02 (3H, s), 0.05 (3H, s), 0.84 (9H, s), 1.06
(9H, s), 1.43 (1H, brt, J ¼ 6:2 Hz), 2.35 (2H, d, J ¼ 6:1 Hz), 3.61–
3.75 (3H, m), 3.80 (3H, s), 4.23 (1H, dt, J ¼ 2:3, 6.1 Hz), 4.28
(2H, d, J ¼ 6:2 Hz), 4.58 (1H, d, J ¼ 11:3 Hz), 4.67 (1H, d, J ¼
11:3 Hz), 5.28 (1H, brs), 5.39 (1H, brd, J ¼ 1:9 Hz), 6.84 (2H,
d, J ¼ 8:8 Hz), 7.24 (2H, d, J ¼ 8:8 Hz), 7.32–7.45 (6H, m), 7.64–
7.69 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ4:6 (CH3), ꢂ4:3
(CH3), 18.1 (C), 19.1 (C), 25.9 (CH3 ꢅ 3), 26.8 (CH3 ꢅ 3), 40.6
(CH2), 51.5 (CH2), 55.2 (CH3), 63.9 (CH2), 71.3 (CH), 72.8
(CH2), 82.9 (CH), 86.3 (C), 87.4 (C), 113.6 (CH ꢅ 2), 124.7

1180 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
(CH2), 127.7 (CH ꢅ 4), 128.1 (C), 129.2 (CH ꢅ 2), 129.7 (CH ꢅ
2), 131.1 (C), 133.3 (C), 133.5 (C), 135.6 (CH ꢅ 4), 159.0 (C);
LR-EIMS, m=z 601 (0.61%, ½M ꢂ t-Buꢆþ), 121 (bp, [C8H9O]þ);
HR-EIMS, calcd for C35H45O5Si2 ½M ꢂ t-Buꢆþ: 601.2806, found:
601.2801.
3.37 (1H, d, J ¼ 2:1 Hz), 3.55–3.67 (2H, m), 3.71 (2H, d, J ¼
6:2 Hz), 3.80 (3H, s), 3.85 (1H, brddd, J ¼ 2:8, 5.3, 12.5 Hz),
4.02–4.08 (1H, m), 4.62 (2H, s), 5.03 (1H, s), 5.22 (1H, s), 6.84
(2H, d, J ¼ 8:5 Hz), 7.23 (2H, d, J ¼ 8:5 Hz), 7.32–7.45 (6H, m),
7.64–7.69 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ4:41 (CH3),
ꢂ4:36 (CH3), 18.0 (C), 19.1 (C), 25.9 (CH3 ꢅ 3), 26.8 (CH3 ꢅ
3), 34.9 (CH2), 55.2 (CH3), 57.5 (CH), 59.0 (CH), 61.4 (CH2),
64.3 (CH2), 72.8 (CH), 72.9 (CH2), 83.0 (CH), 113.6 (CH ꢅ 2),
115.7 (CH2), 127.7 (CH ꢅ 4), 129.2 (CH ꢅ 2), 129.6 (CH), 129.7
(CH), 131.0 (C), 133.3 (C ꢅ 2), 135.6 (CH ꢅ 4), 141.9 (C),
159.0 (C); LR-EIMS, m=z 645 (0.26%, ½M ꢂ CH3Oꢆþ), 121 (bp,
[C8H9O]þ); HR-EIMS, calcd for C38H53O5Si2 ½M ꢂ CH3Oꢆþ:
645.3432, found: 645.3433.
(2E,6S,7R)-6-(t-Butyldimethylsilyloxy)-8-(t-butyldiphenyl-
silyloxy)-7-(4-methoxybenzyloxy)-4-methyleneoct-2-en-1-ol (15).
To a solution of 14 (6.590 g, 10.00 mmol) in ether (100 mL) was
added Red-AlÒ (7.0 mL, 65% solution in toluene, 23.3 mmol) at
ꢂ25 ꢁC. After the mixture was stirred for 1 h, the reaction was
quenched with EtOAc (7 mL) and 2 M aqueous NaOH (7 mL).
The mixture was stirred for 30 min at ambient temperature, filtered
through a celite pad, and condensed under reduced pressure. The
residue was purified by silica-gel chromatography (300 g, hexane/
EtOAc = 5) to give 15 (5.455 g, 83%).
(2S,3S,6S,7R)-6-(t-Butyldimethylsilyloxy)-8-(t-butyldiphenyl-
silyloxy)-2,3-epoxy-4-methyleneoctane-1,7-diol (5). To a solu-
tion of 16 (4.212 g, 6.221 mmol) in CH2Cl2–H2O (20:1, 63 mL)
was added DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)
(2.824 g, 12.442 mmol) at 0 ꢁC, and the mixture was stirred for
50 min. The reaction was quenched with saturated aqueous
NaHCO3, and the mixture was extracted with ether (ꢅ3). The
combined organic layers were washed with brine, dried over anhy-
drous MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica-gel chromatography (5 g,
hexane/EtOAc = 15) to give 5 (3.259 g, 94%).
17
15: a colorless oil; ½ꢁꢆD ¼ 3:32 (c 1.50, CHCl3); IR (neat) ꢇmax
3421, 3071, 3050, 3030, 3010, 2998, 2950, 2926, 2890, 2855,
1611, 1588, 1513, 1472, 1462, 1428, 1389, 1360, 1302, 1248,
1173, 1112, 1037, 1006, 971, 937, 895, 826, 776, 741, 702 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ ꢂ0:07 (3H, s), ꢂ0:06 (3H, s), 0.82
(9H, s), 1.06 (9H, s), 1.23 (1H, brt, J ¼ 5:8 Hz), 2.36 (1H, dd,
J ¼ 8:4, 14.1 Hz), 2.45 (1H, dd, J ¼ 3:7, 14.1 Hz), 3.60 (1H, dt,
J ¼ 2:4, 6.0 Hz), 3.70–3.86 (2H, m), 3.80 (3H, s), 4.03–4.12 (1H,
m), 4.13 (2H, brt, J ¼ 5:6 Hz), 4.60 (1H, d, J ¼ 11:4 Hz), 4.65
(1H, d, J ¼ 11:4 Hz), 5.02 (1H, brs), 5.07 (1H, brs), 5.77 (1H,
td, J ¼ 5:6, 16.0 Hz), 6.22 (1H, d, J ¼ 16:0 Hz), 6.84 (2H, d,
J ¼ 8:5 Hz), 7.24 (2H, d, J ¼ 8:5 Hz), 7.32–7.45 (6H, m), 7.63–
7.69 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ4:5 (CH3), ꢂ4:3
(CH3), 18.0 (C), 19.1 (C), 25.9 (CH3 ꢅ 3), 26.8 (CH3 ꢅ 3), 35.9
(CH2), 55.2 (CH3), 63.5 (CH2), 64.1 (CH2), 71.7 (CH), 72.9
(CH2), 83.0 (CH), 113.6 (CH ꢅ 2), 119.0 (CH2), 127.7 (CH ꢅ 4),
128.0 (CH), 129.3 (CH ꢅ 2), 129.6 (CH ꢅ 2), 131.1 (C), 133.3
(C þ CH), 133.5 (C), 135.6 (CH ꢅ 4), 142.1 (C), 158.9 (C);
LR-EIMS, m=z 603 (0.69%, ½M ꢂ t-Buꢆþ), 121 (bp, [C8H9O]þ);
HR-EIMS, calcd for C35H47O5Si2 ½M ꢂ t-Buꢆþ: 603.2962, found:
603.2952.
18
5: a colorless oil; ½ꢁꢆD ¼ ꢂ0:19 (c 0.460, CHCl3); IR (neat)
ꢇmax 3445, 3071, 3049, 3013, 2954, 2928, 2885, 2856, 1472,
1462, 1428, 1390, 1361, 1253, 1112, 1085, 1006, 937, 904, 836,
776, 740, 701 cmꢂ1; 1H NMR (300 MHz, CDCl3) ꢂ ꢂ0:03 (3H, s),
0.02 (3H, s), 0.80 (9H, s), 1.07 (9H, s), 1.58–1.65 (1H, m), 2.17
(2H, d, J ¼ 5:7 Hz), 2.49 (1H, d, J ¼ 2:0 Hz), 3.06 (1H, td,
J ¼ 2:5, 4.0 Hz), 3.41 (1H, brd, J ¼ 2:1 Hz), 3.60–3.78 (4H, m),
3.85–3.97 (2H, m), 5.05 (1H, brs), 5.24 (1H, brs), 7.34–7.44 (6H,
m), 7.62–7.68 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ4:7 (CH3),
ꢂ4:2 (CH3), 18.0 (C), 19.2 (C), 25.8 (CH3 ꢅ 3), 26.8 (CH3 ꢅ 3),
34.5 (CH2), 57.5 (CH), 59.0 (CH), 61.4 (CH2), 64.7 (CH2), 72.7
(CH), 74.3 (CH), 116.1 (CH2), 127.8 (CH ꢅ 4), 129.8 (CH ꢅ 2),
133.1 (C ꢅ 2), 135.5 (CH ꢅ 4), 141.3 (C); LR-FDMS, m=z 557
(bp, ½M þ Hꢆþ), 499 (bp, ½M ꢂ t-Buꢆþ); HR-FDMS, calcd for
C31H49O5Si2 ½M þ Hꢆþ: 557.3119, found: 557.3133.
(2S,3S,6S,7R)-6-(t-Butyldimethylsilyloxy)-8-(t-butyldiphenyl-
silyloxy)-2,3-epoxy-7-(4-methoxybenzyloxy)-4-methyleneoctan-
1-ol (16). To a suspension of MS4A (powder, 5.0 g) in CH2Cl2
(100 mL) were added (+)-DET (diethyl tartrate) (0.21 mL, 1.24
mmol) and Ti(Oi-Pr)4 (0.24 mL, 0.83 mmol) at ꢂ40 ꢁC, and the
mixture was stirred for 30 min. TBHP (t-butyl hydroperoxide)
(3.2 mL, 5.29 M in toluene, 16.5 mmol) was then added at the
same temperature. After the mixture was stirred for 30 min, a
solution of 15 (5.4546 g, 8.2516 mmol) in CH2Cl2 (10 mL) was
added dropwise to the mixture at ꢂ40 ꢁC. Then, the mixture
was warmed to ꢂ25 ꢁC and stirred for 27 h. Dimethyl sulfide
(2.7 mL) was added to the mixture, and the mixture was stirred
for 30 min. Then, 10% aqueous DL-tartaric acid (0.5 mL) was add-
ed at ambient temperature. After the mixture was stirred for
30 min, NaF (250 mg) was added, and the mixture was further stir-
red for 1 h. The reaction mixture was filtered through a celite pad
and condensed under the reduced pressure. The residue was puri-
fied by silica-gel chromatography (20 g, hexane/EtOAc = 10) to
give 16 (5.253 g, 94%).
(1S)-1-[(2R,5S,6R)-5-(t-Butyldimethylsilyloxy)-6-(t-butyldi-
phenylsilyloxymethyl)-3-methyleneoxan-2-yl]-1,2-ethanediol
(4). To a solution of 5 (120 mg, 0.215 mmol) in CH2Cl2 (2.2 mL)
was added CSA (dl-camphor-10-sulfonic acid) (5 mg, 0.022
mmol) at 0 ꢁC, and the mixture was stirred for 10 min. The reac-
tion was quenched with saturated aqueous NaHCO3, and the mix-
ture was extracted with ether (ꢅ3). The combined organic layers
were washed with brine, dried over anhydrous MgSO4, filtered,
and concentrated under reduced pressure. The residue was purified
by silica-gel chromatography (10 g, hexane/EtOAc = 6) to give 4
(72 mg, 60%).
15
4: a colorless oil; ½ꢁꢆD ¼ 0:73 (c 0.545, CHCl3); IR (neat) ꢇmax
3398, 3070, 3040, 3013, 2955, 2925, 2855, 1470, 1460, 1425,
1380, 1355, 1340, 1245, 1180, 1105, 1005, 905, 850, 830, 775,
740, 700 cmꢂ1; 1H NMR (300 MHz, CDCl3) ꢂ ꢂ0:09 (3H, s), 0.02
(3H, s), 0.79 (9H, s), 1.05 (9H, s), 2.22 (1H, brdd, J ¼ 8:6, 13.3
Hz), 2.34 (1H, brdd, J ¼ 4:5, 8.0 Hz), 2.39 (1H, d, J ¼ 7:5 Hz),
2.60 (1H, dd, J ¼ 5:2, 13.3 Hz), 3.33 (1H, ddd, J ¼ 2:3, 6.1, 8.3
Hz), 3.63–3.94 (6H, m), 4.02 (1H, d, J ¼ 5:3 Hz), 4.92 (1H, brs),
4.97 (1H, brs), 7.33–7.45 (6H, m), 7.63–7.69 (4H, m); 13C NMR
(75 MHz, CDCl3) ꢂ ꢂ5:0 (CH3), ꢂ4:2 (CH3), 17.8 (C), 19.2 (C),
25.6 (CH3 ꢅ 3), 26.8 (CH3 ꢅ 3), 42.1 (CH2), 63.8 (CH2), 63.9
(CH2), 68.1 (CH), 71.2 (CH), 80.5 (CH), 83.0 (CH), 110.4 (CH2),
18
16: a colorless oil; ½ꢁꢆD ¼ ꢂ5:87 (c 0.490, CHCl3); IR (neat)
ꢇmax 3447, 3070, 3047, 3000, 2950, 2926, 2890, 2854, 1611, 1585,
1512, 1472, 1460, 1427, 1249, 1170, 1112, 1085, 1040, 1005, 970,
1
940, 905, 825, 775, 745, 701 cmꢂ1; H NMR (300 MHz, CDCl3)
ꢂ ꢂ0:02 (3H, s), 0.00 (3H, s), 0.82 (9H, s), 1.06 (9H, s), 1.62
(1H, dd, J ¼ 5:3, 7.8 Hz), 2.13 (1H, dd, J ¼ 3:5, 14.2 Hz), 2.21
(1H, dd, J ¼ 8:1, 14.2 Hz), 3.02 (1H, brtd, J ¼ 2:4, 3.9 Hz),

K. Fujiwara et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007) 1181
127.7 (CH ꢅ 4), 129.6 (CH ꢅ 2), 133.4 (C), 133.5 (C), 135.6
(CH ꢅ 4), 141.7 (C); LR-EIMS, m=z 499 (14.8%, ½M ꢂ t-Buꢆþ),
73 (bp, [C3H5O2]þ); HR-EIMS, calcd for C27H39O5Si2 ½M ꢂ
t-Buꢆþ: 499.2336, found: 499.2349.
(1H, dd, J ¼ 5:1, 10.6 Hz), 4.34 (1H, s), 4.74 (1H, s), 4.80 (1H, s),
7.20–7.28 (6H, m), 7.78–7.84 (4H, m); 13C NMR (75 MHz,
CDCl3) ꢂ 19.1 (C), 26.8 (CH3 ꢅ 3), 40.3 (CH2), 52.1 (CH3), 66.7
(CH2), 71.2 (CH), 78.7 (CH ꢅ 2), 111.9 (CH2), 127.9 (CH ꢅ 4),
130.0 (CH ꢅ 2), 132.2 (C), 135.5 (CH ꢅ 4), 139.2 (C ꢅ 2), 169.2
(C); LR-FDMS, m=z 441 (9.5%, ½M þ Hꢆþ), 383 (bp, ½M ꢂ
t-Buꢆþ); HR-FDMS, calcd for C25H33O5Si ½M þ Hꢆþ: 441.2097,
found: 441.2099.
(1S)-1-[(2R,5S,6R)-6-(t-Butyldiphenylsilyloxymethyl)-5-hy-
droxy-3-methyleneoxan-2-yl]-1,2-ethanediol (17). To a mix-
ture of 4 (59.3 mg, 0.106 mmol) in acetonitrile (1.5 mL) was added
29 drops of pyridine HF complex (70% in pyridine) at 0 ꢁC, and
ꢃ
the mixture was stirred for 1.5 h. The reaction was quenched with
saturated aqueous NaHCO3, and the mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by silica-gel chroma-
tography (10 g, hexane/EtOAc = 1/3) to give 17 (19.5 mg, 42%).
(2R,3R,6S,7R)-6-(t-Butyldimethylsilyloxy)-8-(t-butyldiphenyl-
silyloxy)-2,3-epoxy-7-(4-methoxybenzyloxy)-4-methyleneoctan-
1-ol (19). To a suspension of MS4A (powder, 15 g) in CH2Cl2
(120 mL) were added (ꢂ)-DET (0.41 mL, 2.39 mmol) and Ti(O-
i-Pr)4 (0.47 mL, 1.58 mmol) at ꢂ40 ꢁC, and the mixture was stir-
red for 30 min. TBHP (7.2 mL, 4.92 M in toluene, 35.4 mmol) was
then added at the same temperature. After the mixture was stirred
for 30 min, a solution of 15 (10.6 g, 16.0 mmol) in CH2Cl2
(40 mL) was added dropwise to the mixture at ꢂ40 ꢁC. Then,
the mixture was warmed to ꢂ25 ꢁC and stirred for 33 h. Dimethyl
sulfide (5.4 mL) was added to the mixture, and the mixture was
stirred for 30 min. Then, 10% aqueous DL-tartaric acid (0.94 mL)
was added at ambient temperature. After the mixture was stirred
for 30 min, NaF (403 mg) was added, and the mixture was further
stirred for 5 h. The reaction mixture was filtered through a celite
pad and concentrated under the reduced pressure. The residue
was purified by silica-gel chromatography (200 g, hexane/
EtOAc = 6) to give 19 (10.62 g, 98%).
23
17: a colorless oil; ½ꢁꢆD ¼ ꢂ24:0 (c 0.980, CHCl3); IR (neat)
ꢇ
max 3411, 3070, 3050, 2960, 2927, 2855, 1470, 1460, 1425, 1390,
1355, 1250, 1190, 1110, 1060, 1000, 905, 820, 740, 700 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ 1.06 (9H, s), 2.19 (1H, brs), 2.26
(1H, dd, J ¼ 8:4, 13.5 Hz), 2.50 (1H, brs), 2.65 (1H, brs), 2.72
(1H, dd, J ¼ 5:6, 13.5 Hz), 3.35 (1H, ddd, J ¼ 5:1, 5.6, 8.4 Hz),
3.60–3.95 (6H, m), 4.03 (1H, d, J ¼ 4:6 Hz), 4.93 (1H, brs), 5.05
(1H, brs), 7.36–7.50 (6H, m), 7.63–7.69 (4H, m); 13C NMR (75
MHz, CDCl3) ꢂ 19.1 (C), 26.8 (CH3 ꢅ 3), 40.4 (CH2), 63.4 (CH2),
65.4 (CH2), 69.8 (CH), 70.8 (CH), 80.1 (CH), 80.7 (CH), 111.4
(CH2), 127.9 (CH ꢅ 4), 130.0 (CH ꢅ 2), 132.5 (C ꢅ 2), 135.5
(CH ꢅ 4), 141.1 (C); LR-EIMS, m=z 385 (2.6%, ½M ꢂ t-Buꢆþ),
199 (bp, [C12H11OSi]þ); HR-EIMS, calcd for C21H25O5Si ½M ꢂ
t-Buꢆþ: 385.1472, found: 385.1502.
19
19: a colorless oil; ½ꢁꢆD ¼ 0:34 (c 1.055, CHCl3); IR (neat)
ꢇmax 3450, 3073, 3050, 2999, 2950, 2930, 2895, 2858, 1610,
1585, 1514, 1472, 1460, 1429, 1390, 1360, 1300, 1249, 1170,
Methyl (2R,5S,6R)-6-(t-Butyldiphenylsilyloxymethyl)-5-hy-
droxy-3-methyleneoxane-2-carboxylate (3). To a solution of 17
(19.5 mg, 0.044 mmol) in methanol (1.0 mL) was added a solution
of NaIO4 (14.0 mg, 0.065 mmol) in water (0.5 mL) dropwise at
0 ꢁC, and the mixture was then stirred for 15 min at 25 ꢁC. The
mixture was diluted with water and extracted with ether (ꢅ3).
The combined organic layers were washed with brine, dried over
anhydrous MgSO4, filtered, and concentrated under reduced pres-
sure. The resulting crude (2R,5S,6R)-6-(t-butyldiphenylsilyloxy-
methyl)-5-hydroxy-3-methyleneoxane-2-carbaldehyde (18) was
dissolved in t-BuOH–H2O (3.5:1, 4.5 mL). To the solution were
1113, 1085, 1036, 1005, 940, 905, 836, 776, 745, 701 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ ꢂ0:03 (3H, s), 0.00 (3H, s), 0.82
(9H, s), 1.06 (9H, s), 2.15–2.30 (2H, m), 2.98 (1H, brtd, J ¼ 2:3,
3.6 Hz), 3.36 (1H, brd, J ¼ 1:9 Hz), 3.54–3.65 (2H, m), 3.69–3.88
(3H, m), 3.80 (3H, s), 4.03 (1H, dt, J ¼ 3:3, 6.2 Hz), 4.61 (2H, s),
5.03 (1H, s), 5.21 (1H, s), 6.84 (2H, d, J ¼ 8:7 Hz), 7.23 (2H, d,
J ¼ 8:7 Hz), 7.32–7.45 (6H, m), 7.63–7.69 (4H, m); 13C NMR
(75 MHz, CDCl3) ꢂ ꢂ4:5 (CH3 ꢅ 2), 18.0 (C), 19.2 (C), 25.9
(CH3 ꢅ 3), 26.9 (CH3 ꢅ 3), 35.4 (CH2), 55.3 (CH3), 56.8 (CH),
59.2 (CH), 61.3 (CH2), 64.3 (CH2), 71.7 (CH), 72.7 (CH2),
82.2 (CH), 113.6 (CH ꢅ 2), 116.1 (CH2), 127.7 (CH ꢅ 4), 129.2
(CH ꢅ 2), 129.6 (CH), 129.7 (CH), 131.1 (C), 133.3 (C), 133.4
(C), 135.6 (CH ꢅ 4), 141.0 (C), 159.0 (C); LR-FDMS, m=z 676
(46.0%, [M]þ), 121 (bp, [C8H9O]þ); HR-FDMS, calcd for
C39H56O6Si2 [M]þ: 676.3616, found: 676.3624.
added 2-methyl-2-butene (0.37 mL, 4.4 mmol) and NaH2PO4
ꢃ
2H2O (69 mg, 0.44 mmol) at 25 ꢁC, and the mixture was stirred
for 1 h. Then, NaClO2 (20 mg, 0.22 mmol) was added, and the
mixture was stirred for 30 min. The reaction was quenched with
saturated aqueous NaHSO3, and the mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under re-
duced pressure. The resulting crude carboxylic acid was dissolved
in THF (2.0 mL), and a solution of diazomethane in ether, pre-
pared from N-nitro-N-nitrosomethylguanidine, was added drop-
wise to the solution at 0 ꢁC until the solution turned yellow. After
the mixture was stirred for 10 min, it was concentrated under
the reduced pressure. The residue was purified by silica-gel chro-
matography (1 g, hexane/EtOAc = 6) to give 3 (13.7 mg, 71%
from 17).
(2R,3R,6S,7R)-6-(t-Butyldimethylsilyloxy)-8-(t-butyldiphen-
ylsilyloxy)-2,3-epoxy-4-methyleneoctan-1,7-diol (20). To a so-
lution of 16 (10.62 g, 15.69 mmol) in CH2Cl2–H2O (10:1, 176 mL)
was added DDQ (7.123 g, 31.38 mmol) at 0 ꢁC, and the mixture
was stirred for 40 min. The reaction was quenched with saturated
aqueous NaHCO3, and the mixture was extracted with ether (ꢅ3).
The combined organic layers were washed with brine, dried over
anhydrous MgSO4, filtered, and concentrated under reduced pres-
sure. The residue was purified by silica-gel chromatography
(200 g, hexane/EtOAc = 5) to give 20 (7.17 g, 82%).
22
17
3: colorless needles; mp 118.0–118.3 ꢁC; ½ꢁꢆD ꢂ9:07ꢁ (c
20: a colorless oil; ½ꢁꢆD ¼ 2:78 (c 1.04, CHCl3); IR (neat) ꢇmax
0.710, CHCl3); IR (KBr) ꢇmax 3508, 3077, 3069, 3010, 2997,
2960, 2928, 2855, 1748, 1475, 1465, 1440, 1430, 1305, 1278,
1270, 1113, 1069, 1048, 1005, 902, 880, 825, 800, 745, 706, 690,
3447, 3071, 3049, 2955, 2930, 2890, 2857, 1472, 1460, 1428,
1390, 1361, 1253, 1113, 1085, 1006, 940, 907, 836, 776, 740,
701 cmꢂ1; 1H NMR (300 MHz, CDCl3) ꢂ ꢂ0:05 (3H, s), 0.02 (3H,
s), 0.79 (9H, s), 1.07 (9H, s), 1.74 (1H, brt, J ¼ 7:0 Hz), 2.22 (1H,
dd, J ¼ 5:1, 14.4 Hz), 2.28 (1H, dd, J ¼ 5:8, 14.4 Hz), 2.59 (1H,
d, J ¼ 2:9 Hz), 2.98–3.02 (1H, m), 3.39 (1H, brd, J ¼ 2:1 Hz),
3.63–3.93 (6H, m), 5.02 (1H, brs), 5.22 (1H, brs), 7.34–7.47
620 cmꢂ1 1H NMR (300 MHz, C6D6) ꢂ 1.13 (9H, s), 2.03 (1H,
;
brdd, J ¼ 9:5, 13.0 Hz), 2.17 (1H, brs), 2.57 (1H, dd, J ¼ 5:5,
13.0 Hz), 3.30–3.23 (1H, brtd, J ¼ 5:1, 9.5 Hz), 3.32 (3H, s), 3.70
(1H, brdt, J ¼ 5:5, 9.5 Hz), 3.95 (1H, dd, J ¼ 5:1, 10.6 Hz), 3.98

1182 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
(6H, m), 7.62–7.67 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ4:8
(CH3), ꢂ4:2 (CH3), 18.0 (C), 19.2 (C), 25.8 (CH3 ꢅ 3), 26.9
(CH3 ꢅ 3), 55.4 (CH2), 57.2 (CH), 59.7 (CH), 61.5 (CH2), 64.7
(CH2), 71.5 (CH), 73.7 (CH), 115.7 (CH2), 127.8 (CH ꢅ 4),
129.8 (CH ꢅ 2), 133.1 (C ꢅ 2), 135.5 (CH ꢅ 4), 140.5 (C); LR-
EIMS, m=z 499 (6.2%, ½M ꢂ t-Buꢆþ), 73 (bp, [C3H5O2]þ); HR-
EIMS, calcd for C27H39O5Si2 ½M ꢂ t-Buꢆþ: 499.2336, found:
499.2330.
tion of NaIO4 (28.0 mg, 0.13 mmol) in water (1.0 mL) dropwise at
0 ꢁC, and the mixture was then stirred for 15 min at 25 ꢁC. The
mixture was diluted with water and extracted with ether (ꢅ3).
The combined organic layers were washed with brine, dried over
anhydrous MgSO4, filtered, and concentrated under reduced pres-
sure. The resulting crude (2S,5S,6R)-6-(t-butyldiphenylsilyloxy-
methyl)-5-hydroxy-3-methyleneoxane-2-carbaldehyde (23) was
dissolved in t-BuOH–H2O (3.5:1, 4.5 mL). To the solution were
(1R)-1-[(2S,5S,6R)-5-(t-Butyldimethylsilyloxy)-6-(t-butyldi-
phenylsilyloxymethyl)-3-methyleneoxan-2-yl]-1,2-ethanediol
added 2-methyl-2-butene (0.72 mL, 8.6 mmol) and NaH2PO4
ꢃ
2H2O (134 mg, 0.859 mmol) at 25 ꢁC, and the mixture was stirred
for 1 h. Then, NaClO2 (39 mg, 0.430 mmol) was added, and the
mixture was stirred for 40 min. The reaction was quenched with
saturated aqueous NaHSO3, and the mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under re-
duced pressure. The resulting crude carboxylic acid was dissolved
in THF (2.0 mL), and a solution of diazomethane in ether, pre-
pared from N-nitro-N-nitrosomethylguanidine, was added drop-
wise to the solution at 0 ꢁC until the solution turned yellow. After
the mixture was stirred for 15 min, it was concentrated under
the reduced pressure. The residue was purified by silica-gel chro-
matography (1 g, hexane/EtOAc = 6) to give 24 (24.4 mg, 64%
from 22).
(21).
To a solution of 20 (7.17 g, 12.88 mmol) in CH2Cl2
(150 mL) was added CSA (300 mg, 1.291 mmol) at ꢂ20 ꢁC, and
the mixture was stirred for 30 min. The reaction was quenched
with saturated aqueous NaHCO3, and the mixture was extracted
with ether (ꢅ3). The combined organic layers were washed with
brine, dried over anhydrous MgSO4, filtered, and concentrated un-
der reduced pressure. The residue was purified by silica-gel chro-
matography (200 g, hexane/EtOAc = 3) to give 21 (6.45 g, 90%).
17
21: a colorless oil; ½ꢁꢆD ¼ 20:3 (c 0.745, CHCl3); IR (neat)
ꢇ
max 3399, 3089, 3071, 3034, 2955, 2926, 2890, 2854, 1472, 1462,
1427, 1389, 1361, 1340, 1251, 1180, 1106, 1006, 905, 888, 855,
836, 776, 740, 701, 676 cmꢂ1 1H NMR (300 MHz, CDCl3) ꢂ
;
ꢂ0:17 (3H, s), ꢂ0:01 (3H, s), 0.76 (9H, s), 1.06 (9H, s), 1.70
(1H, t, J ¼ 3:4 Hz), 2.35 (1H, brdd, J ¼ 10:6, 13.3 Hz), 2.54 (1H,
brdd, J ¼ 5:0, 13.3 Hz), 3.43 (1H, ddd, J ¼ 5:0, 9.1, 10.6 Hz),
3.53 (1H, dd, J ¼ 7:4, 10.5 Hz), 3.65 (1H, ddd, J ¼ 1:5, 7.4,
9.1 Hz), 3.78–4.10 (5H, m), 5.00 (1H, brs), 5.02 (1H, brs), 7.30–
7.45 (6H, m), 7.64–7.71 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ
ꢂ5:2 (CH3), ꢂ4:2 (CH3), 17.7 (C), 19.1 (C), 25.6 (CH3 ꢅ 3),
26.7 (CH3 ꢅ 3), 39.2 (CH2), 64.6 (CH2), 64.8 (CH2), 67.7 (CH),
68.5 (CH), 78.2 (CH), 79.7 (CH), 114.1 (CH2), 127.6 (CH ꢅ 4),
129.6 (CH ꢅ 2), 133.1 (C), 133.4 (C), 135.6 (CH ꢅ 4), 141.1
(C); LR-EIMS, m=z 499 (7.8%, ½M ꢂ t-Buꢆþ), 57 (bp, [C4H9]þ);
HR-EIMS, calcd for C27H39O5Si2 ½M ꢂ t-Buꢆþ: 499.2336, found:
499.2321.
25
24: a colorless oil; ½ꢁꢆD þ68:75 (c 1.095, CHCl3); IR (film)
ꢇ
max 3511, 3074, 3051, 2955, 2934, 2859, 1748, 1473, 1463, 1429,
1391, 1362, 1341, 1327, 1264, 1210, 1113, 1010, 998, 913, 823,
789 cmꢂ1 1H NMR (300 MHz, C6D6) ꢂ 1.14 (9H, s), 2.38 (1H,
;
tdd, J ¼ 1:8, 11.4, 13.0 Hz), 2.43–2.50 (1H, brs), 2.56 (1H, dd,
J ¼ 5:1, 13.0 Hz), 3.22 (3H, s), 3.73–3.83 (1H, m), 4.00 (1H,
dd, J ¼ 5:5, 10.6 Hz), 4.12 (1H, dd, J ¼ 4:4, 10.4 Hz), 4.28 (1H,
brtd, J ¼ 4:4, 9.4 Hz), 4.58 (1H, s), 4.78–4.80 (2H, m), 7.15–
7.24 (6H, m), 7.74–7.81 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ
19.1 (C), 26.8 (CH3 ꢅ 3), 37.8 (CH2), 52.2 (CH3), 66.5 (CH2),
70.8 (CH), 75.0 (CH), 77.2 (CH), 115.5 (CH2), 127.9 (CH ꢅ 4),
130.0 (CH ꢅ 2), 132.5 (C), 135.6 (CH ꢅ 4), 139.0 (C ꢅ 2), 170.8
(C); LR-FDMS, m=z 441 (10%, ½M þ Hꢆþ), 383 (bp, ½M ꢂ
t-Buꢆþ); HR-FDMS, calcd for C25H33O5Si ½M þ Hꢆþ: 441.2097,
found: 441.2076.
(1R)-1-[(2S,5S,6R)-6-(t-Butyldiphenylsilyloxymethyl)-5-hy-
droxy-3-methyleneoxan-2-yl]-1,2-ethanediol (22). To a mix-
ture of 21 (78.7 mg, 0.141 mmol) in acetonitrile (1.5 mL) was add-
ed 29 drops of HF pyridine complex (70% in pyridine) at 0 ꢁC,
(3R)-5-(t-Butyldimethylsilyloxy)-3-methylpentanoic Acid
(36). To a solution of 34 (290.7 mg, 1.262 mmol) in t-BuOH–
H2O (3.5:1, 11.7 mL) were added 2-methyl-2-butene (10.6 mL,
ꢃ
and the mixture was stirred for 1.5 h. The reaction was quenched
with saturated aqueous NaHCO3, and the mixture was extracted
with ether (ꢅ3). The combined organic layers were washed with
brine, dried over anhydrous MgSO4, filtered, and concentrated un-
der reduced pressure. The residue was purified by silica-gel chro-
matography (10 g, hexane/EtOAc = 1/3) to give 22 (38.2 mg,
61%).
126 mmol) and NaH2PO4 2H2O (1.969 g, 12.62 mmol) at 25 ꢁC,
ꢃ
and the mixture was stirred for 1 h. Then, NaClO2 (570 mg,
6.302 mmol) was added, and the mixture was stirred for 30 min.
The reaction was quenched with saturated aqueous NaHSO3,
and the mixture was extracted with ether (ꢅ3). The combined or-
ganic layers were washed with brine, dried over anhydrous
MgSO4, filtered, and concentrated under reduced pressure. The
residue was purified by silica-gel chromatography (20 g, hexane/
EtOAc = 15) to give 36 (290 mg, 93%).
18
22: a colorless oil; ½ꢁꢆD ¼ 13:1 (c 1.69, CHCl3); IR (neat) ꢇmax
3436, 3072, 3051, 2955, 2929, 2894, 2857, 1470, 1463, 1428,
1390, 1360, 1253, 1113, 1085, 1006, 938, 910, 836, 776, 740,
1
701 cmꢂ1; H NMR (300 MHz, CDCl3) ꢂ 1.06 (9H, s), 1.97 (1H,
18
brs), 2.22 (1H, brs), 2.34 (1H, brdd, J ¼ 10:9, 13.4 Hz), 2.68
(1H, dd, J ¼ 4:9, 13.4 Hz), 3.16 (1H, brs), 3.50–4.05 (8H, m),
5.00 (1H, brs), 5.07 (1H, brs), 7.36–7.49 (6H, m), 7.63–7.70 (4H,
m); 13C NMR (75 MHz, CDCl3) ꢂ 19.0 (C), 26.8 (CH3 ꢅ 3), 37.4
(CH2), 63.7 (CH2), 66.4 (CH2), 67.8 (CH), 70.6 (CH), 74.4 (CH),
78.1 (CH), 114.6 (CH2), 127.8 (CH ꢅ 4), 130.0 (CH ꢅ 2), 132.4
(C ꢅ 2), 135.5 (CH ꢅ 4), 140.5 (C); LR-EIMS, m=z 385 (1.3%,
½M ꢂ t-Buꢆþ), 199 (bp, [C12H11OSi]þ); HR-EIMS, calcd for
C21H25O5Si ½M ꢂ t-Buꢆþ: 385.1471, found: 385.1442.
36: a colorless oil; ½ꢁꢆD ¼ ꢂ0:92 (c 0.495, CHCl3); IR (neat)
ꢇmax 3600–2500 (br), 2960, 2930, 2855, 1709, 1472, 1463, 1381,
1
1256, 1174, 1097, 836, 776 cmꢂ1; H NMR (300 MHz, CDCl3) ꢂ
0.06 (6H, s), 0.89 (9H, s), 1.00 (3H, d, J ¼ 6:5 Hz), 1.41–1.66
(2H, m), 2.04–2.26 (2H, m), 2.41 (1H, dd, J ¼ 5:6, 14.5 Hz),
3.61–3.75 (2H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ5:4 (CH3 ꢅ
2), 18.3 (C), 19.8 (CH3), 25.9 (CH3 ꢅ 3), 27.3 (CH), 39.1 (CH2),
41.4 (CH2), 61.1 (CH2), 178.8 (C); LR-EIMS, m=z 189 (39.8%,
½M ꢂ t-Buꢆþ), 75 (bp, ½M þ Hꢆþ); HR-EIMS, calcd for C8H17-
O3Si ½M ꢂ t-Buꢆþ: 189.0947, found: 189.0948.
Methyl (2S,5S,6R)-6-(t-Butyldiphenylsilyloxymethyl)-5-hy-
droxy-3-methyleneoxane-2-carboxylate (24). To a solution of
22 (38.2 mg, 0.086 mmol) in methanol (2.0 mL) was added a solu-
(4S)-4-Benzyl-3-[(3R)-5-(t-butyldimethylsilyloxy)-3-methyl-
pentanoyl]oxazolidin-2-one (38). To a solution of 36 (84.9 mg,

K. Fujiwara et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007) 1183
0.345 mmol) in CH2Cl2 (1.5 mL) were added Et3N (0.14 mL,
1.003 mmol) and trimethylacetyl chloride (0.051 mL, 0.414 mmol)
at 0 ꢁC, and the mixture was stirred for 30 min. Then, THF
(1.5 mL), LiCl (29 mg, 0.684 mmol), and (S)-(ꢂ)-4-benzyl-2-oxa-
zolidinone (37) (79 mg, 0.446 mmol) were added, and the mixture
was warmed to 25 ꢁC and stirred for 9 h. The reaction was
quenched with 0.5 M aqueous NaOH, and the mixture was extract-
ed with ether (ꢅ3). The combined organic layers were washed
with brine, dried over anhydrous MgSO4, filtered, and concentrat-
ed under reduced pressure. The residue was purified by silica-gel
chromatography (10 g, hexane/EtOAc = 7) to give 38 (105.9 mg,
76%).
dium tartrate, and the mixture was stirred at ambient temperature
until the solution became clear. The mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under re-
duced pressure. The residue was purified by silica-gel chromatog-
raphy (10 g, hexane/EtOAc = 6) to give 40 (164.8 mg, 67%).
16
40: a colorless oil; ½ꢁꢆD ¼ 4:0 (c 0.725, CHCl3); IR (neat) ꢇmax
3357, 2955, 2927, 2880, 2857, 1472, 1465, 1385, 1360, 1256,
1
1095, 1030, 1005, 940, 895, 835, 805, 774 cmꢂ1; H NMR (300
MHz, CDCl3) ꢂ 0.05 (6H, s), 0.81 (3H, d, J ¼ 7:0 Hz), 0.84
(3H, d, J ¼ 7:0 Hz), 0.90 (9H, s), 1.32–1.45 (1H, m), 1.53–1.82
(3H, m), 3.43–3.75 (4H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ5:3
(CH3 ꢅ 2), 11.8 (CH3), 14.7 (CH3), 18.3 (C), 26.0 (CH3 ꢅ 3),
30.1 (CH), 37.8 (CH2), 39.8 (CH), 61.7 (CH2), 66.7 (CH2); LR-
FDMS, m=z 247 (1.7%, ½M þ Hꢆþ), 189 (bp, ½M ꢂ t-Buꢆþ); HR-
FDMS, calcd for C9H21O2Si ½M ꢂ t-Buꢆþ: 189.1311, found:
189.1313.
23
38: a colorless oil; ½ꢁꢆD ¼ 32:1 (c 0.965, CHCl3); IR (neat)
ꢇmax 3090, 3060, 3028, 2955, 2926, 2880, 2854, 1780, 1696,
1495, 1475, 1460, 1450, 1385, 1349, 1250, 1210, 1193, 1094,
1045, 1005, 835, 775, 760, 745, 700 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) ꢂ 0.05 (6H, s), 0.89 (9H, s), 1.02 (3H, d, J ¼ 6:7 Hz),
1.40–1.54 (1H, m), 1.59–1.71 (1H, m), 2.16–2.33 (1H, m), 2.75
(1H, dd, J ¼ 9:8, 13.3 Hz), 2.82–2.97 (2H, m), 3.32 (1H, dd,
J ¼ 3:3, 13.3 Hz), 3.62–3.75 (2H, m), 4.12–4.22 (2H, m), 4.68
(1H, tdd, J ¼ 3:3, 6.8, 9.8 Hz), 7.19–7.37 (5H, m); 13C NMR
(75 MHz, CDCl3) ꢂ ꢂ5:3 (CH3 ꢅ 2), 18.3 (C), 19.8 (CH3), 25.9
(CH3 ꢅ 3), 26.7 (CH), 38.0 (CH2), 39.4 (CH2), 42.4 (CH2), 55.2
(CH), 61.1 (CH2), 66.0 (CH2), 127.3 (CH), 128.9 (CH ꢅ 2),
129.4 (CH ꢅ 2), 135.3 (C), 153.4 (C), 172.6 (C); LR-EIMS, m=z
405 (3.6%, [M]þ), 348 (bp, ½M ꢂ t-Buꢆþ); HR-EIMS, calcd for
C18H26NO4Si ½M ꢂ t-Buꢆþ: 348.1631, found: 348.1628.
(2R,3S,4R)- and (2S,3S,4R)-1-(Benzyloxy)-6-(t-butyldimeth-
ylsilyloxy)-3,4-dimethylhexan-2-ol (42). To a solution of 40
(137.0 mg, 0.556 mmol) in CH2Cl2 (6.0 mL) were added MS4A
(powder, 150 mg), NMO (4-methylmorpholine N-oxide) (130 mg,
1.11 mmol), and TPAP (20 mg, 0.057 mmol) at 25 ꢁC, and the
mixture was stirred for 20 min. Then, the mixture was immediate-
ly filtered through a Florisil pad, and the filtrate was condensed
under reduced pressure. The resulting aldehyde was dissolved in
THF (2 mL), and the solution was added dropwise at ꢂ78 ꢁC to
a solution of benzyloxymethyllithium, generated in situ from
(benzyloxymethyl)tributylstannane (41) (1.011 g, 2.459 mmol)
and BuLi (1.5 mL, 1.58 M in hexane, 2.37 mmol) in THF (5.0 mL)
at ꢂ78 ꢁC for 30 min. After the mixture was stirred for 30 min, the
reaction was quenched with MeOH. The mixture was condensed
under reduced pressure, and the residue was diluted with ether
and saturated aqueous NaHCO3. The mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under re-
duced pressure. The residue was purified by silica-gel chromatog-
raphy (15 g, hexane/EtOAc = 10) to give 42 (108.0 mg, 66%
from 40) as a 5:1 mixture of diastereomers.
(4S)-4-Benzyl-3-[(2S,3R)-5-(t-butyldimethylsilyloxy)-2,3-di-
methylpentanoyl]oxazolidin-2-one (39). To a solution of 38
(105.9 mg, 0.261 mmol) in THF (2.6 mL) was added NHMDS (so-
dium hexamethyldisilazanide) (0.3 mL, 1.0 M solution in THF,
0.3 mmol) at ꢂ78 ꢁC, and the mixture was stirred for 30 min.
Then, MeI (0.08 mL, 1.285 mmol) was added, and the mixture
was stirred for 33 h. The reaction was quenched with saturated
aqueous NH4Cl. After the mixture was warmed to ambient tem-
perature, saturated aqueous Na2S2O3 was added, and the mixture
was extracted with ether (ꢅ3). The combined organic layers were
washed with brine, dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified
by silica-gel chromatography (10 g, hexane/EtOAc = 20) to give
39 (96.1 mg, 88%).
42: a colorless oil; IR (neat) ꢇmax 3484, 3092, 3067, 3034,
2963, 2932, 2900, 2861, 1500, 1473, 1463, 1454, 1390, 1360,
1257, 1099, 1025, 1005, 940, 900, 836, 810, 776, 740, 698,
18
39: a colorless oil; ½ꢁꢆD ¼ 62:8 (c 0.630, CHCl3); IR (neat)
668 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ 0.037 (6H ꢅ 5=6, s),
ꢇmax 3090, 3060, 3030, 2950, 2929, 2880, 2857, 1783, 1698,
1498, 1472, 1460, 1455, 1384, 1349, 1289, 1239, 1208, 1195,
1100, 1051, 1030, 1015, 990, 975, 903, 836, 812, 776, 763, 747,
0.041 (6H ꢅ 1=6, s), 0.80 (3H ꢅ 1=6, d, J ¼ 6:9 Hz), 0.81 (3H ꢅ
5=6, d, J ¼ 6:7 Hz), 0.87–0.90 (3H ꢅ 1=6, m), 0.88 (9H ꢅ 5=6,
s), 0.89 (9H ꢅ 1=6, s), 0.90 (3H ꢅ 5=6, d, J ¼ 7:0 Hz), 1.32–
1.73 (4H, m), 2.28 (1H ꢅ 1=6, d, J ¼ 3:4 Hz), 2.32 (1H ꢅ 5=6,
d, J ¼ 3:3 Hz), 3.39 (1H ꢅ 5=6, t, J ¼ 8:8 Hz), 3.43 (1H ꢅ 1=6,
t, J ¼ 8:8 Hz), 3.51–3.70 (3H, m), 3.70–3.80 (1H, m), 4.56 (2H,
s), 7.25–7.40 (5H, m); 13C NMR (75 MHz, CDCl3) (major isomer)
ꢂ ꢂ5:3 (CH3 ꢅ 2), 9.7 (CH3), 14.9 (CH3), 18.3 (C), 26.0 (CH3 ꢅ
3), 30.6 (CH), 38.2 (CH2), 39.4 (CH), 61.4 (CH2), 72.5 (CH),
73.34 (CH2), 73.39 (CH2), 127.7 (CH ꢅ 2), 127.8 (CH), 128.4
(CH ꢅ 2), 138.0 (C); LR-EIMS, m=z 366 (0.5%, [M]þ), 309
(1.4%, ½M ꢂ t-Buꢆþ), 91 (bp, [C7H7]þ); HR-EIMS, calcd for
C17H29O3Si ½M ꢂ t-Buꢆþ: 309.1886, found: 309.1884.
1
702 cmꢂ1; H NMR (300 MHz, CDCl3) ꢂ 0.05 (6H, s), 0.89 (9H,
s), 0.91 (3H, d, J ¼ 6:8 Hz), 1.16 (3H, d, J ¼ 6:7 Hz), 1.34–1.47
(1H, m), 1.58–1.70 (1H, m), 1.89–2.05 (1H, m), 2.76 (1H, dd,
J ¼ 9:7, 13.3 Hz), 3.29 (1H, dd, J ¼ 3:2, 13.3 Hz), 3.57–3.77
(3H, m), 4.10–4.21 (2H, m), 4.65 (1H, brtdd, J ¼ 3:5, 6.2, 9.7
Hz), 7.19–7.37 (5H, m); 13C NMR (75 MHz, CDCl3) ꢂ ꢂ5:37
(CH3), ꢂ5:32 (CH3), 12.7 (CH3), 15.4 (CH3), 18.3 (C), 25.9
(CH3 ꢅ 3), 32.1 (CH), 37.8 (CH2), 38.1 (CH2), 42.2 (CH), 55.5
(CH), 61.5 (CH2), 65.9 (CH2), 127.3 (CH), 128.9 (CH ꢅ 2),
129.4 (CH ꢅ 2), 135.4 (C), 153.0 (C), 176.7 (C); LR-EIMS, m=z
419 (3.8%, [M]þ), 362 (bp, ½M ꢂ t-Buꢆþ); HR-EIMS, calcd for
C19H28NO4Si ½M ꢂ t-Buꢆþ: 362.1788, found: 362.1783.
(2S,3S,4R)-2-Benzyloxymethyl-3,4-dimethyloxan-2-ol (28).
To a solution of 42 (10.3 mg, 0.028 mmol) in CH2Cl2 (1.0 mL)
was added DMPI (Dess–Martin periodinane) (24 mg, 0.056 mmol)
at 25 ꢁC, and the mixture was stirred for 6 h. Then, saturated aque-
ous Na2S2O3 and saturated aqueous NaHCO3 were added, and the
mixture was extracted with ether (ꢅ3). The combined organic
layers were washed with brine, dried over anhydrous MgSO4,
(2S,3R)-5-(t-Butyldimethylsilyloxy)-2,3-dimethylpentanol
(40). To a solution of LiAlH4 (113 mg, 2.978 mmol) in THF
(10 mL) was added a solution of 39 (416 mg, 0.991 mmol) in
THF (3.0 mL) at 0 ꢁC, and the mixture was stirred for 10 min.
The reaction was quenched with saturated aqueous potassium so-

1184 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
filtered, and concentrated under reduced pressure. The residue was
passed through a short silica-gel column (1 g) with hexane–EtOAc
(30:1), and the eluate was condensed under reduced pressure. The
resulting crude ketone was dissolved in THF (0.8 mL), and Bu4NF
(0.057 mL, 1.0 M in THF, 0.057 mmol) was added to the solution
at 25 ꢁC. After the mixture was stirred for 40 min, water was add-
ed to the mixture. The resulting mixture was extracted with ether
(ꢅ3). The combined organic layers were washed with brine, dried
over anhydrous MgSO4, filtered, and concentrated under reduced
pressure. The residue was purified by silica-gel chromatography
(1 g, hexane/EtOAc = 7) to give 28 (5.9 mg, 81% from 42).
(300 MHz, CDCl3) ꢂ 0.91 (3H, d, J ¼ 6:6 Hz), 1.38–1.51 (2H,
m), 1.52–1.81 (3H, m), 3.42–3.57 (2H, m), 3.58–3.76 (2H, m),
3.80 (3H, s), 4.43 (2H, s), 6.87 (2H, d, J ¼ 8:8 Hz), 7.25 (2H, d,
J ¼ 8:8 Hz); 13C NMR (75 MHz, CDCl3) ꢂ 19.8 (CH3), 26.7 (CH),
36.5 (CH2), 39.8 (CH2), 55.2 (CH3), 60.7 (CH2), 68.1 (CH2), 72.6
(CH2), 113.7 (CH ꢅ 2), 129.2 (CH ꢅ 2), 130.5 (C), 159.1 (C);
LR-EIMS, m=z 238 (6.1%, [M]þ), 121 (bp, [C8H9O]þ); HR-
EIMS, calcd for C14H22O3 [M]þ: 238.1569, found: 238.1570.
(3S)-5-(4-Methoxybenzyloxy)-3-methylpentanoic Acid (45).
To a solution of 44 (640.0 mg, 2.685 mmol) in CH2Cl2 (25.0
mL) were added MS4A (powder, 600 mg), NMO (799 mg, 6.82
mmol), and TPAP (96 mg, 0.273 mmol) at 25 ꢁC, and the mixture
was stirred for 20 min. Then, the mixture was immediately filtered
through a Florisil pad, and the filtrate was condensed under re-
duced pressure. The resulting aldehyde was dissolved in t-BuOH–
H2O (3.5:1, 18 mL), and 2-methyl-2-butene (22 mL, 262 mmol)
24
28: a colorless oil; ½ꢁꢆD ¼ ꢂ50:9 (c 1.70, CHCl3); IR (neat)
ꢇmax 3434, 3090, 3070, 3030, 2975, 2950, 2931, 2877, 1495,
1455, 1375, 1260, 1205, 1155, 1092, 1060, 995, 975, 950, 910,
880, 840, 740, 700 cmꢂ1; 1H NMR (300 MHz, CDCl3) ꢂ 0.90 (3H,
d, J ¼ 6:6 Hz), 0.92 (3H, d, J ¼ 6:6 Hz), 1.23 (1H, dqd, J ¼ 1:7,
6.6, 11.0 Hz), 1.36 (1H, brdq, J ¼ 4:8, 12.8 Hz), 1.52 (1H, dddd,
J ¼ 1:5, 2.6, 4.0, 13.2 Hz), 1.70 (1H, dqdd, J ¼ 4:0, 6.6, 11.0,
12.8 Hz), 2.93 (1H, d, J ¼ 1:7 Hz), 3.40 (1H, d, J ¼ 9:5 Hz), 3.52
(1H, d, J ¼ 9:5 Hz), 3.66 (1H, ddd, J ¼ 1:5, 4.8, 11.2 Hz), 3.97
(1H, ddd, J ¼ 2:6, 11.2, 12.8 Hz), 4.62 (1H, d, J ¼ 12:2 Hz), 4.66
(1H, d, J ¼ 12:2 Hz), 7.24–7.39 (5H, m); 1H NMR (300 MHz,
C6D6) ꢂ 0.79 (3H, d, J ¼ 6:6 Hz), 0.94 (3H, d, J ¼ 6:6 Hz), 1.14
(1H, dqd, J ¼ 1:0, 6.6, 10.6 Hz), 1.23 (2H, m), 1.72 (1H, qndd,
J ¼ 6:6, 9.2, 10.6 Hz), 2.83 (1H, d, J ¼ 1:0 Hz), 3.34 (1H, d, J ¼
9:9 Hz), 3.41 (1H, d, J ¼ 9:9 Hz), 3.57 (1H, ddd, J ¼ 2:9, 4.4,
11.0 Hz), 3.98 (1H, m), 4.43 (1H, d, J ¼ 12:1 Hz), 4.47 (1H, d,
J ¼ 12:1 Hz), 7.03–7.19 (3H, m), 7.23–7.28 (2H, m); 13C NMR
(75 MHz, CDCl3) ꢂ 13.5 (CH3), 20.3 (CH3), 31.1 (CH), 34.4
(CH2), 41.7 (CH), 60.5 (CH2), 73.89 (CH2), 73.94 (CH2), 97.3
(C), 127.7 (CH), 127.8 (CH ꢅ 2), 128.4 (CH ꢅ 2), 137.8 (C); LR-
FDMS, m=z 250 (11.5%, [M]þ), 129 (bp, ½M ꢂ BnOCH2ꢆþ); HR-
FDMS, calcd for C15H22O3 [M]þ: 250.1568, found: 250.1548.
(3R)-5-(4-Methoxybenzyloxy)-3-methylpentan-1-ol (44). To
a solution of LiAlH4 (164 mg, 4.32 mmol) in THF (20 mL) was
added a solution of 34 (684 mg, 2.97 mmol) in THF (5.0 mL) at
25 ꢁC, and the mixture was stirred for 30 min. Then, water
(0.7 mL), 15% aqueous NaOH (0.7 mL), and water (2.1 mL) were
added dropwise in turn to the stirred reaction mixture. The mixture
was filtered through a celite pad, and the pad was washed with
EtOAc several times. The combined filtrate and washings were
condensed under reduced pressure. The crude alcohol 43 was dis-
solved in DMF (30 mL), and NaH (724 mg, 60% oil suspension,
18.1 mmol) was added to the mixture at 0 ꢁC. After the mixture
was vigorously stirred for 15 min, 4-methoxybenzyl chloride
(0.82 mL, 6.05 mmol) and Bu4NI (111 mg, 0.301 mmol) were add-
ed. Then, the mixture was warmed to 25 ꢁC and stirred for 18 h.
The reaction was quenched with saturated aqueous NH4Cl, and
the mixture was extracted with ether (ꢅ3). The combined organic
layers were washed with brine, dried over anhydrous MgSO4, fil-
tered, and concentrated under reduced pressure. The residue was
dissolved in THF (30 mL), and Bu4NF (6.0 mL, 1.0 M in THF,
6.0 mmol) was added to the solution at 25 ꢁC. After the mixture
was stirred for 30 min, water was added to the mixture. The result-
ing mixture was extracted with ether (ꢅ3). The combined organic
layers were washed with brine, dried over anhydrous MgSO4, fil-
tered, and concentrated under reduced pressure. The residue was
purified by silica-gel chromatography (20 g, hexane/EtOAc = 7)
to give 44 (710 mg, 100% from 34).
and NaH2PO4 2H2O (4.2 g, 26.9 mmol) were added to the mix-
ꢃ
ture at 25 ꢁC. After the mixture was stirred for 10 min, NaClO2
(1.214 g, 13.42 mmol) was added, and the mixture was stirred
for 30 min. The reaction was quenched with saturated aqueous
NaHSO3, and the mixture was extracted with ether (ꢅ3). The
combined organic layers were washed with brine, dried over anhy-
drous MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica-gel chromatography (20 g,
hexane/EtOAc = 2) to give 45 (534 mg, 79% from 44).
18
45: a colorless oil; ½ꢁꢆD ¼ ꢂ0:81 (c 0.520, CHCl3); IR (neat)
ꢇmax 3600–2400 (br), 2959, 2930, 2870, 1709, 1611, 1586, 1514,
1463, 1443, 1421, 1410, 1380, 1366, 1303, 1249, 1173, 1096,
1035, 947, 850, 822, 665, 636 cmꢂ1; 1H NMR (300 MHz, CDCl3)
ꢂ 0.99 (3H, d, J ¼ 6:5 Hz), 1.55 (1H, brqd, J ¼ 6:6, 13.9 Hz), 1.69
(1H, brqd, J ¼ 6:4, 13.9 Hz), 2.07–2.25 (2H, m), 2.39 (1H, dd,
J ¼ 5:5, 14.5 Hz), 3.44–3.56 (2H, m), 3.80 (3H, s), 4.43 (2H, s),
6.87 (2H, d, J ¼ 8:6 Hz), 7.25 (2H, d, J ¼ 8:6 Hz); 13C NMR
(75 MHz, CDCl3) ꢂ 19.8 (CH3), 27.6 (CH), 36.1 (CH2), 41.3
(CH2), 55.2 (CH3), 67.8 (CH2), 72.6 (CH2), 113.8 (CH ꢅ 2),
129.3 (CH ꢅ 2), 130.4 (C), 159.2 (C), 178.7 (C); LR-EIMS, m=z
252 (9.0%, [M]þ), 137 (bp, [C8H9O2]þ); HR-EIMS, calcd for
C14H20O4 [M]þ: 252.1362, found: 252.1362.
(4S)-4-Benzyl-3-[(3S)-5-(4-methoxybenzyloxy)-3-methylpen-
tanoyl]oxazolidin-2-one (46). To a solution of 45 (69.6 mg,
0.276 mmol) in CH2Cl2 (1.5 mL) were added Et3N (0.11 mL,
0.794 mmol) and trimethylacetyl chloride (0.041 mL, 0.333 mmol)
at 0 ꢁC, and the mixture was stirred for 30 min. Then, THF (1.5
mL), LiCl (23 mg, 0.543 mmol), and (S)-(ꢂ)-4-benzyl-2-oxazoli-
dinone (37) (63 mg, 0.356 mmol) were added, and the mixture
was warmed to 25 ꢁC and stirred for 3 h. The reaction was
quenched with 0.5 M aqueous NaOH, and the mixture was extract-
ed with ether (ꢅ3). The combined organic layers were washed
with brine, dried over anhydrous MgSO4, filtered, and concentrat-
ed under reduced pressure. The residue was purified by silica-gel
chromatography (2 g, hexane/EtOAc = 8) to give 46 (76.6 mg,
68%).
16
46: a colorless oil; ½ꢁꢆD ¼ 30:7 (c 0.545, CHCl3); IR (neat)
ꢇmax 3090, 3060, 3030, 2955, 2927, 2850, 1780, 1696, 1610,
1585, 1510, 1455, 1380, 1350, 1300, 1245, 1095, 1030, 820,
1
760, 745, 700 cmꢂ1; H NMR (300 MHz, CDCl3) ꢂ 1.00 (3H, d,
J ¼ 6:7 Hz), 1.51–1.64 (1H, m), 1.69–1.81 (1H, m), 2.19–2.36
(1H, m), 2.66 (1H, dd, J ¼ 9:8, 13.3 Hz), 2.77 (1H, dd, J ¼ 7:9,
16.4 Hz), 3.00 (1H, dd, J ¼ 5:8, 16.4 Hz), 3.30 (1H, dd, J ¼ 3:3,
13.3 Hz), 3.53 (2H, brt, J ¼ 6:7 Hz), 3.79 (3H, s), 4.07–4.19
(2H, m), 4.42 (1H, d, J ¼ 11:5 Hz), 4.45 (1H, d, J ¼ 11:5 Hz),
4.65 (1H, tdd, J ¼ 3:3, 6.9, 9.8 Hz), 6.87 (2H, d, J ¼ 8:7 Hz),
24
44: a colorless oil; ½ꢁꢆD ¼ ꢂ3:01 (c 0.760, CHCl3); IR (neat)
ꢇ
max 3399, 3070, 3030, 3000, 2955, 2931, 2871, 1614, 1587, 1514,
1465, 1366, 1302, 1249, 1173, 1095, 1036, 821 cmꢂ1 1H NMR
;

K. Fujiwara et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007) 1185
7.17–7.36 (7H, m); 13C NMR (75 MHz, CDCl3) ꢂ 19.9 (CH3),
26.9 (CH), 36.2 (CH2), 37.9 (CH2), 42.4 (CH2), 55.1 (CH), 55.2
(CH3), 66.0 (CH2), 67.9 (CH2), 72.5 (CH2), 113.7 (CH ꢅ 2),
127.2 (CH), 128.9 (CH ꢅ 2), 129.2 (CH ꢅ 2), 129.3 (CH ꢅ 2),
130.6 (C), 135.3 (C), 153.4 (C), 159.0 (C), 172.4 (C); LR-EIMS,
m=z 411 (6.8%, [M]þ), 121 (bp, [C8H9O]þ); HR-EIMS, calcd for
C24H29NO5 [M]þ: 411.2046, found: 411.2047.
(2R,3S,4S)- and (2S,3S,4S)-1-(Benzyloxy)-3,4-dimethyl-6-(4-
methoxybenzyloxy)hexan-2-ol (49).
To a solution of 48
(128.7 mg, 0.510 mmol) in CH2Cl2 (5.0 mL) were added MS4A
(powder, 130 mg), NMO (150 mg, 1.28 mmol), and TPAP
(18 mg, 0.051 mmol) at 25 ꢁC, and the mixture was stirred for
20 min. Then, the mixture was immediately filtered through a Flo-
risil pad, and the filtrate was condensed under reduced pressure.
The resulting aldehyde was dissolved in THF (2 mL), and the so-
lution was added dropwise at ꢂ78 ꢁC to a solution of benzyloxy-
methyllithium, generated in situ from (benzyloxymethyl)tributyl-
stannane (41) (1.049 g, 2.551 mmol) and BuLi (1.55 mL, 1.58 M
in hexane, 2.45 mmol) in THF (5.0 mL) at ꢂ78 ꢁC for 30 min. Af-
ter the mixture was stirred for 30 min, the reaction was quenched
with MeOH. The mixture was condensed under reduced pressure,
and the residue was diluted with ether and saturated aqueous
NaHCO3. The mixture was extracted with ether (ꢅ3). The com-
bined organic layers were washed with brine, dried over anhy-
drous MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica-gel chromatography (15 g,
hexane/EtOAc = 10) to give 49 (92.5 mg, 48% from 48) as a
3:2 mixture of diastereomers.
49: a colorless oil; IR (neat) ꢇmax 3447, 3080, 3060, 3028,
2957, 2929, 2861, 1612, 1512, 1495, 1453, 1380, 1360, 1300,
1247, 1175, 1095, 1035, 820, 740, 698 cmꢂ1; 1H NMR (300 MHz,
CDCl3) ꢂ 0.82 (3H ꢅ 2=5, d, J ¼ 6:8 Hz), 0.89 (3H ꢅ 2=5, d,
J ¼ 7:0 Hz), 0.91 (3H ꢅ 3=5, d, J ¼ 7:0 Hz), 0.92 (3H ꢅ 3=5, d,
J ¼ 6:8 Hz), 1.20–1.81 (4H, m), 2.25 (1H ꢅ 3=5, d, J ¼ 3:4 Hz),
2.32 (1H ꢅ 2=5, d, J ¼ 3:4 Hz), 3.33–3.60 (4H, m), 3.72–3.90
(1H, m), 3.79 (3H, s), 4.34–4.48 (2H, m), 4.49–4.58 (2H, m),
6.86 (2H, d, J ¼ 8:6 Hz), 7.18–7.38 (7H, m); 13C NMR (75 MHz,
CDCl3) ꢂ 9.6 (CH3 ꢅ 2=5), 10.4 (CH3 ꢅ 3=5), 15.0 (CH3 ꢅ 2=5),
18.0 (CH3 ꢅ 3=5), 31.0 (CH ꢅ 2=5), 32.0 (CH ꢅ 3=5), 32.4
(CH2 ꢅ 3=5), 35.0 (CH2 ꢅ 2=5), 39.3 (CH ꢅ 2=5), 40.5 (CH ꢅ
3=5), 55.2 (CH3), 68.3 (CH2 ꢅ 2=5), 68.7 (CH2 ꢅ 3=5), 71.8
(CH ꢅ 3=5), 72.5 (CH ꢅ 2=5), 72.6 (CH2), 73.3 (CH2), 73.4
(CH2 ꢅ 2=5), 73.6 (CH2 ꢅ 3=5), 113.7 (CH ꢅ 2), 127.7 (CH ꢅ
2), 128.3 (CH), 128.4 (CH ꢅ 2), 129.2 (CH ꢅ 2), 130.7 (C), 138.0
(C), 159.1 (C); LR-EIMS, m=z 372 (0.5%, [M]þ), 121 (bp,
[C8H9O]þ); HR-EIMS, calcd for C23H32O4 [M]þ: 372.2301,
found: 372.2300.
(4S)-4-Benzyl-3-[(2S,3S)-2,3-dimethyl-5-(4-methoxybenzyl-
oxy)pentanoyl]oxazolidin-2-one (47). To a solution of 46 (84.9
mg, 0.206 mmol) in THF (2 mL) was added NHMDS (0.23 mL,
1.0 M solution in THF, 0.23 mmol) at ꢂ78 ꢁC, and the mixture
was stirred for 30 min. Then, MeI (0.063 mL, 1.012 mmol) was
added, and the mixture was stirred for 33 h. The reaction was
quenched with saturated aqueous NH4Cl. After the mixture was
warmed to ambient temperature, saturated aqueous Na2S2O3
was added, and the mixture was extracted with ether (ꢅ3). The
combined organic layers were washed with brine, dried over anhy-
drous MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica-gel chromatography (5 g,
hexane/EtOAc = 9) to give 47 (46.1 mg, 53%) and unreacted
46 (20.5 mg, 24% recovery).
18
47: a colorless oil; ½ꢁꢆD ¼ 44:1 (c 0.760, CHCl3); IR (neat)
ꢇ
max 3091, 3071, 3035, 2965, 2937, 2876, 1780, 1699, 1613, 1586,
1514, 1499, 1480, 1455, 1384, 1350, 1303, 1247, 1209, 1100,
1035, 972, 920, 823, 762, 749, 731, 703, 682 cmꢂ1 1H NMR
;
(300 MHz, CDCl3) ꢂ 0.97 (3H, d, J ¼ 6:7 Hz), 1.17 (3H, d, J ¼
6:9 Hz), 1.30–1.43 (1H, m), 1.73–1.87 (1H, m), 1.96–2.07 (1H,
m), 2.74 (1H, dd, J ¼ 9:6, 13.3 Hz), 3.28 (1H, dd, J ¼ 3:2,
13.3 Hz), 3.39–3.57 (2H, m), 3.71 (1H, qn, J ¼ 6:9 Hz), 3.77
(3H, s), 3.97 (1H, brdd, J ¼ 7:7, 8.9 Hz), 4.07 (1H, dd, J ¼ 2:4,
8.9 Hz), 4.38 (1H, d, J ¼ 11:4 Hz), 4.41 (1H, d, J ¼ 11:4 Hz),
4.57 (1H, dddd, J ¼ 2:4, 3.2, 7.7, 9.6 Hz), 6.84 (2H, d, J ¼ 8:7
Hz), 7.18–7.36 (7H, m); 13C NMR (75 MHz, CDCl3) ꢂ 13.0
(CH3), 18.0 (CH3), 32.0 (CH2), 32.6 (CH), 37.8 (CH2), 42.5 (CH),
55.2 (CH3), 55.6 (CH), 65.9 (CH2), 68.1 (CH2), 72.6 (CH2), 113.7
(CH ꢅ 2), 127.3 (CH), 128.9 (CH ꢅ 2), 129.2 (CH ꢅ 2), 129.4
(CH ꢅ 2), 130.7 (C), 135.4 (C), 153.2 (C), 159.1 (C), 176.7 (C);
LR-EIMS, m=z 425 (7.4%, [M]þ), 121 (bp, [C8H9O]þ); HR-
EIMS, calcd for C25H31NO5 [M]þ: 425.2202, found: 425.2202.
(2S,3S)-2,3-Dimethyl-5-(4-methoxybenzyloxy)pentan-1-ol
(48).
To a solution of LiAlH4 (96 mg, 2.53 mmol) in THF
(2R,3S,4S)-2-Benzyloxymethyl-3,4-dimethyloxan-2-ol (29).
To a solution of 49 (12.9 mg, 0.034 mmol) in CH2Cl2 (1.0 mL)
was added DMPI (29 mg, 0.068 mmol) at 25 ꢁC, and the mixture
was stirred for 2 h. Then, saturated aqueous Na2S2O3 and saturat-
ed aqueous NaHCO3 were added, and the mixture was extracted
with ether (ꢅ3). The combined organic layers were washed with
brine, dried over anhydrous MgSO4, filtered, and concentrated un-
der reduced pressure. The residue was passed through a short sili-
ca-gel column (1 g) with hexane–EtOAc (10:1), and the eluate was
condensed under reduced pressure. The resulting crude ketone was
dissolved in CH2Cl2 (1.0 mL), and water (0.05 mL) and DDQ
(10 mg, 0.044 mmol) was added to the solution at 0 ꢁC. After
the mixture was stirred for 1 h, DDQ (10 mg, 0.044 mmol) was
added. The reaction mixture was warmed to 25 ꢁC and stirred
for 30 min. Then, saturated aqueous NaHCO3 was added, and
the mixture was extracted with ether (ꢅ3). The combined organic
layers were washed with brine, dried over anhydrous MgSO4, fil-
tered, and concentrated under reduced pressure. The residue was
purified by silica-gel chromatography (2 g, hexane/EtOAc = 15)
to give 29 (7.0 mg, 82% from 49).
(6.0 mL) was added a solution of 39 (270 mg, 0.635 mmol) in
THF (6.0 mL) at 0 ꢁC, and the mixture was stirred for 30 min.
The reaction was quenched with saturated aqueous potassium so-
dium tartrate, and the mixture was stirred at ambient temperature
until the solution became clear. The mixture was extracted with
ether (ꢅ3). The combined organic layers were washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated under re-
duced pressure. The residue was purified by silica-gel chromatog-
raphy (2 g, hexane/EtOAc = 2) to give 48 (128.7 mg, 80%).
19
48: a colorless oil; ½ꢁꢆD ¼ ꢂ10:2 (c 0.530, CHCl3); IR (neat)
ꢇ
max 3416, 2959, 2930, 2875, 1613, 1590, 1514, 1465, 1380, 1370,
1303, 1249, 1173, 1093, 1037, 820 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) ꢂ 0.84 (3H, d, J ¼ 7:0 Hz), 0.90 (3H, d, J ¼ 6:9 Hz),
1.23–1.36 (1H, m), 1.57–1.85 (3H, m), 3.39–3.59 (4H, m), 3.80
(3H, s), 4.42 (1H, d, J ¼ 11:5 Hz), 4.44 (1H, d, J ¼ 11:5 Hz), 6.87
(2H, d, J ¼ 8:6 Hz), 7.25 (2H, d, J ¼ 8:6 Hz); 13C NMR (75 MHz,
CDCl3) ꢂ 12.7 (CH3), 17.5 (CH3), 30.9 (CH2), 32.0 (CH), 40.3
(CH), 55.3 (CH3), 65.9 (CH2), 68.9 (CH2), 72.7 (CH2), 113.8
(CH ꢅ 2), 129.3 (CH ꢅ 2), 130.4 (C), 159.1 (C); LR-EIMS, m=z
252 (11.9%, [M]þ), 121 (bp, [C8H9O]þ); HR-EIMS, calcd for
C15H23O3 [M]þ: 252.1725, found: 252.1722.
23
29: a colorless oil; ½ꢁꢆD ¼ 39:9 (c 1.085, CHCl3); IR (neat)
ꢇmax 3444, 3090, 3070, 3030, 2960, 2934, 2876, 1500, 1454,

1186 Bull. Chem. Soc. Jpn. Vol. 80, No. 6 (2007)
Partial Synthesis of Goniodomin A
1440, 1410, 1380, 1340, 1310, 1290, 1270, 1210, 1200, 1180,
346, 119. c) K. Matsunaga, K. Nakatani, M. Murakami, K.
Yamaguchi, Y. Ohizumi, J. Pharmacol. Exp. Ther. 1999, 291,
1121.
1094, 1064, 1029, 990, 945, 920, 910, 875, 736, 698 cmꢂ1
;
1H NMR (300 MHz, CDCl3) ꢂ 0.76 (3H, d, J ¼ 7:0 Hz), 0.87
(3H, d, J ¼ 7:0 Hz), 1.23 (1H, brtddd, J ¼ 1:1, 3.1, 4.0, 13.4 Hz),
1.46 (1H, brdq, J ¼ 5:3, 13.0 Hz), 1.64 (1H, brdq, J ¼ 4:0, 7.0
Hz), 2.36 (1H, tqd, J ¼ 4:0, 7.0, 13.0 Hz), 3.31 (1H, d, J ¼ 9:5
Hz), 3.50 (1H, s), 3.53 (1H, d, J ¼ 9:5 Hz), 3.66 (1H, brddd, J ¼
1:1, 5.3, 11.2 Hz), 3.97 (1H, brddd, J ¼ 3:1, 11.2, 13.0 Hz), 4.56
(1H, d, J ¼ 11:9 Hz), 4.72 (1H, d, J ¼ 11:9 Hz), 7.25–7.39 (5H,
3
K. Mizuno, N. Nakatani, Y. Ohizumi, E. Ito, M.
Murakami, K. Yamaguchi, J. Pharm. Pharmacol. 1998, 50, 645.
M. Abe, D. Inoue, K. Matsunaga, Y. Ohizumi, H. Ueda, T.
Asano, M. Murakami, Y. Sato, J. Cell. Physiol. 2002, 190, 109.
M. H. Hsia, S. L. Morton, L. L. Smith, K. R. Beauchesne,
K. M. Huncik, P. D. R. Moeller, Harmful Algae 2006, 5, 290.
a) V. S. Martin, M. T. Nun˜ez, C. E. Tonn, Tetrahedron
4
5
1
m); H NMR (300 MHz, C6D6) ꢂ 0.66 (3H, d, J ¼ 7:0 Hz), 0.75
6
(3H, d, J ¼ 7:0 Hz), 0.96 (1H, brddd, J ¼ 2:9, 4.0, 13.2 Hz), 1.33
(1H, brdq, J ¼ 5:5, 13.0 Hz), 1.63 (1H, dq, J ¼ 4:0, 7.0 Hz), 2.48
(1H, tqd, J ¼ 4:0, 7.0, 12.5 Hz), 3.27 (1H, d, J ¼ 9:9 Hz), 3.45
(1H, d, J ¼ 9:9 Hz), 3.47 (1H, brs), 3.60 (1H, brdd, J ¼ 5:5,
11.0 Hz), 4.03 (1H, ddd, J ¼ 2:9, 11.0, 12.8 Hz), 4.32 (1H, d,
J ¼ 12:1 Hz), 4.47 (1H, d, J ¼ 12:1 Hz), 7.04–7.25 (5H, m);
13C NMR (75 MHz, CDCl3) ꢂ 6.8 (CH3), 19.0 (CH3), 27.1 (CH),
27.7 (CH2), 38.9 (CH), 61.1 (CH2), 73.9 (CH2), 74.9 (CH2), 97.1
(C), 127.8 (CH ꢅ 2 þ CH), 128.4 (CH ꢅ 2), 137.7 (C); LR-
FDMS, m=z 250 (6.0%, [M]þ), 232 (bp, ½M ꢂ H2Oꢆþ); HR-
FDMS, calcd for C15H22O3 [M]þ: 250.1568, found: 250.1568.
Lett. 1988, 29, 2701. b) W. R. Roush, J. A. Straub, M. S. Van-
Nieuwenhze, J. Org. Chem. 1991, 56, 1636.
7
8
9
M. Caron, K. B. Sharpless, J. Org. Chem. 1985, 50, 1557.
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We thank Mr. Kenji Watanabe and Dr. Eri Fukushi (GC-
MS & NMR Laboratory, Graduate School of Agriculture,
Hokkaido University) for the measurements of mass spectra.
We are also grateful to Prof. Makoto Sasaki and Prof. Masato
Oikawa (Graduate School of Life Sciences, Tohoku Universi-
ty) for helpful discussions. This work was supported in part by
Grant-in-Aid (Nos. 18510179 and 18032001) from the Minis-
try of Education, Culture, Sports, Science and Technology of
Japan.
12 The optical purity of 3, determined by NMR analysis of
the corresponding (+)- and (ꢂ)-Mosher’s ester derivatives, was
>95%ee. The enhanced optical purity resulted from optical reso-
lution during the asymmetric epoxidation reaction of 15.
13 D. A. Evans, M. D. Ennis, D. J. Mathre, J. Am. Chem. Soc.
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19 The F-ring exists at the end of 1 outside of the macrocycle.
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