Systematic strategy for the synthesis of cyanobacterin and its stereoisomers. 1. Asymmetric total synthesis of dechloro-cyanobacterin and its enantiomer

Article abstract of DOI:10.1271/bbb.67.2183

The stereocontrolled total synthesis of the non-chlorinated analog of cyanobacterin, a potent photosynthesis inhibitor, was achieved by 12 steps in a 10.0% overall yield. Its enantiomer was also synthesized from the same starting material. This synthetic strategy is expected to be applicable to prepare cyanobacterin and all its stereoisomers, together with other similar bioactive compounds.

Full text of DOI:10.1271/bbb.67.2183

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Systematic Strategy for the Synthesis of
Cyanobacterin and Its Stereoisomers. 1. Asymmetric
Total Synthesis of Dechloro-cyanobacterin and Its
Enantiomer
Yasushi HAGAa, Momotoshi OKAZAKIa & Yoshihiro SHUTOa
a The United Graduate School of Agricultural Science, Ehime UniversityTarumi 3-5-7,
Matsuyama 790-8566, Japan
Published online: 22 May 2014.
To cite this article: Yasushi HAGA, Momotoshi OKAZAKI & Yoshihiro SHUTO (2003) Systematic Strategy for the Synthesis
of Cyanobacterin and Its Stereoisomers. 1. Asymmetric Total Synthesis of Dechloro-cyanobacterin and Its Enantiomer,
Bioscience, Biotechnology, and Biochemistry, 67:10, 2183-2193, DOI: 10.1271/bbb.67.2183
To link to this article: http://dx.doi.org/10.1271/bbb.67.2183
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Biosci. Biotechnol. Biochem., 67 (10), 2183–2193, 2003
Systematic Strategy for the Synthesis of Cyanobacterin and Its Stereoisomers. 1.
Asymmetric Total Synthesis of Dechloro-cyanobacterin and Its Enantiomer
Yasushi HAGA,† Momotoshi OKAZAKI, and Yoshihiro SHUTO
The United Graduate School of Agricultural Science, Ehime University, Tarumi 3-5-7,
Matsuyama 790-8566, Japan
Received May 6, 2003; Accepted June 16, 2003
The stereocontrolled total synthesis of the non-chlori-
nated analog of cyanobacterin, a potent photosynthesis
inhibitor, was achieved by 12 steps in a 10.0
% overall
yield. Its enantiomer was also synthesized from the
same starting material. This synthetic strategy is expect-
ed to be applicable to prepare cyanobacterin and all its
stereoisomers, together with other similar bioactive
compounds.
Fig. 1. Structure of Cyanobacterin 1.
Key words: cyanobacterin;photosynthesisinhibitor;
b-
However, the stereoselective synthesis of 1 has not
previously been achieved.
hydroxy- -ylidene- -butyrolactone frame-
g
g
work; enantiodivergent synthesis; Evans
and non-Evans aldol reaction
We are therefore studying the stereoselective syn-
thesis of 1, since it has a fascinating structure, sig-
niˆcant bioactivity and an interesting mode of ac-
tion. In this paper, we describe the total synthesis of
both enantiomers of dechloro-cyanobacterin as a
model compound of 1.
Cyanobacterin 1 has been isolated as a secondary
metabolite from the freshwater cyanobacterium,
1)
Scytonema hofmanni
.
The structure of this com-
pound was determined as a diaryl-substituted
b-
hydroxy-g-ylidene-g-butyrolactone framework with
Results and Discussion
chlorine substituted on one of the aromatic rings,2)
and its absolute conˆguration at both asymmetric
The synthesis of both enantiomers of 2 started with
the preparation of chiral imide 5, which is a common
starting material for our synthetic strategy as shown
in Scheme 1. Condensation of commercially availa-
ble piperonal 3 and malonic acid in the presence of
piperidine9) and subsequent catalytic reduction gave
carbons is
R
3) as shown in Fig. 1. It has been found in
a biological investigation to inhibit the Hill reaction
in isolated chloroplasts and showed high toxicity
toward other cyanobacteria, green algae and higher
plants.4) A further investigation suggested that the

site of action of this compound was photosystem
z
propionic acid derivative 4 in a 74.6 yield in 2

(PS ). The minimum concentration to inhibit the
electron transport in PS was lower than that of the
inhibitor, 3-(3,4-dichlorophenyl)-1,1-
steps. After treating 4 with oxalyl chloride in CH2Cl2
to transform it to acyl chloride, imidation10) to 5 was
accomplished by condensation with the lithium salt


typical PS
dimethylurea (DCMU). However further studies with
the herbicide-resistant mutant showed that the bind-
ing site of 1 was diŠerent from that of DCMU5,6) and
of (4
readily prepared in 2 steps from
The diastereoselective aldol reaction between (
S
)-4-benzyl-2-oxazolidinone, which had been
-phenylalanine.11)
)-
L
Z
suggested that 1 acted on another site in PS

. Syn-
boron-enolate, which had been derived from corre-
sponding imide 5, and 4-methoxyphenylpropynal 6
prepared from 4-anisaldehyde12,13) in the presence of
thesized racemic 17) has been tested for its biological
activity and found to need twice the minimum dose
required of with natural compound.8) This result im-
plies that the unnatural isomer seemed to be inactive.
In order to investigate the structure-activity relation-
ship and mode of action in detail, it was necessary to
prepare each enantiomer with high optical purity
and to subject it to further biochemical research.

TiCl4 ( ) aŠorded a mixture of two isomers, 7-a and
7-b, which are frequently called non-Evans aldol
adducts,14,15) in a combined yield of 72.4
z
as depict-
ed in Scheme 2. Although the diastereomeric ratio of
1
these adducts was determined as 79:21 by their H-
NMR spectra, it is not always necessary to separate
†
To whom correspondence should be addressed. Fax:
81-89-943-5242; E-mail: haga agr.ehime-u.ac.jp
＋ ＠

2184
Y. HAGA et al
.
3
S
), respectively. Thus, a pair of diols which com-
pletely controlled the stereochemistry at C-2 position
were in hand.
Regioselective silylation of the primary hydroxyl
group in 9 and 10 then proceeded e‹ciently with tert
-
butyldimethylsilyl chloride (TBS-Cl), imidazole and
a catalytic amount of 4-(dimethylamino)pyridine
(DMAP) in DMF (Scheme 3). Obtained 12 and 13
were subjected to oxidation with dimethyl sulfoxide
(DMSO) and 1,3-dicyclohexylcarbodiimide (DCC) in
the presence of pyridinium tri‰uoroacetate (TFA-
pyr) to respectively provide silyloxy ketones 14 and
15. Furthermore, acid-catalyzed cleavage of the silyl
Scheme 1. Synthesis of Imide 5.
Reagents and conditions: (a) CH2(CO2H)2, piperidine, pyri-
protection in 14 and 15 furnished
b
-hydroxy ketones
dine, re‰ux, 81.9
z; (b) H2, 10
z
Pd–C, AcOH, re‰ux, 91.1
z;
(c) (1) (COCl)2, CH2Cl2; (2) (4
S
)-4-benzyl-2-oxazolidinone,
16 and 17 in 52.9
z z
and 57.0 yields respectively, in
n
－
BuLi, THF, 789C–09C, 99.2z.
3 steps.
As shown in Scheme 4, a diastereoselective
nucleophilic addition reaction of isopropylmagnesi-
um bromide with 16 and 17 respectively gave 1,3-
these isomers, since the epimeric secondary hydroxyl
group was oxidized to a ketone in the subsequent
step. The other Lewis acids such as two equivalents
of nBu2BOTf and Et2AlCl were examined in this reac-
tion. However, in the case of the former reagent, the
diols 18-a and 19-a in isolated yields of 66.6
56.2 , together with small amounts of undesired
3-epimers 18-b and 19-b in 4.2 and 3.0 yields. In
z
and
z
z
z
this reaction, an excess of the Grignard reagent was
required to give su‹cient yield and selectivity com-
pared with the conditions for the stoichiometric
nucleophile with silyloxy ketones 14 and 15. The
relative stereochemistry of 18-a was conˆrmed by
NOEDIF spectra after cyclization to acetonide 20 by
treating with 2,2-dimethoxypropane and a catalytic
amount of PPTS in toluene (Scheme 5). NOE was
observed between Ha and Hb in 20, proving that they
were situated in close proximity, this also being sup-
yield of 7-b was 48.4
z, but undesired (2
S, 3S)-
isomer 8 was also obtained in a 21.7
z
yield, and the
latter case by-product was obtained instead of the
objective aldol adducts. On the other hand, under the
normal conditions for Evans aldol condensation,16,17)

), the reaction
which do not involve TiCl4
(
proceeded simply and gave single product 8 in a
1
79.3
z
yield. According to the H-NMR spectra of
7-a, 7-b and 8, no peaks could be detected apart from
the objective isomers. The stereochemistry of these
compounds was next determined. After reductive
removal of the chiral auxiliary in isolated 7-a and 7-b
with LiBH4 in aqueous Et2O, resulting 9-a and 9-b
were respectively transformed to acetonides 11-a and
11-b by treating with 2,2-dimethoxypropane and a
ported by the low
J value ( Jab 4.2 Hz). NOE was
＝
absent between Ha and Hc, as was expected, proving
that they were in 1,2-diaxial proximity, this being
＝
J value (Jac 11.7 Hz). NOE
further proved by high
between Ha and Hd was also observed, proving that
they too were situated in close proximity. Although
catalytic amount of pyridinium
p
-toluenesulfonate
deprotonation of the a-hydrogen by the Grignard
(PPTS) in toluene. According to the analyses of these
reagent as a strong base can cause racemization, this
1
compounds by H-NMR, all coupling constants (
J
reaction fortunately gave a single isomer of 18-a with
values) supported the conformation of the isomers as
shown in Scheme 2, and the observation of expected
NOE further proved these structure. Thus, the rela-
tive stereochemistry at the C-2 and C-3 positions in
7-a and 7-b was conˆrmed. Similarly, 8 was reduced
to 10, and the physical properties of the three
stereoisomers of the diol, 9-a, 9-b and 10, were
scanned. The result showed agreement between the
data for 10 and those for 9-a, which had been deter-
mined as a syn isomer as already stated, except for
the opposite sign of speciˆc rotation. It is di‹cult to
think that the conditions for the non-Evans and
Evans aldol reaction gave a product with the opposite
stereo conˆguration to that in previous litera-
tures.14–17) It was therefore found that the absolute
conˆguration of the C-2 and C-3 positions in 7-a, 7-b
high optical purity (À99z enantiomeric excess) as
observed by an HPLC analysis.
The direct oxidation of 18-a and 19-a to acids 21
and 22 was examined by the use of oxidizing reagents
such as pyridinium dichromate (PDC) in DMF18) and
tetrapropylammonium perruthenate (TPAP) in
aqueous CH3CN.19) However, the former resulted in
decomposition and the latter proceeded slowly.
Thus, the oxidation was carried out in 2 steps to
achieve more suitable conditions; the reactions of
18-a and 19-a with a combination of TPAP and
N
-methylmorpholine-N-oxide (NMO) in CH2Cl2 pro-
vided intermediate aldehydes, and their further oxi-
dation with sodium chlorite in the presence of
2-methyl-2-butene led to carboxylic acids 21 and 22
in respective 64.4
z and 70.2z yields.
and 8 corresponded to (2R, 3R), (2R, 3S) and (2S,
Finally, lactonization of 21 and 22 with silver ni-

Total Synthesis of Dechloro-cyanobacterin
2185
Scheme 2. Synthesis and Identiˆcation of Diols 9 and 10.
i
Reagents and conditions: (a) 4-methoxyphenylpropynal (6), nBu2BOTf, Pr2NEt, TiCl4, CH2Cl2,
－
78
(9-b), 100
(11-b). Abbreviations: Ar1, 3,4-methylenedioxyphenyl; Ar2, 4-methoxyphenyl.
9
C–0
9 z
C, 72.4 (7-a:7-b
＝
i
79:21); (b) 6, nBu2BOTf, Pr2NEt, CH2Cl2,
－
78
9
C, 79.3
z
; (c) LiBH4, Et2O, 100
z
(9-a), 100
z
z
(10); (d) Me2C(OMe)2,
PPTS, toluene, 99.4
z
(11-a), 100
z
Scheme 3. Synthesis of b-Hydroxy Ketones 16 and 17.
Reagents and conditions: (a) TBS-Cl, Et3 N, DMAP, DMF, 72.7
z
(12-a), 70.0 (12-b), 70.9
z
z
(13); (b) DMSO, DCC, TFA-pyr,
toluene, 84.1 (14), 90.2 (15); (c) AcOH-THF-H2O (2:1:1), 86.6
z
z
z
(16), 89.1 (17).
z
trate in CH3OH20) furnished desired products 2 and
23 in respective 81.9 and 67.1 yields. This step
was conducted under the same conditions as those
was irradiated, the signal of the methine hydrogen in
the isopropyl group was not enhanced, while NOE
was observed between the vinyl hydrogen and methyl
hydrogen in the isopropyl group. Accordingly, it is
obvious that the conˆguration of 2 was identical with
that of 1. Furthermore, the enantiomeric excess of 2
z
z
7)
described by Jong et al
. for the synthesis of dl-1,
and the reaction gave the desired exo-cyclic product
in a good yield, as in their report. In addition to the
relative stereochemistry at C-2 and C-3, the geometry
of the exocyclic oleˆn in 2 was conˆrmed by
NOEDIF experiments. When the C-2 hydrogen in 2
was evaluated to be
z
À99 by an HPLC analysis,
and the speciˆc rotations of 2 and 23 showed approx-
imately the same value but with opposite signs

2186
Y. HAGA et al.
Scheme 4. Synthesis of Dechloro-cyanobacterin 2 and Its Enantiomer 22.
－
＝
＝
Reagents and conditions: (a) Me2CHMgBr, THF, 78
TPAP, NMO, MS-4A, CH2Cl2; (2) NaClO2, 2-methyl-2-butene, NaH2PO4, tBuOH-H2O (4:1), 0
AgNO3, CH3OH, 81.9 (2), 67.1 (23).
9
C, 66.6
z
(18-a), (18-a:18-b 94:6), 56.2
z
9
(19-a), (19-a:19-b 95:5); (b) (1)
C, 64.4 (21), 70.2 (22); (c)
z
z
z
z
determined with a Horiba SEPA-200 polarimeter.
HPLC was performed with a Shimadzu LC-10AS
liquid chromatograph equipped with an integrator
(Shimadzu C-R6A Chromatopac) and UV-VIS detec-
tor (Shimadzu SPD-10A). Ten microliter of a sample
were injected into the column and detected by its UV
absorption at 254 nm. Details of the analytical condi-
tions (e.g., the column, solvent and ‰ow rate) are
shown in each subsequent section. Silica gel 60
Scheme 5. NOEDIF Experiment on Acetonide 20.
(100–210 mm) was obtained from Kanto Chemical
Co. TLC and preparative TLC were respectively car-
ried out by using Merck silica gel 60 F254 precoated
plastic plates of 0.2 mm in thickness and Merck silica
gel 60 F254 precoated glass plates of 0.5 mm in
thickness.
＋
－
94.7 and 98.8, respectively). As a consequence
(
of these analyses, both enantiomers were found to be
in an optically pure form.
In summary, we accomplished the total synthesis
of the non-chlorinated analog of cyanobacterin and
its enantiomer in 12 steps in overall yields of 10.0
and 8.9 , respectively, with high optical purity
99 enantiomeric excess) from the same starting
z
(3,4-Methylenedioxy)phenylpropionic acid
(4).
z
Malonic acid (20.85 g, 200.4 mmol) was added to a
stirred solution of piperonal (15.18 g, 101.1 mmol) in
pyridine (50 ml) at room temperature. After dissolv-
ing the acid, piperidine (1.50 ml, 15.2 mmol) was
added to this solution. After re‰uxing for 8 h, the
reaction mixture was poured into cold water (200 ml)
and acidiˆed with conc. HCl. The resulting
precipitate was collected and recrystallized from
(
À
z
material. The synthetic method described in this
paper will be useful for the synthesis of 1 and other
natural products with various biological activities
possessing a similar framework.
Experimental
acetic acid to aŠord white crystals (mp 238
15.90 g, 81.9 ).
9C,
All melting point (mp) data are uncorrected. IR
spectra were recorded by a Shimadzu FTIR-8100
spectrometer. 1H- and 13C-NMR spectra were
measured with a JEOL JNM-EX400 spectrometer at
400 MHz and 100 MHz, respectively. Chemical shifts
are reported relative to internal tetramethylsilane
z
This unsaturated acid (15.54 g, 80.87 mmol) was
reduced with a catalytic amount of Pd–C in acetic
acid (200 ml). After re‰uxing for 2 days under H2
while vigorously stirring, Pd–C was removed from
the reaction mixture, and the resulting light-brown
solution was concentrated in vacuo. The residue was
1
(TMS, 0.00 ppm) for H and chloroform-d (CDCl3,
77.0 ppm) for 13C. Optical rotation values were
extracted with CH2Cl2 (30 ml) and EtOAc (2
×

Total Synthesis of Dechloro-cyanobacterin
2187
20 ml), and the combined organic layer was washed
three times with 1 -NaOH. The combined aqueous
1700, 1508, 1491, 1448, 1388, 1247, 1209, 1110, 1042,
M
940, 730. Anal. Found: C, 67.66; H, 5.58; N, 3.90
z
.
.
layer was acidiˆed with conc. HCl, and then extract-
Calcd. for C20H19NO5: C, 67.98; H, 5.42; N, 3.96
z
×
ed with CH2Cl2 (20 ml) and EtOAc (2 20ml) again.
The combined organic phase was washed with brine
and dried over Na2SO4. After evaporating the sol-
vent, the residue was recrystallized from petroleum
(4S)-4-Benzyl-[(2R,3R S)-3-hydroxy-5-(4-methox-
W
yphenyl)-2-(3,4-methylenedioxybenzyl )-4-pen-
tynoyl]-2-oxazolidinone (7). To a stirred solution of
ether-CHCl3 (2:1) to give 14.31 g (91.1
z
) of acid 4 as
C; H-NMR (CDCl3)
2–CO2H), 2.87 (2H, t,
2), 5.92 (2H, s, O–C 2–O), 6.64–6.74
), 8.56 (1H, br, –CO2
); 13C-NMR
5 (2.12 g, 6.00 mmol) in CH2Cl2 (20 ml) were added
dibutylboron tri‰ate (5.8 ml of a 1.0 solution in
-diisopropylethylamine
1
white crystals, mp 85–86
2.62 (2H, t, 7.6 Hz, C
7.6 Hz, Ar–C
(3H, m, Ar–
(CDCl3)
9
d
:
M
J
＝
H
H
H
J
＝
CH2Cl2, 5.8 mmol) and
(1.18 ml, 6.57 mmol) at
N, N
－
209C under an N2 at-
H
H
mosphere. The reaction mixture was allowed to
warm to 0 C and then stirred for 1.5 h, before being
d
: 30.38, 35.98, 100.85, 108.28, 108.76,
121.09, 133.99, 146.02, 147.67, 178.83; IR nmax
9
－
recooled to 78
9C. In another ‰ask, to a solution of
(CHCl3) cm－1: 1717, 1512, 1495, 1452, 1256, 1196,
1046, 944, 820. Anal. Found: C, 61.79; H, 5.22
TiCl4 ( ) (1.34 ml, 12.2 mmol) in CH2Cl2 (50 ml)

z
.
was added dropwise the solution of 4-methox-
Calcd. for C10H10O4: C, 61.85; H, 5.19
z.
yphenylpropynal (6, 0.96 g, 6.05 mmol) in CH2Cl2
－
9
(2 ml) at 78 C under an N2 atmosphere, and the
(4S )-4-Benzyl-2-[3-(3,4-methylenedioxyphen-
mixture stirred for 15 min. To the reaction mixture
was added foregoing solution of the boron enolate
via a cannula under N2 pressure. The resulting solu-
tion was stirred for 1 h at the same temperature,
yl)propionyl]-2-oxazolidinone (5). To a stirred solu-
tion of 4 (13.86 g, 71.37 mmol) in CH2Cl2 (100 ml)
was added oxalyl chloride (6.85 ml, 78.5 mmol) at
0
9
C. The reaction mixture was allowed to warm to
9
before being allowed to warm to 0 C, and then
room temperature and stirred for 12 h. The solvent
was evaporated, and the residue was diluted with
stirred more for 4 h. The reaction mixture was
quenched by adding the mixed solvent of a phosphate
buŠer solution (pH 6.86, 25 ml) and MeOH (25 ml),
THF
(12.65 g, 71.39 mmol) in THF (120 ml) in another
‰ask was cooled to 78 C under an N2 atmosphere,
and then -butyllithium (50.0 ml of a 1.57 solution
(30 ml).
(4S)-4-Benzyl-2-oxazolidinone
and then 30
After stirring vigorously for 1 h at 0
layer was separated, and the aqueous layer was ex-
tracted with Et2O (2 25 ml). The combined organic
z-H2O2 (25 ml) and MeOH (25 ml).
－
C, the organic
9
9
n
M
in hexane, 78.5 mmol) was added dropwise. After 40
min, to the reaction mixture was added the solution
of the acyl chloride from 4, and the mixture stirred
for 1 h at the same temperature. The mixture was
×
phase was successively washed with sat. NaHCO3 and
brine. After drying (Na2SO4) and concentrating, the
residue was puriˆed by column chromatography on
silica gel (toluene-EtOAc, 20:1) to provide syn-ad-
duct 7-a, anti-adduct 7-b and their mixture. 7-a was
recrystallized from hexane-EtOAc (2:1), while 7-b
was recrystallized from toluene. After combing their
mother liquors and the mixture, the solvent was
removed in vacuo, and the residue was puriˆed by
column chromatography on silica gel (hexane-
EtOAc, 3:2) to provide 7 (combined yield of 2.23 g,
allowed to warm to 09C, and then stirred for 2 h
before being quenched by water (100 ml). The organ-
ic layer was separated, and the aqueous phase was
extracted with EtOAc (20 ml). The combined organic
layer was successively washed with 2 -HCl, sat.
M
NaHCO3 and brine, before being dried over Na2SO4.
After removing the solvent in vacuo, the residue was
recrystallized from petroleum ether-CHCl3 (1:1) to
give 5 as white crystals. The mother liquor was con-
centrated, and the residue was puriˆed by column
chromatography on silica gel (hexane-EtOAc, 3:2) to
72.4
z).
7-a: Rf 0.25 (toluene-EtOAc, 20:1), mp 114
9
d:
C,
25
D
1
＋
[a
]
32.8
9(
c
4.20, CHCl3); H-NMR (CDCl3)
9.8, 13.2 Hz, Ph–C 2), 2.68 (1H,
give a second crop of 5 (combined yield of 25.01 g,
2.67 (1H, dd,
J
＝
H
H
＝
25
＋
＝
99.2
1H-NMR (CDCl3)
Ph–C 2), 2.93 (2H, t,
3.21 (2H, t,
z
), mp 85–87
9
d
C, [
a
]
55.5
9
J
(
c
2.29, CHCl3);
d,
J
5.4 Hz, –O
), 3.12 (1H, dd,
J
9.3, 13.4 Hz,
5.6, 13.6 Hz,
3.4, 13.2 Hz,
D
＝
＝
＝
: 2.76 (1H, dd,
9.5, 13.4 Hz,
Ar1–C
Ar1–C
H
H
2–CHCO), 3.20 (1H, dd,
J
J
H
J
＝
H
7.3 Hz, ArCH2–C 2),
H
2–CHCO), 3.27 (1H, dd,
＝
＝
J
7.3 Hz, ArC
2–CH2), 3.27 (1H, dd,
Ph–C
H
2), 3.81 (3H, s, –OC
H
3), 3.95 (1H, dd,
J
＝
＝
＝
J
3.2, 13.4 Hz, Ph–C
H
2), 4.17 (1H, dd,
J
3.4,
8.6, 9.4 Hz, CH–C
H
2–O), 4.04 (1H, dd,
J
2.4,
m,
＝
7.9 Hz, CH–C
CH–C
5.92 (2H, s, O–C
7.16–7.19 (2H, m, Ph–
Ph–
); 13C-NMR (CDCl3)
H
2–O), 4.20 (1H, dd,
J
6.6, 7.9 Hz,
–CH2O),
),
), 7.27–7.35 (3H, m,
: 29.92, 37.38, 37.74,
9.4 Hz,
CH–C
H
2–O),
4.52–4.60
(2H,
H
2–O), 4.64–4.70 (1H, m, N–C
H
Ar1CH2–C
H
–CO and N–C
H
–CH2), 4.91 (1H, dd,
J
H
2–O), 6.73–6.77 (3H, m, Ar–
H
＝
5.4, 5.7 Hz, C
H
OH), 5.89 (2H, s, O–C
H
2–O),
2.0, 6.8
),
2.0,
＝
H
6.69–6.77 (3H, m, Ar1–
Hz, Ar2–
7.24–7.36 (3H, m, Ph–
6.8 Hz, Ar2–
H
), 6.84 (2H, dd,
J
＝
H
d
H
), 7.16 (2H, d,
J
6.4 Hz, Ph–
H
＝
50.01, 66.12, 100.76, 108.15, 109.00, 121.29, 127.29,
128.87, 129.35, 134.20, 135.12, 145.87, 147.55,
153.33, 172.24; IR nmax (CHCl3) cm－1: 2363, 1786,
H
), 7.39 (2H, dd,
J
H
); 13C-NMR (CDCl3)
d
: 34.15, 37.74,
50.99, 55.29, 55.46, 63.95, 66.01, 85.72, 87.26,

2188
Y. HAGA et al
.
100.85, 108.18, 109.64, 113.96, 114.29, 122.12,
127.31, 128.99, 129.41, 132.05, 133.37, 135.18,
146.50, 147.55, 152.95, 160.03, 172.87; IR nmax
(CHCl3) cm－1: 1782, 1705, 1615, 1517, 1449, 1393,
1256, 1200, 1046, 781, 760, 739.
vide a second crop of 8 (combined yield of 2.19 g,
79.3
130
(CDCl3)
dd, 9.0, 13.4 Hz, Ph–C
13.4 Hz, Ph–C
z), Rf 0.20 (hexane-EtOAc, 2:1), mp 129.5–
9
C, [
a
]
9
58.3 (c
1.55, CHCl3); 1H-NMR
25
＋
D
＝
d
: 2.50 (1H, d,
J
5.4 Hz, –O
H
), 2.55 (1H,
J
＝
H
2), 3.02 (1H, dd, 3.4,
J
＝
＝
7-b: Rf 0.27 (toluene-EtOAc, 20:1), mp 124.5–
H
2), 3.18 (1H, dd,
J
8.6, 13.2 Hz,
126
9
(CDCl3)
C, [
a
]
39.3
9
(
c
1.22, CHCl3); 1H-NMR
Ar1C
Ar1C
H
H
6.1, 13.2 Hz,
25
＋
＝
2–CH), 3.22 (1H, dd, J
D
＝
d
: 2.74 (1H, dd,
J
9.5, 13.7 Hz, Ph–C
H
2),
2–CH), 3.80 (3H, s, –OC
2–O), 4.03 (1H, dd,
2–O), 4.65–4.71 (2H, m, C
H
3), 3.99 (1H, dd,
J
＝
＝
＝
＝
3.00 (1H, dd,
3.08 (1H, dd,
J
J
＝
8.0, 12.6 Hz, Ar1C
7.3, 12.6 Hz, Ar1C
H
H
2–CHCO),
2–CHCO),
7.8, 8.8 Hz, CH–C
8.8 Hz, CH–C
and N–C –CH2), 4.81 (1H, dd,
OH), 5.86 (1H, d,
H
J
2.9,
H
H
–CO
＝
3.30 (1H, dd,
J
3.6, 13.7 Hz, Ph–C
H
H
2), 3.45 (1H,
3), 4.03
2–O), 4.10 (1H,
H
J
5.9, 6.4 Hz,
1.5 Hz, O–C 2–O), 5.91
2–O), 6.73
, 6.80–6.86 2H, m, Ar1–
8.8 Hz, Ar2– ), 6.99 (2H, d,
), 7.25–7.26 (3H, m, Ph–
8.8 Hz, Ar2–
); 13C-NMR (CDCl3)
＝
＝
d,
J
10.0 Hz, –O
), 3.79 (3H, s, –OC
H
C
H
J
H
＝
＝
＝
J
(1H, dd,
J
8.4, 10.2 Hz, CH–C
H
(1H, d,
8.3 Hz, Ar1–
(2H, d,
Ph–
J
1.5 Hz, O–C
H
s
1H, d,
＝
dd,
6.1, 7.3, 8.0 Hz, C
N–C –CH2), 4.67 1H, dd,
(OH) , 5.91 (2H, s, O–C 2–O), 6.71–6.78 (3H,
m, Ar1–
7.18 (2H, dd,
m, Ph– ), 7.34 (2H, dd,
13C-NMR (CDCl3)
J
2.1, 10.2 Hz, CH–C
H
2–O), 4.50 (1H, ddd,
J
H
t
s
H
t
, 6.82
＝
H
–CO), 4.56–4.62 (1H, m,
J
＝
H
J
＝
7.8 Hz,
＝
＝
J
H
s
J
6.1, 10.0 Hz,
H
H
), 7.37 (2H, d,
: 34.25, 37.36,
C
H
t
H
H
d
＝
H
), 6.80 (2H, dd,
J
2.0, 6.8 Hz, Ar2–
2.4, 7.6 Hz, Ph–
2.0, 6.8 Hz, Ar2–H
H
),
);
51.01, 54.93, 55.11, 63.87, 65.61, 85.78, 86.47,
100.68, 108.07, 109.76, 113.83, 114.03, 122.27,
127.14, 128.68, 129.26, 132.07, 133.17, 134.83,
146.05, 147.47, 153.24, 159.74, 172.53; IR nmax
(CHCl3) cm－1: 1782, 1705, 1615, 1546, 1517, 1495,
1393, 1256, 1200, 1115, 1046, 940, 764, 739. Anal.
＝
J
H
), 7.25–7.29 (3H,
H
J
＝
d
: 34.84, 37.74, 50.90, 55.27,
55.37, 63.06, 65.99, 85.73, 86.99, 100.89, 108.22,
109.66, 113.95, 114.30, 122.30, 127.37, 128.94,
129.43, 131.35, 133.14, 134.99, 146.33, 147.50,
153.07, 159.78, 174.91; IR nmax (CHCl3) cm－1: 1782,
1611, 1517, 1491, 1388, 1252, 1196, 1042, 760, 734.
Found: C, 69.95; H, 5.72; N, 2.60
z. Calcd. for
C30H27NO7: C, 70.16; H, 5.30; N, 2.73
z
.
Anal. Found: C, 70.28; H, 5.49; N, 2.53
z
. Calcd.
General procedure for preparing 5-(4-methox-
yphenyl)-2-(3,4-methylenedioxyphenyl)methyl-4-
for C30H27 NO7: C, 70.16; H, 5.30; N, 2.73
z
.
pentyne-1,3-diol (9-a
was added to the solution of
(1.0 eq) in Et O (15 ml mmol) at 0
,
9-b and 10). LiBH4 (1.5 eq)
-hydroxyimide 7 or 8
C. The reaction
mixture was allowed to warm to room temperature
and stirred for 6 h, before being slowly added to 2
HCl at 0 C. After decomposing the excess reducing
(4S )-4-Benzyl-[(2S,3S )-3-hydroxy-5-(4-methox-
yphenyl)-2-(3,4-methylenedioxybenzyl)-4-pen-
b
9
W
2
tynoyl]-2-oxazolidinone (
(1.89 g, 5.38 mmol) in CH2Cl2 (50 ml) were added
dibutylboron tri‰ate (5.1 ml of a 1.0 solution in
-diisopropylethylamine
8). To a stirred solution of 5
M
-
M
9
CH2Cl2, 5.1 mmol) and
(1.05 ml, 5.80 mmol) at
N
,
N
agent, the ethereal layer was separated. The aqueous
－
×
20
9
C under an N2 at-
phase was extracted with EtOAc (2 10 ml), and the
mosphere. The reaction mixture was allowed to
combined organic extract was successively washed
with sat. NaHCO3 and brine. After drying (Na2SO4)
and concentrating, each product was puriˆed.
warm to 0
9
C and stirred for 1.5 h, before being
－
recooled to
789C. The solution of 4-methox-
yphenylpropynal (6, 0.86 g, 5.34 mmol) in CH2Cl2
(5 ml) was added to this mixture, and the resulting
solution was stirred for 2.5 h at the same tempera-
ture. The reaction mixture was quenched by adding a
mixed solvent of a phosphate buŠer solution (pH
The product from 7-a was recrystallized from
hexane-EtOAc (3:2) to give 9-a as white crystals. The
mother liquor was evaporated, and the residue was
puriˆed by column chromatography on silica gel
(hexane-EtOAc, 2:1 to 1:1) to provide a second crop
25
6.86, 20 ml) and MeOH (20 ml), and then 30
(20 ml) and MeOH (20 ml). After stirring vigorously
for 1 h at 0 C, the organic layer was separated, and
the aqueous layer was extracted with Et2O (2
z
-H2O2
of 9-a (total 100
z
yield), mp 126.5–128
9
d
C, [
a
]
D
1
－
144
9
(
c
1.72, acetone); H-NMR (CDCl3)
: 2.19
), 2.25–2.33 (1H,
7.8, 13.7 Hz,
7.3, 13.7 Hz, Ar–C 2),
＝
9
(1H, dd,
J
4.9, 5.3 Hz, prim-O
H
×
m, C
H
H
–CH2OH), 2.62 (1H, dd, J
2), 2.70 (1H, dd,
＝
＝
20 ml). The combined organic phase was successively
washed with sat. NaHCO3 and brine. After drying
(Na2SO4) and concentrating, the residue was puriˆed
by column chromatography on silica gel (hexane-
EtOAc, 2:1) to provide crude 8. After removing the
solvent in vacuo, the resulting yellow crystal was
recrystallized from hexane-EtOAc (3:1) to give 8 as
white crystals. The mother liquor was evaporated,
and the residue was puriˆed by column chro-
matography on silica gel (hexane-EtOAc, 2:1) to pro-
Ar–C
J
H
＝
＝
J
3.03 (1H, d,
J
6.4 Hz, sec–O
2OH), 3.82 (3H, s, OC
5.3, 8.7, 10.9 Hz, C 2OH), 4.74 (1H,
4.0, 6.4 Hz, C OH), 5.9 (2H, s, O–C 2–O),
6.67–6.75 (3H, m, Ar1–
H
), 3.79 (1H, dd,
4.9, 10.9 Hz, C
H
H
3), 3.99
＝
(1H, ddd,
dd,
J
H
J
＝
H
H
＝
H
), 6.86 (2H, d,
J
8.3 Hz,
); 13C-NMR
: 33.58, 47.50, 55.32, 64.13, 66.17, 86.18,
＝
8.3 Hz, Ar2–H
Ar2–
H
), 7.41 (2H, d,
J
(CDCl3)
d
86.96, 100.86, 108.26, 109.37, 114.00, 114.48,
121.91, 133.14, 133.24, 146.01, 147.71, 159.85; IR

Total Synthesis of Dechloro-cyanobacterin
2189
nmax (CHCl3) cm－1: 3025, 2384, 1602, 1508, 1491,
1448, 1290, 1252, 1213, 1038, 940, 833, 773. Anal.
white crystals, respectively. The mother liquors were
each evaporated, and the residue was puriˆed by
column chromatography on silica gel (hexane-
EtOAc, 4:1) to provide a second crop of 11-a and
Found: C, 70.31; H, 5.94
70.57; H, 5.92
z
. Calcd. for C20H20O5: C,
z.
The product from 7-b was puriˆed by column
11-b.
25
－
1279(c
chromatography on silica gel (hexane-EtOAc, 2:1 to
11-a: 99.4
z
yield, mp 105–106
9
d
C, [
a
]
D
1:1) to provide 9-b as a colorless oil in a 100
z
yield,
1.58, CHCl3); 1H-NMR (CDCl3)
C
C
: 1.50 (3H, s,
25
D
1
－
[
a
]
7.5
9
(
c
1.06, CHCl3); H-NMR (CDCl3)
d
:
H
H
3), 1.56 (3H, s, C
–CH2O), 2.98 (1H, dd,
2), 3.09 (1H, dd, 4.4, 13.7 Hz, Ar–C
3.4, 11.7 Hz, CH–C 2O), 3.81
3.4, 12.2 Hz,
H3), 1.83–1.90 (1H, m,
＝
2.02–2.10 (1H, m, C
prim–O ), 2.72 (1H, dd,
2.83 (1H, d,
H
–CH2OH), 2.13 (1H, br,
J
10.3, 13.7 Hz,
2),
H
J
＝
8.5, 13.9 Hz, Ar–C
H
2),
Ar–C
3.69 (1H, dd,
(3H, s, OC 3), 3.86 (1H, dd,
CH–C 2O), 5.09 (1H, d,
5.92 (2H, s, O–C 2–O), 6.72–6.75 (3H, m, Ar1–
6.84 (2H, d, 8.8 Hz, Ar2– ), 7.42 (2H, d,
Hz, Ar2–
); 13C-NMR (CDCl3)
H
J
＝
H
＝
＝
J
4.9 Hz, sec–O
H
), 2.96 (1H, dd,
J
H
＝
＝
＝
J
J
6.6, 13.9 Hz, Ar–C
H
2), 3.73 (1H, dd,
J
5.4,
H
＝
11.0 Hz, C
H
2OH), 3.81 (3H, s, OC
H
3), 4.10 (1H,
H
J
3.4 Hz, C
ø
C–C
H
O),
＝
＝
4.9,
dd,
J
2.9, 11.0 Hz, C
H
2OH), 4.69 (1H, dd,
J
H
H
),
5.4 Hz, C
H
OH), 5.93 (2H, s, O–C
H
＝
2–O), 6.69–6.75
J
＝
H
J
＝
8.8
(3H, m, Ar1–
H
), 6.84 (2H, d,
J
8.8 Hz, Ar2–
); 13C-NMR (CDCl3)
: 33.86, 48.05, 55.28, 63.26, 65.46, 86.25, 87.63,
H
),
H
d
: 21.09, 28.41,
＝
7.38 (2H, d,
J
8.8 Hz, Ar2–
H
31.81, 40.40, 55.28, 61.15, 64.94, 85.34, 86.81,
99.42, 100.78, 108.20, 109.64, 113.91, 114.55,
122.21, 133.35, 134.05, 145.83, 147.65, 159.95; IR
nmax (CHCl3) cm－1: 3025, 1611, 1512, 1491, 1444,
1380, 1290, 1252, 1217, 1196, 1128, 1042, 974, 935,
833, 773, 743, 760. Anal. Found: C, 72.51; H,
d
100.83, 108.23, 109.53, 113.96, 114.45, 122.06,
133.14, 133.48, 145.96, 147.69, 159.79; IR nmax
(CHCl3) cm－1: 2961, 2363, 1615, 1517, 1495, 1448,
1290, 1256, 1046, 940, 837, 773.
The product from 8 was recrystallized from hex-
ane-EtOAc (3:2) to give 10 as white crystals. The
mother liquor was evaporated, and the residue was
puriˆed by column chromatography on silica gel
6.25
z z
. Calcd. for C23H24O5: C, 72.61; H, 6.36 .
25
－
7.69(c
11-b: 100
z
yield, mp 96–97
9C, [
a
]
D
1.32, CHCl3); 1H-NMR (CDCl3)
d
: 1.47 (6H, s, CH3
×
＝
2), 2.17–2.27 (1H, m, C
H
–CH2O), 2.36 (1H, dd,
J
＝
(hexane-EtOAc, 2:1 to 1:1) to provide a second crop
9.8, 14.2 Hz, Ar–C
H
2), 2.98 (1H, dd,
2), 3.62 (1H, dd,
J
3.7,
25
of 10 (total 100
z
yield), mp 127–128.5
9
d
C, [
a
]
14.2 Hz, Ar–C
H
J
＝
10.8, 12.2 Hz,
＝
4.9, 12.2 Hz,
D
1
＋
151
9(c
1.26, acetone); H-NMR (CDCl3)
4.4, 5.1 Hz, prim–O ), 2.25–2.33 (1H,
–CH2OH), 2.60 (1H, dd,
: 2.24
CH–C
H
H
2O), 3.73 (1H, dd,
2O), 3.81 (3H, s, –OC
C–C O), 5.91 (2H, s, O–C
6.61–6.73 (3H, m, Ar1–
Ar2– ), 7.41 (2H, d,
(CDCl3) : 19.42, 29.22, 34.83, 41.84, 55.27, 63.66,
J
(1H, dd,
J
＝
H
CH–C
H
3), 4.62 (1H, d,
J
＝
＝
m, C
H
H
J
7.8, 13.9 Hz,
2),
), 3.77–3.83 (4H, m,
10.3 Hz, C
ø
H
H
2–O),
＝
＝
8.8 Hz,
Ar–C
2), 2.70 (1H, dd,
J
7.3, 13.9 Hz, Ar–C
H
H
), 6.83 (2H, d,
8.8 Hz, Ar2–
J
3.07 (1H, d,
2OH and OC
11.1 Hz, C
OH), 5.93 (2H, s, O–CH
J
＝
5.9 Hz, sec–O
H
H
J
＝
H
); 13C-NMR
＝
C
H
H
3), 3.99 (1H, ddd,
J
5.1, 8.3,
3.9, 5.9 Hz,
2–O), 6.67–6.75 (3H, m,
8.8 Hz, Ar2– ), 7.41 (2H,
); 13C-NMR (CDCl3)
: 33.58,
d
H
2OH), 4.72 (1H, dd,
J
＝
65.96, 85.34, 86.07, 98.97, 100.87, 108.18, 109.29,
113.84, 114.25, 122.81, 131.99, 133.41, 146.05,
147.68, 159.80.
C
H
＝
Ar1–
d,
H
), 6.86 (2H, d,
J
H
J
＝
8.8 Hz, Ar2–
H
d
47.49, 55.31, 64.12, 66.14, 86.20, 86.96, 100.86,
108.25, 109.37, 114.00, 114.50, 121.90, 133.14,
133.24, 146.02, 147.71, 159.85; IR nmax (CHCl3)
cm－1: 3047, 2392, 1602, 1517, 1487, 1448, 1290,
1247, 1217, 1038, 940, 837. Anal. Found: C, 70.13;
General procedure for preparing 1-tert-butyl-
dimethylsilyloxy-5-(4-methoxyphenyl)-2-(3,4-
methylenedioxyphenyl)methyl-4-pentyn-3-ol
(12-a,
12-b and 13). To a stirred solution of 9 or 10 (1.0 eq)
in DMF (5 ml mmol) were added Et N (2.5 eq), a
W
3
H, 6.13
z. Calcd. for C20H20 O5: C, 70.57; H, 5.92
z.
catalytic amount of DMAP and TBS-Cl (1.0 eq) at
－
9
15 C. The reaction mixture was stirred for 4 h at
(4R S, 5S)-2,2-Dimethyl-4-(4-methoxyphen-
the same temperature. After being quenched by sat.
NH4Cl (20 ml), the organic layer was separated, and
the aqueous phase was extracted with Et2O (2
×
10 ml). The combined organic extract was successive-
ly washed with sat. NaHCO3 and brine. After drying
(Na2SO4) and concentrating, the residue was puriˆed
by column chromatography on silica gel (hexane-
EtOAc, 9:1 to 7:1) to provide silyl ethers each as a
W
yl)ethynyl-5-(3,4-methylenedioxybenzyl)-1,3-dioxo-
lane (11-a and 11-b). To a stirred solution of 9-a or
9-b (1.0 eq) in toluene (20 ml mmol) were added
W
2,2-dimethoxypropane (5.0 eq) and
a
catalytic
amount of PPTS at room temperature under an N2
atmosphere. After stirring for 12 h, the reaction mix-
ture was poured into water (30 ml). The organic layer
was separated, and the aqueous phase was extracted
with Et2O (10 ml). The combined organic layer was
successively washed with sat. NaHCO3 and brine.
After drying (Na2SO4) and concentrating, the residue
was recrystallized from iPr2O to give 11-a and 11-b as
colorless oil.
25
－
12-a: 72.7
z
yield, [
a
]
96.1
9
(
c
1.81, CHCl3);
3), 0.11 (3H,
3t, 2.27–2.34 (1H,
–CH2OSi), 2.55 (1H, dd, 7.3, 14.2 Hz,
D
1H-NMR (CDCl3)
s, Si–C 3), 0.92
m, C
d
: 0.09 (3H, s, Si–C
9H, s, C(CH3
H
H
s
)
H
J
＝

2190
Y. HAGA et al.
＝
Ar–C
H
2), 2.64 (1H, dd,
J
7.8, 14.2 Hz, Ar–C
H
2),
temperature under an N2 atmosphere. After 1 day,
water (30 ml) was added to the reaction mixture while
stirring for 5 min. The organic layer was separated,
and the aqueous phase was extracted with Et2O
(15 ml). The combined organic layer was successively
washed with sat. NaHCO3 and brine, before being
dried over Na2SO4. After removing the solvent in
vacuo, the residue was puriˆed by column chro-
matography on silica gel (hexane-EtOAc, 12:1) to
＝
3.76 (1H, dd,
J
4.2, 10.4 Hz, C
H
2OSi), 3.81 (3H, s,
＝
H
–OC
4.08 (1H, d,
7.8 Hz,
H
3), 3.97 (1H, dd,
J
9.8, 10.4 Hz, C
H
J
2OSi),
＝
(OH)
＝
J
7.8 Hz, O
), 4.65
s
1H, dd,
3.4,
2–O),
C
H
t
,
5.92 (2H, s, O–C
H
＝
6.65–6.74 (3H, m, Ar1–H), 6.85 (2H, d,
J
8.8 Hz,
Ar2–
H
), 7.41 (2H, d,
J
8.8 Hz, Ar2–H
5.62, 18.09, 25.80, 33.51,
); 13C-NMR
＝
－
－
(CDCl3)
d
:
5.66,
47.14, 55.24, 64.98, 66.10, 86.11, 86.64, 100.79,
108.16, 109.29, 113.88, 115.01, 121.82, 133.10,
133.15, 145.95, 147.66, 159.57; IR nmax (CHCl3)
cm－1: 2983, 2940, 2384, 1611, 1512, 1491, 1444,
1290, 1252, 1175, 1076, 1042, 940, 837, 816, 790.
provide a
14: 84.1
NMR (CDCl3)
s, Si–C 3), 0.88
5.8, 12.1 Hz, Ar–C
O), 3.03 (1H, dd,
b
-silyloxy ketone 14 or 15 as a colorless oil.
z
yield, [
a
]
10.49(c
2.90, CHCl3); 1H-
25
－
D
d
: 0.037 (3H, s, Si–C
H
3), 0.042 (3H,
×
H
s
9H, s, (CH3
2), 2.97–3.01 (1H, m, C
6.8, 12.1 Hz, Ar–C 2), 3.84
5.8, 10.3 Hz,
2OSi),
),
)
3
t
, 2.88 (1H, dd, J
＝
＝
HC
Anal. Found: C, 68.39; H, 7.57
z. Calcd. for
H
＝
C26H34O5Si: C, 68.69; H, 7.54
z
9.2
.
J
H
25
－
＝
12-b: 70.0
z
yield, [
d
a
]
9
(
c
5.07, CHCl3);
3), 0.93 9H,
CH2OSi), 2.74
2), 2.97 (1H, dd,
(3H, s, OC
H
3), 3.87 (1H, dd,
J
D
1H-NMR (CDCl3)
: 0.08 (3H, s, Si–C
3t, 1.92–2.01 (1H, m, C
H
s
C
H
2OSi), 3.93 (1H, dd,
J
5.0, 10.3 Hz, CH
＝
s, C(CH3
(1H, dd,
)
J
H
5.90 (2H, s, O–C
H
2–O), 6.65–6.73 (3H, m, Ar1–
H
＝
＝
＝
J
8.8, 13.7 Hz, Ar–C
H
6.89 (2H, d,
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.51 (2H, d,
5.51, 18.20,
J
＝
6.8, 13.7 Hz, Ar–C
H
＝
2), 3.61 (1H, d,
4.3, 10.0 Hz, C
J
＝
7.8 Hz,
H
); 13C-NMR (CDCl3)
d:
－
–O
(3H, s, OC
2OSi), 4.63
5.93 (2H, s, O–C
H
), 3.67 (1H, dd,
J
H
2OSi), 3.80
25.79, 32.97, 55.40, 58.55, 62.45, 87.54, 92.85,
100.79, 108.16, 109.48, 111.84, 114.34, 122.03,
132.71, 135.04, 145.98, 147.58, 161.62, 189.06; IR
nmax (CHCl3) cm－1: 2940, 2213, 1653, 1606, 1546,
1512, 1491, 1512, 1491, 1252, 1222, 1106, 1040, 935,
＝
H
3), 4.19 (1H, dd,
J
3.5, 10.0 Hz,
＝
4.7, 7.8 Hz, CH (OH)t,
C
H
s
1H, dd,
J
H
＝
2–O), 6.65–6.73 (3H, m, Ar1–H ),
6.83 (2H, d,
8.3 Hz, Ar2–
－
J
H
8.3 Hz, Ar2–
H
), 7.36 (2H, d,
J
＝
); 13C-NMR (CDCl3)
d
:
5.63,
837, 739. Anal. Found: C, 68.92; H, 7.10
z
. Calcd.
9
a] 10.8 (c
＋
3.16, CHCl3); 1H-
D
－
5.60, 18.17, 25.84, 33.92, 47.46, 55.26, 63.66,
for C26H32O5Si: C, 68.99; H, 7.13
z.
25
65.42, 85.45, 88.21, 100.80, 108.18, 109.54, 113.89,
114.98, 122.10, 133.78, 133.78, 145.87, 147.63,
159.57; IR nmax (CHCl3) cm－1: 2983, 2940, 2384,
1615, 1517, 1495, 1444, 1294, 1256, 1175, 1102, 1042,
15: 90.2
NMR (CDCl3)
Si–C 3), 0.87
5.9, 12.2 Hz, Ar–C
z
yield, [
: 0.03 (3H, s, Si–C
9H, s, (CH3 , 2.87 (1H, dd,
2), 2.96–3.01 (1H, m, C
d
s
H
3), 0.04 (3H, s,
H
)
×
3
t
J
＝
＝
2), 3.83
H
J
H
C
＝
940, 841, 816. Anal. Found: C, 68.84; H, 7.51
z
.
O), 3.03 (1H, dd,
6.8, 12.2 Hz, Ar–C
H
Calcd. for C26H34O5Si: C, 68.69; H, 7.54
z
.
(3H, s, OC
H
3), 3.87 (1H, dd,
J
＝
5.6, 10.1 Hz,
2OSi),
),
13: 70.9
NMR (CDCl3)
Si–C 3), 0.91
z
yield, [
a
]
95.9
9
(
c
0.74, CHCl3); 1H-
C
H
2OSi), 3.92 (1H, dd,
J
4.9, 10.1 Hz, CH
25
＋
＝
D
d
: 0.08 (3H, s, Si–C
H
3), 0.10 (3H, s,
3t, 2.27–2.34 (1H, m,
5.89 (2H, s, O–C
H
2–O), 6.65–6.72 (3H, m, Ar1–
H
＝
＝
5.57,
H
s
9H, s, C(CH3
)
6.89 (2H, d,
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.50 (2H, d,
J
＝
－
C
H
–CH2OSi), 2.53 (1H, dd,
Ar–C 2), 2.63 (1H, dd,
3.76 (1H, dd,
J
7.3, 13.7 Hz,
2),
H
); 13C-NMR (CDCl3)
d
:
H
J
＝
7.8, 13.7 Hz, Ar–C
H
－
5.54, 18.16, 25.79, 32.92, 55.32, 58.51, 62.42,
＝
J
4.2, 10.0 Hz, C
H
2OSi), 3.82 (3H, s,
87.50, 92.85, 100.76, 108.12, 109.47, 111.77, 114.29,
122.00, 132.66, 134.96, 145.96, 147.55, 161.59,
189.03; IR nmax (CHCl3) cm－1: 2940, 2170, 1653,
1606, 1546, 1508, 1491, 1256, 1222, 1106, 1042, 940,
OC
H
3), 3.98 (1H, dd,
J
＝
H
9.5, 10.0 Hz, C
H
J
2OSi),
＝
＝
4.07 (1H, d,
7.8 Hz, C
(3H, m, Ar1–
J
7.8 Hz, O
), 4.64 (1H, dd,
3.9,
H
OH), 5.92 (2H, s, O–C
), 6.85 (2H, d,
H2–O), 6.65–6.74
H
J
＝
8.8 Hz, Ar2–
7.40 (2H, d,
); 13C-NMR (CDCl3)
－
5.63, 5.59, 18.12, 25.82, 35.56, 47.13, 55.27,
H
),
837, 747. Anal. Found: C, 68.77; H, 7.12
for C26H32O5Si: C, 68.99; H, 7.13
z
. Calcd.
＝
J
8.8 Hz, Ar2–
H
z.
d
:
－
65.05, 66.19, 86.14, 86.64, 100.83, 108.19, 109.32,
113.91, 115.05, 121.85, 133.13, 133.17, 145.97,
147.68, 159.60; IR nmax (CHCl3) cm－1: 2983, 2940,
2384, 1615, 1517, 1495, 1452, 1290, 1256, 1175, 1076,
1042, 940, 837, 816. Anal. Found: C, 68.25; H,
General procedure for preparing (2R S)-1-hy-
W
droxy-5-(4-methoxyphenyl)-2-(3,4-methylene-
dioxyphenyl)methyl-4-pentyn-3-one
(16 and 17).
Acetic acid (10.0 ml) was added to a stirred solution
of 14 or 15 (0.50 g, 1.10 mmol) in THF (5.0 ml) and
water (5.0 ml) at room temperature. After 15 h,
water (10 ml) and EtOAc (10 ml) were added to the
reaction mixture, and the organic layer was separat-
ed. The aqueous phase was extracted with EtOAc
(10 ml), and the combined organic layer was succes-
sively washed with sat. NaHCO3 and brine, before
being dried over Na2SO4. After removing the solvent
in vacuo, the residue was puriˆed by column chro-
7.34
z z
. Calcd. for C26H34O5Si: C, 68.69; H, 7.54 .
General procedure for preparing (2R S)-1-tert-
W
butyldimethylsilyloxy-5-(4-methoxyphenyl)-2-(3,4-
methylenedioxyphenyl)methyl-4-pentyn-3-one
(14
and 15). To a stirred solution of 12 or 13 (1.0 eq) in
toluene (20 ml mmol) were added DMSO (30 eq),
W
DCC (3.0 eq) and TFA-pyridine (1.5 eq) at room

Total Synthesis of Dechloro-cyanobacterin
2191
25
D
matography on silica gel (hexane-EtOAc, 2:1) to pro-
perature of 25
NMR (CDCl3)
＝
9
d
C
t
, [
a
]
0.97, CHCl3); 1H-
－
33.19(c
＝
6.4 Hz, CH3), 1.15
vide a hydroxyketone 16 or 17 as a colorless oil.
: 1.13 (3H, d,
6.8 Hz,
), 2.16–2.23
11.5, 14.1 Hz, Ar–CH
J
16: 86.6
NMR (CDCl3)
–OH), 2.88 (1H, dd,
z
yield, [
a
]
92.0
9
(
c
1.71, CHCl3); 1H-
(3H, d,
J
C
H
s
3), 2.10–2.15 (1H, m,
1H, m, (CH3)2C , 2.65
2), 2.83 (1H, s,
2.9, 14.1 Hz, Ar–C 2), 3.36
(1H, br, OH), 3.75–3.84 (5H, m, OCH3 and
2–OH), 5.93 (2H, s, O–CH2–O), 6.68–6.76 (3H,
25
－
D
＝
d
: 2.01 (1H, dd,
8.0, 13.4 Hz, Ar–C
J
6.1, 6.7 Hz,
Ar–CH2–C
(1H, dd,
＝
), 3.04 (1H, dd, J
H
H t
J
＝
H
2),
J
＝
＝
＝
2.99–3.08 (1H, m, C
13.2 Hz, Ar–C 2), 3.81 (1H, dd,
CH2OH), 3.83–3.91 (4H, m, OCH3 and C
H
C
O), 3.16 (1H, dd,
J
5.9,
O
H
H
＝
6.7, 11.8 Hz,
H
J
H
2OH),
2–O), 6.68–6.75 (3H, m, Ar1– ),
2.5, 6.8 Hz, Ar2– ), 7.53 (2H, dd,
); 13C-NMR (CDCl3)
: 33.64,
CH
m, Ar1–
(2H, d,
＝
5.92 (2H, s, O–C
H
H
H
J
), 6.86 (2H, d,
8.8 Hz, Ar2–
16.42, 18.09, 33.15, 35.34, 47.47, 55.30, 61.96,
79.21, 86.29, 88.38, 100.80, 108.17, 109.45, 113.95,
114.73, 122.00, 133.18, 134.19, 145.84, 147.65,
159.71; IR nmax (CHCl3) cm－1: 2983, 2363, 1715,
1615, 1546, 1517, 1495, 1448, 1279, 1256, 1179, 1110,
J
H
8.8 Hz, Ar2–
H ), 7.41
6.90 (2H, dd,
J
＝
H
＝
); 13C-NMR (CDCl3)
d:
＝
J
2.5, 6.8 Hz, Ar2–
H
d
55.45, 57.84, 61.49, 87.40, 92.24, 100.91, 108.31,
109.37, 111.37, 114.43, 122.03, 132.09, 135.28,
146.40, 147.74, 161.90, 189.85; IR nmax (CHCl3)
cm－1: 2213, 1735, 1653, 1607, 1508, 1491, 1444,
1252, 1110, 1042, 944, 837. Anal. Found: C, 70.62;
1046, 935, 841. Anal. Found: C, 72.15; H, 6.84
Calcd. for C23H26O5: C, 72.23; H, 6.85
z
.
H, 5.39
17: 89.1
NMR (CDCl3)
8.4, 13.7 Hz, Ar–C
O), 3.15 (1H, dd,
3.83–3.90 (5H, m, OCH3 and C
z
. Calcd. for C20H19 O5: C, 70.99; H, 5.36
z
.
z.
z
yield, [
a
]
87.9
9
(c
1.84, CHCl3); 1H-
18-b (2
S
,3
R
): 4.2
z
yield,
2.58, CHCl3); 1H-NMR (CDCl3)
6.8 Hz, C 3), 1.19 (1H, d,
3), 1.94–2.02 (1H, m, ArCH2–C
2H, m, (CH3)2C and O , 2.86 (2H, d,
2), 3.66 (1H, dd,
2OH), 3.78 (1H, s, O ), 3.81 (3H, s, OC
2.0, 11.0 Hz, C 2OH), 5.93 (2H, s,
), 6.83 (2H, d,
Rf 0.48 (hexane-EtOAc,
25
＋
D
25
D
＋
d
: 2.00 (1H, br, O
H
), 2.88 (1H, dd,
J
＝
2),
3:2), [
a
]
15.99(c
＝
H
2), 3.01–3.13 (1H, m, C
H
C
d
: 1.09 (1H, d,
6.4 Hz, C
2.20–2.32
J
＝
H
J
＝
＝
J
6.1, 13.7 Hz, Ar–C
H
H
H ),
H
2OH), 5.92 (2H, s,
s
H
H t
＝
H
＝
O–C
H
2–O), 6.69–6.75 (3H, m, Ar1–
H
), 6.90 (2H,
J
C
9.8 Hz, Ar–C
H
J
3.4, 11.0 Hz,
3),
＝
＝
dd,
J
2.0, 6.8 Hz, Ar2–
H
), 7.53 (2H, dd,
J
2.0,
H
H
6.8 Hz, Ar2–
H
); 13C-NMR (CDCl3)
d
: 33.56, 55.36,
4.38 (1H, dd,
J
＝
H
58.02, 61.46, 87.35, 94.15, 100.80, 108.22, 109.32,
111.35, 114.35, 121.96, 132.12, 135.19, 146.11,
147.65, 161.81, 189.84; IR nmax (CHCl3) cm－1: 2213,
1735, 1653, 1606, 1508, 1491, 1444, 1252, 1110, 1042,
O–C
＝
H
2–O), 6.70–6.76 (3H, m, Ar1–
H
＝
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.37 (2H, d,
J
H );
13C-NMR (CDCl3)
d
: 17.69, 18.46, 29.85, 34.98,
47.20, 55.75, 63.16, 79.55, 86.73, 88.93, 101.28,
108.72, 110.09, 114.35, 115.27, 122.48, 133.56,
134.64, 146.26, 148.11, 160.04.
944, 837. Anal. Found: C, 70.60; H, 5.12
for C20H19O5: C, 70.99; H: 5.36
z
. Calcd.
z
.
19-a (2
R,3S): 56.2z yield, Rf 0.43 (hexane-
25
General procedure for preparing (2R S,3R S)-3-
EtOAc, 3:2), tR 55.7 min, [
a
]
＋
28.7
: 1.13 (3H, d,
6.4 Hz, CH3), 2.10–2.16
2.17–2.23 1H, m,
11.5, 14.0 Hz,
), 3.05 (1H, dd, 3.0,
2), 3.34 (1H, br, O ), 3.78–3.87
(5H, m, OCH3 and 2–OH), 5.92 (2H, s,
O–CH2–O), 6.67–6.74 (3H, m, Ar1– ), 6.85 (2H, d,
9
(c 2.33,
W
W
D
1
＝
6.4
isopropyl-5-(4-methoxyphenyl)-2-(3,4-methylene-
CHCl3); H-NMR (CDCl3)
Hz, C 3), 1.15 (3H, d,
1H, m, Ar–CH2–C
(CH3)2C 2.65 (1H, dd,
Ar–C 2), 2.81(1H, s, –O
14.0 Hz, Ar–C
d
J
dioxybenzyl)-4-pentyne-1,3-diol (18 and 19). To a
H
J
＝
stirred solution of 16 or 17 (1.0 eq) in THF (60 ml
s
H
t
,
s
W
＝
J
mmol) was added a solution of isopropyl magnesium
bromide prepared from Mg (large excess) in THF
(1.0 ml) and 2-bromopropane (3.0 eq). The reaction
H
t,
H
H
J
＝
H
H
mixture was then diluted with THF (10 ml) at
－
78
9
C
CH
via a cannula under N2 pressure. After 1 h, the reac-
tion mixture was quenched by adding sat. NH4Cl
(60 ml) and allowed to warm to room temperature.
The organic layer was separated, and the aqueous
H
＝
＝
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.40 (2H, d,
J
H );
13C-NMR (CDCl3)
d
: 16.41, 18.09, 33.15, 35.34,
47.47, 55.30, 61.97, 79.21, 86.30, 88.38, 100.80,
108.17, 109.45, 113.95, 114.73, 122.00, 133.17,
134.19, 145.84, 147.65, 159.71; IR nmax (CHCl3)
cm－1: 2983, 2363, 1715, 1615, 1546, 1508, 1495,
1448, 1287, 1247, 1179, 1110, 1038, 935, 841. Anal.
×
phase was extracted with Et2O (2 20 ml). The com-
bined organic layer was successively washed with sat.
NaHCO3 and brine, before being dried over Na2SO4.
After concentrating the residue was puriˆed by
column chromatography on silica gel (hexane-
EtOAc, 3:1) to provide the 1,3-diol as a mixture of
diastereomers. Each isomer was separated by PTLC
(hexane-EtOAc, 3:1) and 17 and 18 were obtained as
colorless oils.
Found: C, 72.04; H, 6.95
72.23; H, 6.85
z. Calcd. for C23H26O5: C,
z
): 3.0
.
19-b (2
R
,3
R
z
yield,
0.68, CHCl3); 1H-NMR (CDCl3)
6.4 Hz, C 3), 1.19 (1H, d, 6.8
Rf 0.48 (hexane-EtOAc,
25
D
－
3:2), [
a
]
10.79(c
d
: 1.08 (1H, d,
Hz,
2.19–2.29
2.82–2.88 (2H, m, Ar–C
Hz, C
(1H, d,
J
＝
H
J
＝
18-a (2
S
,3
R
): 66.6
z
yield, Rf 0.42 (hexane-
a CHIRALCEL OF
C
H
3), 1.96–2.00 (1H, m, Ar–CH2C
H
),
),
EtOAc, 3:2), tR 50.2 min
s
s
1H, m, (CH3)2C
H
t, 2.35 (1H, br, –OH
×
＝
column (4.6 250 mm, Daicel Chemical Industries)
H
2), 3.65 (1H, d,
J
H
10.3
was used with hexane-2-propanol (9:1) as the mobile
H
2OH), 3.81 (4H, s, OCH3 and –O
), 4.38
phase at a ‰ow rate of 0.5 ml min and column tem-
J
＝
10.7 Hz,
C
H
2OH), 5.92 (2H, s,
W

2192
Y. HAGA et al.
O–C
H
2–O), 6.70–6.75 (3H, m, Ar1–
H
), 6.82 (2H, d,
ing of NaClO2 (80z purity, 1.1 eq). After 1 h at the
＝
＝
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.36 (2H, d,
J
H
);
same temperature, the resulting solution was diluted
with EtOAc (5 ml) and water (5 ml). The organic lay-
er was separated, and the aqueous phase was extract-
ed with EtOAc (5 ml). The combined organic layer
was washed with brine, before being dried over
Na2SO4. After concentrating, the residue was puri-
ˆed by column chromatography on silica gel (hexane-
13C-NMR (CDCl3)
46.81, 55.27, 62.98, 79.08, 86.27, 88.51, 100.79,
108.24, 109.55, 113.91, 114.85, 122.02, 133.09,
134.21, 145.81, 147.66, 159.61.
d
: 17.22, 17.99, 29.44, 34.52,
(4R,5S)-2,2-Dimethyl-4-isopropyl-4-(4-methox-
yphenyl)ethynyl-5-(3,4-methylenedioxybenzyl)-1,3-
dioxolane (20). To a stirred solution of 18-a (0.14 g,
0.37 mmol) in toluene (10 ml) were added to 2,2-
dimethoxypropane (0.27 ml, 2.20 mmol) and a cata-
lytic amount of PPTS at room temperature under an
N2 atmosphere. After stirring for 18 h, the reaction
mixture was poured into water (20 ml). The organic
layer was separated, and the aqueous phase was ex-
EtOAc, 2:1 to 1:2) to provide 21 or 22.
25
21: 64.4
z
yield, [
a
]
－
76.1
9
(
c
1.86, CHCl3); 1H-
D
＝
NMR (CDCl3)
d
: 1.12 (3H, d,
J
6.4 Hz, C
H
3),
＝
1.19 (3H, d,
1.90–2.00 1H, m, (CH3)2C
9.4 Hz, Ar–C
Ar–CH2–C
Ar–C
O–C
J
6.4 Hz, C
H
3), 1.26 (1H, s, –O
H
H
),
＝
s
t, 3.08 (1H, d, J
＝
H
2), 3.15 (1H d,
J
11.4 Hz,
9.7, 10.4 Hz,
3), 5.92 (2H, s,
2–O), 6.65–6.74 (3H, m, Ar1– ), 6.86 (2H, d,
H
), 3.38 (1H, dd, J
＝
H
2), 3.82 (3H, s, –OCH
×
tracted with Et2O (2 5ml). The combined organic
H
H
＝
＝
8.8 Hz, Ar2–
layer was successively washed with sat. NaHCO3 and
brine before being dried over Na2SO4. After concen-
trating, the residue was puriˆed by column chro-
J
8.8 Hz, Ar2–
H
), 7.41 (2H, d,
J
H );
13C-NMR (CDCl3)
d
: 17.59, 18.52, 35.20, 37.69,
55.01, 55.32, 77.08, 85.41, 86.96, 100.88, 108.30,
109.25, 113.98, 114.27, 121.82, 132.46, 133.32,
146.26, 147.70, 159.90, 177.86.
matography on silica gel (hexane-EtOAc, 9:1) to pro-
vide 0.14 g (90.5
25
z) of 20 as a colorless oil, [a]
D
3.9
9
(
c
2.29, CHCl3); 1H-NMR(CDCl3)
d
: 1.04
22: 70.2
z
yield, [
a
]
9
75.6 (c
3.33, CHCl3); 1H-
25
＋
＋
D
＝
＝
＝
J 6.4 Hz, C
(3H, d,
J
6.6 Hz, C
H
3), 1.18 (3H, d,
3), 1.75 (3H, s, C
1H, m, (CH3)2C , 2.22–2.30 (1H, m,
), 2.35 (1H, dd,
3.4, 13.7 Hz, Ar–C
4.2, 10.9 Hz, CH–C 2O), 3.82 (3H,
3), 3.90 (1H, dd, 10.9, 11.7 Hz,
2O), 5.91 (2H, s, O–C 2–O), 6.59–6.72 (3H,
J
6.6 Hz,
NMR (CDCl3)
d
: 1.12 (3H, d,
6.4 Hz, C
1H, m, (CH3)2C
H
3), 1.19
),
C
H
3), 1.32 (3H, s, C
H
H
3),
(3H, d,
1.87–1.97
9.8 Hz, Ar–C
J
s
＝
H
3), 1.25 (1H, s, O
H
＝
2.01–2.10
ArCH2–C
s
H
H
t
H
t
, 3.08 (1H, d,
J
＝
＝
11.7 Hz,
J
11.2, 13.7 Hz,
2),
H
H
2), 3.15 (1H, d,
J
Ar–C
H
2), 2.79 (1H, dd,
J
＝
H
ArCH2C
Ar–C
O–C
H
), 3.37 (1H, dd,
J
＝
10.0, 10.7 Hz,
3), 5.90 (2H, s,
2–O), 6.65–6.72 (3H, m, Ar1– ), 6.85 (2H, d,
＝
3.55 (1H, d,
J
H2), 3.82 (3H, s, OCH
s, OC
H
J
＝
H
H
＝
＝
8.8 Hz, Ar2–
CH–C
H
H
J
8.8 Hz, Ar2–
H
), 7.40 (2H, d,
J
H );
m, Ar1–
(2H, d,
H
J
), 6.86 (2H, d,
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.39
13C-NMR (CDCl3)
d
: 17.57, 18.49, 35.16, 37.67,
＝
＝
H
); 13C-NMR (CDCl3)
d
:
54.99, 55.27, 77.06, 85.43, 86.79, 100.82, 108.23,
109.20, 113.93, 114.29, 121.77, 132.50, 133.25,
146.17, 147.63, 159.81, 178.77.
14.11, 16.01, 17.86, 30.75, 33.5, 35.80, 55.34, 61.41,
76.29, 87.40, 89.67, 99.21, 100.84, 108.15, 109.29,
114.02, 115.35, 151.81, 132.74, 133.09, 145.90,
147.67, 159.59; IR nmax (CHCl3) cm－1: 2961; 1611,
1517, 1495, 1462, 1388, 1290, 1256, 1179, 1115, 1046,
935, 837, 760. Anal. Found: C, 73.84; H, 7.41
Calcd. for C26H30O5: C, 73.91; H, 7.16
General method for preparing (2R S,3R S,4Z )-3-
W
W
hydroxy-3-isopropyl-5-(4-methoxyphenyl)-2-(3,4-
z.
methylenedioxybenzyl)-4-penten-4-olide (
2 and 23).
z
.
To a stirred solution of acid 21 or 22 (1.0 eq) in
CH OH (15.0 ml mmol) was added 0.1
M
aq. AgNO3
W
3
General procedure for preparing (2R S,3R S)-3-
(0.15 ml mmol) at room temperature. After stirring
W
W
W
hydroxy-3-isopropyl-5-(4-methoxyphenyl)-2-(3,4-
methylenedioxybenzyl)-4-pentynoic acid (21 and 22).
To a stirred solution of 1,3-diol 18-a or 19-a (1.0 eq)
for 2 days in the dark, the solvent was concentrated
in vacuo, and the residue was puriˆed by column
chromatography on silica gel (CCl4-EtOAc, 9:1). The
obtained crystals were recrystalized from a mixed
solvent of CH2Cl2-petroleum ether (1:3) to give the
desired compound.
in CH Cl (10 ml mmol) were added NMO (2.5 eq)
W
2
2
and crushed 4A molecular sieves at room tempera-
ture under an N2 atmosphere. After 5 min, a catalytic
amount of TPAP was added to the reaction mixture
which was stirred for 6 h. The solvent was removed in
vacuo, and the residue was puriˆed by column chro-
matography on silica gel (hexane-EtOAc, 3:1) to
provide an aldehyde which was used in the next step
without further puriˆcation.
2: 81.9
z yield, mp 140–1419C, tR 33.1 min sa
×
CHIRALCEL OD-H column (4.6 250 mm, Daicel
Chemical Industries) was used with hexane-2-
propanol (3:1) as the mobile phase at a ‰ow rate of
25
9 t
0.5 ml min and column temperature of 25 C , [a]
W
D
1
＋
94.7
(3H, d,
3), 1.75 (1H, s, O
(CH3)2C 2.91 (1H, dd,
Ar–C 2), 3.17 (1H, dd, 6.3, 6.8 Hz, CHC
＝
9(c 0.88, CHCl3); H-NMR (CDCl3) d: 0.93
＝
＝
To a stirred solution of this aldehyde (1.0 eq) in
tBuOH and water (4:1) were added NaH2PO4 (2.7 eq)
and 2-methyl-2-butene (10 eq) at room temperature.
J
6.8 Hz, C
H
3), 1.08 (3H, d,
J
6.8 Hz,
1H, m,
6.8, 14.2 Hz,
O),
C
H
H
), 2.17–2.27 s
＝
J
H
t,
The reaction mixture was cooled to 0
9
C, before add-
H
J
＝

Total Synthesis of Dechloro-cyanobacterin
2193
＝
natural herbicide, cyanobacterin. Plant Sci., 60,
149–154 (1989).
7) Jong, T., Williard, P., and Porwoll, J., Total synthe-
sis and X-ray structure determination of cyanobacte-
rin. J. Org. Chem., 49, 735–736 (1984).
8) Gleason, F., and Paulson, L., Site of action of the
natural algicide, cyanobacterin, in the blue-green
3.22 (1H, dd,
J
6.3, 14.2 Hz, Ar–C
3), 5.70 (1H, s, Ar2–C ), 5.94 (2H, s,
), 6.87 (2H, d,
H2), 3.81 (3H, s,
OC
H
H
O–C
H
2–O), 6.75–6.84 (3H, m, Ar1–H
＝
＝
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.53 (2H, d,
J
H );
13C-NMR (CDCl3)
d
: 15.69, 17.96, 29.05, 33.39,
53.16, 55.27, 82.36, 101.03, 105.69, 108.41, 109.20,
113.93, 121.72, 125.82, 130.14, 132.12, 146.35,
147.80, 148.28, 158.79, 173.05; IR nmax (CHCl3)
cm－1: 2363, 1807, 1692, 1615, 1517, 1499, 1452,
1287, 1256, 1187, 1042, 940, 841. Anal. Found: C,
alga, Synechococcus sp. Arch. Microbiol.
273–277 (1984).
, 138,
9) Koo, J., Fish, M. S., Walker, G. N., and Balake,
J., 2,3-Dimethoxycinnamic acid. Org. Synth., Col-
lect. Vol. 4, 327–329 (1963).
69.35; H, 6.05
6.10
23: 67.1
z. Calcd. for C23 H24O6: C, 69.68; H,
10) Gage, J. R. and Evans, D. A., (S)-4-(Phenylmethyl)-
z.
25
2-oxazolidione. Org. Synth., Collect. Vol. 8, 528–531
(1993).
z
yield, mp 140–141
9
C, tR 23.9 min, [
1.84, CHCl3); H-NMR (CDCl3)
6.4 Hz, C 3), 1.08 (3H, d,
3), 1.76 (1H, s, O ), 2.17–2.26
(CH3)2C 2.90 (1H, dd,
Ar–C 2), 3.17 (1H, dd,
3.22 (1H, dd,
a]
D
1
－
98.8
9
J
(
c
d
: 0.92
6.4 Hz,
1H, m,
6.8, 14.2 Hz,
11) Gage, J. R., and Evans, D. A., Diastereoselective
(3H, d,
＝
H
J
＝
aldol condensation using
a
chiral oxazolidinone
*
)-3-hydroxy-3-phenyl-2-methyl-
C
H
H
s
*
S , 3S
auxiliary: (2
＝
J
H
t,
propanoic acid. Org. Synth., Collect. Vol. 8, 339–343
(1993).
＝
＝
O),
H
J
6.4, 6.8 Hz, C
6.4, 14.2 Hz, Ar–C 2), 3.81 (3H, s,
3), 5.70 (1H, s, Ar2–C ), 5.94 (2H, s,
), 6.88 (2H, d,
H
C
＝
J
H
12) Corey, E. J., and Fuchs, P. L., A synthetic method
OC
H
H
for formyl
ªethynyl conversion. Tetrahedron Lett.,
O–C
H
2–O), 6.75–6.84 (3H, m, Ar1–H
3769–3772 (1972).
＝
＝
8.8 Hz, Ar2–
J
8.8 Hz, Ar2–
H
), 7.54 (2H, d,
J
H );
13) Olah, G. A., and Arvanaghi, M., Aldehyde by for-
mylation of Grignard or organolithium reagents with
13C-NMR (CDCl3)
d
: 15.67, 17.94, 29.02, 33.36,
N
-formylpiperidine. Angew. Chem. Int. Ed. Engl.
,
53.13, 55.25, 82.32, 100.99, 105.65, 108.37, 109.21,
113.91, 121.71, 125.84, 130.13, 132.17, 146.32,
147.86, 148.34, 158.77, 173.09. Anal. Found: C,
20, 878–879 (1981).
14) Danda, H., Hansen, M. M., and Heathcock, C. H.,
Reversal of stereochemistry in the aldol reactions of a
chiral boron enolate. J. Org. Chem., 55, 173–181
(1990).
69.38; H, 6.10
6.10
z. Calcd. for C23 H24O6: C, 69.68; H,
z
.
15) Walker, M. A., and Heathcock, C. H., Extending the
scope of the Evans aldol reactions: preparation of
anti and ``non-Evans'' syn aldols. J. Org. Chem., 56,
5747–5750 (1991).
16) Evans, D. A., Bartroli, J., and Shih, T. L., Enan-
tioselective aldol condensations. 2. Erythro-selective
chiral aldol condensation via boron enolates. J. Am.
Chem. Soc., 103, 2127–2129 (1981).
17) Evans, D. A., Nelson, J. V., Vogel, E., and Taber, T.
R., Stereoselective aldol condensation via boron
enolates. J. Am. Chem. Soc., 103, 3099–3111 (1981).
18) Corey, E. J., and Schmidt, G., Useful procedures for
the oxidation of alcohols involving pyridinium
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