Substrate-controlled stereoselective synthesis of ophiocerin C

Article abstract of DOI:10.1055/s-0029-1218708

A novel stereoselective total synthesis of ophiocerin C was accomplished starting from l-(+)-tartaric acid. The C3,C4 vic-diol moiety was obtained from tartaric acid, and the stereogenic centre at C6 was created by substrate-controlled epoxidation and subsequent regioselective cleavage of the epoxide ring. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218708

PAPER
1621
Substrate-Controlled Stereoselective Synthesis of Ophiocerin C
S
tereosele
h
ctive
S
ynthe
i
sis of
O
l
phioce
l
rinC u S. Yadav,* N. Rami Reddy, B. Bala Murali Krishna, Ch. Vijaya Vardhan, Basi V. Subba Reddy
Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 1 February 2010; revised 17 February 2010
which could, in turn, be obtained from olefin 8 by a sub-
strate-controlled stereoselective epoxidation and subse-
quent regioselective opening of the epoxide ring. The
final cyclization could be achieved by nucleophilic substi-
tution.
Abstract: A novel stereoselective total synthesis of ophiocerin C
was accomplished starting from L-(+)-tartaric acid. The C3,C4 vic-
diol moiety was obtained from tartaric acid, and the stereogenic
centre at C6 was created by substrate-controlled epoxidation and
subsequent regioselective cleavage of the epoxide ring.
Key words: Wittig reactions, tartaric acid, epoxidations, ring open-
ing, ophiocerin C, stereoselective synthesis
According to our synthetic strategy, alcohol 6 was pre-
pared from L-(+)-tartaric acid.8 Compound 6 was subject-
ed to Swern oxidation give the corresponding aldehyde,
which underwent Wittig olefination by ethylidene(triphe-
nyl)phosphorane to give the olefin 7 in 85% yield for the
two steps (Scheme 2).
The ophiocerins A–D (1–4, Figure 1) are natural products
with a tetrahydropyran skeleton, isolated from the fresh-
water fungus Ophioceras venezuelense (Magnapor-
thaceae) by Shearer and co-workers.1,2 The absolute
stereochemistry of 1–4 was assigned through circular
dichroism spectroscopy by the exciton chirality method.3,4
The substituted pyran moiety5 is found in a wide variety
of natural products that show a broad spectrum of biolog-
ical activities.6 Because of the interesting array of substit-
uents on their tetrahydropyran rings, ophiocerins have
attracted the attention of synthetic organic chemists.7
Treatment of compound 7 with a catalytic amount of 4-
toluenesulfonic acid in methanol followed by epoxidation
of the resulting allylic alcohol 8 gave the threo-2,3-epoxy
alcohol 9 in 90% yield.9 The epoxide 9 was treated with
Red-Al [sodium bis(2-methoxyethoxy)dihydridoalumi-
num] to afford the triol 10 in 92% yield by regioselective
ring opening.10 The triol 10 was monosilylated with tert-
butyl(dimethyl)silyl chloride, and the resulting diol 11
was protected by treatment with 2,2-dimethoxypropane
and a catalytic amount of pyridinium 4-toluenesulfonate
in dichloromethane to give the acetonide 12 in 94% yield.
Debenzylation of 12 by hydrogenation over palladium/
carbon gave the primary alcohol 13 quantitatively. Ester-
ification of 13 with tosyl chloride afforded the O-tosyl de-
rivative 14. Desilylation of 14 with tetrabutylammonium
fluoride gave the secondary alcohol 15. Base-induced cy-
clization of 15 with potassium tert-butoxide in diethyl
ether at 0 °C,7a and subsequent deprotection of the ace-
tonide using a catalytic amount of 4-toluenesulfonic acid
in methanol gave ophiocerin C (3) in 12 steps and 44%
overall yield. The analytical data for 3 were in agreement
with those reported in the literature.1
By retrosynthetic analysis (Scheme 1), we envisaged that
ophiocerin C (3) could be prepared from the dioxolane 12,
OH
OH
OH
HO
HO
HO
O
O
O
ophiocerin C (3)
ophiocerin A (1)
ophiocerin B (2)
OH
O
HO
O
O
In conclusion, we have developed a concise and efficient
stereocontrolled and stereoselective synthesis of ophio-
cerin C in a high overall yield; the application of this strat-
egy to the synthesis of the other ophiocerins is underway.
ophiocerin D (4)
Figure 1 Ophiocerins A–D
OH
OTBS
O
OH
HO
OBn
L-(+)-tartaric acid
OBn
O
O
OH
3
12
8
Scheme 1 Retrosynthetic analysis of ophiocerin C
SYNTHESIS 2010, No. 10, pp 1621–1624
x
x.
x
x
.
2
0
1
0
Advanced online publication: 24.03.2010
DOI: 10.1055/s-0029-1218708; Art ID: Z02010SS
© Georg Thieme Verlag Stuttgart · New York

1622
J. S. Yadav et al.
PAPER
O
O
OH
HO
a
ref. 8
b
COOH
OBn
OBn
HOOC
O
O
OH
5
6
7
OH
OH
OH
OH
c
d
e
OBn
OBn
OBn
OH
OH
OH
O
8
9
10
TBSO
TBSO
O
O
TBSO
OH
f
g
OBn
OH
OBn
O
O
OH
11
12
13
OH
TBSO
OH
O
O
HO
h
j
i
OTs
OTs
O
O
O
14
15
ophiocerin C
Scheme 2 Reagents and conditions: (a) (1) (COCl)2, DMSO, CH2Cl2, –78 °C to r.t., 2 h; (2) Ph3P+C2H5I–, t-BuOK, THF, 0 °C, 1 h, 85% (2
steps); (b) PTSA, MeOH, r.t., 2 h, 90%; (c) MCPBA, NaHCO3, CH2Cl2, 0 °C to r.t., 10 h, 90%; (d) Red-Al, THF, 0 °C to r.t., 5 h, 92%; (e)
TBDMSCl, imidazole, CH2Cl2, r.t., 3 h, 90%; (f) Me2C(OMe)2, PPTS, CH2Cl2, r.t., 3 h, 94%; (g) H2, 10% Pd/C, EtOAc, r.t., 2 h, 96%; (h) TsCl,
TEA, DMAP (cat.), CH2Cl2, r.t., 3 h, 92%; (i) TBAF, THF, r.t., 2 h, 90%; (j) (1) t-BuOK, Et2O, 0 °C, 2 h; (2) PTSA (cat.), MeOH, r.t., 2 h, 88%
(2 steps).
All commercial reagents were used without further purification, and
all solvents were purified by standard techniques. The crude prod-
ucts were purified by column chromatography on silica gel (60–120
mesh) with EtOAc and hexane as eluents. IR spectra were recorded
on a Perkin-Elmer 683 spectrometer. Optical rotations were mea-
sured on Perkin-Elmer Model 343 polarimeter with CHCl3 as the
solvent. 1H and 13C NMR spectra were recorded in CDCl3 on Varian
Gemini 200 and Bruker 300 NMR spectrophotometers; chemical
shifts (d) are quoted in parts per million and are referred to TMS as
the internal standard. Coupling constants (J) are quoted in Hz. ESI
HRMS were recorded on a high-resolution QSTAR XL hybrid MS/
MS system (Applied Biosystems), and the sample solns were pre-
pared in MeOH.
and concentrated. The residue was purified by column chromatog-
raphy [silica gel, EtOAc–hexane (1:9)] to give compound 7 as a col-
orless oil; yield: 85% (2 steps); [a]D27 +3.2 (c 1.4, CHCl3).
IR (neat): 3026, 2938, 1663, 1494, 1452, 740, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33–7.26 (m, 5 H), 5.70 (m, 1 H),
5.38 (m, 1 H), 4.65 (m, 1 H), 4.57 (ABq, 2 H), 3.77 (m, 1 H), 3.57
(dd, J = 10.5, 3.7 Hz, 1 H), 3.51 (dd, J = 10.5, 5.3 Hz, 1 H), 1.68 (d,
J = 6.8 Hz, 3 H), 1.40 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 143.2, 137.9, 130.4, 128.33, 127.5,
127.0, 109.1, 80.3, 73.5, 73.1, 69.1, 27.1, 26.9, 13.3.
ESI-HRMS: m/z [M + Na]+ calcd for C16H22NaO3: 285.3366; found:
285.3362.
(4S,5R)-4-[(Benzyloxy)methyl]-2,2-dimethyl-5-[(1Z)-prop-1-
en-1-yl]-1,3-dioxolane (7)
(2R,3R,4Z)-1-(Benzyloxy)-4-hexene-2,3-diol (8)
PTSA (238 mg, 1.4 mmol) was added to a stirred soln of acetonide
7 (3.60 g, 13.9 mmol) in MeOH (25 mL) at r.t., and the mixture was
stirred for 2 h. The reaction was then quenched with sat. aq NaHCO3
(20 mL) and the MeOH was removed. The aqueous layer was ex-
tracted with CH2Cl2 (3 × 15 mL), and the combined organic layers
were washed with brine, dried (Na2SO4), and concentrated. The res-
idue was purified by column chromatography [silica gel, EtOAc–
hexane (4:6)] to give a white solid; yield: 90%; mp 55–56 °C; [a]D
+4.7 (c 0.9, CHCl3).
IR (KBr): 3412, 3917, 1658, 1450, 1110, 1045, 736, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.21 (m, 5 H), 5.63 (m, 1 H),
5.40 (m, 1 H), 4.51 (s, 2 H), 4.40 (m, 1 H), 3.61–3.49 (m, 2 H), 3.42
(m, 1 H), 2.90 (br s, 2 H, OH), 1.67 (d, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.5, 128.9, 128.8, 128.3, 127.8,
127.7, 73.6, 73.5, 71.1, 67.9, 13.5.
ESI-HRMS: m/z [M + Na]+ calcd for C13H18NaO3: 245.2720; found:
245.2724.
A soln of DMSO (3.1 mL, 43.7 mmol) in CH2Cl2 (15 mL) was add-
ed to a stirred soln of (COCl)2 (3.5 mL, 39.7 mmol) in CH2Cl2 (15
mL) at –78 °C. After 20 min, a soln of 6 (5.0 g, 19.8 mmol) in
CH2Cl2 (20 mL) was added at –78 °C. The mixture was stirred for
another 20 min at –78 °C and then Et3N (13.7 mL, 99.2 mmol) was
added, also at –78 °C. The mixture was brought to r.t. and stirred for
30 min. Sat. aq NH4Cl (50 mL) was added to quench the reaction
and the resulting mixture was extracted with CH2Cl2 (3 × 20 mL).
The organic layer was washed with H2O and brine then dried
(Na2SO4) and concentrated in vacuo. The crude aldehyde was used
in the next step without further purification.
t-BuOK (6.72 g, 59.5 mmol) was added to a stirred soln of Ph3P+Et
I– (24.82 g, 59.5 mmol) in THF (200 mL), and the mixture was
stirred for 30 min at 0 °C. A soln of the crude aldehyde in THF (20
mL) was then added through a cannula, and the resulting mixture
was stirred for 1 h. The reaction was quenched with sat. aq NH4Cl
(100 mL) and the mixture was extracted with Et2O (3 × 40 mL). The
combined organic layers were washed with brine, dried (Na2SO4),
27
Synthesis 2010, No. 10, 1621–1624 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of Ophiocerin C
1623
2,3-Anhydro-6-O-benzyl-1-deoxy-D-galactitol (9)
6-O-Benzyl-2-O-[tert-butyl(dimethyl)silyl]-1,3-dideoxy-4,5-O-
(1-methylethylidene)-D-xylo-hexitol (12)
A stirred soln of diol 8 (2.47 g, 11.1 mmol) in CH2Cl2 (30 mL) was
cooled to 0 °C and then NaHCO3 (1.21 g, 14.4 mmol) and MCPBA
(2.48 g, 14.4 mmol) were added successively at 0 °C, and the mix-
ture was stirred at r.t. for 10 h. The reaction was quenched with sat.
aq NaHCO3. The mixture was extracted with CH2Cl2 (3 × 20 mL),
and the combined organic layers were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The residue was purified by
column chromatography [silica gel, EtOAc–hexane (1:1)] to give a
white solid; yield: 90%; mp 49–50 °C; [a]D26 +3.4 (c 0.6, CHCl3).
Me2C(OMe)2 (2.4 mL, 19.2 mmol) and PPTS (230 mg, 1.0 mmol)
were added to a soln of diol 11 (3.40 g, 9.6 mmol) in CH2Cl2 (30
mL), and the mixture was stirred at r.t. for 3 h. The reaction was then
quenched with sat. aq NaHCO3 (20 mL). The aqueous layer was ex-
tracted with CH2Cl2 (2 × 20 mL) and the combined organic layers
were dried (Na2SO4) and concentrated under reduced pressure. The
crude product was purified by column chromatography [silica gel,
EtOAc–hexane (1:9)] to give a pale yellow oil; yield: 94%;
[a]D27 –16.3 (c 1.8, CHCl3)
IR (KBr): 3319, 2928, 1452, 1129, 1057, 742 cm–1.
IR (neat): 2931, 1456, 1252, 1096, 834, 736 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.31 (m, 5 H), 4.54 (s, 2 H),
3.78 (m, 1 H), 3.59–3.53 (m, 3 H), 3.14–3.03 (m, 2 H), 2.71 (br s, 2
H, OH), 1.31 (d, J = 5.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.5, 128.3, 127.7, 127.6, 73.4,
71.3, 71.1, 69.7, 57.9, 53.2, 13.6.
ESI-HRMS: m/z [M + Na]+ calcd for C13H18NaO4: 261.2710; found:
261.2718.
1H NMR (300 MHz, CDCl3): d = 7.38–7.19 (m, 5 H), 4.56 (ABq, 2
H), 4.06–3.91 (m, 2 H), 3.69 (m, 1 H), 3.57–3.47 (m, 2 H), 1.68–
1.45 (m, 2 H), 1.37 (s, 3 H), 1.34 (s, 3 H), 1.15 (d, J = 6.0 Hz, 3 H),
0.87 (s, 9 H), 0.05 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 138.0, 128.3, 127.6, 127.5, 108.6,
80.1, 74.8, 73.5, 70.4, 65.5, 43.0, 27.4, 26.8, 25.8, 24.7, 18.0, –4.4,
–4.9.
6-O-Benzyl-1,3-dideoxy-D-xylo-hexitol (10)
ESI-HRMS: m/z [M + Na]+ calcd for C22H38NaO4Si: 417.6130;
found: 417.6126.
A 65% w/v soln of Red-Al in toluene (8.3 mL, 26.7 mmol) was add-
ed to a stirred soln of 9 (2.11 g, 8.9 mmol) in THF (30 mL) under
N2 at 0 °C. The mixture was allowed to warm to r.t. over 1 h and
stirred for a further 4 h. The reaction was quenched with sat. aq
NH4Cl (30 mL), and the mixture was filtered through Celite. The
filtrate was extracted with CH2Cl2 (3 × 20 mL) and the organic layer
was washed with brine, dried (Na2SO4), and concentrated in vacuo.
The residue was purified by column chromatography [silica gel,
EtOAc–hexane (2:1)] to give a colorless oil; yield 92%; [a]D26 –3.4
(c 0.6, CHCl3).
2-O-[tert-Butyl(dimethyl)silyl]-1,3-dideoxy-4,5-O-(1-methyleth-
ylidene)-D-xylo-hexitol (13)
A soln of 12 (0.90 g, 2.3 mmol) in EtOAc (5 mL) was treated with
10% Pd/C (121 mg, 0.1 mmol) under H2 pressure for 2 h. Then the
mixture was then filtered through Celite, which was washed with
EtOAc (10 mL). The combined organic layers were concentrated in
vacuo to give a residue that was purified by column chromatogra-
phy [silica gel, EtOAc–hexane (3:7)] to give a colorless oil; yield:
96%; [a]D27 –21 (c 0.2, CHCl3).
IR (neat): 3388, 2924, 1459, 1052, 767 cm–1.
IR (neat): 3456, 2931, 1465, 1252, 1049, 834 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.28 (m, 5 H), 4.54 (ABq, 2
H), 4.15 (dd, J = 7.5, 14.3 Hz, 2 H), 3.91 (br s, 1 H), 3.69–3.54 (m,
3 H), 1.80 (m, 1 H), 1.61 (m, 1 H), 1.18 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.5, 128.4, 127.8, 127.7, 73.4,
72.8, 71.9, 69.2, 64.7, 41.4, 23.4.
ESI-HRMS: m/z [M + Na]+ calcd for C13H20NaO4: 263.2868; found:
263.2863.
1H NMR (300 MHz, CDCl3): d = 4.04–3.94 (m, 2 H), 3.72 (m, 1 H),
3.64–3.49 (m, 2 H), 1.90 (br s, 1 H, OH), 1.62–1.47 (m, 2 H), 1.38
(s, 3 H), 1.35 (s, 3 H), 1.16 (d, J = 5.9 Hz, 3 H), 0.88 (s, 9 H), 0.06
(s, 6 H).
13C NMR (100 MHz, CDCl3): d = 108.6, 81.5, 73.6, 65.6, 61.9, 42.8,
27.4, 26.9, 25.8, 24.7, 18.0, –4.4, –4.9.
ESI-HRMS: m/z [M + Na]+ calcd for C15H32NaO4Si: 327.4886;
6-O-Benzyl-2-O-[tert-butyl(dimethyl)silyl]-1,3-dideoxy-D-xylo-
hexitol (11)
found: 327.4891.
Imidazole (1.36 g, 20.0 mmol) and TBDMSCl (2.26 g, 15.0 mmol)
were added to a stirred soln of triol 10 (3.0 g, 12.5 mmol) in CH2Cl2
(30 mL) at r.t., and the resulting mixture was stirred for 3 h. The re-
action was quenched with sat. aq NH4Cl (20 mL), and the mixture
was extracted with CH2Cl2 (3 × 15 mL). The combined organic lay-
ers were washed with H2O, brine, dried (Na2SO4), and concentrated
under reduced pressure. The residue was purified by column chro-
matography [silica gel, EtOAc–hexane (3:7)] to give a pale yellow
oil; yield: 90%; [a]D26 –6.1 (c 0.8, CHCl3).
2-O-[tert-Butyl(dimethyl)silyl]-1,3-dideoxy-4,5-O-(1-methyleth-
ylidene)-6-O-[(4-methylphenyl)sulfonyl]-D-xylo-hexitol (14)
Et3N (0.5 mL, 3.6 mmol) and DMAP (22 mg, 0.2 mmol) were added
to a soln of alcohol 13 (555 mg, 1.8 mmol) in CH2Cl2 (5 mL) at r.t.,
and the mixture was stirred for 10 min. TsCl (451 mg, 2.4 mmol)
was then added and stirring was continued at r.t. for 3 h. The reac-
tion was quenched with sat. aq NH4Cl (20 mL), and the mixture was
extracted with CH2Cl2 (3 × 15 mL). The combined organic layers
were washed with H2O and brine then dried (Na2SO4) and concen-
trated under reduced pressure. The residue was purified by column
chromatography [silica gel, EtOAc–hexane (3:7)] to give a pale yel-
low oil; yield: 92%; [a]D27 –16.8 (c 0.5, CHCl3)
IR (neat): 3442, 2929, 1462, 1252, 1076, 834, 737 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.21 (m, 5 H), 4.53 (ABq, 2
H), 4.16 (m, 1 H), 3.90 (m, 1 H), 3.58–3.47 (m, 3 H), 3.12 (br s, 1
H, OH), 2.56 (br s, 1 H, OH), 1.73 (m, 1 H), 1.41 (m, 1 H), 1.20 (d,
J = 5.8 Hz, 3 H), 0.89 (s, 9 H), 0.08 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 137.8, 128.4, 127.7, 73.5, 73.1,
72.1, 68.5, 66.7, 41.2, 25.7, 23.1, 17.9, –4.5, –5.0.
IR (neat): 2930, 1463, 1252, 1180, 834, 777 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.79 (d, J = 8.3 Hz, 2 H), 7.33 (d,
J = 7.9 Hz, 2 H), 4.11 (m, 1 H), 4.05–3.92 (m, 3 H), 3.72 (m, 1 H),
2.44 (s, 3 H), 1.61–1.49 (m, 2 H), 1.35 (s, 3 H), 1.29 (s, 3 H), 1.13
(d, J = 6.0 Hz, 3 H), 0.86 (s, 9 H), 0.04 (s, 3 H), 0.03 (s, 3 H)
13C NMR (75 MHz, CDCl3): d = 144.6, 133.2, 129.8, 128.1, 109.2,
78.2, 74.3, 68.7, 65.2, 42.8, 27.5, 26.7, 24.9, 24.8, 21.7, 18.1, –4.2,
–4.8.
ESI-HRMS: m/z [M + Na]+ calcd for C19H34NaO4Si: 400.5386;
found: 400.5384.
ESI-HRMS: m/z [M + Na]+ calcd for C22H38NaO6SSi: 481.6710;
found: 481.6716.
Synthesis 2010, No. 10, 1621–1624 © Thieme Stuttgart · New York

1624
J. S. Yadav et al.
PAPER
1,3-Dideoxy-4,5-O-(1-methylethylidene)-6-O-[(4-methylphe-
nyl)sulfonyl]-D-xylo-hexitol (15)
J = 1.5, 4.5, 12.8 Hz, 1 H), 1.31 (ddd, J = 10.8, 10.8, 12.8 Hz, 1 H),
1.17 (d, J = 6.1 Hz, 3 H)
A 1 M soln of TBAF in THF (0.7 mL, 0.7 mmol) was added to a
stirred soln of 14 (250 mg, 0.5 mmol) in dry THF (10 mL) at r.t.,
and the mixture was stirred for 2 h. The reaction was quenched with
sat. aq NH4Cl (20 mL), and the mixture was extracted with CH2Cl2
(3 × 15 mL). The combined organic layers were washed with H2O
and brine then dried (Na2SO4) and concentrated in vacuo. The crude
product was purified by column chromatography [silica gel,
EtOAc–hexane (1:5)] to give a colorless oil; yield: 90%; [a]D27 +2
(c 0.2, CHCl3).
13C NMR (75 MHz, CDCl3): d = 73.3, 72.6, 72.3, 69.6, 40.5, 21.2.
ESI-HRMS: m/z [M + Na]+ calcd for C6H12NaO3: 155.1476; found:
155.1472.
Acknowledgment
N.R.R., B.B.M.K. and Ch.V.V. thank CSIR, New Delhi, for the
award of fellowships.
IR (neat): 3443, 2926, 1456, 1178, 780 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 8.3 Hz, 2 H), 7.34 (d,
J = 8.3 Hz, 2 H), 4.19–3.89 (m, 4 H), 3.82 (m, 1 H), 2.47 (s, 3 H),
1.74–1.64 (m, 2 H), 1.36 (s, 3 H), 1.30 (s, 3 H), 1.21 (d, J = 6.2 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 145.0, 135.1, 129.8, 127.9, 109.5,
77.9, 75.2, 68.8, 65.0, 40.9, 29.6, 27.1, 26.5, 21.6.
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29, 1671. (d) Lee, D. M.; Kang, H. Y. Bull. Korean Chem.
Soc. 2009, 30, 1929.
(8) El-Hamamsy, M. H. R. I.; Smith, A. W.; Thompson, A. S.;
Threadgill, M. D. Bioorg. Med. Chem. 2007, 15, 4552.
(9) (a) Chautemps, P.; Pierre, J.-L. Tetrahedron 1976, 32, 549.
(b) Shang, S.; Iwadare, H.; Macks, D. E.; Ambrosini, L. M.;
Tan, D. S. Org. Lett. 2007, 9, 1895.
ESI-HRMS: m/z [M + Na]+ calcd for C16H24NaO6S: 367.4094;
found: 367.4097.
Ophioerin C (3)
A soln of the tosylate 15 (151 mg, 0.4 mmol) in dry Et2O (3 mL)
was added to a stirred suspension of t-BuOK (99.4 mg, 0.9 mmol)
in dry Et2O (5 mL) at 0 °C, and the mixture was stirred for 2 h at
0 °C. The reaction was quenched with sat. aq NH4Cl (20 mL), and
the mixture was extracted with Et2O (2 × 5 mL). The combined or-
ganic layers were washed with H2O and brine then treated with
PTSA (10 mg) and MeOH (10 mL) with stirring at r.t. for 2 h. The
reaction was quenched with sat. aq NaHCO3 soln, and the solvents
(MeOH and Et2O) were evaporated under reduced pressure. The
residue was extracted with CH2Cl2 (3 × 20 mL) and the combined
organic layers were washed with H2O and brine then dried (Na2SO4)
and concentrated. The residue was purified by column chromatog-
raphy [silica gel, EtOAc–hexane (6:4)] to give a white solid; yield:
88% (2 steps); m.p. 82–83 °C; [a]D26 +42 (c 0.1, CHCl3)
IR (KBr): 3390, 2921, 1460, 1376, 1176, 1025 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.90 (dd, J = 5.3, 11.3 Hz, 1 H),
3.58–3.36 (m, 3 H), 3.08 (dd, J = 10.5, 11.3 Hz, 1 H), 1.94 (ddd,
(10) Hatakeyama, S.; Satoh, K.; Takano, S. Tetrahedron Lett.
1993, 34, 7425.
Synthesis 2010, No. 10, 1621–1624 © Thieme Stuttgart · New York