A concise stereoselective total synthesis of synargentolide a from 3,4,6-Tri- O -acetyl- D -glucal

Article abstract of DOI:10.1055/s-0030-1258458

A short and highly stereoselective synthesis of the naturally occurring,-unsaturated lactone synargentolide A is described from the chiral starting material 3,4,6-tri-O-acetyl-d-glucal. Key steps of the synthesis are lactol opening, Brown's asymmetric all

Full text of DOI:10.1055/s-0030-1258458

PAPER
1279
A Concise Stereoselective Total Synthesis of Synargentolide A from
3,4,6-Tri-O-acetyl-D-glucal
Total
S
ynthesis of
o
Synargentoli
w
de A from 3, 4,6-T
r
r
i-
O
-ace
a
tyl-
D
-gluca
v
l
aram Sabitha,* S. Siva Sankara Reddy, Atla Raju, Jhillu S. Yadav1
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India
Fax +91(40)27160512; E-mail: gowravaramsr@yahoo.com; E-mail: sabitha@iict.res.in
Received 31 December 2010
temperature provided the methyl compound 11 in 85%
yield (Scheme 2). Subsequent pyridinium chlorochromate
oxidation of the di-MOM ether 11 gave lactone 6 in 84%
yield. The lactone 6 was reduced to a lactol using diisobu-
tylaluminum hydride, which without purification was
subjected to Wittig olefination using the stabilized two
carbon ylide, ethyl (triphenylphosphoranylidene)acetate
in refluxing benzene to furnish the required open chain
a,b-unsaturated ester 12 with three requisite chiral centers
at C4¢, C5¢, and C6¢. Protection of the free hydroxy group
as its MOM ether afforded tri-MOM ether 7.
Abstract: A short and highly stereoselective synthesis of the natu-
rally occurring, a,b-unsaturated lactone synargentolide A is de-
scribed from the chiral starting material 3,4,6-tri-O-acetyl-D-glucal.
Key steps of the synthesis are lactol opening, Brown’s asymmetric
allylation, and a ring-closing metathesis (RCM) reaction.
Key words: 3,4,6-tri-O-acetyl-D-glucal, d-lactones, synargento-
lide, Brown’s allylation, RCM
(+)-Synargentolide A (1) (Figure 1) belongs to a family of
polyacetate pyranone-containing natural products that
have been found to exhibit a broad spectrum of biological
activity. In 1998, Davies-Coleman and Rivett2 isolated
synargentolide A from Syncolostemon argenteus and the
structure was proposed as 2 on the basis of spectroscopic
analysis, Mosher’s method, and acetonide formation.
However, chemical synthesis of the proposed structure of
2 by the Marco group revealed that synthetic 2 was not
identical to natural synargentolide A.3 Recently, we re-
ported that the correct structure of natural synargentolide
A is structure 1 following total synthesis.4 The synthesis
used a cross-metathesis (CM) reaction as a key step.
Based on our revised structure 1, a report appeared.5 With-
in our recently initiated program on the synthesis of natu-
ral lactones cryptopyramnoscatone B1 (3)6a and A1 (4)6b
from the chiral pool compound 3,4,6-tri-O-acetyl-D-glu-
cal (5), we have now devised a concise stereoselective to-
tal synthesis for synargentolide A.
OAc
1'
5
3'
6'
4'
5'
4
3
6
2'
OAc
OAc
O
OAc
1
1'
2
3'
5
4'
6'
5'
4
3
O
6
2'
revised structure of
synargentolide A (1)
OAc
OAc
O
1
2
O
published structure of
synargentolide A (2)
OH
HO
O
O
OH
HO
O
O
O
cryptopyranmoscatone B1 (3)
The retrosynthetic concept is depicted in Scheme 1. It was
envisaged that the target molecule 1 could be achieved
from 8 by acrylation followed by RCM reaction, whereas
8 can be obtained from 7 by Brown’s asymmetric allyla-
tion. Compound 7 in turn could be made from 6 by lactone
opening. Lactone 6 is accessible from 3,4,6-tri-O-acetyl-
D-glucal (5) by a successive sequence of reactions.
O
cryptopyranmoscatone A1 (4)
Figure 1 a,b-Unsaturated d-lactones
OAc
OMOM
The synthesis of 1 began with commercially available tri-
O-acetyl-D-glucal (5), deacetylation of which followed by
selective silylation at the CH2OH group, followed by
MOM protection at C3 and C4, and then removal of the si-
lyl protecting group afforded the alcohol 9 as reported.6a
Tosylation of the primary hydroxy group in 9 (TsCl, Et3N,
CH2Cl2) furnished tosylate 10, which on treatment with
lithium aluminum hydride in tetrahydrofuran at reflux
O
OAc OAc
MOMO
OMOM
OH
8
synargentolide A (1)
O
OAc
AcO
OMOM
OMOM
MOMO
CO2Et
AcO
O
O
O
MOMO
OMOM
5
6
7
SYNTHESIS 2011, No. 8, pp 1279–1282
Advanced online publication: 03.03.2011
x
x
.
x
x
.2
0
1
1
Scheme 1 Retrosynthetic analysis for synargentolide A (1)
DOI: 10.1055/s-0030-1258458; Art ID: Z58410SS
© Georg Thieme Verlag Stuttgart · New York

1280
G. Sabitha et al.
PAPER
To establish a chiral center at C6, the diastereoselective hydroxy functions was achieved in 79% overall yield to
allylation reaction was studied. In this context, the ester afford 1, identical in its physical and spectral properties to
group in compound 7 was directly converted into the alde- the natural compound2 and synthetic material.4
hyde by diisobutylaluminum hydride affording E-enal 13
In summary, a concise total synthesis of the natural lac-
tone synargentolide A (1) has been achieved in a highly
stereoselective way using 3,4,6-tri-O-acetyl-D-glucal (5)
as the chiral starting material.
in 75% yield followed by Brown’s asymmetric allylation7
using B-allyldiisocampheylborane to furnish the homoal-
lylic alcohol 8 as a single diastereomer in 70% yield. Acy-
lation of 8 with acryloyl chloride furnished acrylate 14,
which was then subjected to ring-closing metathesis in the
Reactions were conducted under N2 in anhyd solvents such as
presence of Grubbs’ standard ruthenium catalyst
CH2Cl2, THF, and EtOAc. All reactions were monitored by TLC
[PhCH=RuCl2(PCy3)2].8
(silica-coated plates and visualizing under UV light). n-Hexane (bp
60–80 °C) was used. Yields refer to chromatographically and spec-
troscopically (1H and 13C NMR) homogeneous material. Air-sensi-
tive reagents were transferred by syringe or double-ended needle.
Evaporation of solvents was performed at reduced pressure on a
OMOM
O
OAc
OMOM
MOMO
AcO
AcO
MOMO
RO
ref. 5
b
1
Buchi rotary evaporator. H and 13C NMR spectra of samples in
O
O
CDCl3 were recorded on Varian FT-400 and Bruker UXNMR FT-300
(Avance) spectrometers; spectra are reported relative to TMS as an
internal standard. Mass spectra were recorded E1 conditions at 70
eV on ES-MSD (Agilent technologies) spectrometers. Column
chromatography was performed on silica gel (60–120 mesh) sup-
plied by Acme Chemical Co., India. TLC was performed on Merck
60 F-254 silica gel plates. Optical rotations were measured with a
Jasco DIP-370 Polarimeter.
5
9 R = H
10 R = Ts
11
a
OMOM
OMOM
MOMO
c
d
f
CO2Et
O
O
OR
e
OMOM
12 R = H
7 R = MOM
6
[(2R,3S,4R)-3,4-Bis(methoxymethoxy)-3,4-dihydro-2H-pyran-
2-yl]methyl 4-Methylbenzenesulfonate (10)
OMOM
OMOM
g
h
Et3N (0.91 mL, 6.39 mmol), and DMAP (cat.) were added to a soln
of 9 (1.0 g, 4.27 mmol) in anhyd CH2Cl2 (15 mL) at 0 °C. TsCl (977
mg, 5.12 mmol) was then added to the stirred soln. The resulting
mixture was allowed to warm to r.t., stirred for 0.5 h, treated with 1
M aq HCl (3 mL), and extracted with CH2Cl2 (3 × 100 mL). The or-
ganic layer was washed sequentially with sat. NaHCO3 (30 mL) and
H2O (20 mL), and the combined organic phases were dried
(Na2SO4) and concentrated. The residue was purified by column
chromatography (silica gel, PE–EtOAc, 7:3) to give 10 (1.48 g,
90%) as a colorless syrup; Rf = 0.6 (PE–EtOAc, 7:3).
CHO
MOMO
OMOM
8
OH
MOMO
MOMO
OMOM
13
OMOM
OMOM
i
OMOM
O
OMOM
O
MOMO
O
O
14
15
[a]D25 +60.5 (c 0.9, CHCl3).
IR (neat): 2949, 2826, 2360, 1447, 1177, 1034, 972, 815, 760 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.79 (d, J = 8.30 Hz, 2 H), 7.32 (d,
J = 8.30 Hz, 2 H), 6.20 (dd, J = 6.04, 1.51 Hz, 1 H), 4.85–4.73 (m,
2 H), 4.69–4.61 (m, 3 H), 4.32–4.24 (m, 2 H), 4.18–4.10 (m, 1 H),
4.05–3.99 (m, 1 H), 3.78–3.72 (m, 1 H), 3.36 (s, 3 H), 3.33 (s, 3 H),
2.46 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 144.7, 143.5, 132.8, 129.7, 127.9,
100.0, 96.5, 95.2, 74.1, 71.8, 70.5, 67.6, 55.9, 55.4, 21.5.
P
Ru
P
OAc
Cl
Ph
j
Cl
O
OAc OAc
O
synargentolide A (1)
MS (ESI): m/z = 411 [M + Na]+.
Grubbs I catalyst
(2R,3R,4R)-3,4-Bis(methoxymethoxy)-2-methyl-3,4-dihydro-
2H-pyran (11)
Scheme 2 Reagents and conditions: (a) TsCl, Et3N, DMAP (cat.),
CH2Cl2, 0 °C–r.t., 0.5 h, 90%; (b) LiAlH4, THF, reflux, 1 h, 85%; (c)
PCC, silica gel, CH2Cl2, reflux, 8 h, 84%; (d) (i) DIBAL-H, CH2Cl2,
0 °C, 1 h; (ii) Ph3P=CHCOO2Et, benzene, reflux, 6 h, 89% (over 2
steps); (e) MOMCl, DIPEA, CH2Cl2, 0 °C–r.t., 8 h, 93%; (f) DIBAL-
H, CH2Cl2, –78 °C, 0.5 h, 75%; (g) 1.0 M (+)-IPC2B(allyl) in pentane,
Et2O, –100 °C, 3 h, 70%; (h) acryloyl chloride, Et3N, CH2Cl2, 0 °C–
r.t., 0.5 h, 86%; (i) Grubbs I catalyst (10 mol%), CH2Cl2, reflux, 5 h,
85%; (j) (i) 4 M HCl, MeCN–H2O (4:1), 0 °C, 6 h; (ii) Ac2O, py,
CH2Cl2, 0 °C, 1 h, 79% (over 2 steps).
To a stirred suspension of LiAlH4 (190 mg, 5.0 mmol) in anhyd
THF (40 mL) at 0 °C was added dropwise a soln of 10 (1.3 g, 3.35
mmol) in anhyd THF (10 mL). The mixture was allowed to warm to
reflux temperature and stirred for 1 h. It was then cooled to 0 °C, di-
luted with EtOAc (20 mL), and quenched by dropwise addition of
sat. Na2SO4 soln (10 mL). The solid material was filtered through a
Celite pad and washed thoroughly with hot EtOAc (3 × 30 mL). The
combined organic layers were dried (anhyd Na2SO4). Removal of
solvent under reduced pressure and purification by column chroma-
tography (silica gel, PE–EtOAc, 7:3) afforded 11 (620 mg, 85%) as
a colorless oil; Rf = 0.8 (PE–EtOAc, 7:3).
The expected conjugated d-lactone 15 was formed in good
yield. Finally, cleavage of all three MOM protecting
groups of 15 followed by acetylation of the three liberated
[a]D25 +24.2 (c 0.95, CHCl3).
IR (neat): 2937, 2892, 1218, 1106, 1035 cm–1.
Synthesis 2011, No. 8, 1279–1282 © Thieme Stuttgart · New York

PAPER
Total Synthesis of Synargentolide A from 3,4,6-Tri-O-acetyl-D-glucal
1281
1H NMR (300 MHz, CDCl3): d = 6.29 (dd, J = 6.04, 1.32 Hz, 1 H),
4.87 (d, J = 6.61 Hz, 1 H), 4.78 (dd, J = 6.23, 2.83 Hz, 1 H), 4.70–
4.64 (m, 3 H), 4.14–4.09 (m, 1 H), 4.01–3.90 (m, 1 H), 3.58–3.52
(m, 1 H), 3.39 (s, 3 H), 3.37 (s, 3 H), 1.36 (d, J = 6.61 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 144.3, 100.3, 96.8, 95.6, 77.1, 73.6,
73.5, 55.9, 55.4, 17.0.
Ethyl (E,5R,6R,7R)-5,6,7-Tris(methoxymethoxy)oct-2-enoate
(7)
To a cooled (0 °C) soln of 12 (300 mg, 0.98 mmol) in CH2Cl2 (10
mL) were added sequentially DIPEA (0.48 mL, 2.94 mmol) and
MOMCl (0.11 mL, 1.45 mmol) and the mixture was stirred at r.t. for
8 h. The solvent was removed in vacuo and the residue was purified
by column chromatography (silica gel, PE–EtOAc, 7:3) to afford 7
(318 mg, 93%) as a colorless liquid; Rf = 0.5 (PE–EtOAc, 7:3).
MS (ESI): m/z = 241 [M + Na]+.
[a]D25 +8.3 (c 0.9, CHCl3).
IR (neat): 2937, 2825, 2360, 1719, 1655, 1446, 1269, 1029 cm–1.
(4R,5R,6R)-4,5-Bis(methoxymethoxy)-6-methyltetrahydro-2H-
pyran-2-one (6)
To a soln of 11 (500 mg, 2.29 mmol) in CH2Cl2 (30 mL) was added
a mixture of PCC (1.48 g, 6.88 mmol) and silica gel (2 g). The
stirred suspension was refluxed for 8 h and then cooled and filtered
through Celite. The Celite pad was washed several times with
EtOAc, and the combined filtrates were concentrated. The crude
product was purified by column chromatography (silica gel, PE–
EtOAc, 7:3) to give 6 (450 mg, 84%) as a white solid; Rf = 0.2 (PE–
EtOAc, 7:3); mp 56–58 °C.
1H NMR (300 MHz, CDCl3): d = 7.06–6.94 (m, 1 H), 5.93 (dt,
J = 15.86, 1.51 Hz, 1 H), 4.81–4.63 (m, 6 H), 4.19 (q, J = 7.55 Hz,
2 H), 3.91–3.78 (m, 2 H), 3.61 (t, J = 4.53 Hz, 1 H), 3.43 (s, 3 H),
3.39 (s, 3 H), 3.37 (s, 3 H), 2.67–2.55 (m, 1 H), 2.52–2.40 (m, 1 H),
1.29 (t, J = 7.55 Hz, 3 H), 1.25 (d, J = 6.79 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.1, 144.7, 123.7, 97.6, 96.9,
95.0, 80.9, 76.6, 72.8, 60.1, 55.9, 55.8, 55.3, 34.6, 15.9, 14.1.
MS (ESI): m/z = 373 [M + Na]+.
[a]D25 +95.0 (c 0.8, CHCl3).
IR (neat): 2941, 2896, 1749, 1445, 1238, 1025 cm–1.
(E,5R,6R,7R)-5,6,7-Tris(methoxymethoxy)oct-2-enal (13)
DIBAL-H (0.35 mL, 0.57 mmol) was added to a stirred soln of ester
7 (200 mg, 0.57 mmol) in CH2Cl2 (5 mL) at –78 °C and the mixture
was allowed to stir at this temperature for 0.5 h (TLC monitoring).
The reaction was quenched with aq MeOH at 0 °C. Then sat. sodi-
um potassium tartrate soln was added, and the mixture was extract-
ed with CH2Cl2 (3 × 5 mL). The combined organic layers were
washed with brine (2 × 2 mL) and H2O (2 × 2 mL), dried (anhyd
Na2SO4), and concentrated under vacuum. The crude aldehyde was
purified by column chromatography (silica gel, PE–EtOAc, 7:3) to
afford 13 (131 mg, 75%) as a colorless liquid; Rf = 0.4 (PE–EtOAc,
7:3).
[a]D25 +4.3 (c 1.15, CHCl3).
IR (neat): 2939, 2826, 2362, 1692, 1447, 1150, 1031 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.52 (d, J = 7.74 Hz, 1 H), 6.93–
6.81 (m, 1 H), 6.19 (dt, J = 15.86, 1.32 Hz, 1 H), 4.80–4.57 (m, 6
H), 3.90–3.75 (m, 2 H), 3.60 (t, J = 4.53 Hz, 1 H), 3.40 (s, 3 H), 3.36
(s, 3 H), 3.34 (s, 3 H), 2.79–2.67 (m, 1 H), 2.62–2.48 (m, 1 H), 1.22
(d, J = 6.42 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 4.80 (d, J = 6.79 Hz, 1 H), 4.70–
4.60 (m, 3 H), 4.21–4.10 (m, 1 H), 4.07–4.02 (m, 1 H), 3.59 (dd,
J = 7.74, 2.45 Hz, 1 H), 3.38 (d, J = 7.93 Hz, 6 H), 2.80 (dd,
J = 16.05, 4.34 Hz, 1 H), 2.68 (dd, J = 15.48, 4.15 Hz, 1 H), 1.48 (d,
J = 6.42 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 169.8, 96.1, 95.2, 78.3, 75.9, 73.5,
55.9, 55.6, 34.2, 18.8.
MS (ESI): m/z = 257 [M + Na]+.
Ethyl (E,5R,6R,7R)-7-Hydroxy-5,6-bis(methoxymethoxy)oct-2-
enoate (12)
A stirred soln of 6 (350 mg, 1.49 mmol) in CH2Cl2 (15 mL) was
cooled to 0 °C, then 1.6 M DIBAL-H in toluene (1.86 mL) was add-
ed slowly. After 1 h, the reaction was quenched with MeOH (1 mL)
and aq potassium sodium tartrate (5 mL), and stirred at r.t. for 0.5 h.
The layers were separated and the aqueous layer was extracted with
CH2Cl2 (3 × 20 mL). The combined organic layers were washed
with brine (2 × 10 mL), dried (anhyd Na2SO4), filtered, and concen-
trated in vacuo to afford the crude lactol. This was used for the next
step without further purification.
13C NMR (75 MHz, CDCl3): d = 193.7, 154.3, 134.9, 97.7, 97.2,
95.1, 81.0, 76.8, 72.9, 56.0 (d, 2 C), 55.5, 35.3, 16.1.
To a soln of the above lactol in benzene (10 mL) was added
Ph3P=CHCO2Et (572 mg, 1.64 mmol) and the mixture was stirred
at reflux for 6 h. After completion of the reaction (TLC monitoring),
benzene was removed under reduced pressure, the residue was dis-
solved in Et2O, and petroleum ether was added. The triphenylphos-
phine oxide that crystallized out was filtered off and the filtrate was
concentrated to dryness. The crude product was purified by column
chromatography (silica gel, PE–EtOAc, 7:3) to afford the pure a,b-
unsaturated ester 12 (406 mg, 89%) as a colorless oil; Rf = 0.3 (PE–
EtOAc, 7:3).
MS (ESI): m/z = 329 [M + Na]+.
(4R,5E,8R,9R,10R)-8,9,10-Tris(methoxymethoxy)undeca-1,5-
dien-4-ol (8)
A soln of 1.0 M (+)-IPC2B(allyl) in pentane (0.21 mL, 0.47 mmol)
in Et2O (2 mL) was cooled to –100 °C and a soln of aldehyde 13
(100 mg, 0.32 mmol) in Et2O (10 mL) was added slowly. The mix-
ture was stirred at –100 °C for 3 h and then warmed to 0 °C. The
reaction was quenched by the dropwise addition of aq 30% H2O2
(0.2 mL) and 1 M NaOH (0.3 mL). The mixture was diluted with
EtOAc (10 mL) and the layers were separated. The aqueous layer
was extracted with EtOAc (3 × 10 mL). The combined organic lay-
ers were washed with brine (2 × 4 mL), dried (MgSO4), filtered, and
concentrated. The crude mixture was further purified by column
chromatography (silica gel, PE–EtOAc, 7:3) to give homoallyl al-
cohol 8 (79 mg, 70%) as a clear liquid; Rf = 0.3 (PE–EtOAc, 7:3).
[a]D25 –10.4 (c 1.15, CHCl3).
IR (neat): 3456, 2932, 2825, 2337, 1444, 1218, 1103, 1032 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.88–5.46 (m, 3 H), 5.17–5.02 (m,
2 H), 4.77–4.53 (m, 6 H), 4.14–4.01 (m, 1 H), 3.88–3.76 (m, 1 H),
3.74–3.53 (m, 2 H), 3.37 (s, 9 H), 2.57–2.02 (m, 4 H), 1.16 (d,
J = 6.04 Hz, 3 H).
[a]D25 +6.8 (c 0.95, CHCl3).
IR (neat): 3488, 2937, 2826, 1719, 1653, 1447, 1269, 1177, 1024
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.00–6.88 (m, 1 H), 5.89 (dt,
J = 15.67, 1.32 Hz, 1 H), 4.73–4.59 (m, 4 H), 4.17 (q, J = 7.17 Hz,
2 H), 3.90–3.78 (m, 2 H), 3.48–3.46 (m, 1 H), 3.42 (s, 3 H), 3.39 (s,
3 H), 3.28–3.22 (br m, OH), 2.63–2.51 (m, 1 H), 2.50–2.38 (m, 1 H),
1.30 (t, J = 7.17 Hz, 3 H), 1.20 (d, J = 6.23 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.0, 144.4, 123.8, 98.2, 96.9,
84.5, 77.1, 66.6, 60.1, 56.0 (d, 2 C), 33.9, 18.9, 14.1.
MS (ESI): m/z = 329 [M + Na]+.
Synthesis 2011, No. 8, 1279–1282 © Thieme Stuttgart · New York

1282
G. Sabitha et al.
PAPER
(1R,2R,4E)-2-Acetoxy-1-[(1R)-1-acetoxyethyl]-5-[(2R)-6-oxo-
3,6-dihydro-2H-pyran-2-yl]pent-4-enyl Acetate [Synargen-
tolide A (1)]
13C NMR (75 MHz, CDCl3): d = 135.9, 134.4, 126.7, 117.5, 97.5,
96.7, 94.6, 79.5, 77.6, 72.3, 72.1, 55.8 (d, 2 C), 55.4, 41.6, 34.6,
15.4.
To a stirred soln of 15 (25 mg, 0.067 mmol) in MeCN–H2O (4:1, 5
mL) was added 4 M HCl (2 mL) at 0 °C and the mixture was stirred
at this temperature for 6 h. The mixture was quenched with solid
NaHCO3 (20 mg) and filtered, the solvent was removed under re-
duced pressure and the crude triol was used for further reactions.
MS (ESI): m/z = 371 [M + Na]+.
(1R,2E,5R,6R,7R)-1-Allyl-5,6,7-tris(methoxymethoxy)oct-2-
enyl Acrylate (14)
Acryloyl chloride (0.02 mL, 0.24 mmol) was added dropwise under
N2 to a soln of 8 (70 mg, 0.20 mmol) and Et3N (0.06 mL, 0.42
mmol) in CH2Cl2 (5 mL). The mixture was stirred at 0 °C for 0.5 h.
After completion, the mixture was poured into brine (2 mL) and ex-
tracted with CH2Cl2 (2 × 5 mL). The combined organic phases were
washed with 1 M aq HCl, dried (Na2SO4), and concentrated. The
crude product was purified by column chromatography (silica gel,
PE–EtOAc, 7:3) to afford the corresponding acrylic ester 14 (68
mg, 86%) as a colorless oil; Rf = 0.8 (PE–EtOAc, 7:3).
Pyridine (0.03 mL, 0.37 mmol) and Ac2O (0.02 mL, 0.20 mmol)
were added sequentially to a stirred soln of the above triol in anhyd
CH2Cl2 (3 mL) at 0 °C. The mixture was stirred for 1 h and then di-
luted with CH2Cl2 (10 mL). The organic layer was washed sequen-
tially with 5% aq NaHCO3 (2 × 3 mL) and brine (2 × 3 mL), dried
(Na2SO4), and concentrated under reduced pressure. The residue
was purified by column chromatography (silica gel, PE–EtOAc,
6:4) to give 1 (18 mg, 79% over 2 steps) as a colorless oil; Rf = 0.5
(PE–EtOAc, 6:4).
[a]D25 –5.5 (c 1.0, CHCl3).
[a]D25 +35 (c 1.0, CHCl3).
IR (neat): 1739, 1371, 1225, 1024, 980 cm–1.
IR (neat): 2934, 2824, 2361, 1724, 1620, 1406, 1268, 1192, 1033
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.37 (d, J = 17.18 Hz, 1 H), 6.14–
6.01 (m, 1 H), 5.83–5.68 (m, 2 H), 5.54 (dd, J = 15.67, 6.98 Hz, 1
H), 5.33 (q, J = 6.61 Hz, 1 H), 5.13–5.02 (m, 2 H), 4.75–4.54 (m, 7
H), 3.87–3.75 (m, 1 H), 3.68–3.55 (m, 2 H), 3.39 (s, 3 H), 3.34 (d,
J = 4.15 Hz, 6 H), 2.50–2.16 (m, 4 H), 1.19 (d, J = 6.42 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 6.87–6.79 (m, 1 H), 6.01 (dt,
J = 9.82, 1.70 Hz, 1 H), 5.77–5.58 (m, 2 H), 5.19–5.10 (m, 1 H),
5.07–5.01 (m, 1 H), 4.99–4.90 (m, 1 H), 4.89–4.80 (m, 1 H), 2.44–
2.37 (m, 2 H), 2.31–2.23 (m, 2 H), 2.15 (s, 3 H), 2.05 (s, 3 H), 2.01
(s, 3 H), 1.17 (d, J = 6.23 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.3, 133.1, 130.5, 130.0, 129.8,
128.7, 117.9, 97.7, 96.9, 95.1, 80.7, 77.4, 73.7, 73.1, 55.9 (d, 2 C),
55.4, 38.9, 34.7, 16.1.
13C NMR (75 MHz, CDCl3): d = 170.2, 171.0, 169.9, 163.8, 144.5,
130.8, 128.3, 121.5, 77.5, 73.7, 69.5, 67.3, 33.9, 29.6, 21.0, 20.9,
20.7, 16.0.
MS (ESI): m/z = 425 [M + Na]+.
MS (ESI): m/z = 391 [M + Na]+.
(6R)-6-[(E,4R,5R,6R)-4,5,6-Tris(methoxymethoxy)hept-1-
enyl]-5,6-dihydro-2H-pyran-2-one (15)
Acknowledgment
A soln of Grubbs I catalyst (10 mg, 0.01 mmol, 10 mol%) in CH2Cl2
(20 mL) was added dropwise to a soln of 14 (50 mg, 0.12 mmol) in
CH2Cl2 (30 mL) at r.t., and stirring was continued for 5 h under re-
flux conditions. The solvent was evaporated and the crude product
was purified by column chromatography (silica gel, PE–EtOAc,
6:4) to give lactone 15 (39 mg, 85%) as a colorless oil; Rf = 0.3 (PE–
EtOAc, 6:4).
S. S. S. Reddy thanks CSIR and A.R. thanks UGC, New Delhi for
the award of fellowships.
References
(1) Visiting Professor, King Saud University, P.O. Box 2455,
Riyadh 11451, Saudi Arabia.
(2) Collett, L. A.; Davies-Coleman, M. T.; Rivett, D. E. A.
Phytochemistry 1998, 48, 651.
[a]D25 –12.1 (c 0.9, CHCl3).
IR (neat): 2930, 2825, 2337, 1722, 1383, 1217, 1102, 1031 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.86–6.80 (m, 1 H), 6.02 (d,
J = 9.92 Hz, 1 H), 5.94–5.85 (m, 1 H), 5.69 (dd, J = 15.87, 6.94 Hz,
1 H), 4.91–4.84 (m, 1 H), 4.78–4.56 (m, 6 H), 3.86–3.77 (m, 1 H),
3.69–3.58 (m, 2 H), 3.39 (s, 3 H), 3.37 (s, 3 H), 3.35 (s, 3 H), 2.53–
2.23 (m, 4 H), 1.20 (d, J = 6.94 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 163.9, 144.5, 130.7, 129.7, 121.6,
97.7, 97.0, 95.1, 80.7, 80.4, 77.8, 73.0, 55.9 (d, 2 C), 55.5, 34.6,
29.6, 16.1.
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Aldrichimica Acta 2002, 35, 23.
MS (ESI): m/z = 397 [M + Na]+.
(8) (a) Fürstner, A. Angew. Chem. Int. Ed. 2000, 39, 3012.
(b) Trnka, T.; Grubbs, H. Acc. Chem. Res. 2001, 34, 18.
Synthesis 2011, No. 8, 1279–1282 © Thieme Stuttgart · New York