First enantioselective total synthesis of (S)-(-)-longianone

Article abstract of DOI:10.1016/j.tet.2012.03.021

An efficient stereoselective synthesis of (S)-(-)-longianone was achieved from sugar derived 1,2-cyclopropanecarboxylate involving bromonium ion mediated solvolytic ring opening and a one-pot dehydrohalogenation, stereoselective intramolecular hetero Mich

Full text of DOI:10.1016/j.tet.2012.03.021

Tetrahedron 68 (2012) 3725e3728
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First enantioselective total synthesis of (S)-(ꢀ)-longianone
*
Ramu Sridhar Perali , Seshadri Kalapati
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient stereoselective synthesis of (S)-(ꢀ)-longianone was achieved from sugar derived
1,2-cyclopropanecarboxylate involving bromonium ion mediated solvolytic ring opening and a one-pot
dehydrohalogenation, stereoselective intramolecular hetero Michael addition (IHMA) and ester hydro-
lysis as key steps.
Received 8 February 2012
Received in revised form 28 February 2012
Accepted 6 March 2012
Available online 13 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
1,2-Cyclopropanecarboxylate
One-pot reaction
Intramolecular hetero Michael addition
1,7-Dioxaspiro[4,4]nonane
Carbohydrates
1. Introduction
nonane systems.11 Herein, we report the first stereoselective syn-
thesis of longianone and revealed the absolute configuration of the
1,7-Dioxaspiro[4.4]nonane is one of the significant structural
unit present in a number of bioactive natural products.1 Some of
these include bacterial metabolites secosyrins 1, syringolides
22 isolated from Pseudomonas syringae as well as sphydrofuran
33 obtained from a strain of Actinomycetes. Longianone 44 is
a structurally related but biosynthetically different natural product
containing this spirobicyclic system. Longianone was also proposed
to be an intermediate during the biosynthesis of secosyrins 1 and
syringolides 2.5 Hyperolactone A 5,6 also a structurally similar
natural product possessing an alternative 1,7-dioxaspiro[4.4]non-
ane skeleton7 (Fig. 1). Interestingly, a number of methods for the
stereoselective synthesis of all the above-mentioned spirobicyclic
natural products were reported except longianone, where the ab-
solute configuration was also unknown.
natural product.
The first total synthesis of racemic longianone was reported by
Steel,12 12 years ago, involving a free radical cyclization of an
enyne as a key step to construct the
b-disubstituted-g-butyr-
olactone. Recently Stratakis et al.,13 reported a divergent synthesis
of racemic longianone along with isopatulin and (Z)-ascladiol
starting from furan diol. A formal synthesis of (ꢁ)-longianone was
also reported recently using acyl radical cyclizations with
b
-alkoxyacrylates.14
Longianone is produced along with its isomeric mycotoxin
metabolites patulin8 and isopatulin9 by the fungus Xylaria longiana,
an uncommon member of the fungus genus Xylaria.4 All these three
metabolites are originated from a single biosynthetic origin derived
from oxidative ring opening of the aromatic polyketide metabolide,
6-methylsalicylic acid (6-MSA).5 In our investigations towards the
synthetic application of 1,2-cyclopropanecarboxylated sugar de-
rivatives,10 we recently reported a stereoselective method for the
construction of C-spiroglycosides possessing 1,7-dioxaspiro[4.4]
* Corresponding author. Tel.: þ91 40 6679 4823; fax: þ91 40 2301 2460; e-mail
address: prssc@uohyd.ernet.in (R.S. Perali).
Fig. 1. Natural products possessing 1,7-dioxaspiro[4.4]nonane core.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.021

3726
R.S. Perali, S. Kalapati / Tetrahedron 68 (2012) 3725e3728
2. Results and discussion
enantiomer in good yield (Scheme 3). Bromonium ion mediated
electrophilic ring opening of 10 with N-bromosuccinimide in
a mixture of dioxane/water (2:1) gave the bromohydrin 9. Treat-
ment of 9 with K2CO3/MeOH provided a diastereomeric mixture of
spirocyclic lactol 6 involving a one-pot dehydrohalogenation, IHMA
and ester hydrolysis. Dehydroxylation of 6 using Et3SiH/TFA in
CH2Cl2 provided an enantiomerically pure spirolactone 17. The
stereochemistry at spiro centre was assigned based on observing
strong NOE between 4-CH and 6-CH2 (please see Supplementary
data). Hydrogenolysis of 17 to give alcohol 18 followed by Swern
Towards the stereoselective synthesis of longianone, we envis-
aged that the a,b-unsaturated ketone functionality in 4 could be
attained from spirocyclic lactol 6, which could be obtained from
hydroxyaldehyde 7 via a stereoselective intramolecular hetero
Michael addition (IHMA) followed by ester hydrolysis. Compound 7
could exist in equilibrium with the more stable hemi-acetal 8,
which could be synthesized from bromohydrin
9 by dehy-
drohalogenation. Bromohydrin 9 will be easily accessible by an
electrophilic ring opening of known 1,2-cyclopropanecarboxylate
1015 (Scheme 1).
oxidation provided the (S)-(ꢀ)-dihydrolongianone 19 (lit. [
a
]
20 ꢀ63
D
25
(c 1.0, CHCl3))4
[
a
]
ꢀ66 (c 0.8, CHCl3). Dehydrogenation of com-
D
pound 19 using stabilized IBX (SIBX)13 provided enantiomerically
pure (S)-(ꢀ)-longianone 4 (lit. [
a
]
20 ꢀ85 (c 1.0, EtOH))4 [
a
]
D
25 ꢀ90 (c
D
0.9, EtOH) in 50% yield based on recovered starting material with
a conversion of only w60% (Scheme 3). The absolute configuration
of natural longianone was assigned by comparing the optical ro-
tation of natural and synthetic longianones. To the best of our
knowledge, this is the first report on the stereoselective total syn-
thesis of (S)-(ꢀ)-longianone.
Scheme 1. Retrosynthetic analysis of longianone.
The immediate precursor for the preparation of 10 would be the
corresponding glycal derivative 16, which could be synthesized
from commercially available 3,4,6-tri-O-acetyl- -glucal 11. Thus,
D
Pd/C mediated catalytic hydrogenation of 11 provided 1,2-dideoxy-
-glucose 12,16 which upon Zemplen deacetyla-
ꢀ
3,4,6-tri-O-acetyl-
D
tion with NaOMe in MeOH followed by selective isopropylidine
protection of 4- and 6-hydroxyls using 2,2-dimethoxypropane/
pyridinium p-toluene sulfonate in DMF gave the acetonide 1317 in
quantitative yield after three steps. Benzylation of free hydroxyl in
13 provided 14, which upon acetonide deprotection using p-tol-
uenesulfonic acid in methanol gave the diol 1516 in excellent yield.
Selective oxidation of the primary alcohol to the corresponding
carboxylic acid using diacetoxy iodobenzene (DAIB)/TEMPO in
a mixture of dichloromethane/water (2:1) followed by decarbox-
ylative elimination using N,N-dimethylformamide dineopentyl ac-
etal (DMFDNA) in toluene under reflux conditions lead to the
formation of glycal derivative 1615 in good yield (67% over two
steps) (Scheme 2).
Scheme 3. Stereoselective synthesis of S-(ꢀ)-longianone.
3. Conclusion
In conclusion,
a
concise stereoselective synthesis of (S)-
-glucal via
(ꢀ)-longianone was achieved from 3,4,6-tri-O-acetyl-
D
1,2-cyclopropanecarboxylate 10 involving a total of 14 steps with an
overall 8% yield. Also, the absolute configuration of the longianone
that was isolated from the fungus X. longiana (Rehm.)4 was
revealed.
4. Experimental section
4.1. General
Scheme 2. Synthesis of glycal precursor for cyclopropanation reaction.
All the reactions were carried out under an inert atmosphere
with dry solvents under anhydrous conditions unless otherwise
mentioned. Dichloromethane, dimethyl sulfoxide, methanol and
ꢁ
Stereoselective cyclopropanation of glycal 16 using methyl
triethyl amine were initially dried and stored over 4 A molecular
diazoacetate (MDA) under catalytic Rh2(OAc)4 conditions in CH2Cl2
sieves. TLC was run on silica gel 60 F254 (Merck) and the spots were
detected by staining with H2SO4 in methanol (5%, v/v) or
provided the 1,2-cyclopropanecarboxylate 10 as
a
single

R.S. Perali, S. Kalapati / Tetrahedron 68 (2012) 3725e3728
3727
phosphomolybdic acid in ethanol (5%, w/v) and heat. Silica gel
(100e200 mesh) was used as a stationary phase for column chro-
matography. NMR spectra were recorded at 25 ꢂC on a Bruker
Avance III 400 (400 MHz for 1H and 100 MHz for 13C) or 500
(500 MHz for 1H and 125 MHz for 13C) instrument with CDCl3 re-
anhydrous Na2SO4 and concentrated. The resulting yellow oil was
evaporated three times with toluene (50 mL) under reduced pres-
sure and was kept under high vacuum for 2 h prior to use. The crude
oil was dissolved in toluene (100 mL) and N,N-dimethylformamide
dineopentyl acetal (20.7 mL, 90.0 mmol) was added. The resulting
mixture was stirred at 120 ꢂC under argon for 1 h, cooled to 40 ꢂC
and the solvent was evaporated to obtain a brown oil containing the
crude product, which upon column chromatography using EtOAc/
hexane (1:19) provided compound 16 (2.5 g, 67% over two steps) as
sidual CHCl3 (dH 7.26 ppm) as internal standard for 1H and CDCl3 (
dC
77.0 ppm) as internal standard for 13C. Chemical shifts are given in
(ppm) and coupling constants (J) in hertz. IR spectra were recorded
d
on JASCO FT/IR-5300. Low-resolution mass spectra were recorded
on a Shimadzu-LCMS-2010A mass spectrometer. High-resolution
mass spectra were recorded on Bruker maXis ESI-TOF spectrometer.
a yellow oil. Rf (10% EtOAc/hexane) 0.72; [
a
]
25 þ148 (c 1.0, CHCl3). IR
D
(neat): 2957, 2868, 1637, 1454 cmꢀ1
.
dH NMR (400 MHz, CDCl3):
7.28e7.39 (m, 5H), 6.54 (d, 1H, J¼6.0 Hz), 5.00 (td, 1H, J¼1.2, 4.8 Hz),
4.61 (d, 1H, J¼11.6 Hz), 4.55 (d, 1H, J¼12.0 Hz), 4.05e4.10 (m, 2H),
3.90e3.92 (m, 1H), 1.98e2.02 (m, 1H), 1.90e1.93 (m, 1H). dC NMR
(100 MHz, CDCl3): 147.0, 138.8, 128.4, 127.6, 127.5, 100.9, 69.4, 65.6,
62.3, 28.7. Low-resolution MS (EI): m/z: 190 (Mþ); HRMS (ESI) calcd
for C12H14O2þNa 213.0892, found 213.0892.
4.2. 1,2-Dideoxy-3-O-benzyl-4,6-O-isopropylidene-D-glucose
(14)
To a cooled (0 ꢂC) suspension of sodium hydride (1.27 g,
31.9 mmol) in DMF (10 mL) was added a solution of compound 13
(5.0 g, 26.6 mmol) in DMF (50 mL) for a period of 10 min and the
mixture was stirred for another 20 min (until the H2 evolution
ceases). Benzyl bromide (3.48 mL, 29.2 mmol) was added dropwise
to the reaction mixture for a period of 10 min and then TBAI
(100 mg) was added. The reaction mixture was allowed to stir at
room temperature for 6 h. After completion of the reaction, water
(20 mL) was added slowly and the reaction mixture was extracted
with diethyl ether (3ꢃ50 mL). The combined organic extracts were
washed with saturated aq NaCl (3ꢃ50 mL), dried over anhydrous
Na2SO4, concentrated under reduced pressure and purified by
column chromatography EtOAc/hexane (1:6) to afford the benzy-
lated isopropylidene derivative 14 (6.3 g, 85%) as a colourless gum.
4.5. (1R,5R,6S)-Methyl 5-(benzyloxy)-2-oxabicyclo[4.1.0]
heptane-(7R)-carboxylate (10)
To
a solution of compound 16 (2.0 g, 10.5 mmol) in dry
dichloromethane (40 mL) was added Rh2(OAc)4 (92.8 mg,
0.21 mmol) at room temperature and stirred for 5 min then methyl
diazoacetate (3.0 ml, 31.5 mmol) in 50 ml of dry dichloromethane
was added dropwise over a period of 90 min. The reaction mixture
was filtered through a pad of Celite and the filtrate was concentrated
under reduced pressure and purified by column chromatography
using EtOAc in hexane (1:6) to afford the product 10 (1.65 g, 60 %) as
25
Rf (20% EtOAc/hexane) 0.53; [
a
]
25 þ11 (c 1.0, CHCl3). IR (neat): 2873,
a colourless gum. Rf (20% EtOAc/hexane) 0.56; [
a
]
ꢀ26 (c 1.0,
D
D
1454 cmꢀ1
.
dH NMR (400 MHz, CDCl3): 7.30e7.41 (m, 5H), 4.83 (d,
CHCl3). IR (neat): 2924, 1720, 1441 cmꢀ1
. dH NMR (400 MHz, CDCl3):
1H, J¼12.4 Hz), 4.71 (d, 1H, J¼12.4 Hz), 3.94 (dd, 1H, J¼5.2, 11.4 Hz),
3.90 (dd, 1H, J¼5.6, 10.8 Hz), 3.69e3.78 (m, 2H), 3.54e3.60 (m, 1H),
3.47 (td, 1H, J¼2.4, 12.8 Hz), 3.19 (dt, 1H, J¼5.2, 10.0 Hz), 1.98e2.03
(m, 1H), 1.74e1.84 (m, 1H), 1.54 (s, 3H), 1.47 (s, 3H). dC NMR
(100 MHz, CDCl3): 139.1, 128.3, 127.5, 127.4, 99.4, 76.5, 76.3, 72.6,
72.3, 66.4, 62.4, 32.4, 29.3, 19.2. Low-resolution MS (EI): m/z: 278
(Mþ); HRMS (ESI) calcd for C16H22O4þNa 301.1416, found 301.1416.
7.28e7.37 (m, 5H), 4.65 (d, 1H, J¼11.6 Hz), 4.59 (d, 1H, J¼12.0 Hz),
3.99e4.03 (m, 2H), 3.80 (m,1H), 3.67 (s, 3H), 3.44e3.49 (m, 1H), 2.00
(dd, 1H, J¼2.4, 5.6 Hz), 1.77e1.81 (m, 1H), 1.63e1.68 (m, 2H). dC NMR
(100 MHz, CDCl3): 172.1, 138.1, 128.4, 127.7, 127.5, 70.7, 68.1, 59.8,
59.2, 51.8, 28.4, 25.9, 25.3. Low-resolution MS (EI): m/z: 262 (Mþ);
HRMS (ESI) calcd for C15H18O4þNa 285.1103, found 285.1104.
4.6. (R)-Methyl 2-((3S,4R)-4-(benzyloxy)-2-hydroxytetrahydro-
2H-pyran-3-yl)-2-bromoacetate (9)
4.3. 1,2-Dideoxy-3-O-benzyl-D-glucose (15)
To a solution of acetonide 14 (5.5 g,19.7 mmol) in MeOH (50 mL)
was added p-toluenesulfonic acid (3.7 g, 19.7 mmol) and the mix-
ture was stirred for 30 min at room temperature. The solvent was
evaporated under reduced pressure and the crude product was
purified by column chromatography EtOAc/hexane (1:2) to afford
To a stirred solution of 1,2-cyclopropanecarboxylate 10 (0.80 g,
3.04 mmol) in 1,4-dioxane/water (15 mL (2:1)) was added N-bromo-
succinimide (0.65 g, 3.64 mmol) and stirring was continued until the
reaction mixture showed the absence of starting material on TLC
(w8 h). The reaction mixturewas then concentrated to halfitsvolume
in vacuo and extracted with CH2Cl2 (2ꢃ30 mL). The combined extracts
were dried over anhydrous Na2SO4, filtered and concentrated. The
crude product was purified by column chromatography over silica gel
using EtOAc/hexane (1:3) to give bromohydrin 9 (0.72 g, 66%) as
a colourlessgum. Formajordiastereomer: Rf (20%EtOAc/hexane) 0.32.
the product 15 (4.7 g, 99%) as a colourless gum. Rf (50% EtOAc/
25
hexane) 0.21; [
a]
ꢀ32 (c 1.0, CHCl3). IR (neat): 3409, 2857,
D
1454 cmꢀ1
.
dH NMR (400 MHz, CDCl3): 7.29e7.36 (m, 5H), 4.70 (d,
1H, J¼12.0 Hz), 4.57 (d, 1H, J¼12.0 Hz), 3.94e3.98 (m, 1H), 3.84 (dd,
1H, J¼2.8, 11.6 Hz), 3.75 (dd, 1H, J¼5.2, 12.0 Hz), 3.52 (t, 1H,
J¼8.8 Hz), 3.36e3.45 (m, 2H), 3.18e3.22 (m, 2H), 1.99e2.04 (m, 1H),
1.62 (dq, 1H, J¼5.2, 12.8 Hz). dC NMR (100 MHz, CDCl3): 138.3, 128.4,
127.8, 127.7, 80.3, 79.9, 71.1, 70.9, 65.5, 62.5, 30.6. Low-resolution
MS (EI): m/z: 238 (Mþ); HRMS (ESI) calcd for C13H18O4þNa
261.1103, found 261.1103.
IR (neat): 2924,1719,1454 cmꢀ1
. dH NMR(500 MHz, CDCl3): 7.28e7.37
(m, 5H), 4.89 (d, 1H, J¼4.0 Hz), 4.69 (br d, 1H, J¼6.0 Hz), 4.56 (d, 1H,
J¼11.0 Hz), 4.48e4.51 (m, 1H), 4.47 (d, 1H, J¼11.0 Hz), 4.05 (dt, 1H,
J¼4.0, 11.0 Hz), 3.92 (td, 1H, J¼4.5, 9.0 Hz), 3.50 (s, 3H), 2.38 (ddd, 1H,
J¼4.0, 7.0, 11.0 Hz), 2.01e2.06 (m, 1H), 1.70e1.75 (m, 1H). dC NMR
(125 MHz, CDCl3):168.6,137.5,128.5,128.4,127.9, 95.5, 74.5, 71.5, 60.2,
53.1, 50.6, 48.2, 29.5. Low-resolution MS (EI): m/z: 358 (Mþ); HRMS
(ESI) calcd for C15H19BrO5þNa 381.0314, found 381.0318.
4.4. (R)-4-(Benzyloxy)-3,4-dihydro-2H-pyran (16)
To
a vigorously stirred solution of compound 15 (4.7 g,
19.7 mmol) in dichloromethane and water (2:1, 90 mL) were added
TEMPO (0.6 g, 3.94 mmol) and DAIB (15.9 g, 49.3 mmol). Stirring was
allowed until TLC indicated complete conversion of the starting
material to a lower running spot (w45 min). The reaction mixture
was quenched by the addition of 10% Na2S2O3 (100 mL) solution. The
mixture was then extracted with EtOAc (2ꢃ150 mL), dried over
4.7. (4R,5R)-4-(Benzyloxy)-6-hydroxy-1,7-dioxaspiro[4.4]
nonan-8-one (6)
To a stirred solution of bromohydrin 9 (0.65 g, 1.81 mmol) in
MeOH (8 mL) under nitrogen was added K2CO3 (0.50 g, 3.62 mmol)
at 25 ꢂC. The reaction mixture was stirred for a period of 6 h. MeOH

3728
R.S. Perali, S. Kalapati / Tetrahedron 68 (2012) 3725e3728
was removed under reduced pressure, and the reaction mixture
was diluted with CH2Cl2 (50 mL) and washed with 1% HCl (10 mL)
and water (10 mL). The organic layer was dried over anhydrous
Na2SO4 and concentrated. Column chromatography of the crude
product with EtOAc/hexane (1:2) afforded the pure spirocyclic
lactol 6 (0.45 g, 94%) as a colourless gum. For major diastereomer: Rf
product was purified by column chromatography over silica gel
using EtOAc/hexane (1:3) to afford ketone 19 (42 mg, 85%). Rf (30%
25
20
EtOAc/hexane) 0.40; [
a]
ꢀ66 (c 0.8, CHCl3) (lit. [
a]
ꢀ63 (c 1.0,
D
D
CHCl3)). IR (neat): 2923, 2853, 1728 (br), 1456 cmꢀ1
.
dH NMR
(500 MHz, CDCl3): 4.33 (d, 1H, J¼10.0 Hz), 4.30 (d, 1H, J¼10.0 Hz),
4.18e4.28 (m, 2H), 2.78 (d, 1H, J¼18.0 Hz), 2.64 (d, 1H, J¼7.5 Hz),
2.62 (d, 1H, J¼18.0 Hz), 2.61 (d, 1H, J¼7.5 Hz). dC NMR (125 MHz,
CDCl3): 211.9, 173.1, 84.3, 74.3, 63.3, 37.7, 35.9. Low-resolution MS
(EI): m/z: 156 (Mþ); HRMS (ESI) calcd for C7H8O4þNa 179.0321,
found 179.0328.
(30% EtOAc/hexane) 0.39. IR (neat): 3384, 2925, 1782, 1454 cmꢀ1
NMR (400 MHz, CDCl3): 7.30e7.39 (m, 5H), 5.45 (br s, 1H), 4.66 (d,
. dH
d
1H, J¼11.6 Hz), 4.52e4.59 (m, 1H), 4.48 (d, 1H, J¼11.6 Hz), 3.96e4.11
(m, 2H), 3.66e3.77 (m, 1H), 3.07 (d, 1H, J¼18.0 Hz), 2.61 (d, 1H,
J¼18.0 Hz), 2.01e2.17 (m, 2H). dC NMR (100 MHz, CDCl3): 172.9,
137.1, 128.6, 128.2, 127.8, 100.4, 87.5, 79.3, 72.0, 67.3, 36.1, 31.0. Low-
resolution MS (EI): m/z: 264 (Mþ); HRMS (ESI) calcd for
C14H16O5þNa 287.0896, found 287.0916.
4.11. (S)-1,7-Dioxaspiro[4.4]non-2-ene-4,8-dione or ((S)-(L)-
longianone) (4)
To a 0.5 M solution of dihydro-(ꢀ)-longianone 19 (30 mg,
0.19 mmol) in dry DMSO (0.2 mL) was added 2 equiv of stabilized
IBX (0.38 mmol) and the mixture was heated to 80 ꢂC and stirred at
this temperature for a period of 2 h. After cooling the reaction
mixture to 25 ꢂC, EtOAc (25 mL) was added and the reaction mix-
ture was extracted with a saturated NaHCO3 solution. The organic
residue was carefully purified by column chromatography (EtOAc/
hexane gradually from 1:9 to 1:4), affording 9 mg of (S)-(ꢀ)-long-
ianone 4 and 12 mg of 19 (50% yield of 4 based on recovered 19). Rf
4.8. (4R,5S)-4-(Benzyloxy)-1,7-dioxaspiro[4.4]nonan-8-one
(17)
To a stirred solution of spiro lactol 6 (0.40 g, 1.51 mmol) in
CH2Cl2 (10 mL) at 0 ꢂC were added triethyl silane (0.98 mL,
6.05 mmol) and trifluoroacetic acid (0.22 mL, 0.4 mmol) dropwise,
respectively, and continued stirring while allowing the reaction
mixture to warm to 25 ꢂC. After completion of reaction (2e3 h),
CH2Cl2 (50 mL) and water (20 mL) were added and the organic
phase was separated. The aqueous phase was extracted with CH2Cl2
(2ꢃ25 mL) and the combined organic layers were dried over an-
hydrous Na2SO4, concentrated. The crude product was purified by
column chromatography over silica gel using EtOAc/hexane (1:3) to
25
20
(30% EtOAc/hexane) 0.39; [
a
]
D
ꢀ90 (c 0.9, EtOH) (lit. [
a
]
.
ꢀ85 (c
D
1.0, EtOH)). IR (neat): 2924, 2855, 1728 (br), 1465 cmꢀ1
dH NMR
(400 MHz, CDCl3): 8.31 (d, 1H, J¼2.5 Hz), 5.82 (d, 1H, J¼2.5 Hz),
4.40e4.43 (m, 2H), 3.04 (d, 1H, J¼18.0 Hz), 2.72 (d, 1H, J¼18.0 Hz).
dC NMR (100 MHz, CDCl3): 199.3, 177.6, 172.3, 106.7, 89.4, 73.9, 37.6.
Low-resolution MS (EI): m/z: 154.
afford pure spirolactone 17 (0.34 g, 92%) as a colourless gum. Rf
25
(20% EtOAc/hexane) 0.33; [
a
]
D
ꢀ30 (c 1.0, CHCl3). IR (neat): 2890,
1776,1454 cmꢀ1
.
dH NMR (500 MHz, CDCl3): 7.29e7.37 (m, 5H), 4.66
Acknowledgements
(d,1H, J¼12.0 Hz), 4.47 (d, 1H, J¼12.0 Hz), 4.19 (d,1H, J¼9.5 Hz), 4.11
(d, 1H, J¼9.5 Hz), 3.94e3.97 (m, 1H), 3.85e3.89 (m, 2H), 3.05 (d, 1H,
J¼18.0 Hz), 2.50 (d, 1H, J¼18.0 Hz), 2.16e2.18 (m, 1H), 1.97e2.01 (m,
1H). dC NMR (125 MHz, CDCl3): 175.3, 137.3, 128.6, 128.0, 127.6, 86.6,
79.8, 75.5, 72.0, 65.3, 34.9, 30.7. Low-resolution MS (EI): m/z: 248
(Mþ); HRMS (ESI) calcd for C14H16O4þNa 271.0947, found 271.0960.
P.R.S. thank Council of Scientific and Industrial Research (CSIR),
New Delhi, India for grant No. 01(2408)/10/EMR-II. K.S. thank CSIR
for a senior research fellowship.
Supplementary data
4.9. (4R,5S)-4-Hydroxy-1,7-dioxaspiro[4.4]nonan-8-one (18)
Supplementary data related to this article can be found in the
online version, at doi:10.1016/j.tet.2012.03.021.
A solution of compound 17 (250 mg, 1 mmol) in EtOAc (14 mL)
and MeOH (1 mL) in presence of one drop of hydrochloric acid (1 N)
was hydrogenated over 10% Pd/C (30 mg) under hydrogen atmo-
sphere for 2 h at 25 ꢂC. The catalyst was filtered off and the filtrate
was concentrated. The crude product was purified by flash column
chromatography over silica gel using EtOAc/hexane (2:3) to afford
References and notes
1. For a review: Wong, H. N. C. Eur. J. Org. Chem. 1999, 1757e1765.
2. (a) Smith, M. J.; Mazzola, E. P.; Sims, J. J.; Midland, S. L.; Keen, N. T.; Burton, V.;
Stayton, M. M. Tetrahedron Lett. 1993, 34, 223e226; (b) Midland, S. L.; Keen, N.
T.; Sims, J. J.; Midland, M. M.; Stayton, M. M.; Burton, V.; Smith, M. J.; Mazzola,
E. P.; Gragam, K. J.; Clardy, J. J. Org. Chem. 1993, 58, 2940e2945.
3. (a) Umezawa, S.; Usui, T.; Umezawa, H.; Tsuchiya, T.; Takeuchi, T.; Hamada, M. J.
Antibiot. 1971, 24, 85e92; (b) Umezawa, S.; Tsuchiya, T.; Naganawa, H.; Take-
uchi, T.; Umezawa, H. J. Antibiot. 1971, 24, 93e106.
4. Edwards, R. L.; Maitland, D. J.; Oliver, C. L.; Pacey, M. S.; Shields, L.; Whalley, A. J.
S. J. Chem. Soc., Perkin Trans. 1 1999, 715e719.
5. Goss, R. J. M.; Fuchser, J.; O’Hagan, D. Chem. Commun. 1999, 2255e2256.
6. Tanaka, N.; Okasaka, M.; Ishimaru, Y.; Takaishi, Y.; Sato, M.; Okamoto, M.;
Oshikawa, T. S.; Ahmed, U.; Consentino, L. M.; Lee, K.-H. Org. Lett. 2005, 7,
2997e2999.
7. Midland, S. L.; Keen, N. T.; Sims, J. J. J. Org. Chem. 1995, 60, 1118e1119.
8. Engel, G.; Teuber, M. In MycotoxinsdProduction, Isolation, Separation and Puri-
fication; Betina, V., Ed.; Elsevier: Amsterdam, The Netherlands, 1984;
pp 291e314.
9. Sekiguchi, J.; Gaucher, G. M.; Yamada, Y. Tetrahedron Lett. 1979, 20, 41e42.
10. Sridhar, P. R.; Kumar, P. V.; Seshadri, K.; Satyavathi, R. Chem.dEur. J. 2009, 15,
7526e7529.
11. Sridhar, P. R.; Seshadri, K.; Reddy, G. M. Chem. Commun. 2012, 756e758.
12. Steel, P. G. Chem. Commun. 1999, 2257e2258.
13. Lykakis, I. N.; Zaravinos, I.-P.; Raptis, C.; Stratakis, M. J. Org. Chem. 2009, 74,
6339e6342.
alcohol 18 (0.15 g, 97%) as a colourless gum. Rf (30% EtOAc/hexane)
25
0.20; [
a
]
D
ꢀ36 (c 1.0, CHCl3). IR (neat): 3386, 1775, 1454 cmꢀ1
. dH
NMR (500 MHz, CDCl3): 4.17 (br s, 3H), 3.94e3.97 (m, 1H),
3.85e3.87 (m, 1H), 3.49 (br s, 1H), 3.00 (d, 1H, J¼18.0 Hz), 2.49 (d,
1H, J¼18.0 Hz), 2.17e2.20 (m, 1H), 1.94e1.96 (m, 1H). dC NMR
(125 MHz, CDCl3): 176.3, 87.5, 75.6, 73.2, 65.1, 34.5, 33.8. Low-
resolution MS (EI): m/z: 158 (Mþ); HRMS (ESI) calcd for
C7H10O4þNa 181.0477, found 181.0487.
4.10. (S)-1,7-Dioxaspiro[4.4]nonane-4,8-dione or (dihydro-(S)-
(L)-longianone) (19)
To a solution of oxalyl chloride (30
mL, 0.70 mmol). After 10 min
alcohol 18 (50 mg, 0.32 mmol) in dry CH2Cl2 (1 mL) was added
m
L, 0.35 mmol) in CH2Cl2
(2 mL) at ꢀ78 ꢂC was added DMSO (50
dropwise for a period of 10 min and the stirring was continued
14. Aitken, H. M.; Schiesser, C. H.; Donner, C. D. Aust. J. Chem. 2011, 64, 409e415.
15. Haveli, S. D.; Sridhar, P. R.; Suguna, P.; Chandrasekaran, S. Org. Lett. 2007, 9,
1331e1334.
16. Wang, F.; Tada, M. Agric. Biol. Chem. 1990, 54, 2989e2992.
17. Sasaki, M.; Shida, T.; Tachibana, K. Tetrahedron Lett. 2001, 42, 5725e5728.
further 45 min. Then, Et3N (217 mL, 1.56 mmol) was added and the
solution was allowed to warm upto 0 ꢂC. The reaction mixture was
diluted with CH2Cl2 (20 mL) and extracted with water (3ꢃ5 mL),
dried over anhydrous Na2SO4, filtered and concentrated. The crude