Total synthesis of alboatrin, a phytotoxic metabolite from Verticillium alboatrum

Article abstract of DOI:10.1016/j.tet.2008.01.097

A synthesis of the phytotoxic metabolite alboatrin 1 is described. An intramolecular ketene-olefin cycloaddition followed by an oxidative ring enlargement was employed to generate the tricyclic ring system.

Full text of DOI:10.1016/j.tet.2008.01.097

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3212e3216
www.elsevier.com/locate/tet
Total synthesis of alboatrin, a phytotoxic metabolite
from Verticillium alboatrum
*
Bidyut Biswas, Debayan Sarkar, Ramanathapuram V. Venkateswaran
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
Received 20 September 2007; received in revised form 5 January 2008; accepted 24 January 2008
Available online 31 January 2008
Abstract
A synthesis of the phytotoxic metabolite alboatrin 1 is described. An intramolecular keteneeolefin cycloaddition followed by an oxidative
ring enlargement was employed to generate the tricyclic ring system.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Alboatrin; Total synthesis; Intramolecular keteneeolefin cycloaddition
1. Introduction
convenient access to the central tricyclic core of alboatrin.
We describe here the successful application of this strategy
to realize the synthesis of this metabolite.
Alboatrin is a phytotoxic metabolite isolated from the cul-
ture filtrate of Verticillium alboatrum by Ichihara et al.1 The
originally assigned structure was later modified to 1 involving
inversion of the configuration of the secondary methyl group
at C-3.2 It inhibits the root growth of the host plant (Maris
Kabul) and causes vascular-wilt disease in alfalfa. Alboatrin
incorporates a linearly fused tetrahydrofurano benzopyran
ring system rarely encountered in natural products and has
three contiguous stereogenic centres. The recently isolated
xyloketals are another group of marine metabolites, which
possess this ring structure.3 The unusual structural feature of
1 and the associated biological activity have prompted its syn-
thesis.1,2,4 In connection with our previous efforts on the syn-
thesis of the aplysia group of marine sesquiterpenes, we had
employed an intramolecular keteneealkene cycloaddition
followed by a ring expansion to generate the cyclopentano-
benzofuran network of the natural products.5 It occurred to
us that a similar intramolecular keteneealkene cycloaddition
followed by an oxidative ring enlargement can provide a
11
H
10
4
3
5
8
4a
8a
3a
6
7
2
9a
1
O
9
O
HO
12
1
2. Results and discussion
The synthesis was started with orcinol monomethyl ether
2.6 This was alkylated with allyl bromide in acetone at reflux
in the presence of potassium carbonate to furnish the allyl
ether 3 in 96% yield. Thermal Claisen rearrangement of this
allyl ether afforded a mixture of the rearranged phenols 4a
and 4b in 86% yield in 2:1 proportion. An efficient separation
was achieved through column chromatography. To enable the
assignment of correct structures to these isomers, samples of
both were converted to the dimethyl ethers 5a and 5b. The
13C NMR spectra enabled the ready identification of both iso-
mers with 5b showing the expected nine signals due to its
symmetrical nature (Scheme 1). Continuing with the synthesis,
the phenol 4a was alkylated with a-bromopropionic acid in
* Corresponding author. Tel.: þ91 33 24734971; fax: þ91 33 24732805.
E-mail addresses: ocrvv@iacs.res.in, drvenkatesh46@yahoo.com (R.V.
Venkateswaran).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.097

B. Biswas et al. / Tetrahedron 64 (2008) 3212e3216
3213
THF employing sodium hydride as the base, and furnished the
H
i
ii
alkylated carboxylic acid 6 in 83% yield as a colourless solid,
mp 101e102 ꢀC. The acid 6 on heating with toluene-p-sulfo-
nyl chloride and triethylamine in benzene at reflux, underwent
an intramolecular keteneealkene cycloaddition7,8 reaction and
delivered the tricyclic cyclobutanone 7 as a colourless solid in
50% yield, mp 75e76 ꢀC. The lower yield in the formation of
bicyclic(4.2.0) ring systems from such cycloadditions was in
conformity with the experience of others.7,8 The structure of
cyclobutanone 7 was adequately supported by analytical and
spectral data. The assignment of the cis ring junction to this
cyclobutanone was based on analogy with previous reports
of such cycloadditions.7,8
4a
MeO
O
O
MeO
O
O
O
CO2H
7
6
iii
H
H
iv
O
O
MeO
O
MeO
O
H
8
9
v
H
ii
vi
+
OH
MeO
iii
OR
MeO
OR
MeO
i
OR
O
O
RO
vii
O
MeO
O
11, R = Me
1, R = H
10
2, R = H
3, R = -CH2-CH=CH2
4a, R = H
4b, R = H
5b, R = Me
iii
5a, R = Me
Scheme 2. Reagents and conditions: (i) NaH, CH3CH(Br)CO2H, THF, reflux,
10 h, 83%; (ii) p-TsCl, Et3N, benzene, reflux, 12 h, 50%; (iii) m-CPBA,
NaHCO3, CH2Cl2, rt, 6 h, 80%; (iv) LDA, HMPA, MeI, THF, ꢁ78 ꢀC to rt,
10 h, 94%; (v) DIBAL-H, Et2O, ꢁ78 ꢀC, 2 h, 95%; (vi) CF3CO2H, Et3SiH,
CH2Cl2, ꢁ40 ꢀC to rt, 15 min, 38%; (vii) BBr3, CH2Cl2, ꢁ78 ꢀC, 5 h, 80%.
Scheme 1. Reagents and conditions: (i) K2CO3, CH2]CHCH2Br, acetone,
reflux, 5 h, 96%; (ii) 200 ꢀC, 1 h, 86%; (iii) K2CO3, MeI, acetone, reflux,
8 h, 93%.
For carrying out the next step of oxidative ring enlarge-
ment, cyclobutanone 7 was treated with m-chloroperbenzoic
acid in methylene chloride with added sodium bicarbonate
and furnished the g-lactone 8 as a colourless solid in 80%
yield, mp 63e64 ꢀC. The synthesis of lactone 8 thus generated
the key tricyclic core of alboatrin 1. The next step involved the
stereocontrolled introduction of a secondary methyl group
adjacent to the lactone carbonyl group. It was anticipated
that during methylation of the lactone 8, the methyl group
will preferentially approach from the more accessible exo
face of the molecule leading to the desired b-configuration
of the secondary methyl group. In the event, when the lactone
8 was subjected to a methylation with iodomethane in the
presence of LDA, it afforded the methylated lactone 9 as a col-
synthesis thus additionally confirmed the assignment of the
b-configuration to the C-3 methyl group.
In summary, we have described a synthesis of the phytotoxic
metabolite alboatrin, employing an intramolecular ketenee
olefin cycloaddition followed by an oxidative ring enlargement
to generate the tricyclic structure of the compound.
3. Experimental
3.1. General
All non aqueous reactions were carried out under an inert
atmosphere (nitrogen). Melting points were taken in open
capillary tubes in a sulfuric acid bath and are uncorrected.
Dry solvents and reagents were prepared from reagent grade
materials by conventional methods. Petroleum ether refers to
the fraction of bp 60e80 ꢀC. The purity of the products was
routinely monitored by TLC. Drying of organic layers was
1
ourless solid in 94% yield as a single isomer. The H NMR
spectrum showing a doublet at d 1.25 confirmed the introduc-
tion of the methyl group and was assigned the b-configuration
based on the arguments stated above. A final confirmation of
this assignment however, hinged on its conversion to alboatrin
1 itself. For the reductive removal of the carbonyl oxygen it
was reduced first with DIBAL-H to furnish lactol 10 as a mix-
ture of isomers in 95% yield. No effort was made to separate
the mixture since the next step involved a reductive removal of
the hydroxy group. Treatment of the lactols 10 with triethylsi-
lane in dichloromethane in the presence of trifluoroacetic acid9
followed by chromatographic purification of the product af-
forded O-methylalboatrin 11 in 38% yield as a colourless
low melting solid, mp 53e54 ꢀC. Finally demethylation of
11 with boron tribromide in dichloromethane at ꢁ78 ꢀC
yielded the desired (ꢂ)-alboatrin 1 as colourless crystals, mp
146e147 ꢀC (Scheme 2), which displayed spectral data [1H
and 13C NMR] fully matching with reported values.1,4 The
1
done with sodium sulfate. H NMR spectra were recorded at
300 MHz in CDCl3 solutions. 13C NMR spectra were recorded
in CDCl3 solution at 75 MHz. Peak positions are indicated in
parts per million downfield from an internal TMS standard. IR
spectra of liquid products were recorded as thin films or in
CHCl3 solution. IR spectra of solids were recorded as KBr
pellets.
3.1.1. 1-Allyloxy-3-methoxy-5-methylbenzene (3)
A mixture of monomethyl orcinol 2 (1.30 g, 9.40 mmol),
anhydrous potassium carbonate (1.60 g, 11.6 mmol) and allyl
bromide (1.40 g, 11.6 mmol) in acetone (30 mL) was heated

3214
B. Biswas et al. / Tetrahedron 64 (2008) 3212e3216
at reflux for 5 h. The reaction mixture was then cooled and
most of the acetone was distilled off. The residue was poured
into water and extracted with ether (3ꢃ20 mL). The organic
extract was washed with water, brine and dried. The residue
after removal of solvent was subjected to column chromatog-
raphy over silica gel. Elution with ethyl acetateepetroleum
ether (1:24) furnished the allyl ether 3 (1.61 g, 96%) as a col-
3.1.4. 2-Allyl-1,3-dimethoxy-5-methylbenzene (5b)
Similarly the phenol 4b was converted to the dimethyl ether
5b. 1H NMR (300 MHz, CDCl3) d 2.25 (s, 3H), 3.28 (d,
J¼6.0 Hz, 2H), 3.70 (s, 6H), 4.79e4.90 (m, 2H), 5.79e5.92
(m, 1H), 6.29 (s, 2H); 13C NMR (75 MHz, CDCl3) d 22.4,
27.4, 56.2, 105.2, 113.9, 114.2, 137.5, 137.6, 158.5. Anal.
Calcd for C12H16O2: C, 74.97; H, 8.39. Found: C, 75.92; H,
8.41.
1
ourless liquid. H NMR (300 MHz, CDCl3) d 2.30 (s, 3H),
3.77 (s, 3H), 4.50 (d, J¼4.6 Hz, 2H), 5.26e5.30 (m, 1H),
5.37e5.44 (m, 1H), 6.00e6.10 (m, 1H), 6.31 (br s, 1H),
6.34 (br s, 2H); 13C NMR (75 MHz, CDCl3) d 22.2, 55.6,
69.2, 98.7, 107.7, 108.3, 117.9, 133.7, 140.6, 160.1, 161.0.
Anal. Calcd for C11H14O2: C, 74.13; H, 7.92. Found: C,
74.09; H, 7.93.
3.1.5. 2-(2-Allyl-5-methoxy-3-methylphenoxy)-propionic
acid (6)
To a magnetically stirred solution of 2-allyl-5-methoxy-3-
methylphenol 4a (300 mg, 1.68 mmol) and a-bromopropionic
acid (257 mg, 1.68 mmol) in freshly distilled THF (10 mL) at
ꢁ10 ꢀC was added sodium hydride (150 mg, 60% dispersion
in mineral oil, 3.74 mmol) portionwise during 45 min. Stirring
was continued at ꢁ10 ꢀC for 20 min and at room temperature
for 30 min. The reaction mixture was then heated at reflux
with vigorous stirring for 10 h. Upon cooling the reaction mix-
ture was diluted with water, acidified with dilute HCl (6 M),
and extracted with ether. The ether extract was washed with
water, dried and concentrated. The residue was chromato-
graphed through silica gel eluting with ethyl acetateepetro-
leum ether (1:4) to afford the acid 6 (350 mg, 83%) as
a colourless solid, crystallized from etherepetroleum ether,
3.1.2. 2-Allyl-5-methoxy-3-methylphenol (4a) and 2-allyl-3-
methoxy-5-methylphenol (4b)
The allyl ether 3 (200 mg, 1.12 mmol) was quickly heated
to 220 ꢀC and kept at that temperature for 1 h. Then it was al-
lowed to cool to room temperature and the dark-brown rear-
ranged product was subjected to column chromatography
over silica gel. Elution with ethyl acetateepetroleum ether
(1:24) furnished the rearranged phenol 4b (57 mg, 28%) as
a viscous oil. IR (neat) 3444 cmꢁ1 1H NMR (300 MHz,
;
CDCl3) d 2.26 (s, 3H), 3.38 (d, J¼6.9 Hz, 2H), 3.77 (s, 3H),
5.02e5.16 (m, 2H), 5.89e6.02 (m, 1H), 6.29 (s, 1H), 6.31
(s, 1H); 13C NMR (75 MHz, CDCl3) d 21.6, 27.2, 55.8,
104.4, 109.5, 110.7, 115.1, 136.6, 137.7, 154.9, 158.0. Anal.
Calcd for C11H14O2: C, 74.13; H, 7.92. Found: C, 74.14; H,
7.89.
1
mp 101e102 ꢀC; IR (KBr) 1708 cmꢁ1; H NMR (300 MHz,
CDCl3) d 1.67 (d, J¼6.9 Hz, 3H), 2.30 (s, 3H), 3.34e3.51
(m, 2H), 3.78 (s, 3H), 4.78 (q, J¼6.9 Hz, 1H), 4.92e4.99
(m, 2H), 5.88e5.99 (m, 1H), 6.26 (s, 1H), 6.41 (s, 1H),
10.44 (br s, 1H); 13C NMR (75 MHz, CDCl3) d 18.8, 20.2,
30.5, 55.6, 72.7, 97.9, 108.4, 114.6, 120.0, 136.9, 139.5,
156.2, 158.7, 178.1. Anal. Calcd for C14H18O4: C, 67.18; H,
7.25. Found: C, 67.19; H, 7.32.
Continued elution afforded the phenol 4a (115 mg, 58%) as
1
a colourless oil. IR (neat) 3440 cmꢁ1; H NMR (300 MHz,
CDCl3) d 2.16 (s, 3H), 3.26 (d, J¼5.7 Hz, 2H), 3.64 (s, 3H),
4.87e4.97 (m, 2H), 5.80e5.89 (m, 1H), 6.18 (d, J¼2.4 Hz,
1H), 6.27 (d, J¼2.4 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 20.3, 30.5, 55.6, 99.9, 108.8, 115.5, 116.7, 136.5, 139.3,
155.3, 158.9. Anal. Calcd for C11H14O2: C, 74.13; H, 7.92.
Found: C, 74.11; H, 7.90.
3.1.6. 5-Methoxy-2a,7-dimethyl-8,8a-dihydro-1H,2aH-3-
oxacyclobuta[b]naphthalen-2-one (7)
To a magnetically stirred solution of triethylamine (600 mg,
5.94 mmol) and toluene-p-sulfonyl chloride (460 mg, 2.4 mmol)
in dry benzene (50 mL) at reflux was added dropwise a solution
of the acid 6 (300 mg, 1.20 mmol) in dry benzene (50 ml) over
6 h. After addition was complete, reflux was continued for another
6 h. The reaction mixture was then cooled and washed with water
(3ꢃ50 mL)andconcentratedtoone-thirdofthevolume.Thiscon-
centrated solution was stirred with 3% aqueous sodium hydroxide
solution (100 mL) for 10 h. The benzene layer was washed with
water, driedandconcentrated.Theresiduewaspurifiedbycolumn
chromatography over silica gel. Elution with ethyl acetateepetro-
leum ether furnished the cycloaddition product cyclobutanone 7
(140 mg, 50%) as a colourless solid, crystallized from ethere
petroleum ether; mp 75e76 ꢀC; IR (KBr) 1786 cmꢁ1; 1H NMR
(300 MHz, CDCl3) d 1.55 (s, 3H), 2.22 (s, 3H), 2.35 (dd,
J¼18.3,5.7 Hz, 1H), 2.79e2.81 (m, 2H), 2.86e2.92 (m, 1H),
3.12 (dd, J¼18.3, 9.5 Hz, 1H), 3.72 (s, 3H), 6.38 (d, J¼2.4 Hz,
1H), 6.41 (d, J¼2.4 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 19.8, 20.3, 24.7, 35.0, 48.1, 55.6, 92.9, 101.4, 111.3, 114.4,
138.2, 156.2, 159.1, 210.8. Anal. Calcd for C14H16O3: C, 72.39;
H, 6.94. Found: C, 72.43; H, 6.92.
3.1.3. 2-Allyl-1,5-dimethoxy-3-methylbenzene (5a)
A mixture of the phenol 4a (50 mg, 0.28 mmol), anhydrous
potassium carbonate (50 mg, 0.29 mmol) and iodomethane
(45 mg, 0.32 mmol) in acetone (5 mL) was heated at reflux
for 6 h. The reaction mixture was cooled and most of the
acetone was distilled off. The residue was poured into water
and extracted with ether (2ꢃ20 mL). The organic extract
was washed with water and dried. The residue after removal
of the solvent was subjected to column chromatography over
silica gel. Elution with ethyl acetateepetroleum ether (1:19)
furnished the dimethyl ether (5a) (50 mg, 93%) as a colourless
oil. 1H NMR (300 MHz, CDCl3) d 2.17 (s, 3H), 3.26 (d,
J¼6.0 Hz, 2H), 3.69 (s, 6H), 4.78e4.86 (m, 2H), 5.74e5.87
(m, 1H), 6.25 (s, 2H); 13C NMR (75 MHz, CDCl3) d 20.2,
30.2, 55.6, 56.0, 96.6, 107.0, 114.3, 119.3, 137.1, 138.9,
158.8, 158.9. Anal. Calcd for C12H16O2: C, 74.97; H, 8.39.
Found: C, 75.01; H, 8.35.

B. Biswas et al. / Tetrahedron 64 (2008) 3212e3216
3215
3.1.7. 7-Methoxy-5,9a-dimethyl-3a,9a-dihydro-3H,4H-1,9-
dioxacyclopenta[b]naphthalene-2-one (8)
0.20 mmol) was added dropwise. After stirring at that tempera-
ture for 2 h, the reaction was quenched with aqueous saturated
ammonium chloride solution. The organic layer was separated
and the aqueous part thoroughly extracted with ether
(3ꢃ15 mL). The combined ethereal extract was washed with
water and dried. The residue after evaporation of the solvent
was chromatographed over silica gel. Elution with ethyl ace-
tateepetroleum ether (1:4) furnished the lactol(s) 10 (48 mg,
95%) as a colourless solid, crystallized from methylene chlori-
deepetroleum ether, mp 118e119 ꢀC; IR (neat) 3436 cmꢁ1; 1H
NMR (300 MHz, CDCl3) d 0.95, 1.09 (2d, J¼6.6 Hz, 3H), 1.39,
1.60 (2s, 3H), 1.76e1.98 (m, 1H), 2.11, 2.13 (s, 3H), 2.22e2.29
(m, 1H), 2.55e2.67 (m, 2H), 3.64, 3.64 (2s, 3H), 4.99, 5.31 (2d,
J¼5.1 Hz, 1H), 6.12, 6.17 (2d, J¼2.6 Hz, 1H), 6.22, 6.23 (2d,
J¼2.6 Hz, 1H); 13C NMR (75 MHz, CDCl3) 11.4, 14.8, 19.4,
19.5, 20.9, 21.7, 22.7, 25.5, 39.5, 44.2, 45.2, 48.0, 54.8, 54.8,
98.8, 99.7, 99.9, 105.3, 105.5, 107.3, 108.5, 109.6, 109.8,
110.7, 136.9, 137.5, 153.2, 153.7, 158.7, 158.9. Anal. Calcd
for C15H20O4: C, 68.16; H, 7.63. Found: C, 68.15; H, 7.65.
A mixture of sodium bicarbonate (150 mg, 1.79 mmol) and
m-chloroperbenzoic acid (220 mg, 50% pure; 0.64 mmol) was
added portionwise to a vigorously stirred solution of the ketone
7 (130 mg, 0.56 mmol) in dry methylene chloride (10 mL) at
0 ꢀC during 5 min. The reaction mixture was then stirred at
ambient temperature for 3 h, diluted with methylene chloride
(30 mL) and quenched with 10% aqueous sodium carbonate
solution. The organic layer was washed with 10% aqueous
sodium carbonate solution, brine and dried. The residue after
evaporation of the solvent was chromatographed over silica
gel. Elution with ethyl acetateepetroleum ether (1:9) furnished
the g-lactone 8 (111 mg, 80%) as a colourless solid, crystallized
from etherepetroleum ether, mp 63e64 ꢀC; IR (KBr)
1
1791 cmꢁ1; H NMR (300 MHz, CDCl3) d 1.76 (s, 3H), 2.20
(s, 3H), 2.31 (dd, J¼17.7, 10.0 Hz, 1H), 2.61 (dd, J¼17.7,
8.9 Hz, 1H), 2.74e2.75 (m, 2H), 2.94e2.99 (m, 1H), 3.73 (s,
3H), 6.35 (d, J¼2.5 Hz, 1H), 6.44 (d, J¼2.5 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d 19.5, 22.9, 25.2, 33.7, 39.2, 55.7,
101.0, 108.3, 111.2, 111.3, 138.3, 153.5, 159.5, 174.9. Anal.
Calcd for C14H16O4: C, 67.73; H, 6.50. Found: C, 67.78; H, 6.70.
3.1.10. O-Methylalboatrin (11)
To a cooled and stirred solution of lactol 10 (30 mg,
0.114 mmol) in dichloromethane (2 mL), trifluoroacetic
acid (0.02 mL, 0.228 mmol) and triethylsilane (0.018 mL,
0.114 mmol) were added dropwise at ꢁ40 ꢀC, and stirred for
5 min and left to warm to room temperature. After stirring for
15 min at room temperature the reaction mixture was quenched
withwater. Theorganiclayer wasseparated andthe aqueouslayer
was extracted with methylene chloride (3ꢃ10 mL). The com-
bined organic extracts were washed with sodium bicarbonate
and brine, dried and concentrated. The residue was subjected to
column chromatography over silica gel. Elution with ethyl aceta-
teepetroleum ether (2%) furnished O-methylalboatrin 11
3.1.8. 7-Methoxy-3,5,9a-trimethyl-3a,9a-dihydro-3H,4H-
1,9-dioxacyclopenta[b]naphthalene-2-one (9)
To a well-stirred solution of LDA [prepared from n-butyl-
lithium (0.26 mL of 1.6 M solution in hexane, 0.42 mmol) and
diisopropylamine (45 mg, 0.44 mmol)] in THF (1 mL) at
ꢁ78 ꢀC, a solution of the g-lactone 8 (100 mg, 0.40 mmol) in
THF (1 mL) was added dropwise under argon and the resulting
solution was stirred for 30 min. Then the reaction mixture was
allowed to warm to ꢁ30 ꢀC and kept at that temperature for an-
other 30 min. Again the reaction mixture was cooled to ꢁ78 ꢀC
and HMPA (0.1 mL) followed by freshly distilled methyl iodide
(170 mg, 1.20 mmol) was added dropwise. After 2 h the reac-
tion mixture was allowed to attain room temperature and stirred
for 10 h. The reaction mixture was then quenched with saturated
aqueous ammonium chloride solution and extracted with ether
(3ꢃ15 mL). The combined ethereal extracts were washed with
water, dried, and the solvent removed. The residue was sub-
jected to column chromatography over silica gel. Elution with
ethyl acetateepetroleum ether (2:23) afforded the methylated
lactone 9 (98 mg, 94%) as a colourless solid, crystallized from
methylene chlorideepetroleum ether, mp 68e70 ꢀC; IR (KBr)
1790 cmꢁ1; 1H NMR (300 MHz, CDCl3) d 1.25 (d, J¼6.7 Hz,
3H), 1.72 (s, 3H), 2.22 (s, 3H), 2.42e2.45 (m, 2H), 2.70e2.80
(m, 2H), 3.74 (s, 3H), 6.31 (d, J¼2.4 Hz, 1H), 6.43 (d,
J¼2.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 13.4, 19.3,
21.2, 23.9, 37.8, 46.0, 55.2, 99.9, 105.1, 109.2, 110.6, 138.1,
153.2, 159.1, 177.5. Anal. Calcd for C15H18O4: C, 68.68; H,
6.92. Found: C, 68.74; H, 6.89.
1
(11 mg, 38%) as a colourless solid, mp 53e54 ꢀC; H NMR
(300 MHz, CDCl3) d 1.06 (d, J¼6.5 Hz, 3H), 1.51 (s, 3H), 1.93
(ddd, J¼10.9, 5.3, 2.5 Hz, 1H), 2.10e2.16 (m, 1H), 2.21 (s,
3H), 2.69e2.71 (m, 2H), 3.51 (t, J¼8.5 Hz, 1H), 3.73 (s, 3H),
4.18 (t, J¼8.5 Hz, 1H), 6.27 (d, J¼2.1 Hz, 1H), 6.36 (d,
J¼2.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) 16.4, 19.9, 21.9,
23.2, 35.8, 48.6, 55.5, 74.4, 100.0, 107.4, 109.6, 109.8, 138.3,
154.2, 159.2; HRMS (ES þve) calcd for C15H21O3 [MþH]þ
249.1492, found 249.1476.
3.1.11. Alboatrin (1)
To a stirred mixture of O-methylalboatrin 11 (40 mg,
0.028 mmol) in dry methylene chloride (3 mL) at ꢁ78 ꢀC, bo-
ron tribromide (0.01 mL, 0.034 mmol) was added dropwise.
The reaction mixture was stirred to ꢁ60 ꢀC and this tempera-
ture was maintained for 2 h. Then the reaction mixture was
quenched with ice cold water, and the organic layer was sep-
arated and the aqueous layer was further extracted with meth-
ylene chloride. The organic layers were combined and dried
and then subjected to column chromatography with silica
gel. Purification with petroleum ethereethyl acetate (25:3)
finally produced alboatrin 1 (32 mg, 80%) as a colourless
solid. The compound was further crystallized from ethere
petroleum ether, mp 146e147 ꢀC (lit.1,2,4 mp 146e148 ꢀC).
3.1.9. 7-Methoxy-3,5,9a-trimethyl-2,3,3a,9a-tetrahydro-4H-
1,9-dioxa-cyclopentan[b]naphthalene-2-ol (10)
To awell-stirred solution of the lactone 9 (50 mg, 0.19 mmol)
at ꢁ78 ꢀC in dry diethyl ether (3 mL), diisobutylaluminum
hydride solution (0.20 mL of 1.0 M solution in hexane,

3216
B. Biswas et al. / Tetrahedron 64 (2008) 3212e3216
1H NMR (300 MHz, CDCl3) d 0.84 (d, J¼6.0 Hz, 3H), 1.54 (s,
3H), 1.92e1.98 (m, 1H), 2.10e2.14 (m,1H), 2.18 (s, 3H), 2.68
(d, J¼2.7 Hz, 2H), 3.51 (t, J¼8.5 Hz, 1H), 4.17 (t, J¼8.5 Hz,
1H), 6.31 (br s,1H), 6.33 (s, 1H), 6.37 (s 1H); 13C NMR
(75 MHz CDCl3) 16.0, 19.4, 21.6, 23.2, 35.5, 48.4, 74.0,
101.9, 107.5, 109.5, 110.1, 138.2, 153.7, 155.3. HRMS (ES
þve) calcd for C14H17O3Na [MþNa]þ 257.1153, found
References and notes
1. Ichihara, A.; Nonaka, M.; Sakamura, S.; Sato, R.; Tajimi, A. Chem. Lett.
1988, 27.
2. Graham, S. R.; Murphy, J. A.; Kennedy, A. R. J. Chem. Soc., Perkin
Trans. 1 1999, 3071.
3. Lin, Y.; Wu, X.; Feng, S.; Jiang, G.; Luo, J.; Zhou, S.; Vrijmoed, L. L. P.;
Jones, E. B. G.; Krohn, K.; Steingrover, K.; Zsila, F. J. Org. Chem. 2001,
66, 6252.
4. Rodriguez, R.; Mosses, J. E.; Adlington, R. M.; Baldwin, J. E. Org. Biomol.
Chem. 2005, 3, 3488.
¨
257.1154.
The spectral data of 1 were identical with the reported
values.1,4
5. Biswas, S.; Ghosh, A.; Venkateswaran, R. V. J. Org. Chem. 1990, 55, 3498.
6. Mirrington, R. N.; Feutrill, G. I. Org. Synth. 1988, Coll. Vol. 6, 859.
7. Brady, W. T.; Marchand, A. P.; Giang, Y. F. J. Org. Chem. 1985, 50, 5177.
8. Brady, W. T.; Marchand, A. P.; Giang, Y. F.; Wu, A.-H. Synthesis 1987, 395.
9. Kraus, G. A.; Molina, M. T.; Walling, J. A. J. Chem. Soc., Chem. Commun.
1986, 1568.
Acknowledgements
We sincerely acknowledge the financial support from the
Department of Science and Technology, Govt. of India.