Carbocyclization of d-glucose: Syntheses of gabosine i and streptol

Article abstract of DOI:10.1016/j.tet.2011.06.028

d-Glucose was differentially protected with a trans-diacetal at C-2,3, an ethoxymethyl ether at C-4, and a tert-butyldimethylsilyl ether at C-6, and then carbocyclized via a key Horner-Wadsworth-Emmons (HWE) olefination to give a versatile synthetic inter

Full text of DOI:10.1016/j.tet.2011.06.028

Tetrahedron 67 (2011) 6001e6005
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Carbocyclization of
D
-glucose: syntheses of gabosine I and streptol
*
Tony K.M. Shing , Y. Chen, Wai-Lung Ng
Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, Hong Kong, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 April 2011
Received in revised form 3 June 2011
Accepted 10 June 2011
Available online 16 June 2011
D
-Glucose was differentially protected with a trans-diacetal at C-2,3, an ethoxymethyl ether at C-4, and
a tert-butyldimethylsilyl ether at C-6, and then carbocyclized via a key HornereWadswortheEmmons
(HWE) olefination to give a versatile synthetic intermediate, enone 13, which was readily transformed
into gabosine I and streptol.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Carbohydrate
Synthesis
Wittig reaction
Natural products
H
H
O
AcO
HO
HO
1. Introduction
H
O
O
H
O
O
O
Gabosines1 belong to a family of unusual, hydroxylated cyclo-
hexenones or hexanones that may be classified as pseudo- or
carba-sugars.2 Gabosines AeK were isolated in 1993 and have been
shown to display interesting bioactivities, such as antibiotic,1b an-
ticancer,3 and DNA binding properties.1c A total of 14 gabosines
have been identified since the first isolation of gabosine C and its
crotonyl ester, COTC, from Streptomyces strains in 1974.1a Since
then, 18 total syntheses have been described. Ten enantiospecific
syntheses constructed the carbocyclic framework from carbohy-
drates using either an intramolecular nitrile oxide or nitrone cy-
H
H
O
O
H
O
H
O
HO
OH
Gabosine I,
2 Gabosine G
3 Streptol
1
Valienone
Fig. 1. Structures of gabosine I, G, and streptol.
reduction product of 1, the a-allylic alcohol 3, is known as valienol
and also as (þ)-streptol, is a plant-growth inhibitor.21 Streptol (3)
was isolated from a culture of Streptomyces and was shown to in-
hibit the growth of lettuce seedlings at a concentration above
13 ppm.21a
cloaddition,4
a
SnCl4-promoted aldol-type cyclization of
phenylsulfonyl enol silyl ether,5 an intramolecular Noza-
kieHiyamaeKishi reaction,6 a ring-closing alkene metathesis,7
intramolecular HornereWadswortheEmmons (HWE) olefina-
tion,8 intramolecular direct aldol addition,9 or iron-catalyzed aldol
addition10 as the key step. Three other enantiospecific syntheses,
including our earlier endeavor,11 employed (ꢀ)-quinic acid as the
chiral starting material.12,13 The remaining five constructions of
gabosines involved a racemic norbornyl route,14 a chemoenzymatic
synthesis from iodobenzene,15 an asymmetric DielseAlder reaction
of chiral sulfinylacrylate with 2-methoxyufuran,16 enantioselective
acetylation of hydoxyketals,17 and enantioselective synthesis from
[(p-tolylsulfinyl)methyl]-p-quinols18 as the key strategies.
Gabosine I (1) was firstly synthesized by Lubineau and Billault6
in nine steps from tetra-O-benzyl-
molecular NozakieHiyamaeKishi reaction as the key step. Since
tetra-O-benzyl- -glucose was prepared from -glucose in three
steps, the total number of synthetic steps to 1 from -glucose is
D-glucose employing an intra-
D
D
D
therefore 12. A total synthesis of (þ)-streptol (3) was accomplished
by Mehta et al. from cyclopentadiene and benzoquinone as starting
materials via a DielseAlder and a retro-DielseAlder strategy in 11
steps with 14% yield.22
Our present research is focused on facile construction of hy-
droxylated carbocycles from sugars, which was coined carbo-
cyclization of carbohydrates. Our previous work already yielded
Gabosine I (1) is identical to valienone,19 an intermediate for the
biosynthesis of validamycin
A
(Fig. 1).20 The corresponding
gabosine I (1) and G (2) from
nereWadswortheEmmons (HWE) olefination as the key step,
a-D-gluconolactone via a Hor-
* Corresponding author. Tel.: þ852 2609 6344; fax: þ852 2603 5057; e-mail
address: tonyshing@cuhk.edu.hk (T.K.M. Shing).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.028

6002
T.K.M. Shing et al. / Tetrahedron 67 (2011) 6001e6005
and established the absolute configuration of (ꢀ)-gabosine G
(2).8 In that synthesis, we employed a mixed acetal as the
blocking group for the hydroxy function at C-1 and C-2. How-
ever, the mixed acetals were very acid sensitive and readily
decomposed. We therefore searched for a robust alternative so
that the carbocyclized enone could be stable enough to be
elaborated into a variety of target molecules. Furthermore, dif-
ferential protection of the hydroxyls is desirable as regio-
selective deprotection of the blocking group allows facile and
selective functional group manipulation. With this in mind, we
2. Results and discussion
The synthesis of gabosine I (1) from
Scheme 1. Commercially available benzyl a-D
D
-glucose is shown in
-glucopyranoside 425
was transacetalized26 with butadione and camphorsulfonic acid
(CSA) at OH-2,3 to give, preponderantly, diacetal 5 in 53% yield.
Differential protection was executed and the primary alcohol in diol
4 was selectively silylated with tert-butyldimethylsilyl chloride
(TBSCl) and N,N-dimethylaminopyridine (DMAP) to give silyl ether
6 in 94% yield. Alkylation of the remaining free alcohol in 6 with
ethoxymethyl (EOM) chloride in the presence of diisopropylethyl-
amine (DIPEA) afforded an almost quantitative yield of the fully
blocked benzyl glycoside 7. Catalytic hydrogenolysis of the benzyl
ether in 7 furnished lactol 8, which was smoothly oxidized with
pyridinium dichromate (PDC) to form lactone 9 in an excellent
now report from
D-glucose, efficient, and enantiospecific syn-
theses of gabosine I (1), streptol (3) using stable silyl ether, trans-
diacetal, and ethoxymethyl (EOM) ether for the hydroxyl
protection and an intramolecular HWE olefination23,24 as the key
carbocyclization step.
O
HO
TBSO
O
HO
HO
O
O
TBSCl, cat. DMAP
HO
OBn
OBn
O
HO
OBn
(MeO)3CH, MeOH
CSA, r.t., 2d, 53%
Et3N, CH2Cl2, r.t.
12h, 94%
O
MeO
O
OMe
O
MeO
O
HO
OH
OMe
4
5
6
TBSO
O
TBSO
O
EOMCl, DIPEA
CH2Cl2, r.t., 16h
H2, Pd/C
PDC, 3Å MS
CH2Cl2, 6h, r.t.
92%
EOMO
OBn
EOMO
OH
EtOH, r.t., 1h
99%
99%
O
O
O
O
MeO
OMe
MeO
OMe
8
7
TBSO
TBSO
EOMO
TBSO
O
P
O
P
O
P
O
O
OH
O
OH
OH
OMe
OMe
OMe
NaBH4, MeOH
0°C, r.t., 15min
96%
OMe
OMe
EOMO
O
EOMO
OMe
LDA, THF
-78°C, 15min
96%
O
O
O
O
O
MeO
OMe
MeO
OMe
MeO
OMe
11
9
10
TBSO
TBSO
EOMO
1. TFAA, DMSO
O
P
O
O
CH2Cl2, -78°C, 5h
TEA, LiCl
r.t., 1.5h
78%
OMe
OMe
EOMO
O
2. DIPEA, -78°C,
15min
O
O
O
O
MeO
OMe
MeO
OMe
13
12
HO
HO
O
TFA, H2O
r.t., 5min, 96%
13
HO
OH
Gabosine I (1)
TBSO
HO
HO
EOMO
OH
K-selectride
THF, r.t., 30min
98%
TFA, H2O
r.t., 5min, 88%
13
OH
O
O
HO
OH
MeO
OMe
Streptol (3)
14
Scheme 1. Syntheses of gabosine (1) and streptol (3).

T.K.M. Shing et al. / Tetrahedron 67 (2011) 6001e6005
6003
yield. Nucleophilic addition of lithiated dimethyl methyl-
phosphonate to the lactone carbonyl afforded phosphonate-lactol
10 in 96% yield.
million relative to tetramethylsilane (
d
¼0.0). Spinespin coupling
constants (J value) recorded in hertz were measured directly from
the spectra. All reactions were monitored by analytical thin-layer
chromatography (TLC) on aluminum-precoated plates of silica gel
with detection by spraying with 5% (w/v) dodecamolybdophos-
phoric acid in ethanol. Silica gel 60 (230e400 mesh) was used for
flash chromatography. All reagents and solvents were general re-
agent grade unless otherwise stated. DMF was dried by magnesium
sulfate and filtered. It was then freshly distilled under reduced
pressure. THF was freshly distilled from Na/benzophenone ketyl
under nitrogen. Dichloromethane was freshly distilled from P2O5
under nitrogen. Other reagents were purchased from commercial
suppliers and were used without purification.
Direct oxidation of lactol 10 to the corresponding diketone fol-
lowed by HWE cyclization proved difficult, hence the hemiacetal
was reduced by borohydride to give heptitol derivative 11 in an
excellent yield. Several oxidation protocols were attempted and
Swern oxidation27 was found to be the most efficient for the pro-
duction of diketone 12 and the subsequent intramolecular HWE
olefination was effected in the same pot to give enone 13 in 78%
overall yield. The olefination was better induced by triethylamine
than by DIPEA. Since enone of this type is generally unstable in
basic conditions, the addition of LiCl28 was necessary for the HWE
olefination because it shortened the reaction time.
Complete deprotection of enone 13 furnished gabosine I (1) in
96% yield. The trans-diacetal ring in 13 is the most stable protecting
group in acidic conditions, so the hydrolysis conditions of tri-
fluoroacetic acid (TFA) and H2O in a ratio of 20:1 were adopted.
Hence, gabosine I (1) was synthesized from benzyl glucopyranoside
4 in nine steps with 31% overall yield, identical in all respects to the
one synthesized by us8 previously. The overall yield (31%) of the
present work is superior to our last synthesis (20.3%) and is the best
overall yield for the preparation of gabosine I in the literature.6
Since gabosine G was prepared in one step from 1, this synthesis
is also a formal synthesis of gabosine G (2).
4.2. Synthesis
4.2.1. Diacetal 5. To a solution of benzyl glucoside 4 (1.05 g,
3.89 mmol) in dry MeOH (20 mL) were added 2,3-butanedione
(0.44 mL, 5.06 mmol), trimethyl orthoformate (2.55 mL, 23.3 mmol),
and (ꢁ)-10-camphorsulfonic acid (80 mg, 0.39 mmol). The reaction
mixture was stirred for 48 h at room temperature under N2. The
reaction mixture was then treated with triethylamine (1 mL). Con-
centration of the solution followed by flash chromatography
(n-hexane/EtOAc, 1:1) gave diacetal 5 (0.79 g, 53%) as a colorless oil:
20
[a]
ꢀ25.4 (c 0.43, CHCl3); Rf 0.10 (n-hexane/EtOAc, 1:1); IR (thin
D
For the synthesis of streptol, enone 13 was regio-selectively
film) 3406, 2994, 2927, 1456, 1376, 1207, 1135, 1039, 941, 884,
reduced by K-selectride to afford
a
-allylic alcohol 14 as the sole
751 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
1.32 (3H, s), 1.35 (3H, s), 3.23
product in 98% yield. Complete deprotection of the blocking groups
in 14 with aq TFA 12 gave streptol (3) in 88% yield. The spectral data
(1H, 13C NMR) of streptol (3) are in accord with those in the liter-
ature.22 Thus streptol (3) was synthesized from benzyl glucopyr-
anoside 4 in 10 steps with 28% overall.
(3H, s), 3.30 (3H, s), 3.60e3.64 (1H, m), 3.67e3.77 (4H, m), 4.08 (1H,
t, J¼9.8 Hz), 4.69 (1H, d, J¼12.6 Hz), 4.75 (1H, d, J¼12.6 Hz), 4.93 (1H,
d, J¼3.6 Hz), 7.28e7.41 (5H, m); 13C NMR (100 MHz, CDCl3)
d 17.8,
17.9, 48.0, 48.1, 61.9, 68.3, 68.4, 69.5, 70.2, 72.2, 96.9, 99.6, 100.0,
127.8, 128.2, 128.4, 137.7; MS (ESI) m/z (relative intensity) 407
([MþNa]þ, 100); HRMS (ESI) calcd for C19H28O8 [MþNa]þ 407.1676,
found 407.1680.
3. Conclusions
Since the chirality at the anomeric center was removed during
the conversion of benzyl glycoside 7 into lactol 8, we had also
4.2.2. Silyl ether 6. To a solution of diol 5 (232 mg, 0.61 mmol) in
CH2Cl2 (5 mL) were added TBSCl (137 mg, 0.91 mmol), Et3N
(0.21 mL, 1.21 mmol), and DMAP (7.8 mg, 0.06 mmol). The mixture
was stirred for 12 h at room temperature under N2. The solution
was diluted with EtOAc (10 mL). The resultant mixture was filtered
through a pad of silica gel that was eluted with EtOAc. Concentra-
carried out a convenient synthesis of lactol 8 from a mixture of
and
-benzyl glucopyranoside.25a Thus the present synthesis of
gabosine I (1) was achieved in 10 steps with 27% overall yield from
a-
D
b-D
D
-glucose using an HWE olefination as the key step. This synthesis
records a higher overall yield than our previous endeavor8 (20.3%)
and is the best overall yield for the preparation of gabosine I in the
literature.6 Since gabosine I can be converted into gabosine G in one
step,8 the present route is also a formal synthesis of gabosine G (2).
On the other hand, a synthesis of streptol (3) was accomplished in
tion of the filtrate followed by flash chromatography (n-hexane/
20
D
Et2O, 3:1) gave silyl ether 6 (283 mg, 94%) as a colorless oil: [a]
ꢀ27.4 (c 1.60, CHCl3); Rf 0.17 (n-hexane/Et2O, 3:1); IR (thin film)
3506, 2932, 1460, 1376, 1252, 1134, 1045, 885, 840, 779 cmꢀ1 1H
NMR (400 MHz, CDCl3) 0.07 (6H, 2s), 0.90 (9H, s), 1.34 (3H, s), 1.35
;
d
11 steps with 24% overall yield from
D
-glucose. Since the C-6 silyl
(3H, s), 3.24 (3H, s), 3.31 (3H, s), 3.59e3.76 (5H, m), 4.10 (1H, dd,
J¼10.1, 9.3 Hz), 4.70 (1H, d, J¼12.5 Hz), 4.74 (1H, d, J¼12.5 Hz), 4.90
(1H, d, J¼3.6 Hz), 7.27e7.42 (5H, m); 13C NMR (100 MHz, CDCl3)
ether and the C-4-EOM group in enone 13 could be selectively
deprotected according to conditions, the facile construction of
enone 13 provides opportunities for the syntheses of poly-
hydroxylated cyclohexenoid and cyclohexanoid natural products,
such as the recently isolated ampleomins AeG.29 It is also worthy
that the 13 would be an attractive intermediate for elaboration into
a wide variety of hydroxylated cyclohexenoid molecules of phar-
maceutical interests.
d
ꢀ5.4, ꢀ5.3, 17.8, 18.0, 18.4, 26.0, 48.0, 48.0, 64.1, 68.2, 69.4, 69.8,
70.2, 71.5, 96.6, 99.5, 99.9, 127.7, 128.2, 128.3, 137.8; MS (ESI) m/z
(relative intensity) 521 ([MþNa]þ, 100); HRMS (ESI) calcd for
C25H42O8Si [MþNa]þ 521.2541, found 521.2538.
4.2.3. Ethoxyl ether 7. To
a solution of alcohol 6 (250 mg,
0.50 mmol) in dry CH2Cl2 (3.0 mL) was added DIEPA (0.27 mL,
1.51 mmol). Chloromethyl ethyl ether (EOMCl) (0.07 mL,
0.75 mmol) was added dropwise over 10 min at 0 ꢂC. The mixture
was stirred for 16 h at room temperature under N2. The solution was
diluted with EtOAc (10 mL). The resultant mixture was filtered
through a pad of silica gel that was eluted with EtOAc. Concentration
of the filtrate followed by flash chromatography (n-hexane/Et2O,
4. Experimental section
4.1. General procedures
Melting points were measured with in Celsius degrees and were
uncorrected. Optical rotations were operating at 589 nm. Infrared
spectra (IR) were recorded as thin film on potassium bromide discs.
Nuclear magnetic resonance (NMR) spectra were measured at
5:1) gave ethoxyl ether 7 (276 mg, 99%) as a colorless oil: [
a
]
20 þ5.6
(c 0.96, CHCl3); Rf 0.13 (n-hexane/Et2O, 5:1); IR (thin film) 293D3,1461,
300.13 MHz (1H), 400.13 MHz (1H), 75.47 MHz
(
13C) or at
1375, 1253, 1134, 1042, 973, 839, 780 cmꢀ1 1H NMR (400 MHz,
;
100.13 MHz (13C). All chemical shifts were recorded in parts per
CDCl3)
d
0.05 (6H, 2s), 0.89 (9H, s), 1.20 (3H, t, J¼7.1 Hz), 1.29 (3H, s),

6004
T.K.M. Shing et al. / Tetrahedron 67 (2011) 6001e6005
1.33 (3H, s), 3.22 (3H, s), 3.27 (3H, s), 3.58e3.73 (7H, m), 4.14 (1H, dd,
J¼9.9, 9.1 Hz), 4.69 (2H, s), 4.82 (1H, d, J¼6.2 Hz), 4.86e4.89 (2H, m),
J¼6 Hz), 4.88 (1H, d, J¼6 Hz), 5.93 (1H, s, br); 13C NMR (75 MHz,
CDCl3)
d
ꢀ4.9, ꢀ4.7, 15.6, 18.3, 18.8, 26.4, 31.5, 33.3, 48.3, 48.4, 52.5,
7.28e7.40 (5H, m); 13C NMR (100 MHz, CDCl3)
d
ꢀ5.3, ꢀ5.0,15.2,17.8,
52.6, 53.9, 53.9, 62.7,64.4, 70.3, 72.6, 72.8, 73.7, 95.7, 96.5, 99.7,
100.6; MS (ESI) m/z (relative intensity) 611 ([MþNa]þ, 100), HRMS
(ESI) calcd for C24H49O12PSi [MþNa]þ 611.2623, found 611.2603.
18.0, 18.5, 26.1, 47.9, 48.0, 62.2, 64.0, 68.6, 69.3, 70.1, 72.4, 72.5, 96.0,
96.1, 99.5, 99.9, 127.6, 128.3, 128.4, 137.7; MS (ESI) m/z (relative in-
tensity) 579 ([MþNa]þ, 100); HRMS (ESI) calcd for C28H48O9Si
[MþNa]þ 579.2960, found 579.2956.
4.2.7. Diol 11. To a solution of lactol 10 (1.43 g, 2.42 mmol) in
MeOH (25 mL) was added NaBH4 (0.31 g, 9.69 mmol) at room
temperature. Stirring was continued for 0.5 h at the same tem-
perature under N2. The reaction was quenched with saturated aq
NH4Cl (15 mL). The mixture was extracted with EtOAc (4ꢃ30 mL).
The combined organic extracts were dried, filtered, and the filtrate
4.2.4. Lactol 8. To a solution of benzyl glucoside 7 (277 mg,
0.50 mmol) in ethanol (5.0 mL) was added 10% Pd-on-charcoal
(20 mg). The mixture was stirred for 1 h at room temperature un-
der an atmosphere of H2 (balloon) and was then filtered. Concen-
tration of the filtrate followed by flash chromatography (n-hexane/
was concentrated. Flash chromatography (EtOAc) gave diol 11
20
Et2O, 1:1) gave lactol 8 (231 mg, 99%) as a colorless oil: [
a
]
20 ꢀ35.6
(1.37 g, 96%) as a colorless oil. [
a
]
ꢀ92.4 (c 2.97, CHCl3); Rf 0.2
D
(c 4.28, CHCl3); Rf 0.23 (n-hexane/Et2O, 1:1); IR (thin film) 3446,
(EtOAc), IR (thin film) 3385, 2952D, 2930, 2856, 1645, 1462, 1375,
2951, 2931, 2587, 1645, 1472, 1463, 1357, 1252, 1137, 1037 cmꢀ1; 1H
1251, 1184, 1127, 1034 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 0.06 (3H,
NMR (mixture of
a
and
b
isomer with ratio
a
/
b
¼1:0.7) (400 MHz,
s), 0.07 (3H, s), 0.89 (9H, s), 1.94 (3H, t, J¼7.2 Hz), 1.28 (3H, s), 1.29
(3H, s), 1.87e2.03 (1H, m), 2.34e2.47 (1H, m), 3.20 (3H, s), 3.27 (3H,
s), 3.48e3.57 (1H, m), 3.68e3.78 (8H, m), 3.80e3.88 (3H, m),
3.92e3.97 (1H, m), 4.26e4.32 (2H, m), 4.74e4.79 (2H, m); 13C NMR
CDCl3) 0.03e0.06 (10.2H, m), 0.88 (15.3H, s), 1.19 (5.2H, t,
d
J¼7.0 Hz), 1.28e1.30 (10.2H, m), 3.24e3.28 (10.2H, m), 3.34e3.42
(1.7H, m), 3.58e3.89 (12.6H, m), 4.11 (1H, t, J¼9.8 Hz), 4.76 (0.7H, d,
J¼7.8 Hz), 4.80e4.88 (3.4H, m), 5.19 (1H, d, J¼3.5 Hz); 13C NMR
(100 MHz, CDCl3)
d
ꢀ5.52, 14.8, 17.3, 17.4, 18.1, 25.7, 28.2, 29.6, 47.7,
(100 MHz, CDCl3)
d
ꢀ5.3, ꢀ5.2, ꢀ5.0, 15.2, 17.7, 17.8, 17.9, 18.0, 18.6,
47.9, 52.2, 52.3, 52.4, 63.2, 63.7, 63.8, 64.9, 64.9, 67.1, 69.8, 69.9, 70.9,
76.5, 76.6, 77.2, 96.1, 98.6, 98.7; MS (ESI) m/z (relative intensity) 613
([MþNa]þ, 100), HRMS (ESI) calcd for C24H51O12PSi [MþNa]þ
613.2780, found 613.2769.
26.1, 47.9, 47.9, 48.1, 62.4, 62.6, 64.0, 64.1, 68.8, 69.4, 70.1, 71.8, 72.1,
72.5, 72.8, 77.0, 91.3, 94.6, 96.1, 96.1, 99.6, 100.0; MS (ESI) m/z
(relative intensity) 489 ([MþNa]þ, 100); HRMS (ESI) calcd for
C21H42O9Si [MþNa]þ 489.2490, found 489.2507.
ꢀ
4.2.8. Enone 13. To a mixture of 3 A molecular sieves (200 mg) and
4.2.5. Lactone 9. To a solution of lactol 8 (2.24 g, 4.8 mmol) in dry
CH2Cl2 (5 mL) were added 3 A molecular sieves (2 g) and PDC
(2.16 g, 5.75 mmol). The mixture was stirred for 6 h and was diluted
with diethyl ether (10 mL). The reaction mixture was filtered
through a pad of silica gel topped with Celite. The residue was
DMSO (0.23 mL, 3.2 mmol) in CH2Cl2 (2 mL) was added TFAA
(0.27 mL, 1.91 mmol) dropwise at ꢀ78 ꢂC with stirring. Stirring was
continued for 0.5 h under N2 at the same temperature. To the
stirred mixture was added dropwise a solution of diol 11 (168 mg,
0.28 mmol) in CH2Cl2 (2 mL) and then the mixture was stirred for
an additional 5 h at ꢀ78 ꢂC. To the mixture was added DIEPA
(1.1 mL, 6.37 mmol) dropwise with stirring and the stirring was
continued for 15 min at ꢀ78 ꢂC. The reaction mixture was removed
from the cooling bath and allowed to warm to room temperature
with stirring. To the mixture was added LiCl (27 mg, 0.64 mmol)
and TEA (0.2 mL, 1.28 mmol). The mixture was stirred for 1.5 h at
ꢀ
washed with EtOAc. The filtrate was concentrated under reduced
20
pressure to give lactone 9 as a colorless oil (2.056 g, 92%). [a]
ꢀ28.6 (c 2.76, CHCl3); Rf 0.6 (hexane/EtOAc, 3:1), IR (thin film) 295D3,
2931, 2896, 2858, 1773, 1645, 1463, 1379, 1257, 1236, 1214, 1141,
1115, 1036 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 0.01 (3H, s), 0.04 (3H,
s), 0.84 (9H, s), 1.15 (3H, t, J¼7.2 Hz), 1.25 (3H, s), 1.33 (3H, s), 3.21
(3H, s), 3.23 (3H, s), 3.47e3.56 (1H, m), 3.47e3.64 (1H, m), 3.79 (2H,
td, J¼11.4,1.7 Hz), 3.91e3.98 (1H, m), 4.16e4.20 (3H, m), 4.72 (1H, d,
ꢀ
room temperature and then was filtered to get rid of 3 A molecular
sieves. The filtrate was concentrated and the residue was flash
chromatographed (n-hexane/EtOAc, 8:1) to yield enone 13 (102 mg,
J¼6.8 Hz), 4.88 (1H, d, J¼6.8 Hz); 13C NMR (100 MHz, CDCl3)
ꢀ5.8,
d
ꢀ5.6, 14.8, 17.3, 17.4, 18.1, 25.7, 47.8, 48.4, 62.7, 63.6, 65.2, 68.4, 72.2,
82.1, 95.7, 98.6, 99.9, 167.6; MS (ESI) m/z (relative intensity) 487
([MþNa]þ, 100), HRMS (ESI) calcd for C21H40O9Si [MþNa]þ
487.2334, found 487.2338.
78%) as a yellowish oil. [
a
]
20 ꢀ48.4 (c 0.80, CHCl3); Rf 0.5 (n-hexane/
EtOAc, 3:1); IR (thin film)D2930, 2856, 1700, 1632, 1471, 1378, 1257,
1135, 1040, 1016 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 0.07 (6H, s),
0.91 (9H, s), 1.24 (3H, t, J¼7.2 Hz), 1.31 (3H, s), 1.40 (3H, s), 3.24 (3H,
s), 3.29 (3H, s), 3.58e3.61 (1H, m), 3.72e3.75 (1H, m), 4.08 (1H, dd,
J¼8.7, 11.4 Hz), 4.26 (1H, d, J¼11.4 Hz), 4.29 (1H, d, J¼18 Hz), 4.59
(1H, d, J¼9 Hz), 4.58 (1H, dd, J¼1.8, 18 Hz), 4.79 (1H, d, J¼6.6 Hz),
5.08 (1H, d, J¼6.6 Hz), 6.26 (1H, d, J¼2.1 Hz); 13C NMR (75 MHz,
4.2.6. Phosphonate 10. To a solution of diisopropylamine (0.12 mL,
1.19 mmol) in dry THF (2 mL) was added dropwise n-butyllithium
in hexane (1.6 M solution, 0.743 mL, 1.19 mmol) at ꢀ78 ꢂC under N2.
The reaction mixture was stirred for 30 min at ꢀ78 ꢂC under N2 and
dimethyl methylphosphonate (0.07 mL, 0.59 mmol) was then
added. The reaction mixture was stirred for a further 30 min at
ꢀ78 ꢂC and was added slowly to a solution of lactone 9 (138 mg,
0.30 mmol) in dry THF (2 mL) at ꢀ78 ꢂC. Stirring was continued for
an additional 1 h at the same temperature. The reaction was
quenched with saturated aq NH4Cl (1 mL) at ꢀ78 ꢂC and was
warmed to room temperature. The mixture was extracted with
EtOAc (4ꢃ10 mL), the combined organic extracts were dried
(MgSO4) and filtered. Concentration of the filtrate followed by flash
chromatography (n-hexane/EtOAc, 2:1) yielded phosphonate 10
CDCl3)
d
ꢀ5.0, ꢀ4.9, 15.7, 18.1, 18.2, 18.9, 26.4, 48.4, 49.0, 62.8, 64.9,
72.7, 74.6, 75.5, 97.3, 99.6, 100.6, 123.2, 162.1, 193.3; MS (ESI) m/z
(relative intensity) 483 ([MþNa]þ, 100), HRMS (ESI) calcd for
C22H40O8Si [MþNa]þ 483.2385, found 483.2393.
4.2.9. Gabosine I. To enone 13 (70 mg, 0.16 mmol) was added TFA
(2 mL) and H2O (0.1 mL). The solution was stirred at room tem-
perature for 5 min. Concentration of the solution followed by flash
chromatography (CHCl3/MeOH¼8:1) yielded Gabosine I (1) (24 mg,
96%) as a colorless oil, identical in all respects to the one synthe-
sized by us previously.8
(169 mg, 96%) as a colorless oil. [
a
]
20 þ55.6 (c 1.0, CHCl3); Rf 0.5 (n-
D
hexane/EtOAc, 1:1); IR (thin film) 2953, 2856, 1643, 1462, 1376,
4.2.10. Allylic alcohol 14. To a solution of enone 13 (100 mg,
0.22 mmol) in THF (5 mL) was added K-selectride (1.0 M solution,
0.33 mL, 0.33 mmol) at 0 ꢂC. Stirring was continued for 0.5 h at the
same temperature. The excess of the hydride was quenched with
methanol (0.1 mL). The reaction mixture was filtered through silica
1231, 1182, 1137, 1036 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 0.03 (6H,
s), 0.88 (9H, s), 1.18 (3H, t, J¼7.2 Hz), 1.29 (3H, s), 1.35 (3H, s), 1.92
(1H, dd, J¼15.3, 18.3 Hz), 2.60 (1H, dd, J¼15.6, 16.8 Hz), 3.22e3.34
(6H, m), 3.59e3.92 (11H, m), 4.17 (1H, t, J¼9.9 Hz), 4.84 (1H, d,

T.K.M. Shing et al. / Tetrahedron 67 (2011) 6001e6005
6005
ꢁ
ꢁ
2. (a) Arjona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem. Rev. 2007, 107,
gel and the residue was washed with EtOAc. Concentration of the
ꢁ
1919e2036; (b) Plumet, J.; Gomez, A. M.; Lopez, J. C. Mini-Rev. Org. Chem. 2007,
solution followed by flash chromatography (n-hexane/EtOAc, 6:1)
4, 201e216.
yielded allylic alcohol 14 (98 mg, 98%) as a colorless oil. [
(c 0.87, CHCl3); Rf 0.4 (n-hexane/EtOAc, 3:1); IR (thin film) 2952,
a
]
20 ꢀ30.4
3. (a) Huntley, C. F. M.; Hamilton, D. S.; Creighton, D. J.; Ganem, B. Org. Lett. 2000,
2, 3143e3144; (b) Kamiya, D.; Uchihata, Y.; Ichikawa, E.; Kato, K.; Umezawa, K.
Bioorg. Med. Chem. Lett. 2005, 15, 1111e1114.
4. (a) Gabosines ent-C and E: Lygo, B.; Swiatyj, M.; Trabsa, H.; Voyle, M. Tetrahe-
dron Lett. 1994, 35, 4197e4200; (b) Gabosines F, O and 4-epi-O: Shing, T. K. M.;
So, K. H.; Kwok, W. S. Org. Lett. 2009, 11, 5070e5073; (c) Gabosine ent-E: Sta-
thakis, C. I.; Athanatou, M. N.; Gallos, J. K. Tetrahedron Lett. 2009, 50,
6916e6918.
D
2929, 2884, 2857, 1653, 1472, 1375, 1251, 1226, 1130, 1094, 1039,
1015 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 0.06 (6H, s), 0.90 (9H, s),
1.21 (3H, t, J¼7.2 Hz), 1.29 (3H, s), 1.32 (3H, s), 3.25 (3H, s), 3.26 (3H,
s), 3.55e3.63 (2H, m), 3.66e3.74 (1H, m), 3.66e3.74 (1H, m)
4.12e4.33 (5H, m), 4.80 (1H, d, J¼6.5 Hz), 5.01 (1H, d, J¼6.5 Hz),
5. Gabosine C and COTC: Tatsuta, K.; Yasuda, S.; Araki, N.; Takahashi, M.; Kamiya,
Y. Tetrahedron Lett. 1998, 39, 401e402.
5.96 (1H, m); 13C NMR (100 MHz, CDCl3)
d
ꢀ5.5, ꢀ5.3, 15.1, 17.6, 17.8,
6. Gabosine, I.; Lubineau, A.; Billault, I. J. Org. Chem. 1998, 63, 5668e5671.
7. Gabosine C and COTC: Ramana, G. V.; Rao, B. V. Tetrahedron Lett. 2005, 46,
3049e3051; (b) Gabosines A and N: Monard, R. N.; Fanefjord, M.; Hansen, F. G.;
Jensen, N. M. E.; Madsen, R. Eur. J. Org. Chem. 2009, 396e402; (c) Gabosines N
and O: Rao, J. P.; Rao, B. V. Tetrahedron: Asymmetry 2010, 21, 930e935.
8. Gabosines G and I: Shing, T. K. M.; Cheng, H. M. J. Org. Chem. 2007, 72,
6610e6613.
18.3, 25.9, 47.8, 48.0, 62.6, 63.9, 64.7, 67.9, 69.6, 75.4, 96.2, 98.9,
99.5, 120.3, 142.5; MS (ESI) m/z (relative intensity) 485 ([MþNa]þ,
100), HRMS (ESI) calcd for C22H42O8Si [MþNa]þ 485.2541, found
485.2543.
4.2.11. Streptol (3). To the allylic alcohol 14 (50 mg, 0.107 mmol)
were added TFA (2 mL) and H2O (0.1 mL). The solution was stirred
at room temperature for 5 min. Concentration of the solution fol-
9. (a) Gabosines A, D, and E: Shing, T. K. M.; Cheng, H. M. Org. Biomol. Chem. 2009,
7, 5098e5102; (b) Gabosine, K.; Shing, T. K. M.; Cheng, H. M. Synlett 2010,
142e144.
10. Gabosines 4-epi-A and 4-epi-B: Mac, D. H.; Samineni, R.; Petrignet, J.; Sri-
lowed by flash chromatography (CHCl3/MeOH¼4:1) yielded
ꢁ
hari, P.; Chandrasekhar, S.; Yadav, J. S.; Gree, R. Chem. Commun. 2009,
20
4717e4719.
streptol (3) (18 mg, 97%) as a colorless oil. [
a]
þ95.6 (c 0.45,
MeOH), lit.22
[a
]
20 þ91.8 (c 0.25, H2O); Rf 0.2 (CHCDl3/MeOH¼2:1); IR
11. COTC: (a) Shing, T. K. M.; Tang, Y. J. Chem. Soc., Chem. Commun. 1990, 312; (b)
Shing, T. K. M.; Tang, Y. Tetrahedron 1990, 46, 6575e6584.
12. Gabosine C and COTC: Huntley, C. F. M.; Wood, H. B.; Ganem, B. Tetrahedron Lett.
2000, 41, 2031e2034.
13. Gabosines A, B, ent-D, and ent-E: Shinada, T.; Fuji, T.; Ohtani, Y.; Yoshida, Y.;
Ohfune, Y. Synlett 2002, 1341e1343.
(thin film) 3336D, 1676, 1435, 1384, 1203, 1133, 1057 cmꢀ1
;
1H NMR
(400 MHz, methanol-d4)
d
3.43 (1H, dd, J¼4.2, 10.2 Hz), 3.71 (1H,
dd, J¼7.5, 10.2 Hz), 3.96 (1H, d, J¼6.9 Hz), 4.2 (3H, m), 5.78e5.81
(1H, m); 13C NMR (100 MHz, methanol-d4)
d
62.1, 66.9, 71.9, 73.1,
14. (ꢁ)-Gabosine B and putative structure of (ꢁ)-gabosine K: Mehta, G.; Laksh-
73.3, 121.9, 143.3; MS (ESI) m/z (relative intensity) 199 ([MþNa]þ,
100), HRMS (ESI) calcd for C7H12O5 [MþNa]þ 199.0577, found
199.0574.
minath, S. Tetrahedron Lett. 2000, 41, 3509e3512.
15. Gabosine, A.; Banwell, M. G.; Bray, A. M.; Wong, D. J. New J. Chem. 2001, 25,
1351e1354.
16. Gabosine C and COTC: Takahashi, T.; Yamakoshi, Y.; Okayama, K.; Yamada, J.;
Ge, W.-Y.; Koizumi, T. Heterocycles 2002, 56, 209e220.
ꢁ
ꢁ
17. Gabosine N and O: Alibes, R.; Bayon, P.; de March, P.; Figueredo, M.; Font, J.;
Acknowledgements
Marjanet, G. Org. Lett. 2006, 8, 1617e1620.
18. Gabosine, O.; Carreno, M. C.; Merino, E.; Ribagorda, M.; Somoza, A; Urbano, A.
ꢁ
~
Chem.dEur. J. 2007, 13, 1064e1077.
19. Sedmera, P.; Halada, P.; Pospísil, S. Magn. Reson. Chem. 2009, 47, 519e522.
20. (a) Mahmud, T. Curr. Opin. Chem. Biol. 2009, 13, 161e170; (b) Mahmud, T.; Lee,
This work was supported by a Strategic Investments Scheme
administrated by the Center of Novel Functional Molecules, and by
a Direct Grant, The Chinese University of Hong Kong.
ꢂ
S.; Floss, H. G. Chem. Rec. 2001, 1, 300e310.
21. (a) Isogai, A.; Sakuda, S.; Nakayama, J.; Watanabe, S.; Suzuki, A. Agric. Biol. Chem.
1987, 51, 2277e2279; (b) Kroutil, W.; Hagmannb, L.; Schuezb, T. C.; Jungmannb,
V.; Pachlatkob, J. P. J. Mol. Catal. B: Enzym. 2005, 32, 247e252.
22. Mehta, G.; Pujar, S. R.; Ramesh, S. S.; Islam, K. Tetrahedron Lett. 2005, 46,
3373e3376.
23. (a) Shing, T. K. M.; Aloui, M. J. Chem. Soc., Chem. Commun. 1988, 1525e1526; (b)
Shing, T. K. M.; Aloui, M. Can. J. Chem. 1990, 68, 1035e1037.
24. Fukase, H.; Horii, S. J. Org. Chem. 1992, 57, 3651e3658.
25. (a) Pearce, O. M. T.; Varki, A. Carbohydr. Res. 2010, 345, 1225e1229; (b) Park, T.
J.; Weïwer, M.; Yuan, X.; Baytas, S. N.; Munoz, E. M.; Murugesan, S.; Linhardt, R.
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Reynolds, D. J. Chem. Rev. 2001, 101, 53e80.
Supplementary data
1H NMR and 13C NMR spectra for compounds 3, 5e11, 13, and 14.
Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tet.2011.06.028.
References and notes
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