Total synthesis of gabosines via an iron-catalyzed intramolecular tandem aldol process

Article abstract of DOI:10.1016/j.tet.2011.09.121

Several gabosines, belonging to polyhydroxy-cyclohexenone and cyclohexanone class of natural products, are synthesized in various stereoforms using an intramolecular iron-catalyzed tandem aldol process. The reaction, which starts from vinylic pyranoses, i

Full text of DOI:10.1016/j.tet.2011.09.121

Tetrahedron 67 (2011) 9305e9310
Contents lists available at SciVerse ScienceDirect
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journal homepage: www.elsevier.com/locate/tet
Total synthesis of gabosines via an iron-catalyzed intramolecular tandem aldol
process
,
,
,
,
*
Dinh Hung Mac a c, Ramesh Samineni a b, Abdul Sattar a b, Srivari Chandrasekhar b, Jhillu Singh Yadav b
,
a,
*
ꢀ
ꢀ
Rene Gree
a
ꢀ
ꢀ ꢀ
Universite de Rennes 1, Laboratoires CPM CNRS UMR 6510 and SCR CNRS UMR 6226, Avenue du General Leclerc, 35042 Rennes Cedex, France
b Indian Institute of Chemical Technology, 500607 Hyderabad, India
c Hanoi University of Sciences-VNU, Medicinal Chemistry Laboratory, 19 Le Thanh Tong, Ha Noi, Viet Nam
a r t i c l e i n f o
a b s t r a c t
Article history:
Several gabosines, belonging to polyhydroxy-cyclohexenone and cyclohexanone class of natural prod-
ucts, are synthesized in various stereoforms using an intramolecular iron-catalyzed tandem aldol pro-
cess. The reaction, which starts from vinylic pyranoses, is compatible with two different OH protecting
groups (acetyl and benzyl). Further, like the Ferrier carbocyclisation, it is not sensitive to the stereo-
chemistry of sugar molecules used as precursors: six different gabosine-type molecules have been
Received 13 September 2011
Received in revised form 27 September 2011
Accepted 28 September 2011
Available online 5 October 2011
prepared by this route starting from
D-Glucose,
D
-Mannose, and
D-Galactose derivatives.
Keywords:
Gabosine
Ó 2011 Elsevier Ltd. All rights reserved.
Iron pentacarbonyl
Aldolisation
Cyclohexenone
Natural products
1. Introduction
molecules: intramolecular NozakieKishi reaction,4 aldol-type
condensations,5 HornereWadswortheEmmons reactions,6 ring-
closing metathesis,7 intramolecular cycloadditions,8 and Ferrier
carbocyclisation,9 inter alia. Other chiral pool approaches involved
quinic acid10 or [(p-tolylsulfinyl)methyl]-p-quinols11 as starting
materials. The other strategies include the utilisation of norbor-
nene,12 asymmetric DielseAlder reactions,13 masked p-benzoqui-
nones,14 chemoenzymatic approaches,15 inter alia.
The synthesis of polyhydroxycyclohexane derivatives from
natural sugars, popularly called ‘carbohydrates to carbocycles’ is
a powerful tool in natural product synthesis. These carbocycles,
especially in the cyclohexane form, have attracted wider attention
owing to their broad range of biological activities. The hexose
sugars have been the natural choice for construction of this type of
molecules. Excellent reviews have appeared in the literature de-
scribing the methods of synthesis of carbasugars and their
applications.1
Gabosines belong to this set of natural products and over 14
gabosines have been isolated to date from Streptomyces strains. The
first of this class, gabosine C, was isolated way back in 1974,2 and
some members (gabosines L, N, and O) very recently.3 These sec-
ondary metabolites have been shown to display some interesting
antibiotic, anticancer, and weak DNA binding properties (Fig. 1).
Several groups have reported elegant syntheses of various
gabosines. Most of these syntheses have used the carbohydrates as
chiral pool, as expected for the preparation of this class of mole-
cules. They employ different methodologies for building the target
* Corresponding authors. Tel.: þ33 (0) 2 23 23 57 15; fax: þ33 (0) 2 23 23 69 78
(R.G.); tel.: þ91 4027193030; fax: þ91 4027150387 (J.S.Y.); e-mail addresses:
ꢀ
yadavpub@iict.res.in (J.S. Yadav), rene.gree@univ-rennes1.fr (R. Gree).
Fig. 1. Selected members from the gabosine family.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.121

9306
D.H. Mac et al. / Tetrahedron 67 (2011) 9305e9310
Recently we have demonstrated first potentialities of a transi-
With this lactol in hand, we performed the isomer-
izationealdolisation process using Fe(CO)5 as catalyst and under
irradiation. The aldol product 4 (as a stereoisomeric mixture) was
immediately used in a dehydration reaction to give 4-epigabosine
N, under acetate protected form 5, in moderate yield.
tion metal-mediated tandem isomerizationealdolisation re-
action.16 In an intramolecular fashion and starting from vinyl
lactols, it allows efficient construction of cyclopentanoids and
cyclohexenones.17 The precursors for this process are either the
vinyl furanoses or vinyl pyranoses, respectively. The utility of
this procedure was also demonstrated by us in the synthesis of
4-epigabosine A and the dihydro-analogue 4-epigabosine B starting
Using protocol developed as above, from methyl a-D-glucopyr-
anoside, intermediate 6 was prepared easily as described in liter-
ature.21 After two steps of transprotection of benzyl groups by
acetates by the method of Stubbs,22 then deprotection selectively in
anomeric position,23 the lactol 8 was ready for tandem aldol pro-
cess (Scheme 2). The conversion of this vinyl pyranose to cyclo-
hexanols, followed by the dehydratation with MsCl/Et3N gave the
desired product 10 in moderate yield.
from D
-Glucose.18
Herein, in this full article, we wish to report the consolidated
results pertaining to this intramolecular aldolisation process
starting from three different sugars namely
D-Glucose, D-Mannose,
and -Galactose. The vinyl lactols derived from these sugars
D
have been converted to six different derivatives: gabosine A,
4-epigabosine N, 4-epigabosine A, 6-epigabosine O, as well as
4-epigabosine B and 4-epi-6-epigabosine B.
The strategy we have adapted is shown in Fig. 2: from the vinylic
pyranose A, by using the tandem isomerizationealdolisation re-
action with Fe(CO)5 as catalyst, we can get directly the cyclo-
O
OMe
O
OAc
Ref. 21
a
b
Methyl-D-Glucose
BnO
OBn
6
AcO
OAc
OBn
O
OAc
7
hexanols B, which give the cyclohexenones
C by simple
O
OH
OH
O
c
d
dehydratation. In order to obtain D- and E-type cyclohexanone
members, deprotection and hydrogenation steps have to be
employed. Clearly in this strategy, the role of the R protecting group
should be considered.
AcO
OAc
AcO
OAc
AcO
OAc
10
OAc
9
8
OAc
OAc
Scheme 2. Synthesis of cyclohexenone 10. Reagents and conditions: (a) Ac2O, TMSOTf,
56%, (b) Hydrazine acetate, DMF, 50 ꢀC, 76%, (c) Fe(CO)5, h
35% from 8.
n, THF, (d) MsCl, Et3N, CH2Cl2,
Tandem
O
O
isomerization-
aldolisation
Scheme 3 summarizes the synthetic steps from
side to the tri-acetate protected gabosine A 15. The synthesis of
compound 11 was achieved from commercially available methyl-
a-D-mannopyrano-
O
- H2O
OH
OH
(RO)3
O
(RO)3
a-D-
(RO)3
Mannose as reported in literature.8c The benzyl group and anomeric
methyl ether functionality were converted to tetracetate 12 by using
Ac2O/TMSOTf. The precursorfor tandem reaction,13, wasobtained by
selective hydrolysis and anomeric acetoxy group deprotection by
hydrazine hydrate. Once again, this tandem process allowed us to
prepare the cyclohexenone 15, via intermediates 14. These three
targets (5,10, and15)werecharacterizedfromextensiveNMRstudies.
B
C
A
O
O
+ H2
(HO)3
(RO)3
(HO)3
D
C
E
Fig. 2. Strategy for the synthesis of selected members of the gabosine family.
O
OMe
O
OAc
OAc
Ref. 8c
a
b
Methyl-D-Mannose
BnO
OBn
AcO
d
2. Results and discussion
OBn
OAc
12
11
O
OH
Based on the strategy shown in Fig. 2, the initial objective was to
synthesize vinyl pyranoses with different protective and stereo-
meric hydroxyl groups. In this endeavor, we prepared the vinyl
c
O
OH
OAc
O
AcO
OAc
AcO
AcO
OAc
OAc
OAc
OAc
15
14
13
pyranoses of D-Glucose, D-Mannose, and D-Galactose with acetate
Scheme 3. Synthesis of cyclohexenone 15. Reagents and conditions: (a) Ac2O/TMSOTf,
and benzyl as protecting groups for application in the tandem
isomerizationealdolisation process.
59%, (b) Hydrazine acetate, DMF, 50 ꢀC, 68%, (c) Fe(CO)5, h
40% from 13.
n, THF, (d) MsCl, Et3N, CH2Cl2,
From -Galactose, the vinyl pyranose 1 was synthetized as de-
D
scribed in literature.19 The conversion of protecting groups gave
tetraacetate 2,20 which was deprotected selectively by hydrazine
acetate to afford the vinylic lactol 3 with a fair yield (Scheme 1).
By performing this tandem process with three sugar derivatives, we
have demonstrated the capacities of this reaction on the different
substrates. However, the yields in the tandem aldol process were only
moderate. Therefore it was of interest to check the possibility of using
another, more robust, protective group. Toward this goal, benzyl
protection appeared the best choice and the reactions were per-
formed starting from similar vinyl lactols but with benzyl protected
alcohols.Thisstrategyallowedustoprepare4-epigabosineNand4-6-
O
O
O
O
O
OAc
OAc
Ref. 19
a
b
D-Galactose
O
AcO
OAc
2
1
diepigabosine B starting from -Galactose (Scheme 4). The lactol 17
D
O
OH
OAc
O
d
O
OH
was obtained from vinyl pyranose 16 by demethylation using a 70%
AcOH solution, in good yield. The substrate 17, now ready for the
tandem isomerizationealdolisation, was subjected to catalytic re-
action by using Fe(CO)5 at 10 mol % to provide the cyclohexanol de-
rivative 18 in almost quantitative yield and as a diastereomeric
mixture. This crude mixture was exposed to MsCl and triethylamine
to realize the cyclohexanone 19 in 54% overall yield for two steps.
c
AcO
OAc
3
AcO
OAc
AcO
OAc
OAc
5
OAc
4
Scheme 1. Synthesis of cyclohexenone 5. Reagents and conditions: (a) AcOH 70% then
Ac2O, Py, DMAP, 91% for two steps, (b) Hydrazine acetate, DMF, 50 ꢀC, 66%, (c) Fe(CO)5,
hn, THF, (d) MsCl, Et3N, CH2Cl2, 32% from 3.

D.H. Mac et al. / Tetrahedron 67 (2011) 9305e9310
9307
OH
O
OMe
OBn
OH
O
OMe
OBn
O
OH
O
OH
O
O
b
b
a
a
BnO
16
BnO
17
OBn
BnO
11
BnO
OBn
OH
BnO
24
OBn
BnO
OBn
25
OBn
OBn
18
OBn
OH
OBn
OBn
OBn
c
c
O
O
O
d
e
O
O
O
e
d
HO
HO
OH
BnO
19
OBn
OH
4-epi-6-epigabosine B
HO
OH
20
OBn
HO
OH
BnO
OBn
4-epigabosine N
OH
gabosine A
OH
6-epigabosine O
OBn
26
Scheme 4. Synthesis of 4-epi 6-epigabosine B and 4-epigabosine N. Reagents and
conditions: (a) AcOH 70%, H2SO4 cat. 75%, (b) (i) Fe(CO)5 10%, THF, hn, (c) TMsCl, Et3N,
Scheme 6. Synthesis of gabosine A and 6-epigabosine O. Reagents and conditions: (a)
AcOH 70%, H2SO4 cat, 65%, (b) Fe(CO)5 10%, THF, h , (c) TMSCl, Et3N, CH2Cl2, 75% for two
steps, (d) FeCl3, CH2Cl2. 50%, (e): Pd/C, MeOH, 3 days, 60%.
CH2Cl2, 54% for two steps, (d) FeCl3, CH2Cl2, 0 ꢀC, 15 min 50%, (e): Pd/C, EtOH, 3 days,
80%.
n
3. Conclusion
The debenzylation was achieved by using FeCl3 in CH2Cl2,24 to
furnish the 4-epigabosine N in 55% yield. The isolated compound
had spectroscopical data fully matching with literature.14a On the
other hand by using Pd/C in ethanol, a completely stereoselective
hydrogenation of 19 occurs together with tri-debenzylation,
affording the diastereoisomer 20 of gabosine B, in a one-pot 80%
yield reaction. The stereochemistry of this compound was un-
ambiguously established by extensive NMR experiments. Particu-
larly relevant for the axial position of the CHMe proton were the
two J3 coupling constants (13.3 and 6.0 Hz) with the vicinal CH2
protons.
In conclusion, we have demonstrated that the intramolecular
tandem isomerizationealdolisation reaction starting from vinyl
pyranoses allows a short synthesis of natural product gabosine
A as well as 4-epigabosine A, 4-epigabosine B, 4-epigabosine N,
6-epigabosine O, and 4-epi-6-epigabosine B. This process is not
sensitive to the stereochemistry of the starting sugar molecule and
further was developed with two different protective groups for the
alcohol functions. However, for these syntheses the benzyl group
proved to be more appropriate.
The 4-epigabosine A and 4-epigabosine B were similarly syn-
thesized from D-Glucose as depicted in Scheme 5. The intermediate
6 was converted to vinyl lactol pyranose 21 by using a known
protocol.21 This compound, under the usual conditions, underwent
the tandem isomerizationealdolisation, followed by the de-
hydration to give a benzyl protected gabosine derivative 23.
4. Experimental section
4.1. General information
All reactions were carried out under argon or nitrogen atmo-
sphere. TLC spots were examined under UV light and revealed by
sulfuric acideanisaldehyde, KMnO4 solution or phosphomolybdic
acid. Dichloromethane was distilled from calcium hydride, tetra-
hydrofuran and diethylether were distilled from sodium/benzo-
phenone, methanol was distilled over magnesium. NMR spectra
were obtained at 300 MHz or 500 MHz for 1H and 75 MHz or
125 MHz for 13C with BRUCKER AVANCE 300 or 500 spectrometers.
OH
O
OH
O
a
O
b
BnO
21
OBn
BnO
OBn
BnO
OBn
OBn
OBn
22
OBn
23
Chemical shifts are given in parts per million (d) relative to chlo-
d
O
O
roform (7.26 ppm) or benzene (7.16) residual peaks. Assignments of
1H and 13C resonances for complex structures were confirmed by
extensive 2D experiments (COSY, HMQC, and HMBC). Mass spectral
c
HO
OH
HO
OH
OH
OH
4-epigabosine B
ꢀ
analyses have been performed at the Centre Regional de Mesures
4-epigabosine A
Physiques de l’Ouest (CRMPO) in Rennes (France). Caution: all re-
actions involving Fe(CO)5 have to be carried out under a well ven-
tilated hood. These iron carbonyl-mediated reactions have been
performed in usual Pyrex glassware equipment.
Scheme 5. Synthesis of 4-epigabosine A and 4-epigabosine B. Reagents and condi-
tions: (a) Fe(CO)5 10%, THF, h , (b) TMSCl, Et3N, CH2Cl2, 65% for two steps (c) FeCl3,
CH2Cl2, 55%, (d): Pd/C, EtOH, 3 days, 90%.
n
The deprotectionof benzyl groupbyFeCl3 gavethe 4-epigabosine
A in 55% yield. This compound had spectral data in good agreement
with the literature.11 Hydrogenation, followed by complete deben-
zylation, afforded the 4-epigabosine B in 90% yield.
4.2. Synthesis
4.2.1. General procedure A for the tandem aldolisation reaction, fol-
lowed by dehydration. Representative example: preparation of cy-
clohexenone 23. A solution of vinylic lactol 21 (890 mg, 2 mmol)
To complete the research on this reaction a third sugar, namely
the methyl mannoside 11, was converted to the vinyl pyranoside 24,
followed by catalytic aldolisation yielding 26. A simple debenzyla-
tion furnished in 50% yield gabosine A whose spectral data and
optical rotation were in good agreement with literature.7b,9,15 On
the other hand, hydrogenation of double bond and deprotection
of all benzyl groups by using methanol as solvent finally gave
6-epigabosine O in moderate yield. The structure of this compound
was also confirmed by extensive NMR studies. Particularly relevant
for the axial position of the CHMe proton were the two J3 coupling
constants (12.8 and 6.1 Hz) with the vicinal CH2 protons (Scheme 6).
It is worthy of note that hydrogenation of the double bond in 26,
like for 18 and 23, occurred exclusively from the face anti to allylic
OBn groups.
and Fe(CO)5 (26 ml, 10% mol) in anhydrous THF (20 mL) was irra-
diated with a Philips HPK125 W during 1 h. After being cooled to
room temperature and concentrated, the residue was diluted in
ether, filtered on a short pad of silica gel, and concentrated under
vacuum to afford aldol products as a mixture of diastereoisomers:
(45/50/5 by 1H NMR). This mixture was purified by column chro-
matography on silica gel with pentane/AcOEt: 7/3 as eluent to af-
ford 22 (845 mg, 95%). To an ice-cold solution of previous aldol
products 22 (700 mg, 1.57 mmol) and Et3N (1.1 mL, 5 equiv) in an-
hydrous CH2Cl2 (15 mL), was added MsCl (303 m
l, 2.5 equiv) at 0 ꢀC.
After being stirred at room temperature during 24 h, the mixture
was diluted with CH2Cl2 and H2O. The organic phase was separated

9308
D.H. Mac et al. / Tetrahedron 67 (2011) 9305e9310
and the aqueous phase was extracted with CH2Cl2 (3ꢁ20 mL). The
combined organic phases were dried over MgSO4, filtered, and
concentrated under vacuum to afford a residue, which was purified
by chromatography on silica gel with pentane/AcOEt (90/10; Rf: 0.3)
as eluent to afford cyclohexenone 23 as a white solid 464 mg (69%
yield), mp: 64e66 ꢀC.
3.46 (br s, OH), 3.82 (br s, OH), 4.22 (dd, J¼1.4, 5.0 Hz,1H), 4.71 (br s,
1H), 4.76 (d, J¼5.3 Hz, 1H), 5.09 (d, J¼5.2 Hz, 1H), 5.18 (dd, J¼1.6,
3.6 Hz, 1H), 5.22 (dd, J¼1.3, 10.7 Hz, 1H), 5.25 (dd, J¼1.4, 10.7 Hz,
1H), 5.34 (dd, J¼1.4, 17.3 Hz, 1H), 5.35 (dd, J¼1.3, 17.3 Hz, 1H), 5.40
(br s, 1H), 5.54 (br s, 1H), 5.7 (ddd, J¼5.9, 10.8, 17.2 Hz, 1H); 13C NMR
(75 MHz, CDCl3):
d
¼20.56, 20.58, 20.7, 20.8, 67.4, 68.3, 69.1, 70.4,
70.6, 71.0, 73.9, 90.6, 95.8, 118.1, 118.5, 131.7, 132.4, 170.1, 170.4,
170.5, 171.2; HRMS m/z calculated for [MþNa]þ (C13H18O8Na):
325.0899, found 325.0890.
4.2.2. General procedure B for the debenzylation. Representative ex-
ample: synthesis of 4-epigabosine N. To a solution of cyclohexenone
19 (80 mg, 0.18 mmol) in anhydrous CH2Cl2 was added under argon
at 0 ꢀC anhydrous FeCl3 (86 mg, 3 equiv). After 15 min, reaction was
complete, as indicated by TLC analysis, and the reaction mixture
was quenched with H2O (5 mL). It was stirred for 1 min and then
extracted with AcOEt (3ꢁ30 mL). The organic layers were dried
over Na2SO4, filtered, and the solvents were removed under re-
duced pressure. This crude reaction mixture was purified by flash
silica gel column chromatography (AcOEt as eluent) to afford 4-epi-
Gabosine N as a colorless viscous oil: 14 mg (50% yield).
4.2.6. (4S,5R,6R)-4,5,6-Tris(acetoxy)-2-methylcyclohex-2-enone
5. The reaction was realized following the general procedure A
with: lactol 3 (300 mg, 1 mmol), Fe(CO)5 (26
cyclohexenone 5 as a viscous oil (90 mg: 32% for two steps) (pen-
tane/AcOEt: 9/1; Rf: 0.3); 1H NMR (300 MHz, CDCl3):
ml, 20% mol) to give
d
¼1.86 (s, 3H),
2.03 (s, 3H), 2.10 (s, 3H), 2.14 (s, 3H), 5.69 (m, 1H), 5.48 (m, 1H), 5.79
(d, J¼3.0 Hz, 1H), 6.54 (dq, J¼1.4, 4.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3)
d
¼15.6, 20.5, 20.69, 20.72, 66.9, 71.4, 135.1, 138.5, 139.4,
169.5, 169.8, 190.8; HRMS m/z calculated for [MþNa]þ
4.2.3. General procedure C for the hydrogenation. Representative
example: synthesis of 4-epi-6-epigabosine N. To a solution of 19
(30 mg, 0.07 mmol) in absolute ethanol (2.5 mL) was added palla-
dium on activated carbon (5 mg). The flask was flushed with hy-
drogen three times. When analytical TLC showed the
disappearance of starting material, the reaction mixture was fil-
tered through a pad of silica gel. The filtrate was concentrated
under vacuum to afford desired 4-epi-6-epi-gabosine N: 9 mg (80%
yield).
(C13H16O7Na): 307.2517, found 307.2520; ½a D20
ꢂ
þ158.7 (c 0.6,
MeOH).
4.2.7. 1,2,3,4-Tetra-O-acetyl-6,7-dideoxy-
D
-gluco-hept-6-
enopyranose 7. To a solution of the vinyl glucopyranose 6 (3.4 g,
7.9 mmol) in acetic anhydride (20 mL), was added dropwise with
vigorous stirring under nitrogen at room temperature trime-
thylsilyl trifluoromethanesulfonate (0.452 mL, 2.35 mmol). The
reaction mixture was stirred for an additional 10 h. After cooling to
0 ꢀC, the dark solution was diluted with AcOEt (50 mL) and poured
in a cold saturated NaHCO3 solution (50 mL). The organic phase was
4.2.4. 1,2,3,4-Tetra-O-acetyl-6,7-dideoxy-D-galacto-hept-6-
enopyranose 2. A solution of 1 (1.8 g, 7 mmol) in 70% acetic acid
(42 mL) was reflux at 80 ꢀC for 7 h. The solvent was co-evaporated
with toluene under reduced pressure to give crude product as
viscous oil. This crude product was then dissolved in anhydrous
pyridine (30 mL). To this solution, DMAP (50 mg) and acetic an-
hydride (20 mL) were added successively at 0 ꢀC under nitrogen,
then the mixture was kept under stirring for 24 h at room tem-
perature. After addition of water, the aqueous phase was extracted
with CH2Cl2 (3ꢁ50 mL) and the combined organic phases were
dried over MgSO4, filtered, and evaporated under reduced pressure.
The crude product was purified by column chromatography on
silica gel to afford compound 2 as a colorless oil: 2.2 g (yield: 91%
for two steps) (it was obtained as a mixture of two isomers in a 75/
25 ratio by 1H NMR) (eluent pentane/ether: 6/4; Rf: 0.3); 1H NMR
separated and washed with a saturated NaHCO3 solution
(3ꢁ50 mL), brine (100 mL), dried over MgSO4, filtered, and evapo-
rated under reduced pressure. The crude product was purified by
column chromatography on silica gel to afford compound 7 as
a yellowish liquid (1.52 g, 56%) (hexane/ethyl acetate, 9/1 Rf: 0.7);
1H NMR (300 MHz, CDCl3)
d
¼1.94 (s, 6H), 1.96 (s, 3H), 2.11 (s, 3H),
4.20 (dd, J¼7.2, 9.9 Hz, 1H), 4.88 (dd, J¼9.8 Hz, 1H), 5.03 (dd, J¼3.7,
10.3 Hz, 1H), 5.20e5.45 (m, 4H), 5.68 (d, J¼6.2 Hz, 1H), 5.69 (ddd,
J¼4.9, 10.4, 17.3 Hz, 1H), 6.2 (d, J¼3.7 Hz, 1H); 13C NMR (75 MHz,
CDCl3)
168.1, 169.5, 169.7, 169.9.
d
¼20.6, 20.7, 20.8, 68.2, 68.4, 68.4, 74.1, 90.4, 120.1, 132.8,
4.2.8. 1-Hydroxy-2,3,4-tetra-O-acetyl-6,7-dideoxy-D-gluco-hept-6-
enopyranose 8. To a solution of 7 (1.2 g, 3.485 mmol) in anhydrous
DMF (20 mL) was added under nitrogen at 50 ꢀC, hydrazine acetate
(204 mg). The reaction mixture was stirred at this temperature for
another 30 min. When the TLC analysis indicates the complete
consumption of starting material, the mixture was diluted with
ethyl acetate (30 mL). The organic phases were washed with H2O
(3ꢁ30 mL) and brine (20 mL). The organic phases were dried over
MgSO4, filtered, and evaporated under reduced pressure. The crude
product was purified by column chromatography on silica gel to
afford compound 8 as colorless viscous oil (800 mg, 76%) (eluent
(300 MHz, CDCl3):
d
¼2.00 (s, 3H), 2.01 (s, 3H), 2.02 (s, 3H), 2.05 (s,
3H), 2.11 (s, 3H), 2.13 (s, 3H), 2.14 (s, 3H), 2.15 (s, 3H), 2.16 (s, 3H),
4.32 (dd, J¼1.2, 5.1 Hz, 1H), 4.65 (dd, J¼1.2, 5.1 Hz, 1H), 5.10 (d,
J¼3.5 Hz, 1H), 5.15 (d, J¼3.4 Hz, 1H), 5.24e5.48 (m, 4H), 5.67 (ddd,
J¼5.0, 10.6, 15.6 Hz, 1H), 5.73 (s, 1H), 5.76 (s, 1H), 6.44 (d, J¼2.5 Hz,
1H); 13C NMR (75 MHz, CDCl3):
d¼20.5, 20.58, 20.62, 20.8, 66.5,
67.6, 67.9, 69.2, 69.8, 71.0, 71.7, 74.6, 89.8, 92.1, 118.4, 118.9, 131.1,
131.6, 169.0, 169.3, 169.9, 170.2.
4.2.5. 2,3,4-Tri-O-acetyl-6,7-dideoxy-
D
-galacto-hept-6-enopyranose
pentane/ether: 7/3; Rf: 0.2); 1H NMR (300 MHz, CDCl3)
d¼2.00 (s,
3. To a solution of 2 (600 mg, 1.74 mmol) in anhydrous DMF
(20 mL) was added under nitrogen at 50 ꢀC hydrazine acetate
(204 mg) in one portion. The reaction mixture was stirred at this
temperature for another 30 min. When TLC indicates complete
consumption of starting material, the mixture was diluted with
ethyl acetate (30 mL). The organic phase was washed with H2O
(3ꢁ30 mL) and brine (20 mL). The organic phase was dried over
MgSO4, filtered, and evaporated under reduced pressure. The crude
product was purified by column chromatography on silica gel to
3H), 2.02 (s, 3H), 2.04 (s, 3H), 2.86 (d, J¼3.3 Hz, 1H), 4.46 (dd, J¼7.5,
9.9 Hz, 1H), 4.48e4.94 (m, 2H), 5.20e5.33 (m, 2H), 5.47 (t, J¼3.3 Hz,
1H), 5.58 (t, J¼9.8 Hz, 1H), 5.69e5.80 (m, 1H); 13C NMR (75 MHz,
CDCl3)
d
¼20.7, 69.5, 70.6, 71.6, 90.1, 95.4, 119.9, 120.0, 120.8, 124.1,
132.6, 133.3, 169.6, 170.1, 178.1; HRMS m/z calculated for [MþNa]þ
(C13H18 O8Na): 325.0899, found 325.0890.
4.2.9. (4S,5R,6S)-4,5,6-Tris
10. The reaction was realized following the general procedure A
with: lactol 8 (500 mg, 1.66 mmol), Fe(CO)5 (44 l, 20 mol %) to give
(acetoxy)-2-methylcyclohex-2-enone
afford compound 3 as a colorless viscous oil (347 mg, 66%) (eluent
m
1
pentane/ether: 7/3; Rf¼0.2); H NMR (300 MHz, CDCl3):
d
¼1.98 (s,
in two steps cyclohexenone 10 as a viscous oil (165 mg: 35% for two
3H), 1.99 (s, 3H), 2.08 (s, 3H), 2.09 (s, 3H), 2.10 (s, 3H), 2.16 (s, 3H),
steps) (pentane/AcOEt: 9/1; Rf: 0.3); 1H NMR (300 MHz, CDCl3)

D.H. Mac et al. / Tetrahedron 67 (2011) 9305e9310
9309
d
¼1.80 (s, 3H), 2.0 (s, 3H), 2.04 (s, 3H), 2.10 (s, 3H), 5.34 (d,
chromatography on silica gel to afford lactol 17 as colorless viscous
J¼11.5 Hz, 1H), 5.50 (dd, J¼8.4, 11.5 Hz, 1H), 5.70 (ddd, J¼2.2, 8.5,
oil (363 mg, 75%, 70/30 mixture of
a
/
b
d
anomers, pentane/EtOAc: 8/
¼3.86 (dd, J¼1.3, 2.7 Hz, 1H),
12.9 Hz, 1H), 6.44 (d, J¼1.4 Hz, 1H); 13C NMR (75 MHz, CDCl3)
2 Rf¼0.2). 1H NMR (300 MHz, CDCl3):
d
¼15.2, 20.4, 20.6, 20.7, 70.5, 71.9, 74.3, 136.3, 140.3, 169.8, 170.11,
3.98 (d, J¼2.8 Hz, 1H), 4.07 (d, J¼3.6 Hz, 1H), 4.47 (d, J¼6.9 Hz, 1H),
4.70e4.94 (m, 6H), 5.19 (dd, J¼1.4, 10.6 Hz, 1H), 5.33 (dd, J¼1.5,
17.3 Hz, 1H), 5.36 (m, 1H), 5.89 (ddd, J¼6.1, 10.5, 17.2 Hz, 1H),
190.3, 191.6; HRMS m/z calculated for [MþNa]þ (C13H16O7Na):
307.2517, found 307.2520; ½a D20
ꢃ18.7 (c 0.2, MeOH).
ꢂ
7.29e7.41 (m, 15H). 13C NMR (75 MHz, CDCl3):
d¼71.9, 72.9, 73.6,
4.2.10. 1,2,3,4-Tetra-O-acetyl-6,7-dideoxy-
D
-manno-hept-6-enopyr-
74.7, 76.4, 77.5, 78.6, 80.6, 82.0, 91.9, 97.8, 117.1, 127.5, 127.6, 127.8,
128.0, 128.2, 128.3, 128.4, 128.44, 134.6, 134.9, 137.8, 138.1, 138.2,
138.4.
anose 12. To a solution of vinyl glucopyranose 11 (1.5 g, 3.4 mmol)
in acetic anhydride (20 mL), was added dropwise with vigorous
stirring under nitrogen at room temperature trimethylsilyl tri-
fluoromethanesulfonate (0.253 mL, 1.395 mmol). The solution was
stirred for an additional 10 h. After cooling to 0 ꢀC, the dark solution
was diluted with AcOEt (50 mL) and poured in a cold saturated
NaHCO3 solution (50 mL). The organic phases were separated and
washed with a saturated NaHCO3 solution (3ꢁ50 mL), brine
(100 mL), dried over MgSO4, filtered, and evaporated under re-
duced pressure. The crude product was purified by column chro-
matography on silica gel to afford compound 12 as a yellowish
liquid (700 mg, 59%) (hexane/ethyl acetate, 9/1, Rf: 0.7); 1H NMR
4.2.14. (4S,5R,6R)-4,5,6-Tris(benzyloxy)-2-methylcyclohex-2-enone
19. The reaction was realized following the general procedure A
with: lactol 17 (350 mg, 0.78 mmol), Fe(CO)5 (11 ml, 10 mol %) to
give in two steps cyclohexenone 19 as a colorless viscous liquid
(180 mg, 54% for two steps) (pentane/AcOEt: 9/1; Rf: 0.3). 1H NMR
(300 MHz, CDCl3):
d
¼1.83 (t, J¼1.5 Hz, 3H), 3.98 (dd, J¼2.5, 5.5 Hz,
1H), 4.30 (d, J¼2.0 Hz, 1H), 4.42 (br s, 1H), 4.59 (d, J¼12.2 Hz, 1H),
4.66 (d, J¼12.1 Hz, 1H), 4.68 (d, J¼11.5 Hz, 1H), 4.74 (d, J¼11.5 Hz,
1H), 4.75 (d, J¼12.1 Hz, 1H), 4.86 (d, J¼12.2 Hz, 1H), 6.59 (m, 1H),
(300 MHz, CDCl3)
d¼1.99 (s, 3H), 2.15 (s, 3H), 2.16 (s, 3H), 4.21 (dd,
7.32e7.45 (m, 15H); 13C NMR (125 MHz, CDCl3):
d¼15.3, 72.4, 72.6,
J¼1.1, 9.2 Hz, 1H), 5.20 (t, J¼9.9 Hz, 1H), 5.26 (dd, J¼7.4, 10.9 Hz, 2H),
5.32 (t, J¼3.5 Hz, 1H), 5.37 (d, J¼3.2 Hz, 1H), 5.71e5.82 (m, 1H), 6.07
72.9, 75.1, 78.9, 127.71, 127.73, 127.84, 127.86, 127.9, 128.29, 128.32,
128.4, 137.6, 137.8, 137.9, 196.4; HRMS m/z calculated for [MþNa]þ
(d, J¼1.9 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
¼20.6, 20.7, 20.8, 68.2,
(C28H28O4Na): 451.1885, found 451.1876; ½a D20
þ167.1 (c 0.7, MeOH).
ꢂ
68.4, 68.4, 74.1, 90.4, 120.1, 132.8, 168.1, 169.5, 169.7, 169.9.
4.2.15. Synthesis of 4-epigabosine N. The reaction was realized fol-
lowing the general procedure B with cyclohexenone 19 (80 mg,
0.18 mmol), FeCl3 (86 mg, 3 equiv) to afford 4-epi-Gabosine N as
a colorless viscous oil, 14 mg (50% yield) [Rf: 0.2; AcOEt/MeOH: 8/
4.2.11. 1-Hydroxy-2,3,4-tetra-O-acetyl-6,7-dideoxy-D-manno-hept-
6-enopyranose 13. To a solution of 12 (500 mg, 1.45 mmol) in an-
hydrous DMF (20 mL) was added under nitrogen at 50 ꢀC hydrazine
acetate (170 mg, 1.88 mmol) in one portion. The reaction mixture
was stirred at this temperature for another 30 min. When the TLC
shows the complete consumption of starting material, the mixture
was diluted with ether (30 mL). The organic phases were washed
with H2O (3ꢁ30 mL) and brine (20 mL), dried over MgSO4, filtered,
and evaporated under reduced pressure. The crude product was
purified by column chromatography on silica gel to afford com-
pound 13 as colorless viscous oil (300 mg, 68%) (eluent pentane/
2]; 1H NMR (300 MHz, CD3COCD3):
d
¼1.77 (t, J¼1.3 Hz, 3H), 4.07 (d,
J¼4.0 Hz, 1H), 4.13 (m, 1H), 4.28 (J¼3.6 Hz, 1H), 4.37 (m, 1H), 4.51
(dd, J¼2.9, 4.0 Hz, 1H), 4.59 (d, J¼5.4 Hz, 1H), 6.57 (qd, J¼1.7, 4.7 Hz,
1H); 13C NMR (75 MHz, CD3COCD3):
d¼16.2, 69.7, 74.6, 76.8, 135.2,
142.7, 200.6; HRMS m/z calculated for [MþNa]þ (C7H10O4Na):
181.0471, found 181.0474; ½a D20
þ223.7 (c 0.08, MeOH).
ꢂ
4.2.16. Synthesis of 4-epi-6-epigabosine B. The reaction was re-
alized following the general procedure C to afford desired 4-epi-6-
ether: 7/3; Rf: 0.2); 1H NMR (300 MHz, CDCl3)
d
¼1.93 (s, 3H),1.94 (s,
3H), 2.09 (s, 3H), 2.99 (d, J¼3.9 Hz, 1H), 4.36 (dd, J¼7.6, 17.1 Hz, 1H),
5.10 (d, J¼11.5 Hz,1H), 5.17 (d, J¼11.5 Hz,1H), 5.23 (dd, J¼1.9, 3.3 Hz,
1H), 5.24 (d, J¼1.3 Hz, 1H), 5.36 (dd, J¼3.4, 10.1 Hz, 1H), 5.69e5.80
epi-gabosine B, 9 mg (80%); 1H NMR (300 MHz, MeOD):
d¼0.98 (d,
J¼6.6 Hz, 3H), 1.83 (ddd, J¼2.7, 13.0, 13.7 Hz, 1H), 1.96 (ddd, J¼2.7,
6.1, 13.7 Hz, 1H), 2.82 (ddq, J¼13.0, 6.1, 6.6 Hz, 1H), 3.94 (dd, J¼2.7,
6.3 Hz, 1H), 4.17 (ddd, J¼1.7, 3.4, 3.4 Hz, 1H), 4.50 (d, J¼3.4 Hz, 1H);
(m, 1H); 13C NMR (75 MHz, CDCl3)
d
¼20.9, 21.0, 21.0, 68.6, 69.0,
70.1,7 2.32, 92.4, 120.0, 133.8, 170.0, 170.1, 170.3; HRMS m/z calcu-
13C NMR (75 MHz, MeOD):
d
¼13.9, 38.8, 38.9, 70.0, 75.9, 79.1, 213.1;
lated for [MþNa]þ (C13H18O8Na): 325.0899, found 325.0890.
HRMS m/z calculated for [M]þ C7H12O4: 160.0735, found 160.0743;
a 2D0
ꢃ23.3 (c 0.06, MeOH).
½
ꢂ
4.2.12. (4R,5R,6S)-4,5,6-Tris(acetoxy)-2-methylcyclohex-2-enone
15. The reaction was realized following the general procedure A
4.2.17. (3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-vinyl-tetrahydro-2H-
pyran-2-ol 21. Starting from 6, similar synthetic procedure as
adopted for compound 17 was followed to obtain 21. 1H NMR
with: lactol 13 (240 mg, 0.78 mmol), Fe(CO)5 (21
give cyclohexenone 15 as a viscous oil (87 mg: 40% for two steps)
(pentane/AcOEt: 9/1; Rf: 0.3); 1H NMR (300 MHz, CDCl3)
ml, 20 mol %) to
d¼1.82 (s,
(300 MHz, CDCl3):
d
¼2.85 (d, J¼2.4 Hz, 1H), 3.10 (d, J¼5.1 Hz, 1H),
3H),1.99 (s, 3H), 2.06 (s, 3H), 2.1 (s, 3H), 5.33 (dd, J¼3.8, 11.3 Hz,1H),
3.19 (d, J¼9.4 Hz, 1H), 3.32 (dd, J¼7.7, 9.3 Hz, 1H), 3.50 (d, J¼9.4 Hz,
1H), 3.59 (d, J¼9.1 Hz, 1H), 3.76 (dd, J¼6.4, 9.7 Hz, 1H), 3.90 (d,
J¼9.3 Hz, 1H), 4.30 ( dd, J¼6.5, 9.7 Hz, 1H), 4.53e4.89 (m, 7H), 5.16
(t, J¼3.0 Hz, 1H), 5.21 (dt, J¼1.3, 10.6 Hz, 1H), 5.35 (dt, J¼1.4, 17.2 Hz,
1H), 5.83 (ddd, J¼6.5, 10.5, 17.0 Hz,1H), 7.18e7.30 (m, 15H). 13C NMR
5.67 (d, J¼4.2 Hz, 1H), 5.70 (dd, J¼2.6, 5.8 Hz, 1H), 6.62 (dd, J¼1.4,
6.2 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
¼15.5, 20.5, 20.6, 20.7, 65.4,
68.6, 72.0, 135.9, 139.8, 169.6, 170.1, 190.1, 191.3; HRMS m/z calcu-
lated for [MþNa]þ (C13H16O7Na): 307.2517, found 307.2520; ½a 2D0
ꢂ
ꢃ47.0 (c 0.1, MeOH).
(75 MHz, CDCl3):
d
¼71.7, 74.8, 75.1, 75.8, 76.0, 77.2, 80.0, 81.3, 82.1,
82.2,83.1, 84.2, 91.2, 97.3, 99.1, 118.3, 118.4, 127.6, 127.7, 127.8, 127.9,
128.0, 128.1, 128.37,128.40, 128.5, 34.6, 135.1, 137.8, 137.9, 138.1,
138.3, 138.5, 138.7.
4.2.13. (3R,4S,5S,6R)-3,4,5-Tris(benzyloxy)-6-vinyl-tetrahydro-2H-
pyran-2-ol 17. To a solution of 16 (500 mg, 1.09 mmol) in 70% acetic
acid (20 mL) was added dropwise concentrated sulfuric acid (1 mL)
at room temperature. The mixture was heated at 80 ꢀC for 24 h, and
the solvent was evaporated with toluene under reduced pressure.
The residue was dissolved in CH2Cl2 (100 mL) and the organic
phase was washed with water (50 mL), a saturated NaHCO3 solu-
tion then dried over MgSO4, filtered, and evaporated under reduced
pressure. The crude product was purified by column
4.2.18. (4S,5R,6S)-4,5,6-Tris(benzyloxy)-2-methylcyclohex-2-enone
23. The reaction was realized following the general procedure A as
indicated above; 23 was obtained in 65% overall yield (two steps) as
a white solid, mp: 64e66 ꢀC: 1H NMR (300 MHz, CDCl3):
J¼1.8 Hz, 3H), 3.87 (dd, J¼7.8, 10.7 Hz, 1H), 3.95 (d, J¼10.7 Hz, 1H),
4.24 (dt, J¼2.1, 7.8 Hz,1H), 4.67 (d, J¼11.5 Hz,1H), 4.73 (d, J¼10.9 Hz,
d
¼1.75 (t,

9310
D.H. Mac et al. / Tetrahedron 67 (2011) 9305e9310
1H), 4.76 (d, J¼11.6 Hz, 1H), 4.89 (d, J¼10.9 Hz, 1H), 5.03 (d,
J¼10.3 Hz, 1H), 6.52 (t, J¼1.8 Hz, 1H), 7.23e7.39 (m, 15H); 13C NMR
200.4; HRMS m/z calculated for [MþNa]þ C7H10O4Na: 181.0471,
found 181.0474; ½a D20
ꢃ216.5 (c 0.133, MeOH).
ꢂ
(75 MHz, CDCl3):
d¼15.3, 73.5, 74.6, 75.6, 78.5, 83.9, 84.7, 127.78,
127.8, 127.91, 127.98, 128.2, 128.3, 128.38, 128.41, 128.6, 135.0, 137.8,
4.2.24. Synthesis of 6-epigabosine O. The reaction was realized fol-
lowing the general procedure C with 26 (30 mg, 0.07 mmol),
methanol (2.5 mL), and palladium on activated carbon (5 mg) to
afford 6-epigabosine O as a white solid (6.7 mg, 60%), mp: 90e92 ꢀC;
137.9, 138.3, 143.0, 197.6; HRMS m/z calculated for [MþNa]þ
(C28H28O4Na): 451.1885, found 451.1876; ½a D20
ꢃ3.6 (c 0.19, MeOH).
ꢂ
4.2.19. (4S,5R,6S)-4,5,6-Trihydroxy-2-methylcyclohex-2-enone
(4-epigabosine A). The reaction was realized following the general
procedure B with cyclohexenone 23 (142 mg, 0.33 mmol), FeCl3
(162 mg, 3 equiv) in anhydrous CH2Cl2 to afford 4-epi-gabosine A
(32 mg, 55%) (AcOEt as eluent) Rf: 0.2 (AcOEt/MeOH: 8/2); 1H
1H NMR (500 MHz, MeOD):
d
¼1.07 (d, J¼6.8 Hz, 3H),1.80 (dt, J¼10.3,
12.8 Hz, 1H), 1.94 (dddd, J¼1.5, 4.6, 6.1, 10.3 Hz, 1H), 2.91 (ddq, J¼6.1,
12.8, 6.8 Hz, 1H), 3.82 (ddd, J¼1.5, 2.7, 4.3 Hz, 1H), 3.97 (d, J¼5.4 Hz,
1H), 4.33 (ddd, J¼2.7, 4.4, 9.9 Hz, 1H); 13C NMR (75 MHz, MeOD):
d
¼15.6, 36.9, 39.3, 68.6, 77.0, 77.8; ½a D20
ꢃ82.5 (c 0.04, MeOH); HRMS
ꢂ
NMR (300 MHz, MeOD):
d
¼1.82 (t, J¼1.8 Hz, 1H), 3.32 (m, 3H),
m/z calculated for [M]þ C7H12O4: 160.0735, found 160.0743.
3.54 (dd, J¼8.2, 10.9 Hz, 1H), 4.00 (d, J¼10.9 Hz, 1H), 4.30 (td,
J¼2.1, 8.2 Hz, 1H), 6.67 (t, J¼1.6 Hz, 1H); 13C NMR (75 MHz,
Acknowledgements
MeOD):
d
¼13.8, 71.1, 76.6, 78.6, 133.3, 146.4, 198.7; HRMS m/z
calculated for [MþNa]þ C7H10O4Na: 181.0471, found 181.0474;
This research has been performed as part of the Indo-French
‘Joint Laboratory for Sustainable Chemistry at Interfaces’. We
thank CNRS, MESR, French Ministry for foreign affairs (fellowship to
R.S and A.S) and CSIR for support of this research. We thank Mrs. D.
½
a 2D0
ꢂ
þ47.3 (c 0.3, MeOH).
4.2.20. (2S,3R,4S,6R)-2,3,4-Trihydroxy-6-methylcyclohexanone
(4-epi-gabosine B). The reaction was realized following the general
procedure C with 23 (200 mg, 0.467 mmol), absolute ethanol
(2.5 mL), and palladium on activated carbon (7 mg) to afford 4-epi-
gabosine B (67 mg, 90%), mp: 108e110 ꢀC; 1H NMR (300 MHz,
ꢀ
Gree for her help during 500 MHz NMR experiments.
References and notes
1. See for instance: (a) Ferrier, J. R.; Middleton, S. Chem. Rev. 1993, 93, 2779e2831;
(b) Arjona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem. Rev. 2007, 107,
1919e2036 and references cited therein.
2. (a) Tatsuta, K.; Tsuchiya, T.; Mikami, N.; Umezawa, S.; Umezawa, H.; Naganawa,
H. J. Antibiot. 1974, 27, 579e586; (b) Bach, G.; Breiding-Mack, S.; Grabley, S.;
Hammann, P.; Hutter, K.; Thiericke, R.; Uhr, H.; Wink, J.; Zeeck, A. Liebigs Ann.
Chem. 1993, 241e250.
MeOD):
d
¼0.96 (d, J¼6.5 Hz, 3H), 1.18 (dt, J¼13.2, 11.5 Hz, 1H), 2.07
(dt, J¼13.0, 5.0 Hz, 1H), 2.56 (ddq, J¼5.5, 10.3, 6.5 Hz, 1H), 3.15 (dd,
J¼9.3, 9.7 Hz, 1H), 3.79 (ddd, J¼4.7, 9.0, 11.5 Hz, 1H), 3.98 (dd,
J¼10.0, 1.4 Hz). 13C NMR (75 MHz, MeOD):
¼13.9, 39.0, 40.2, 71.8,
d
79.4, 81.4, 210.3; HRMS m/z calculated for [M]þ C7H12O4: 160.0735,
found 160.0743. ½a D20
ꢃ107.8 (c 0.4, CHCl3).
ꢂ
3. Tang, Y.-Q.; Maul, C.; Hofs, R.; Sattler, I.; Grabley, S.; Feng, X.-Z.; Zeeck, A.;
Thiericke, R. Eur. J. Org. Chem. 2000, 149e153.
4. Lubineau, A.; Billault, I. J. Org. Chem. 1998, 63, 5668e5671.
4.2.21. (3S,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-vinyl-tetrahydro-2H-
pyran-2-ol 24. Similar synthetic procedure as adopted for com-
pound 17 was followed to obtain 24. 1H NMR (300 MHz, CDCl3):
5. (a) Corsaro, A.; Pistara, V.; Catelani, G.; D’Andrea, F.; Adamo, R.; Chiacchio, M. A.
Tetrahedron Lett. 2006, 47, 6591e6594; (b) Shing, T. K. M.; Cheng, H. M. Org. Biomol.
Chem. 2009, 7, 5098e5102; (c) Shing, T. K. M.; Cheng, H. M. Synlett 2010, 142e144.
6. (a) Shing, T. K. M.; Cheng, H. M. J. Org. Chem. 2007, 72, 6610e6613; (b) Shing, T.
K. M.; Chen, Y.; Ng, W. L. Synlett 2011, 1318e1320; (c) Shing, T. K. M.; Chen, Y.;
Ng, W. L. Tetrahedron 2011, 67, 6001e6005.
7. (a) Ramana, G. V.; Rao, B. V. Tetrahedron Lett. 2005, 46, 3049e3051; (b) Monrad,
R. N.; Fanefjord, M.; Hansen, F. G.; Jensen, N. M. E.; Madsen, R. Eur. J. Org. Chem.
2009, 396e402; (c) Rao, J. P.; Rao, B. V. Tetrahedron: Asymmetry 2010, 21,
930e935; (d) Prasad, K. R.; Kumar, S. M. Synlett 2011, 1602e1604.
8. (a) Lygo, B.; Swiatyj, M.; Trabsa, H.; Voyle, M. Tetrahedron Lett. 1994, 35,
4197e4200; (b) Shing, T. K. M.; So, K. H.; Kwok, W. S. Org. Lett. 2009, 11,
5070e5073; (c) Stathakis, C. I.; Athanatou, M. N.; Gallos, J. K. Tetrahedron Lett.
2009, 50, 6916e6918.
d
¼2.67 (d, J¼3.4 Hz, 1H), 3.62e3.85 (m, 3H), 3.97 (dd, J¼3.0, 9.4 Hz,
1H), 4.21 (dd, J¼6.8, 9.1 Hz, 1H), 4.61e4.86 (m, 6H), 5.11 (d,
J¼11.6 Hz, 1H), 5.29 (dd, J¼1.6, 10.5 Hz, 1H), 5.46 (dd, J¼1.7, 17.2 Hz,
1H), 6.02 (ddd, J¼6.7, 10.4,17.2 Hz,1H), 7.27e7.39 (m, 15H). 13C NMR
(75 MHz, CDCl3):
d¼72.6, 72.9, 73.15, 73.17, 74.8, 74.9, 75.13, 76.3,
76.5, 77,2, 78.4, 78.8, 79.2, 82.6, 93.0, 93.4118.3, 118.4, 127.5, 127.6,
127.6, 127.7, 127.9, 128.0, 128.1, 128.3, 128.33, 128.34, 128.5, 128.6,
128.9, 134.5, 135.5, 137.9, 138.05, 138.07, 138.2, 138.4, 138.5.
9. Kumar, V.; Das, P.; Ghosal, P.; Shaw, A. K. Tetrahedron 2011, 67, 4539e4546.
10. (a) Huntley, C. F. M.; Wood, H. B.; Ganem, B. Tetrahedron Lett. 2000, 41,
2031e2034; (b) Shinada, T.; Fuji, T.; Ohtani, Y.; Yoshida, Y.; Ohfune, Y. Synlett
2002, 1341e1343.
4.2.22. (4R,5R,6S)-4,5,6-Tris(benzyloxy)-2-methylcyclohex-2-enone
26. The reaction was realized following the general procedure A
with lactol 24 (150 mg, 0.35 mmol), Fe(CO)5 (5 ml, 10 mol %) to give
11. Carreno, M. C.; Merino, E.; Ribagorda, M.; Somoza, A.; Urbano, A. Chem.dEur. J.
2007, 13, 1064e1077.
cyclohexenone 26 as a colorless viscous liquid (104 mg, 75% for two
steps) (pentane/AcOEt: 9/1; Rf: 0.7); 1H NMR (300 MHz, CDCl3)
12. Mehta, G.; Lakshminath, S. Tetrahedron Lett. 2000, 41, 3509e3512.
13. Takahashi, T.; Yamakoshi, Y.; Okayama, K.; Yamada, J.; Ge, W.-Y.; Koizumi, T.
Heterocycles 2002, 56, 209e220.
14. (a) Alibes, R.; Bayon, P.; de March, P.; Figueredo, M.; Font, J.; Marjanet, G. Org.
Lett. 2006, 8, 1617e1620; (b) Toribio, G.; Marjanet, G.; Alibes, R.; de March, P.;
Font, J.; Bayon, P.; Figueredo, M. Eur. J. Org. Chem. 2011, 1534e1543.
15. Banwell, M. G.; Bray, A. M.; Wong, D. J. New J. Chem. 2001, 25, 1351e1354.
d
¼1.80 (t, J¼1.3, 3 Hz), 3.95 (dd, J¼3.2, 8.0 Hz, 1H), 4.34 (d, J¼8.1 Hz,
1H), 4.35e4.37 (m, 1H), 4.65 (d, J¼10.5 Hz, 1H), 4.67 (d, J¼11.5 Hz,
1H), 4.68 (d, J¼10.7 Hz, 1H), 4.78 (d, J¼12.0 Hz, 1H), 4.80 (d,
J¼12.2 Hz, 1H), 4.90 (d, J¼11.5 Hz, 1H), 6.59 (dq, J¼1.5, 3.0 Hz, 1H),
7.28e7.39 (m, 15H); 13C NMR (75 MHz, CDCl3):
d
¼15.6, 72.5, 73.2,
ꢀ
16. (a) Crevisy, C.; Wietrich, M.; Le Boulaire, V.; Uma, R.; Gree, R. Tetrahedron Lett.
ꢀ
2001, 42, 395e398; (b) Uma, R.; Gouault, N.; Crevisy, C.; Gree, R. Tetrahedron
Lett. 2003, 44, 6187e6190; (c) Uma, R.; Davies, M.; Crevisy, C.; Gree, R. Tetra-
hedron Lett. 2001, 42, 3069e3072; (d) Cuperly, D.; Petrignet, J.; Crevisy, C.; Gree,
R. Chem.dEur. J. 2006, 12, 3261e3274.
73.9, 78.6, 80.1, 127.7, 127.8, 127.9, 128.0, 128.3, 128.4, 128.5, 136.1,
ꢀ
137.8, 138.1, 140.4, 197.1; HRMS m/z calculated for [MþNa]þ
ꢀ
(C28H28O4Na): 451.1885, found 451.1876; ½a D20
ꢃ114.3 (c 0.14,
ꢂ
ꢀ
17. (a) Petrignet, J.; Prathap, I.; Chandrasekhar, S.; Yadav, J. S.; Gree, R. Angew. Chem.,
MeOH).
ꢀ
Int. Ed. 2007, 46, 6297e6300; (b) Mac, D. H.; Roisnel, T.; Branchadell, V.; Gree, R.
Synlett 2009, 1969e1973.
4.2.23. Synthesis of gabosine A. The reaction was realized following
the general procedure with cyclohexenone 26 (80 mg,
0.18 mmol), CH2Cl2, and anhydrous FeCl3 (86 mg, 3 equiv) to afford
18. Mac, D. H.; Samineni, R.; Petrignet, J.; Srihari, P.; Chandrasekhar, S.; Yadav, J. S.;
ꢀ
Gree, R. Chem. Commun. 2009, 4717e4719.
B
19. Meinke, S.; Thiem, J. Carbohydr. Res. 2008, 343, 1824e1829.
20. Neumann, J.; Weingarten, S.; Thiem, J. Eur. J. Org. Chem. 2007, 1130e1144.
21. Wang, W.; Zhang, Y.; Sollogoub, M.; Sinay, P. Angew. Chem., Int. Ed. 2000, 39,
2466e2467.
22. Stick, R. V.; Stubbs, K. A. J. Carbohydr. Chem. 2005, 24, 529e547.
23. Tietze, L. F.; Schuster, H. J.; Schmuck, K.; Schuberth, I.; Alves, F. Bioorg. Med.
Chem. 2008, 16, 6312e6318.
gabosine A as a colorless viscous liquid (14 mg, 50% yield) [Rf: 0.2;
AcOEt/MeOH: 8/2]; 1H NMR (300 MHz, CD3COCD3):
d¼1.77 (t,
J¼1 Hz, 3H), 3.76 (dd, J¼4.2, 5.7 Hz, 1H), 4.28 (s, 3H), 4.38 (d,
J¼4.8 Hz, 1H), 4.44 (q, J¼4.3 Hz, 1H), 6.73 (dq, J¼1.5, 5.4 Hz, 1H); 13C
NMR (75 MHz, CD3OCD3):
d¼16.5, 67.8, 74.7, 75.9, 136.6, 143.9,
24. Hansen, F. G.; Bundgaard, E.; Madsen, R. J. Org. Chem. 2005, 70, 10139e10142.