Toward synthesis of carbasugars (+)-gabosine C, (+)-COTC, (+)-pericosine B, and (+)-pericosine C

Article abstract of DOI:10.1016/j.carres.2013.08.008

Asymmetric total synthesis of (+)-gabosine C, (+)-pericosine B, and (+)-pericosine C has been reported from readily available d-(-)-isoascorbic acid and d-ribose involving Grubbs ring closing metathesis, Morita-Baylis-Hillman (MBH) reaction, and Luche red

Full text of DOI:10.1016/j.carres.2013.08.008

Carbohydrate Research 388 (2014) 130–137
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Toward synthesis of carbasugars (+)-gabosine C, (+)-COTC,
(+)-pericosine B, and (+)-pericosine C
⇑
D. Chanti Babu , Ch. Bhujanga Rao, K. Venkatesham, J. Jon Paul Selvam, Y. Venkateswarlu
Division of Natural Product Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 June 2013
Received in revised form 3 August 2013
Accepted 9 August 2013
Available online 20 August 2013
Asymmetric total synthesis of (+)-gabosine C, (+)-pericosine B, and (+)-pericosine C has been reported
from readily available
ta–Baylis–Hillman (MBH) reaction, and Luche reduction.
D
-(ꢀ)-isoascorbic acid and
D-ribose involving Grubbs ring closing metathesis, Mori-
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Carbasugars
Streptomyces
Periconia byssoides
Morita–Baylis–Hillman (MBH) reaction
Luche reduction
-ribose
D-(ꢀ)-isoascorbic acid and
D
1. Introduction
inhibitor.2b,c Pericosines (A–E) were isolated from a micro organ-
ism Perconia byssoides (OUPS-N133) separated from the gastroin-
testinal tract of the sea hare Aplyasia kurodai.4a,h (+)-Pericosine A
(3), (+)-pericosine B (4), and (+)-pericosine C (5) demonstrated
Carbasugars demonstrate glyoxylase inhibitory, antitumor,
antibacterial, antifungal, antimalarial, and antiviral activities.1
Among them gabosines and pericosines exhibit a pivotal role,
which are cyclohexene carbasugars. An account of isolation of
gabosines and pericosines, their synthetic studies and biological
activities has been found in the literature.2–4 In 1974 (ꢀ)-gabosine
C, was isolated from culture broth of Streptomyces filipensis,2a that
has been identical to a known antibiotic KD16-U1. Later its croton-
ic ester was isolated from the culture broth of Streptomyces griseo-
sporeus, known as (ꢀ)-COTC and shown to be a potent glyoxylase I
remarkable activity (ED50 = 0.1, 4 and 10.5 lg/mL, respectively)
against P388 lymphocytic human cancer (leukemia) cells.4a,h,i
Common structural building of (+)-gabosine C (1), (+)-COTC (2),
(+)-pericosine A (3), (+)-pericosine B (4), and (+)-pericosine C (5),
and their biological activity inspired us in their synthesis. For the
past several years we have been engaged in the synthesis of
biologically active compounds by using natural and commercially
available sources.5,6
O
OMe
O
OH
OMe
Cl
O
O
HO
HO
HO
HO
CO2Me HO
HO
CO2Me
HO
HO
HO
HO
CO2Me
OH
OH
OH
OH
OH
(+) Gabosine C (1)
(+) COTC (2)
(+) Pericosine A (3)
(+) Pericosine B (4) (+) Pericosine C (5)
⇑
Corresponding author. Tel.: +91 40 27193167; fax: +91 40 27160512.
E-mail address: chantibabuiict@gmail.com (D.C. Babu).
Condolences: We expressing our deepest grief and sorrow for sudden death of Dr.
Y. Vekateswarlu on 17th July, 2013. He is an excellent teacher and human being; he
supported and encourages us at stages of our research career.
http://dx.doi.org/10.1016/j.carres.2013.08.008
0008-6215/Ó 2013 Elsevier Ltd. All rights reserved.

D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
131
Cl
HO
HO
CO2Me
3
OH
O
OMe
OH
O
HO
HO
HO
HO
CO2Me
OH
OH
OH
4
1
MOMO
O
O
O
O
OMe
18
HO
HO
HO
HO
CO2Me
O
MOMO
O
OH
2
OH
5
O
O
16
HO
O
OH
OH
O
O
6
O
HO
O
O
HO
O
HO
9
OH
OH
7
Scheme 1. The retro synthetic analysis of the (+)-gabosine C (1), (+)-COTC (2), (+)-pericosine A (3), (+)-pericosine B (4), and (+)-pericosine C (5).
HO
O
O
O
6
O
OH
O
O
HO
O
a
+
ref-5a
O
O
O
O
10
O
HO
OH
9
OTBS
8
Scheme 2. Reagents and conditions: (a) (i) TBAF, THF, rt, 8 h, (ii) 2,2 DMP, TsOH, DCM, 12 h, two steps 85%.
11 was converted into compound 9 using Wittig reaction with
methyltriphenylphosphonium bromide salt in the presence of
tBuOK.
O
O
O
OH
OH
O
a
O
ref 7
O
O
O
Hydrolysis of primary acetonide in compound 9 in PPTS/meth-
anol at 0 °C yielded diol 12 (Scheme 4) in 70% yield. The primary
alcohol in compound 12 was selectively protected with benzoyl
chloride in the presence of pyridine to afford benzoyl ester 13 in
92% yield. Further, the secondary alcohol was masked as MOM
ether using MOM-Cl and DIPEA (Hunig’s base), followed by depro-
tection of benzoyl group in compound 13 with K2CO3 leading to the
desired primary alcohol 14. Now, alcohol 14 was oxidized to corre-
sponding aldehyde using Swern oxidation, which on treatment
with vinyl magnesium bromide afforded a diastereomeric mixture
of alcohol 15, which was oxidized to enone 16 by treating with IBX
in DMSO. Compound 16 was subjected to ring closing metathesis
reaction (RCM) using Hoyeda Grubbs catalyst to afford cyclohexe-
none 17 in 60% yield for 8 h. The Morita–Baylis–Hillman reaction
HO
O
O
OH
9
11
7
Scheme 3. Reagents and conditions: (a) BuOK, PPh3PCHþ3 Brꢀ, THF, ꢀ10°, 4 h, 75%.
t
2. Results and discussion
We envisaged (Scheme 1) that a common intermediate 18, that
would give (+)-gabosine C (1), (+)-COTC (2), (+)-pericosine A (3),
(+)-pericosine B (4), and (+)-pericosine C (5) which in turn could
be obtained from Grubbs cross metathesis reaction of allyl ketone
16 followed by employing and Morita–Baylis–Hillman reactions as
key steps. Ketone 16 can be derived from diacetonide 9 using
for
a-hydroxymethylation on cyclohexenone 17 was attempted
sequential reactions, which could be furnished from either
isoascorbic acid 6 or -ribose 7.
D
-(ꢀ)-
with aqueous formaldehyde (37%) in the presence of imidazole
and 1 M NaHCO3 in THF to obtain a mixture of products.8 However,
when compound 17 was reacted with aqueous formaldehyde (37%)
in the presence of DMAP at ꢀ10 °C furnished intermediate 18 in
38% yield for 3 days.9 The protecting groups MOM and acetonide
in compound 18 were removed using trifluoroacetic acid in
methanol to afford (+)-gabosine C (1), [mp 113–115 °C and optical
D
Accordingly, alcohol 8 was obtained from D-isoascorbic acid5a
(Scheme 2). The TBS protecting group in 8 was removed using TBAF
to give diol, which was protected with 2, 2 DMP in DCM to give
separable diastereomers compound 9 and compound 10. In a dif-
ferent route compound 9 was prepared from compound 11 which
in turn prepared from D
-ribose (Scheme 3).7 Accordingly, aldehyde

132
D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
HO
HO
MOMO
HO
O
BzO
c
HO
a
b
O
O
O
O
O
O
13
O
O
12
O
14
9
O
O
MOMO
OH
MOMO
O
MOMO
O
g
d
e
f
O
O
O
O
15
16
17
O
O
OH
O
OH
O
O
O
MOMO
O
HO
HO
HO
h
ref-2d
HO
O
18
OH
1
2
Scheme 4. Reagents and conditions: (a) PPTs, methanol, 0 °C, 6 h, 70%; (b) pyridine, benzoyl chloride, DCM, 7 h, 92%; (c) (i) DIPEA, MOM-Cl, DCM, 12 h, (ii) K2CO3, methanol,
0 °C, 3 h, two steps 83%; (d) (i) (COCl)2, DMSO, triethyl amine, ꢀ78 °C, 1 h, (ii) vinyl Magnesium bromide, THF, 3 h, 0 °C, two steps 84%; (e) IBX, DMSO, 3 h, 0 °C, 91%; (f) Hoyeda
Grubbs catalyst (5 mol %), DCM, reflux, 8 h, 60%; (g) aqueous formaldehyde (37–40%), DMAP, ꢀ10 °C, 3 days, 38%; (h) TFA, methanol 0 °C, 4 h, 70%.
OTBDPS
OH
O
O
OTBDPS
R2
R1
MOMO
O
MOMO
O
MOMO
O
a
c
b
O
O
O
R = OH, R = H, 92%
20
18
19
1
2
f
23 R1= H, R2= OH, 88%
OH
R2
R2
R2
R1
R1
R1
MOMO
O
MOMO
O
COOMe
HO
HO
COOMe
e
d
O
O
OH
R1= OMe, R2= H, 87%
R1= H, R2= OMe, 89%
R1= OMe, R2= H, 70%
R1= H, R2= OMe, 70%
R1= OMe, R2= H, 70%
R = H, R = OMe, 67%
21
24
22
25
4
5
1
2
Scheme 5. Reagents and conditions: (a) TBDPS-Cl, imidazole, DCM, 0 °C, 18 h, 89%; (b) NaBH4, MeOH, 0 °C, 1 h, 92%; (c) (i) NaH, MeI, THF, rt, 6 h, (ii) HF–water, THF, 0 °C, 8 h;
(d) (i) TEMPO, PhI(OAc)2, MeCN:water (2:1), 3 h; (ii) MeI, K2CO3, Me2CO, rt, 3 h; (e) TFA, methanol, rt, 3 h; (f) CeCl3ꢂ7H2O, NaBH4, MeOH, ꢀ78 °C, 1 h, 88%.
rotation ½a 2D5
ꢁ
+175 (c 0.6, H2O)]. The spectroscopic data for (+)-
with trifluoroacetic acid to give (+)-pericosine B (4). {Mp 84–
gabosine C (1) were in agreement with those previously reported
in the literature for the natural antipode, but as expected its spe-
cific rotation was opposite in sign.2r Thus, the synthesis of (+) gabo-
sine C (1) from compound 9 was accomplished in 6.52% in overall
yield. (+)-COTC (2) can be synthesized from (+)-gabosine C (1) fol-
lowing previously reported procedure in the literature.2d
86 °C ½a 2D0
ꢁ
+34.6 (c 0.3, EtOH)}. The spectroscopic data for (+)-peric-
osine B (4) were in good agreement with the literature.4n Thus the
synthesis of (+)-pericosine B (4) from compound 9 was accom-
plished in 2.28% overall yield.
To synthesize (+)-pericosine C (5), initially we examined for the
reduction of 19 with a series of reducing agents like CBS (Corey–
Bakshi–Shibata) catalyst, selectrides, and other borohydrides. How-
ever, all these experiments resulted in poor diastereoselectivity.
Fortunately, Luche reduction10 yielded with a single diastereomeric
alcohol 23 (Scheme 5). We extended the strategy from alcohol 23
to (+)-pericosine C (5), by adopting the similar reaction protocol
used for the construction (+)-pericosine B (4) from alcohol 20.
To accomplish the synthesis of (+)-pericosine B (4), the hydroxy
function of intermediate 18 was masked as TBDPS ether 19
(Scheme 5). Reduction of the keto functional group in compound
19 with NaBH4 at 0 °C gave a single diastereomeric alcohol 20
(C5, C6 anti configuration) in 92% yield. The resulting alcohol in
20 was methylated using NaH/MeI at 0 °C to furnish methylated
compound, which on treatment with aqueous HF in THF gave alco-
hol 21. The primary alcohol in compound 21 was then oxidized to
the corresponding acid using TEMPO/PhI(OAc)2 and the acid was
esterified with MeI/K2CO3 in acetone to yield methoxy ester 22.
The MOM and acetonide group in 22 were removed by reacting
(+)-Pericosine C (5) was obtained as a liquid {½a D20
ꢁ
+72.5 (c 0.3,
EtOH)}. Spectroscopic data of (+)-pericosine C (5) were found to
be identical with those of the literature.4n Thus the synthesis of
(+)-pericosine C (5) was accomplished in 2.13% yield from com-
pound 9. Pericosine A (3) could be derived from alcohol 20 by

D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
133
employing SN2 chlorination,11 following the previous sequential
reactions like TBDPS deprotection, esterification, and deprotection
of acetonide and MOM.
J = 7.5 1H), 1.53 (s, 3H) 1.43 (s, 3H), 1.38 (s, 3H), 1.34 (s, 3H). 13C
NMR (75 MHz, CDCl3): 135.8, 117.0, 109.5, 109.3, 81.0, 80.3, 76.6,
66.9, 26.8 (2C), 26.6, 25.1. HRMS: Calcd for
C12H20O4Na
([M+Na]+) 251.1262. Found: 251.1258.
3. Experimental section
3.1. General methods
3.2.3. (R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)
ethane-1,2-diol (12)
To a solution of compound 9 (3 g, 13.15 mmol) in MeOH
(20 mL) was added PPTS and the reaction mixture was allowed
to stir for 6 h at room temperature. After completion of the reac-
tion as monitored by TLC, the reaction mixture was quenched with
saturated NaHCO3 (10 mL), methanol was evaporated and ex-
tracted into ethyl acetate (3 ꢃ 15 mL), dried over anhydrous Na2-
SO4, and the solvent was evaporated to give crude product,
which was purified over silica gel column chromatography (50%
ethyl acetate in hexane) to afford compound 12 (1.73 g, 70%) as a
Commercial reagents were used without further purification, all
solvents were purified by standard techniques and Infrared spectra
were recorded on PerkinElmer 683 spectrometer. Optical rotations
were obtained on Jasco Dip 360 digital polarimeter. NMR spectra
were recorded in CDCl3 solvent on Brucker 300 and Varian 500
NMR spectrometers. Chemical shifts (d) are quoted in parts per
million and are referenced to tetramethylsilane (TMS) as an inter-
nal standard. Coupling constants (J) are quoted in Hertz. Column
chromatographic separations were carried out on silica gel (60–
120 mesh) and flash chromatographic separations were carried
out using 230–400 mesh, silica gel. HRMS was recorded on Agilent
Technologies 6510 Q-TOF LC/MS.
white solid. ½a 2D5
ꢁ
+4.5 (c 0.4, CHCl3). 1H NMR (300 MHz, CDCl3): d
5.93–5.82 (m, 1H), 5.40 (d, J = 17.8 Hz, 1H), 5.22 (d, J = 9.8 Hz,
1H), 4.48–4.30 (m, 1H), 3.84–3.51 (b m, 4 H), 1.36 (s, 6 H). 13C
NMR (75 MHz, CDCl3): d 133.7, 118.6, 106.4, 78.4, 78.1, 69.7,
64.3, 27.7, 25.2. HRMS: C9H16O4Na ([M+Na]+) 211.0952. Found:
211.0948.
3.2. Experimental procedures and spectral data
3.2.4. (R)-2-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-2-
hydroxyethyl benzoate(13)
3.2.1. (4S,40R,5S)-2,2,20,20-Tetramethyl-5-vinyl-4,40-bi(1,3-dioxo-
lane) 9
To a cooled (0 °C) solution of diol 12 (5 g, 26.59 mmol) in DCM
(50 mL) was added pyridine (2.35 mL, 29.24 mmol) followed by
benzoyl chloride (3.07 mL, 26.59 mmol) and the reaction mixture
stirred at the room temperature for 7 h. After completion of the
reaction, the reaction was diluted with water (20 mL) and ex-
tracted into DCM (3 ꢃ 20 mL). The combined organic layer was
washed with dilute HCl, water, and brine, dried (Na2SO4), and con-
centrated. The residue was purified by column chromatography to
To a cooled (0 °C) solution of compound 8 (9.8 g, 32.45 mmol) in
THF (60 mL) was added tetrabutylammonium fluoride (35.70 mL of
1 M soln in THF, 35.70 mmol) and stirred for 8 h at room temper-
ature. After completion of the reaction as monitored by TLC, satu-
rated NaHCO3 was added and extracted into EtOAc (3 ꢃ 15 mL).
The combined organic layer was washed with saturated NaHCO3,
brine, dried (Na2SO4), concentrated, and the crude residue was dis-
solved in dry dichloromethane (35 mL), was added Me2C(OMe)2
(4.76 mL, 38.94 mmol) and added catalytic amount of p-TsOH at
room temperature and stirred for 12 h. After completion of the
reaction, the reaction was quenched with saturated NaHCO3
(10 mL), extracted into dichloromethane (3 ꢃ 10 mL), and concen-
trated under reduced pressure to give crude product which was
purified over silica gel column chromatography (hexane/ethyl ace-
tate 19:1) to obtain separable compound 9 (74%) and compound 10
26% total yield (6.28 g, 85%).
afford compound 13 (7.76 g, 92%) as a viscous liquid. ½a D20
ꢀ4.8 (c
ꢁ
0.6, CHCl3). 1H NMR (300 MHz, CDCl3): d 8.05–8.01 (m, 2H),
7.58–7.52 (m, 1H), 7.45–7.40 (m, 2H), 5.95–5.84 (m, 1H), 5.43
(dt, J = 1.3, 17.3 Hz, 1H), 5.23 (dt, J = 1.3, 10.3 Hz, 1H), 4.52–4.50
(m, 1H), 4.38–4.32 (m, 1H), 4.12–4.07 (m, 1H), 3.82–3.78 (m,
1H), 2.73–2.65 (br s, 1H), 1.43 (s, 3H), 1.42 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 166.6, 136.0, 133.1, 129.7, 128.3, 118.0, 109.0,
80.5, 79.1, 70.8, 66.0, 26.0 (2C). HRMS: Calcd for C16H20O5Na
([M+Na]+) is 315.1212. Found: 315.1206.
Procedure (II) To a cooled (ꢀ10°) soln of PPh3PCHþBrꢀ (17 g,
3
47.81 mmol) in THF (150 mL) was added tBuOK (4.87 g,
43.46 mmol) portion wise and allowed to stir for 2 h at rt. To this
mixture, a soln of aldehyde 11 (5 g, 21.73 mmol) in dry THF
(20 mL) was added slowly over 10 min and stirred at the same
temperature (ꢀ10°) for 2 h. After completion of the reaction as
monitored by TLC, the mixture was quenched with the addition
of saturated NH4Cl soln (40 mL) and extracted into EtOAc
(3 ꢃ 30 mL). The combined extract was washed with brine, dried
(Na2SO4), concentrated, and the crude residue was purified by CC
(EtOAc/n-hexane, 1:19) to afford compound 9 (3.72 g, 75%) as col-
3.2.5. (R)-2-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-2-
(methoxymethoxy) ethanol (14)
To a cooled (0 °C) solution of secondary alcohol 13 (7.5 g,
25.68 mmol) in dry CH2Cl2 (50 mL) were added N,N-diisopropyl
ethylamine (6.71 mL, 26.4 mmol), methoxymethyl chloride
(2.34 mL, 30.81 mmol), and catalytic amount DMAP and the reac-
tion mass was refluxed for 12 h. After completion of the reaction
as monitored by TLC, the reaction was diluted with water
(20 mL) and extracted with CH2Cl2 (3 ꢃ 20 mL). The combined or-
ganic layer was washed with brine, dried over anhydrous Na2SO4,
and the solvent was removed under reduced pressure to afford
crude mixture, which was dissolved in MeOH (40 mL) and added
K2CO3 (6.40 g, 46.42 mmol), and stirred for 3 h at rt. After comple-
tion of the reaction as monitored by TLC, the mixture was filtered
and the solvent was removed under reduced pressure to afford the
crude reaction mass, which was diluted with H2O (25 mL) and ex-
tracted into EtOAc (3 ꢃ 15 mL). The combined extract was washed
with brine, dried (Na2SO4), concentrated, and the residue was puri-
fied by column chromatography to afford compound 14 (4.95 g,
orless liquid. ½a D25
ꢁ
+4.8 (c 0.3, CHCl3). 1H NMR (300 MHz, CDCl3): d
5.94–5.81 (m, 1H), 5.37 (d, J = 18.1 Hz, 1H), 5.23 (d, J = 10.5 Hz, 1H),
4.64 (t, J = 6.0 Hz, 1H), 4.12–3.99 (m, 3H), 3.90–3.84 (m, 1H), 1.41
(m, 3H), 1.36 (m, 3H), 1.32 (m, 3H), 1.28 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 133.3, 117.6, 109.3, 108.7, 78.7, 78.3, 73.9,
67.2, 27.6, 26.7, 25.4, 25.9. HRMS: Calcd for
C12H20O4Na
([M+Na]+) is 251.1262. Found: 251.1256.
3.2.2. (4S,40R,5R)-2,2,20,20-Tetramethyl-5-vinyl-4,40-bi(1,3-dioxo-
lane) 10
83%) as a colorless liquid. ½a D20
ꢁ
+55.7 (c 0.7, CHCl3). 1H NMR
(300 MHz, CDCl3): d 5.79–5.94 (m, 1H), 5.30–5.37 (m, 1H), 5.19–
5.25 (m, 1H), 4.56–4.69 (m, 3H), 4.11 (dd, J = 8.3, 6.4 Hz, 1H),
3.80–3.86 (m, 1H), 3.59–3.67 (m, 1H), 3.48–3.54 (td, J = 8.4, 6.4,
½
a 2D5
ꢁ
ꢀ6.5 (c 3.2, CHCl3). 1H NMR (300 MHz, CDCl3): d 5.97–5.81
(m, 1H), 5.37 (d, J = 17.3 Hz, 1H), 5.18 (d, J = 10.5 Hz, 1H), 4.32 (t,
J = 6.7 Hz, 1H), 4.12–3.99 (m, 2H), 3.95–3.92 (m, 1H), 3.61 (t,

134
D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
2.4 Hz, 1H), 3.42 (s, 3H), 1.47 (s, 3H), 1.36 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 133.7, 117.5, 108.7, 97.6, 81.2, 78.6, 76.9,
63.7, 55.9, 27.6, 25.2. HRMS: Calcd for C11H20O5Na ([M+Na]+)
255.1212. Found: 255.1210.
a liquid. ½a 2D0
ꢁ
+125.8 (c 0.4, CHCl3). 1H NMR (300 MHz, CDCl3): d
6.62–6.57 (dt, J = 2.6, 10.1 Hz, 1H), 6.05–6.01 (dd, J = 1.1, 10.3 Hz,
1H), 4.98 (d, J = 6.9 Hz, 1H), 4.90–4.83 (m, 3H), 4.52 (d, J = 2.8 Hz,
1H), 3.48 (s, 3H), 1.41 (s, 3H), 1.37 (s, 3H). 13C NMR (75 MHz,
CDCl3): d 194.6, 143.5, 129.7, 110.6, 96.0, 83.9, 78.2, 76.5, 56.1,
27.3, 26.9. HRMS C11H16O5: m/z 251 [M+Na]+. HRMS: Calcd for
3.2.6. (R)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-1-
(methoxymethoxy)but-3-en-2-ol (15)
C
11H16O5 Na ([M+Na]+) is 251.0895. Found: 251.0887.
To
a
cooled (ꢀ78 °C) solution of alcohol 14 (4.9 g,
21.12 mmol) in dry dichloromethane (50 mL) were added
dimethylsulfoxide (3 mL, 42.24 mmol) and oxalyl chloride
(2.7 mL, 31.68 mmol) and was stirred for 30 min and triethyl-
amine (14.7 mL, 105.6 mmol) was added drop wise to the reac-
tion mixture and the reaction mixture was slowly warmed to
room temperature (30 min). After completion of the reaction,
the reaction was quenched with a saturated aqueous solution
of NH4Cl (20 mL) and extracted into dichloromethane
(3 ꢃ 10 mL) and the combined organic layer was washed with
brine (30 mL), dried over anhydrous MgSO4, and concentrated
in vacuo to obtain crude aldehyde and utilized in the next reac-
tion. To a cooled (0 °C) solution of crude aldehyde in dry THF
(60 mL) was added slowly vinyl magnesium bromide (31.6 mL
of a 1 M solution in THF, 31.68 mmol) over 20 min. The reaction
mixture was stirred at the same temperature for 1 h and then
slowly warmed to room temperature over 2 h. After completion
of the reaction as monitored by TLC, the reaction was quenched
with saturated NH4Cl (20 mL) and extracted into EtOAc
(3 ꢃ 15 mL). The combined organic extract was washed with
brine, dried over anhydrous Na2SO4, concentrated under reduced
pressure which was purified over silica gel column to furnish
pure compound 15 as a pale yellow liquid (4.57 g, 84%). 1H
NMR (300 MHz, CDCl3). d 6.11–5.89 (br m, 2H), 5.43–5.33 (m,
2H), 5.28–5.24 (m, 2H), 4.68–4.6 (q, J = 6.6 Hz, 2H), 4.64–4.60
(m, 1H) 4.46–4.40 (b m, 1H), 4.26 (dd, J = 6.2, 1.8 Hz, 1H), 3.37
(br s, 3H), 3.11 (d, J = 8.8 Hz, 1H), 1.50 (s, 3H), 1.35 (s, 3H).
3.2.9. (3aS,4S,7aS)-6-(Hydroxymethyl)-4-(methoxymethoxy)-
2,2-dimethyl-3a,4-dihydrobenzo[d][1,3]dioxol-5(7aH)-one (18)
To a solution of compound 17 (300 mg, 1.31 mmol), in THF
(1 mL), was added 40% aqueous formaldehyde (0.3 mL, 3 mmol),
and DMAP (16 mg, 0.13 mmol). The reaction was stirred for
3 days at ꢀ10 °C. After completion of the reaction, was acidified
with 1 N HCl (0.2 mL) and extracted with ethyl acetate
(3 ꢃ 5 mL). The combined organic layer was washed with water
(5 mL) and brine (5 mL), dried over Na2SO4, and concentrated
under reduced pressure to give crude residue, which was puri-
fied over silica gel column to give compound 18 (128 mg,
38%). ½a 2D0
ꢁ
+64.6, (c 0.3, CHCl3). 1H NMR (300 MHz, CDCl3): d
6.54 (s, 1H), 4.97 (d, J = 6.9 Hz, 1H), 4.90–4.87 (m, 1H), 4.86 (d,
J = 6.9 Hz, 1H), 4.83–4.81 (m, 1H), 4.49 (d, J = 3.5 Hz, 1H), 4.49
(d, J = 3.5 Hz, 1H), 4.32 (br s, 2H), 3.69–3.66 (br s, 1H), 3.47 (s,
3H), 1.41 (s, 3H), 1.35 (s, 3H). 13C NMR (75 MHz, CDCl3): d
195.3, 139.2, 136.5, 111.6, 96.5, 77.5, 74.9, 72.5, 60.6, 56.0,
27.8, 26.8. HRMS: Calcd for C12H18O6Na ([M+Na]+) is 281.1004.
Found: 281.1006.
3.2.10. (4S,5S,6S)-4,5,6-Trihydroxy-2-(hydroxymethyl)cyclohex-
2-enone ((+) gabosine C) (1)
To a solution of compound 18 (70 mg, 0.27 mmol) in methanol
(1 mL), was added TFA (0.5 mL) and the reaction mixture stirred
at room temperature for 4 h. After completion of the reaction, the
reaction was diluted with saturated NaHCO3 solution; methanol
was evaporated and extracted into ethyl acetate (3 ꢃ 5 mL). The
combined organic solvent was the solvent washed with water
(5 mL) and brine (5 mL), dried over Na2SO4, and concentrated under
reduced pressure to give crude residue, which was purified over
silica gel column using MeOH/CHCl3 (1:9) to give (+) gabosine C
HRMS Calcd for
281.1362.
C
13H22O5Na ([M+Na]+) 281.1368. Found:
3.2.7. (S)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-1-
(methoxymethoxy)but-3-en-2-one (16)
To a cooled (0 °C) solution of IBX (813 mg, 2.9 mmol) in dry
DMSO (2 mL) was added alcohol 15 (500 mg, 1.93 mmol) in dry
CH2Cl2 (10 mL). The resulting reaction mixture was stirred at room
temperature for 3 h. After completion of the reaction as monitored
by TLC, solid was filtered and washed with diethyl ether. The fil-
trate was washed with water and brine and dried over anhydrous
Na2SO4, which was concentrated under reduced pressure. The
crude product was subjected to silica gel column chromatography
(1) as solid (33 mg) in a 70% yield. ½a D20
ꢁ
+175 (c 0.6, H2O). 1H NMR
(300 MHz, CD3OD): d 6.70–6.67 (m, 1H), 4.67–4.61 (m, 1H),
4.39–4.35 (dd, J = 3.0, 6.0 Hz, 1H), 4.27–4.23 (m, 3H). 13C NMR
(75 MHz, CD3OD): d 199.3, 145.1, 137.8, 77.7, 76.9, 69.4, 59.3.
HRMS: Calcd for C7H10O5Na ([M+Na]+) is 197.0426. Found:
197.0418.
3.2.11. (3aS,4S,7aS)-6-((tert-Butyldiphenylsilyloxy)methyl)-4-
(methoxymethoxy)-2,2-dimethyl-3a,4-dihydrobenzo[d][1,3]di-
oxol-5(7aH)-one (19)
to give ketone 16 as a liquid (450 mg, 91%). ½a D20
ꢁ
+56.8 (c 0.2,
CHCl3). 1H NMR (300 MHz, CDCl3): d 6.69 (dd, J = 10.5, 6.7 Hz,
1H), 6.39 (dd, J = 1.1, 17.3 Hz, 1H), 5.99–5.88 (m, 1H), d 5.80 (dd,
J = 1.5, 10.5 Hz, 1H), 5.45 (d, J = 16.6 Hz, 1H), (d, J = 10.5 Hz, 1H),
4.76 (t, J = 6.0 Hz, 1H), 4.57 (dd, J = 6.0, 15.8 Hz, 1H), 4.37 (dd,
J = 6.0, 9.0 Hz, 1H), 4.06 (d, J = 4.0 Hz, 1H), 3.29 (s, 3H), 1.46 (s,
3H), 1.33 (s, 3H). 13C NMR (75 MHz, CDCl3): d 197.9, 133.1,
132.71, 128.9, 117.8, 109.4, 97.2, 79.8, 78.4, 77.7, 56.6, 27.4, 25.2.
To a cooled (0 °C) solution of 18 (200 mg, 0.78 mmol) in dry
dichloromethane (25 mL) was added imidizole (63 mg,
0.94 mmol) followed by TBDPSCl (0.12 mL, 0.78 mmol) and stir-
red for 18 h at 0 °C temperature. After completion of the reac-
tion, the solvent was removed under reduced pressure and the
crude was purified over silica gel column chromatography (hex-
ane/ethyl acetate 7:3) to furnish a pure compound 19 (344 mg,
HRMS: Calcd for
279.1208.
C
13H20O5Na ([M+Na]+) is 279.1212. Found:
89%) as a colorless liquid. ½a D25
ꢀ37.7, (c 0.36, CHCl3). Rf: 0.65
ꢁ
(SiO2, 30% EtOAc in petroleum ether). 1H NMR (300 MHz, CDCl3):
d 7.64–7.61 (m, 4 H), 7.44–7.32 (m, 6 H), 6.76 (s, 1H), 4.94–4.88
(m, 2H), 4.84–4.78 (m, 2H), 4.53–4.48 (m, 1H), 4.41 (d, J = 2.8 Hz,
1H), 4.34–4.28 (m, 1H), 3.45 (s, 3H), 1.41 (s, 3H), 1.35 (s, 3H),
3.2.8. (3aS,4S,7aS)-4-(Methoxymethoxy)-2,2-dimethyl-3a,4-di-
hydrobenzo[d][1,3] dioxol-5(7aH)-one (17)
To a degassed solution of ketone 16 (200 mg, 0.78 mmol) in dry
CH2Cl2 (50 mL) was added Hoyeda Grubbs catalyst (24 mg,
5 mol %) and refluxed for 8 h. After completion of the reaction as
monitored by TLC, the reaction mixture was filtered and the sol-
vent was evaporated to give crude product that was purified by
column chromatography to afford compound 17 (106 mg, 60%) as
1.08 (br s, 9H). 13C NMR (75 MHz, CDCl3):
d 193.9, 137.3,
136.9, 135.4 (4C), 132.9 (2C), 129.8 (2C), 127.7 (4C), 111.4,
96.5, 77.6, 74.9, 72.7, 60.1, 55.0, 27.7, 26.9, 26.8 (3C), 19.2.
HRMS: Calcd for C28H36O6SiNa ([M+Na]+) is 519.2180. Found:
519.2184.

D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
135
3.2.12. (3aS,4R,5R,7aS)-6-((tert-Butyldiphenylsilyloxy)methyl)-
4-(methoxymethoxy)-2,2-dimethyl-3a,4,5,7a-tetrahydrobenzo
[d][1,3]dioxol-5-ol (20)
methyl iodide (0.08 mL, 1.32 mmol) and stirred for 3 h. After com-
pletion of the reaction, the reaction mixture was filtered through a
celite pad and washed with ethyl acetate. The filtrate was concen-
trated under vacuum and the residue was dissolved in EtOAc
(50 mL), washed with brine, and dried over Na2SO4. The solvent
was removed under reduced pressure, the crude ester was purified
over silica gel column eluting using EtOAc/hexane (2:3) to give es-
To a cooled (0 °C) solution of ketone 19 (600 mg, 1.21 mmol) in
methanol (10 mL) was added NaBH4 (46 mg, 1.21 mL) and the
reaction mixture was stirred for 1 h. After completion of the reac-
tion, the reaction was quenched with aq NH4Cl (10 mL) and con-
centrated under reduced pressure and extracted into EtOAc
(3 ꢃ 10 mL). The combined organic extracts were dried over anhy-
drous MgSO4 and concentrated under reduced pressure to give
crude product which was purified using silica gel chromatography
(30% ethyl acetate in hexane) to afford allylic alcohol 20 (555 mg,
ter 22 (140 mg, 70%) as a syrup. ½a D20
ꢁ
ꢀ40.6 (c 0.2, CHCl3). 1H NMR
(300 MHz, CDCl3): d 6.78 (dd, J = 3.5, 1.5 Hz, 1H), 4.86 (s, 2H), 4.66
(dd, J = 6.0, 3.7 Hz, 1H), 4.59–4.53 (m, 1H), 4.37 (d, J = 4.5 Hz, 1H),
3.84–3.81 (m, 1H), 3.81 (s, 3H), 3.59 (s, 3H), 3.48 (s, 3H), 1.43 (s,
3H), 1.38 (s, 3H). 13C NMR (75 MHz, CDCl3): d 166.4, 137.0, 130.1,
111.4, 94.9, 73.1, 72.7, 72.5, 71.6, 61.1, 55.7, 52.1, 27.7, 26.0. HRMS:
Calcd for C14H22O7Na ([M+Na]+) is 325.1263. Found: 325.1258.
92% yield) as a colorless oil. Rf = 0.6 (EtOAc/hexane 3:7). ½a D20
ꢁ
ꢀ39.7 (c 0.38, CHCl3). 1H NMR (300 MHz, CDCl3): d 7.68–7.64 (m,
4 H), 7.42–7.34 (m, 6 H), 5.80 (s, 1H), 4.90 (d, J = 6.9 Hz, 1H), 4.79
(d, J = 6.9 Hz, 1H), 4.69–4.67 (m, 1H), 4.60 (d, J = 4.9 Hz, 1H), 4.38
(d, J = 13.9 Hz, 1H), 4.25 (d, J = 14.9 Hz, 1H), 4.10 (dd, J = 2.9,
9.9 Hz, 1H), 3.76–3.75 (m, 1H), 3.45 (s, 3H), 3.21 (d, J = 10.9 Hz,
1H, –OH), 1.44 (s, 3H), 1.38 (s, 3H), 1.07 (br s, 9H). 13C NMR
(75 MHz, CDCl3): d 139.9, 135.4 (4C), 133.3 (2C), 129.7 (2C),
127.6 (4C), 120.0, 110.7, 95.1, 76.2, 73.8, 71.9, 64.8, 64.6, 55.7,
3.2.15. (3S,4S,5S, 6R)-Methyl 3,4,5-trihydroxy-6-methoxycyclo-
hex-1-enecarboxylate (4)
To a solution of compound 22 (50 mg, 0.17 mmol) in methanol
(3 mL), was added TFA (0.5 mL) and stirred at room temperature
for 3 h. After completion of the reaction, the reaction was
quenched with saturated NaHCO3 solution (5 mL), concentrated
under reduced pressure, and extracted into ethyl acetate
(3 ꢃ 10 mL). The combined organic solvent was washed with brine,
dried over Na2SO4, and concentrated under reduced pressure to
give crude residue which was purified over silica gel column using
MeOH/CHCl3 (1:24) to give (+)-pericosine B (4) (26 mg, 70% yield).
28.0, 26.8 (3C), 26.5, 19.2. HRMS: Calcd for
C28H38O6SiNa
([M+Na]+) is 521.2338. Found: 521.2332.
3.2.13. ((3aS,6R,7R,7aS)-6-Methoxy-7-(methoxymethoxy)-2,
2-dimethyl-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxol-5-yl)
methanol (21)
½
a 2D0 +34.6 (c 0.3, EtOH). 1H NMR (300 MHz, CDCl3): d 6.72 (dd,
ꢁ
To an ice-cooled, stirred solution of NaH (132 mg, 60% w/v dis-
persion in mineral oil, 4.20 mmol) in dry THF (5 mL) was added
compound 20 (525 mg, 1.05 mmol) in THF (5 mL) and methyl io-
dide (0.1 mL, 1.58 mmol). The mixture was stirred at room temper-
ature for 6 h, quenched with saturated NH4Cl solution and
extracted into EtOAc (2 ꢃ 10 mL). The combined organic layers
were washed with water and brine, dried over Na2SO4, and concen-
trated in vacuo. The methoxy ether was used as such for the next
reaction without any further characterization. To a cooled (0 °C)
solution of methoxy ether in THF (3 mL), was added aqueous HF
(1 drop) at room temperature for 8 h. After completion of the reac-
tion, the reaction was quenched with NaHCO3 and extracted into
ethyl acetate (3 ꢃ 15 mL). The combined organic solvent was the
solvent washed with brine, dried over Na2SO4, and concentrated
under reduced pressure to give crude residue which was purified
over silica gel column (petroleum ether/ethyl acetate 1:1) to give
J = 3.9, 1.5 Hz, 1H), 4.25 (d, J = 3.9 Hz, 1H), 4.15 (m, 1H), 3.92 (m,
1H), 3.85 (m, 1H), 3.76 (s, 3H), 3.59 (s, 3H). 13C NMR (75 MHz,
CD3COCD3): d 166.9, 141.9, 130.5, 76.9, 72.5, 69.9, 69.5, 61.4,
52.1. HRMS: Calcd for C9H14O6Na ([M+Na]+) is 241.0688. Found:
241.0684.
3.2.16. (3aS,4R,5S,7aS)-6-((tert-Butyldiphenylsilyloxy) methyl)-
4-(methoxymethoxy)-2,2-dimethyl-3a,4,5,7a-tetrahydrobenzo
[d][1,3]dioxol-5-ol (23)
To a cooled (ꢀ78 °C) solution of ketone 19 (620 mg, 1.25 mmol)
in methanol were added CeCl3ꢂ7H2O (930 mg, 2.5 mmol) and
NaBH4 (48 mg, 1.25 mL) and stirred for 1 h. After completion of
the reaction, the reaction was quenched with aq NH4Cl (10 mL),
concentrated under reduced pressure, and extracted into EtOAc
(3 ꢃ 20 mL). The combined organic extract was dried over anhy-
drous MgSO4 and concentrated under reduced pressure to give
crude product which was purified over silica gel column (30% ethyl
acetate in hexane) to afford allylic alcohol 23 (547 mg, 88% yield)
alcohol 21 (250 mg, 87%). ½a D25
ꢁ
+60.3 (c 0.27, CHCl3). 1H NMR
(300 MHz, CDCl3): 5.92 (s, 1H), 4.86 (d, J = 6.9 Hz, 1H), 4.72 (d,
J = 6.9 Hz, 1H), 4.60–4.57 (m, 1H), 4.33–4.29 (m, 1H), 4.26–4.22
(m, 2H), 4.20–4.16 (m, 1H), 3.96–3.94 (m, 1H), 3.92–3.89 (m,
1H), 3.51 (s, 3H), 3.42 (s, 3H), 1.47 (s, 3H), 1.40 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 139.6, 120.5, 110.4, 96.6, 77.8, 74.2, 71.1,
68.9, 64.2, 57.8, 55.4, 26.6, 25.4. HRMS: Calcd for C13H22O6Na
([M+Na]+) is 297.1314. Found: 297.1312.
as a colorless oil. Rf = 0.6 (EtOAc/hexane 3:7). ½a D20
ꢁ
+5.92 (c 0.76,
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.64–7.58 (m, 4 H), 7.40–
7.30 (m, 6 H), 5.66 (s, 1H), 4.78 (d, J = 6.7 Hz, 1H), 4.69 (d,
J = 6.7 Hz, 1H), 4.48–4.43 (m, 4.29–4.25 (m, 1H), 4.18–4.15 (m,
4.13–4.09 (m, 1H), 3.90 (dd, J = 3.7, 9.8 Hz, 1H), 3.51 (d,
J = 10.5 Hz, 1H), 3.35 (s, 3H), 3.11 (br s, 1H), 1.25 (br s, 6 H), 1.04
(br s, 9 H). 13C NMR (75 MHz, CDCl3): d 140.1, 135.5 (4C), 132.8
(2C), 129.7 (2C), 127.9 (4C), 120.8, 114.0, 94.6, 72.7, 72.0, 70.3,
65.4, 64.0, 55.6, 29.7, 26.9, 26.8 (3C), 19.2. HRMS: Calcd for C28H38-
O6SiNa ([M+Na]+) is 521.2338. Found: 521.2334.
3.2.14. (3aS,6R,7R,7aS)-Methyl 6-methoxy-7-(methoxymethoxy)-
2,2-dimethyl-3a,6,7,7a-tetrahydrobenzo [d][1,3]dioxole-5-carbo-
xylate. (22)
To a cooled (ꢀ78 °C) solution of alcohol 21 (180 mg, 0.66 mmol)
in CH3CN (5 mL), H2O (2.5 mL) and was added TEMPO (21 mg,
0.13 mmol) and BAIB (530 mg, 1.65 mmol) and stirred for 3 h.
The reaction mixture was quenched with saturated Na2S2O3 solu-
tion (5 mL) and extracted into ethyl acetate (2 ꢃ 10 mL). The com-
bined organic layer was dried over anhydrous Na2SO4 and
concentrated. The crude acid was purified over silica gel column
using ethyl acetate and hexane (1:1) to obtain pure acid as a vis-
cous liquid. The acid was used as such for the next reaction without
any further characterization. To a cooled solution of acid in dry
acetone (10 mL) were added K2CO3 (137 mg, 1.32 mmol) and
3.2.17. ((3aS,6S,7R,7aS)-6-Methoxy-7-(methoxymethoxy)-2,2-
dimethyl-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxol-5-yl)metha-
nol (24)
To an ice-cooled, stirred solution of NaH (132 mg, 60% w/v dis-
persion in mineral oil, 4.20 mmol) in THF (5 mL) was added com-
pound 23 (525 mg, 1.05 mmol) in THF (5 mL) and methyl iodide
(0.1 mL, 1.58 mmol) and stirred at room temperature for 6 h. After
completion of the reaction, the reaction was quenched with satu-
rated NH4Cl solution and extracted with EtOAc (2 ꢃ 10 mL). The
combined organic layer was washed with water and brine, then

136
D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
dried over Na2SO4, and concentrated in vacuo. The crude material
was used for next step without further purification. To a cooled
(0 °C) solution of methoxy ether (440 mg, 0.86 mmol) in THF
(3 mL), was added aqueous HF (1 drop) and stirred at room tem-
perature for 8 h. After completion of the reaction, the reaction
was quenched with sodium bicarbonate and extracted into ex-
tracted with EtOAc (2 ꢃ 10 mL). The combined organic layer was
washed with water and brine, then dried over Na2SO4, and concen-
trated in vacuo which was purified by silica gel column using
(petroleum ether/ethyl acetate 1:1) to give alcohol 24 (256 mg,
4. Conclusion
In conclusion, we have reported a simple and efficient route for
the total synthesis of the bio-active compounds (+)-gabosine C, (+)-
pericosine B, and (+)-pericosine C from a common intermediate 18.
This approach might be applicable to other gabosines, pericosines,
and biologically important cyclohexene derived carbasugar related
molecules.
Acknowledgments
89%). ½a 2D5
ꢁ
+23.8 (c 0.25, CHCl3). 1H NMR (400 MHz, CDCl3): d
5.90 (s, 1H), 4.88 (d, J = 6.9 Hz, 1H), 4.73 (d, J = 6.9 Hz, 1H), 4.59
(m, 1H), 4.30 (m, 1H), 4.24 (br s, 2H), 4.17 (m, 1H), 3.92 (br s,
1H), 3.51 (s, 3H), 3.42 (s, 3H), 1.48 (s, 3H), 1.39 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 138.9, 124.0, 109.6, 96.7, 78.7, 78.4, 75.1,
73.1, 64.4, 61.0, 55.5, 27.5, 26.3. HRMS: Calcd for C13H22O6Na
([M+Na]+) is 297.1314. Found: 297.1312.
The authors D.C.B., C.B.R., K.V., and J.J.P.S. are thankful to UGC
and CSIR, New Delhi for the financial support and thankful to the
Director, IICT for her constant encouragement.
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(k) Krishna, P. R.; Kadiyala, R. R. Tetrahedron Lett. 2011, 53, 744–747; (l) Prasad,
K. R.; Kumar, S. M. Synlett 2011, 160–1604.
To
a
cooled (ꢀ78 °C) solution of alcohol 24 (180 mg,
0.66 mmol) in CH3CN (5 mL) and H2O (2.5 mL) were added TEM-
PO (21 mg, 0.13 mmol) and BAIB (530 mg, 1.65 mmol) and stir-
red for 3 h. After completion of the reaction, the reaction was
quenched with saturated Na2S2O3 solution (5 mL) and extracted
into ethyl acetate (2 ꢃ 10 mL). The combined organic layer was
dried over anhydrous Na2SO4 and concentrated to get crude acid
as a viscous liquid. The acid was used as such for the next reac-
tion without any further characterization. To a cooled solution of
acid in dry acetone (10 mL) were added K2CO3 (137 mg,
1.32 mmol) and methyl iodide (0.08 mL, 1.32 mmol) and stirred
for 3 h. The reaction mixture was filtered through a celite pad
and washed with ethyl acetate. Then filtrate was concentrated
under vacuum and the residue was dissolved in EtOAc (50 mL),
washed with brine, and dried over Na2SO4. The solvent was re-
moved under reduced pressure, the crude ester was purified over
silica gel column eluting with EtOAc/hexane (2:3) to give ester
25 (140 mg, 70%) as a syrup. ½a D20
ꢁ
+44.7 (c 0.15, CHCl3). 1H
d 6.87 (d, J = 3.2, 1H), 4.86 (d,
NMR (300 MHz, CDCl3):
J = 6.8 Hz, 1H), 4.74 (d, J = 6.8 Hz, 1H), 4.69–4.65 (m, 1H), 4.57
(dd, J = 3.2, 5.6 Hz, 1H), 4.42 (d, J = 6.2 Hz, 1H), 4.08 (dd, J = 3.2,
6.2 Hz, 1H), 3.83 (s, 3H), 3.57 (s, 3H), 3.46 (s, 3H), 1.43 (s, 3H),
1.41 (s, 3H). 13C NMR (75 MHz, CDCl3): d 166.6, 136.0, 132.2,
110.2, 97.0, 75.0, 74.0 (2C), 71.5, 59.6, 55.6, 52.0, 26.9, 25.7.
HRMS: Calcd for
325.1263.
C
14H22O7Na ([M+Na]+) is 325.1263, Found:
3.2.19. (3S,4S,5S,6S)-Methyl 3,4,5-trihydroxy-6-methoxycyclo-
hex-1-enecarboxylate (5)
4. (a) Numata, A.; Iritani, M.; Yamada, T.; Minoura, K.; Matsumura, E.; Yamori, T.;
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8758; (c) Usami, Y.; Hatsuno, C.; Yamamoto, H.; Tanabe, M.; Numata, A. Chem.
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1062–1063; (e) Usami, Y.; Horibe, Y.; Takaoka, I.; Ichikawa, H.; Arimoto, M.
Synlett 2006, 1598–1600; (f) Usami, Y.; Ueda, Y. Synthesis 2007, 3219–3225; (g)
Usami, Y.; Takaoka, I.; Ichikawa, H.; Horibe, Y.; Tomiyama, S.; Ohtsuka, M.;
Imanishi, Y.; Arimoto, M. J. Org. Chem. 2007, 72, 6127–6134; (h) Yamada, T.;
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K.; Ichikawa, H.; Arimoto, M. Org. Biomol. Chem. 2009, 7, 315–318; (l) Usami, Y.;
Ohsugi, M.; Mizuki, K.; Ichikawa, H.; Arimoto, M. Org. Lett. 2009, 11, 2699–
2701; (m) Fejes, Z.; Mándi, A.; Komáromi, I.; Bényei, A.; Naesens, L.; Fenyvesi,
F.; Szilágyi, L.; Herczegh, P. Tetrahedron 2009, 65, 8171–8175; (n) Boyd, D. R.;
Sharma, N. D.; Acaru, C. A.; Malone, J. F.; O’Dowd, C. R.; Allen, C. C. R.;
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Ch.; Rao, J. P.; Rao, B. V. Tetrahedron: Asymmetry 2012, 23, 86–93.
To a solution of compound 25 (50 mg, 0.17 mmol) in methanol
(3 mL), was added TFA (0.5 mL) and stirred at room temperature
for 3 h. After completion of the reaction, the reaction was neutral-
ized with saturated NaHCO3 solution, concentrated under reduced
pressure, and extracted into ethyl acetate (3 ꢃ 10 mL). The com-
bined organic solvent was washed with brine, dried over Na2SO4,
and concentrated under reduced pressure to give crude residue
which was purified over silica gel column using MeOH/CHCl3
(1:24) to give (+)-pericosine C 5 (24 mg, 67%) as a liquid. ½a D20
ꢁ
+72.5 (c 0.3, EtOH). 1H NMR (300 MHz, CDCl3):
d 6.75 (d,
J = 3.7 Hz, 1H), 4.43 (d, J = 6.0 Hz, 1H OH), 4.25–4.21 (m, 1H), 4.17
(d, J = 4.5 Hz, 1H), 3.97–3.92 (m, 2H), 3.85–3.91 (m, 2H), 3.77 (s,
3H), 3.49 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3): d 166.7, 140.4,
131.5, 79.1, 73.3, 70.1, 67.4, 59.4, 52.0 ppm. HRMS: Calcd for C9H14-
O6Na ([M+Na]+) is 241.0688. Found: 241.0684.

D. C. Babu et al. / Carbohydrate Research 388 (2014) 130–137
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