A common and versatile synthetic route to (-) and (+) pentenomycin I, (+) halopentenomycin i and dehydropentenomycin

Article abstract of DOI:10.1016/j.carres.2015.08.003

A versatile and stereoselective total synthesis of (+) and (-) pentenomycin I, (+) halopentenomycins I and dehydropentenomycin from a common chiral polyhydroxylated cyclopentene through oxidation and protection/deprotection has been described. Stereoselec

Full text of DOI:10.1016/j.carres.2015.08.003

Carbohydrate Research 416 (2015) 24–31
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A common and versatile synthetic route to (−) and (+) pentenomycin I,
(
+) halopentenomycin I and dehydropentenomycin
Sulagna Das, Amarendra Panda, Shantanu Pal *
Indian Institute of Technology Bhubaneswar, School of Basic Sciences, Bhubaneswar, Orissa 751007, India
A R T I C L E
I N F O
A B S T R A C T
Article history:
Received 8 May 2015
Received in revised form 9 June 2015
Accepted 12 August 2015
Available online 18 August 2015
A versatile and stereoselective total synthesis of (+) and (−) pentenomycin I, (+) halopentenomycins I and
dehydropentenomycin from a common chiral polyhydroxylated cyclopentene through oxidation and
protection/deprotection has been described. Stereoselective hydroxymethylation, stereoselective Grignard
reaction and ring closing metathesis are the key features of our approach.
©
2015 Published by Elsevier Ltd.
Keywords:
Cyclopentenones
Stereoselectivity
Halopentenomycin
Grignard reaction
Ring closing metathesis
d-Ribose
1
. Introduction
Cyclopentenones and their congeners are widely used as chiral
of Streptomyces eurythermus.5b,c The assemblage of a variety of re-
active functional groups along with the quaternary chiral center
makes the molecule interesting for its synthesis. In addition,
pentenomycin congeners with interesting biological properties have
1
building blocks in organic synthesis and have been used for the syn-
thesis of a large number of natural and unnatural products such as
generated renewed interest in the chemistry of cyclopentanoid
punaglandins 1, xanthocidin 2, untenone A 3,4 and (−)
2
3
within past few years.
14–19
Various synthetic methods such as ring
5
6
7
14
15
pentenomycin I 4, prostaglandins, cyclopentanoid monoterpenoids,
carbocyclic nucleosides, etc. (Fig. 1). In addition, a diverse range
of natural products for example didemnenone 6, parthenin 7,
tricycloclavulone 8, etc.
tities as important segments in their basic core structures (Fig. 1).
Generally such molecules bearing cyclopentenone framework exert
their biological effects through highly reactive α, β unsaturated car-
bonyl center which behaves as an excellent Michael acceptor toward
various cellular nucleophiles.12 Moreover, the highly oxygenated
cyclopentanoid analogues are of increasing interest among the syn-
thetic chemists because of their promising biological activity
closing metathesis, 1,3-dipolar nitrone alkene cycloaddition,
8
16
Pauson–Khand reaction, Diels–Alder cycloaddition followed by
1
7
decarbonylation etc. have been reported regarding the total syn-
thesis of pentenomycin including both racemic as well as enantiopure
forms. Recently, Rao’s group have reported the synthesis of both
natural (−) and unnatural (+) pentenomycin I using Tebbe olefination
and intramolecular aldol condensation as their key steps.
Although many successful synthetic methods have been re-
9
–11
contain cyclopentenone structural en-
1
8
19
ported for the total synthesis of pentenomycin, however, there
is a still demand to synthesize both the isomers of pentenomycin
I from a single precursor. On this line, dehydropentenomycin 5
1
3
13a–g
profiles such as glycosidase inhibitor,
aminoglycosidase
etc. In particular, pentenomycin, a
cyclopentanoid class of antibiotics, exhibits moderate to strong ac-
(Fig. 1) is a closely related member of the pentenomycin
1
3h
13i–l
20a,b
antibiotic,
anticancers,
family and has reasonable antibiotic potency.
However a
limited literature is available for the total synthesis of
5
a
20c
tivity against both Gram-positive and Gram-negative bacteria. It
was isolated by Umino and co-workers in 1973 from culture strains
dehydropentenomycin. Therefore, we wish to report herein the
total synthesis of both natural (−) and unnatural (+) pentenomycin
I, dehydropentenomycin and halo derivatives of unnatural (+)
pentenomycin I from a polyoxygenated cyclopentene as the common
chiral building block, which has been synthesized from easily
available starting material D-ribose via stereoselective
hydroxymethylation, stereoselective Grignard reaction and ring
closing metathesis as key steps.
*
Corresponding author. Indian Institute of Technology Bhubaneswar, School of
Basic Sciences, Bhubaneswar, Orissa 751007, India. Tel.:+91 674 2576054; fax:+91
6
74 2301983.
E-mail address: spal@iitbbs.ac.in (S. Pal).
http://dx.doi.org/10.1016/j.carres.2015.08.003
008-6215/© 2015 Published by Elsevier Ltd.
0

S. Das et al./Carbohydrate Research 416 (2015) 24–31
25
O
O
O
O
X
OH
OH
COOCH3
R1
OH
R2
OH
CH2)15CH3
1
OH
OH
OH
(
4
3
X = I, Br, Cl
R , R = alkyl groups
2
1
2
HO
O
O
H
O
OAc
OH
OH
AcO
H
CO2Me
2
O
OH
O
O
HO
6
5
7
H
8
O
Fig. 1. Naturally occurring biomolecules: punaglandins 1, xanthocidin 2, untenone-A 3, (−) pentenomycin I 4, dehydropentenomycin 5, didemnenone 6, parthenin 7,
tricycloclavulone 8.
2
. Result and discussion
in acetone. It was followed by stereoselective aldol condensation22
using 37% aqueous formaldehyde in methanol to yield
hydroxymethylated compound 13 which established a quarternary
chiral center at the desired position with very good yield.
The hydroxymethylated compound 13 was subjected to a
stereoselective Grignard reaction with vinyl magnesium bromide
in THF under −78 °C to yield the ring opened polyhydroxylated alkene
14. The stereoselectivity of Grignard reaction may be explained via
the Felkin–Anh cyclic chelate transition model as shown in Fig. 2.
This chelate transition state explains the β-attack of nucleophile from
the less hindered face providing a single stereoisomer in a predom-
inant amount. It was observed that Grignard reaction on acetonide
protected D-ribose without hydroxymethylated chain23 and with
hydroxymethylated chain conserves the steroselectivity.
As a part of our ongoing research for the exploration of novel
carbocyclic nucleoside template, and inspiration from the exten-
sive and pioneering work of Jeong and co-workers,2 we devised a
common synthetic strategy for the total synthesis of both (+) and
1
(
−) pentenomycin I, (+) halopentenomycin
I as well as
dehydropentenomycin as shown in Scheme 1.
The carbocyclic framework 10 was envisioned as being a versa-
tile synthetic building block towards the synthesis of pentenomycin
analogues and dehydropentenomycin via oxidation, functional group
transformations and deprotection. The carbocyclic framework 10 in
turn could be obtained from the lactol 11 using Wittig and RCM re-
action. The lactol 11 can be prepared from D-ribose via protection,
stereoselective hydroxymethylation, stereoselective Grignard fol-
lowed by oxidative cleavage.
It was directly used for next step without purification due to its
high polar nature. The ring opened Grignard adduct 14 was sub-
jected to oxidative cleavage with sodium m-periodate in order to
yield the desired lactol intermediate 11. Wittig olefination of lactol
11 with methyl triphenylphosphonium ylide gave the diene 15 in
a satisfactory yield which set the stage for ring closing metathesis.24
Cyclization proceeded smoothly on the substrate 15 by employing
Grubbs’ second generation catalyst providing the cyclopentenol 10
in quantitative yield (Scheme 2). The structure of cyclopentenol 10
A unified and general approach for chiral cyclopentenol 10 was
commenced with the protection of D-ribose to 2,3 acetonide pro-
tected D-ribose 12 by treatment with catalytic amount of conc. H SO
2 4
R
1
13
O
has been deduced through H and C NMR and HRMS. The stereo-
chemical structure of compound 10 was confirmed with the help
of single crystal X-ray structure (Fig. 3).
O
HO
OHOH
OH
OH
Selective allylic oxidation of 10 afforded the cyclopentenone 17
in a good yield. Then acetonide deprotection was accomplished by
9
R = H, I, Cl, F
O
OH
O
5
OH
O
O
Mg+2
HO
HO
OH
10
4
CH3
O
O
H C
3
C
O
HO
O
Nu
D-ribose
CH
CH2
BrMgO
O
O OH
CH
H
OMgBr
BrMgO
C
1
1
H2
Scheme 1. Retrosynthetic analysis.
Fig. 2. Felkin–Anh cyclic chelate transition model.

26
S. Das et al./Carbohydrate Research 416 (2015) 24–31
HO
HO
HO
OR
OR
OR
O
O
O
OH
b
a
d
OH
b
a
OH
OH
O
O
HO
OH
OR
O
O
OH
O
O
O
O
OH
19
O
O
OH
R = TBDPS
1
7
1
1
0 R = H
1
2
13
14
6 R = TBDPS
e
c
c
OR
O
O
O
OH
f
HO
OH
e
d
O
OHOR
R = TBDPS
HO
OHOH
HOHO
OH
O
O
OH
O
O
OH
O
O
OH
4
18
20
ο
Reagents and condtions: (a) TBDPSCl, Imidazole, N,N-Dimethylformamide, 0 C-
ο
ο
1
0
15
11
rt, 24 h, 96%; (b) MnO , Toluene, 90 C, reflux, 24 h, 77%; (c) 50% aq TFA, 0 C-rt,
2
ο
3
0 min, 82%; (d) TFA:THF:H2O (5:4:3), 0 C, 1.5 h, 93%; (e) PDC, CH2Cl2, rt, 5 h,
65%; (f) TBAF, AcOH, THF, 0 C-rt, 1.5 h, 65%
Reagents and condtions: (a) 37% aq. HCHO, K2CO3, methanol, reflux, 72 h, 90%;
ο
ο
ο
(
b) Vinyl magnesium bromide, THF, -78 C-rt, 24 h; (c) NaIO4 (0.65 M), CH2Cl2, 0 C-
ο
rt, 1.5 h, 61% for two steps; (d) CH3PPh3Br, t-BuOK, THF, 0 C-rt, 5 h, 75%; (e)
Grubbs' second generation catalyst, CH2Cl2, rt, 24 h, 93%
Scheme 3. Synthesis of (+) pentenomycin I, 18 and (−) pentenomycin I, 4.
Scheme 2. Synthesis of cyclopentenol 10.
the contrary, the iodinated product 24 was obtained in a quite good
yield from the compound 22 upon treatment with iodine and pyri-
dine in THF. Then, subsequent desilylation of compound 24 followed
by acetonide deprotection led to (+) iodopentenomycin I 28
trifluoroacetic acid and water to achieve synthesis of (+)
pentenomycin I 18 with good yield.
A simple functional group transformation was envisioned for
natural (−) pentenomycin I 4 from the common precursor 10 as per
above mentioned strategy. Compound 10 was protected with
TBDPSCl and imidazole to yield the disilyl ether 16. After that a se-
lective acetonide deprotection was accomplished under mild acidic
condition in order to get the cyclopentenol 19 in a good yield. PDC
oxidation in dry dichloromethane led to the cyclopentenone 20 fol-
lowed by deprotection with TBAF culminated the natural (−)
pentenomycin I 4 in a good yield (Scheme 3).
In order to achieve the halo analogues of (+) pentenomycin I, com-
pound 10 was selectively protected as its mono silyl ether 21 and
subsequently oxidized by PDC to give 22. The compound 22 was
subjected to electrophilic fluorination in the presence of
N-fluorobenzenesulfonimide and n-butyllithium which resulted in
decomposition of product. However, in the presence of bis-
acetoxyiodobenzene and pyridinium hydrochloride the chloro
derivative 23 was isolated with poor yield. Hence, the cyclopentenone
(
Scheme 4).
On the other hand, total synthesis of dehydropentenomycin 5
was achieved from the same common intermediate 10 through ma-
nipulation of a few protection/deprotection steps. The mono-
TBDPS protected cyclopentenol 21 was subjected to acetonide
deprotection under mild acidic conditions to yield the triol 29
(
Scheme 5). Then the dioxidation was investigated by several oxi-
25
2 2
dizing agents such as (i) PDC, CH Cl , 4 Å MS, rt, 2 h, 14%; (ii) MnO2,
2
6
CH
2
2
Cl
2
, rt-reflux, decomposed; (iii) PCC, CH
%; (iv) CrO , pyridine, acetic anhydride, CH
V) DMP, CH
CH Cl , Et N, −78 °C–rt, 2 h, 25%; etc. to provide the dienone 31.
2
Cl
2
, 4 Å MS, rt, 3.5 h,
7
28
9
(
3
2
Cl2, 0 °C–rt, 1.5 h, 35%;
2
9
2 2 2
Cl , 0 °C–rt, 1.5 h, decomposed; (vi) (COCl) , DMSO,
3
0
2
2
3
However, all our efforts were futile and only a trace amount of
product was isolated.
1
7 was directly converted to the chloro analogue 25 effectively using
O
the same reagents. The chloro analogue 25 was then subjected to
acetonide deprotection to yield the (+) chloropentenomycin I 27. On
OH
OH
OH
a
b
O
O
OTBDPS
O
O
O
O
OTBDPS
22
10
21
c
R
R
R
O
O
O
f
d
O
O
OH
HO
OH
OH
O
O
OTBDPS
2
7 R=Cl
2
8 R=I
17 R=H
2
2
3 R=Cl
4 R=I
e
2
5 R=Cl
6 R=I
2
Reagents and condtions: (a) TBDPSCl, Et3N, DMAP, CH2Cl2, 0 οC-rt, 24 h, 93%;
(
2
6
b) PDC, CH2Cl2, rt, 24 h, 79%; (c) i. for 23; BAIB, Py.HCl, CH2Cl2, rt, 6 h, 5% ii. for
4; I2, Pyridine, THF, 0 οC-rt, 2 h, 90%; (d) for 26; TBAF, AcOH, THF, 0 C-rt, 2.5 h,
ο
ο
8%; (e) BAIB, Py.HCl, CH2Cl2, rt, 6 h, 15% (f) i. for 27; TFA:THF:H2O (2.5:1:1), 0 C-
ο
rt, 12 h, 27% ii. for 28; TFA:THF:H2O (2:1:1), 0 C-rt, 2 h, 60%.
Scheme 4. Synthesis of (+) chloropentenomycin I, 27 and (+) iodopentenomycin I,
28.
Fig. 3. X-ray crystal structure of cyclopentenol 10 (30% ellipsoid probability).

S. Das et al./Carbohydrate Research 416 (2015) 24–31
27
under argon atmosphere from sodium benzophenone ketyl.
Dichloromethane was freshly distilled from P under argon at-
OH
OR
O
2 5
O
a
mosphere. All reactions were monitored by analytical thin layer
chromatography (TLC) on aluminium precoated Merck silica gel
plates (EM-60-F254). TLC visualization was accompanied using UV
lamp (254 nm) or charring solution (ethanolic p-anisaldehyde).
Column chromatography was generally performed on silica gel (100–
O
O
O
O
OR
2
1
2
2
R = TBDPS
R = TBDPS
2
00 mesh). Melting points were recorded in BUCHI M-560
1
13
b
c
instrument and are uncorrected. H and C NMR spectra were re-
corded on a Bruker 400 spectrometer H NMR (400 MHz), C NMR
1
13
1
(100 MHz). Chemical shifts for H NMR were reported as δ values
OH
O
1
(in parts per million) and coupling constants were in hertz (Hz). H
NMR spectra were referenced internally to the residual proton res-
onance in CDCl
standard. C NMR spectra were referenced to CDCl
3
(δ 7.26 ppm) or with TMS (δ 0.00 ppm) as internal
(δ 77.0 ppm,
HO
R = TBDPS
OHOR
HO
R = TBDPS
30
OHOR
13
3
middle peak). IR spectra were obtained on NaCl plates (film) with
a Bruker Tensor 27 FT-IR and selected absorbance are reported in
2
9
d
d
−1
cm . High resolution (HR) mass spectrometry data were acquired
by an Agilent 6520 (Q-TOF) mass spectrometer using MeOH as
solvent. Optical rotations were measured in an Anton Paar MCP 100
Polarimeter. Single crystal X-ray structures were determined by
Bruker D8 Venture diffractometer equipped with CMOS detector.
O
O
e
O
O
OH OR
OH
OH
5
R = TBDPS
3
1
4
.2. Synthesis of ((3aR,6aR)-4-hydroxy-2,2-
Reagents and condtions: (a) PDC, CH2Cl2, rt, 24 h, 79%; (b) TFA:THF:H2O
4:3:3), 0 C, 1.5-2 h, 93%; (c) TFA:THF:H2O (3:1:1), 0 C, 3.5 h, 64% (bsr);
d) PDC, CH2Cl2, rt, 5 h, 38% (e) TBAF, AcOH, THF, 0 C-rt, 4.5 h, 85%
dimethyltetrahydrofuro[3,4-d][1,3]dioxole-3a,6-diyl)dimethanol (13)
ο
ο
(
(
ο
The hydroxymethylated compound (13) was prepared accord-
2
2
ing to the reported procedure.
Scheme 5. Synthesis of dehydropentenomycin, 5.
4.3. (3aS,6aS)-6a-(Hydroxymethyl)-2,2-dimethyl-6-
At this juncture, we thought to explore the oxidation in a step
vinyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol (11)
wise manner. Towards this, first the mono-TBDPS protected product
1 was oxidized in PDC in dichloromethane to the cyclopentenone
2 which after acetonide deprotection provided the diol 30 in a good
yield. The allylic alcohol oxidation was then carried out with several
oxidizing agents such as (i) PCC, CH Cl , 4 Å MS, rt, 3.5 h, 15%; (ii)
CrO , pyridine, acetic anhydride, CH Cl , 0 °C–rt, 1.5 h, 12%; (iii) MnO2,
CH Cl , rt-reflux, 35%; (iv) PDC, CH Cl , 4 Å MS, rt, 5 h, 38% to yield
the same dienone 31 (Scheme 5). The low yield of oxidation may
be attributed to the unstable nature of the dienone 31. Finally, the
TBDPS deprotection with TBAF buffered in acetic acid offered
dehydropentenomycin 5 in a good yield.
2
2
To a stirred suspension of hydroxymethylated compound 13
(2.61 g, 11.86 mmol) in dry THF (8 mL) was added vinyl magne-
sium bromide (65.25 mL, 65.25 mmol, 1.0 M solution in THF) at
−78 °C and stirred at 0 °C for 1 h. Then it was stirred for 24 h at room
temperature. It was then refluxed at 60 °C for 2.5 h to ensure the
completion of reaction. The reaction mixture was quenched by slow
addition of saturated ammonium chloride solution at 0 °C and the
resulting precipitate was removed through a celite pad. The fil-
trate was evaporated under reduced pressure to give a crude oil 14
which was directly used for the next step without further
purification.
2
2
3
2
2
2
2
2
2
3
. Conclusion
To the stirred suspension of 14 (2.94 g, 11.85 mmol) in methy-
4
lene chloride (50 mL), an aqueous solution of NaIO (48.94 mmol,
The work described here presents a short and versatile ap-
0.65 M solution) was added dropwise at 0 °C and the reaction
mixture was stirred at room temperature for 1.5 h. After the addi-
tion of water, the mixture was extracted with methylene chloride.
proach for the total synthesis of both (+) and (−) isomers of
pentenomycin I, (+) halopentenomycin as well as
dehydropentenomycin from common polyhydroxylated
I
a
2 4
The combined organic layer was dried over anhydrous Na SO , fil-
cyclopentene intermediate via simple protection and/or deprotection
and functional group interconversion. The common intermediate
has been achieved via stereoselective hydroxymethylation,
stereoselective Grignard reaction and ring closing metathesis as
pivotal steps. The intrinsic flexibility of this approach may be em-
ployed to construct other cyclopentenone derivatives with multi
hydroxyl groups and functionalized carbocycle templates for modi-
fied nucleoside derivatives.
tered and evaporated under reduced pressure to give a crude product.
It was then purified by silica gel column chromatography using
hexane and ethyl acetate (4:1) as eluent to give the lactol 11 (1.38 g,
61% for two steps).
4.4. (−)-(S)-1-((4S,5R)-4-(Hydroxymethyl)-2,2-dimethyl-5-vinyl-
1,3-dioxolan-4-yl)prop-2-en-1-ol (15)
To the stirred suspension of CH
in dry THF (150 mL), was added potassium tert-butoxide (18.93 g,
68.74 mmol) at 0 °C and the mixture was stirred at the same tem-
3 3
PPh Br (60.28 g, 168.74 mmol)
4. Experimental section
1
4
.1. General remarks
perature for 20 minutes. Then it was brought to room temperature
and stirred for 1 h to give a yellow suspension. To this stirred so-
lution was added the lactol 11 (8.1 g, 37.46 mmol) in THF (50 mL)
at 0 °C and the reaction mixture was stirred at room temperature
for 5 h. Then the reaction mixture was partitioned between water
(100 mL) and ethyl acetate (150 mL × 4) and the organic layer was
Unless otherwise noted, all reagents and solvents were pur-
chased from commercial suppliers and used without purification.
All reactions were carried out under ambient atmosphere unless
otherwise mentioned. Tetrahydrofuran (THF) was freshly distilled

28
S. Das et al./Carbohydrate Research 416 (2015) 24–31
dried over Na
2
SO
4
, filtered and evaporated in vacuo. The residue was
4.8. (−)-tert-Butyl(((3aR,4S,6aR)-4-((tert-butyldiphenylsilyl)oxy)-
2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-3a-
yl)methoxy)diphenylsilane (16)
purified by silica gel column chromatography using hexane and ethyl
acetate (5:1) as the eluent to give the diene 15 (5.95 g, 75%) as a
colourless oil; [α]
2
5
D
3 f
−93.848 (c 1.75, CHCl ); R 0.5 (hexane:EtOAc,
−1
1
1
2
:2); IR (film)vmax/cm : 3423, 2988, 2937, 1377, 1248, 1218, 1178,
117, 1043; H NMR (400 MHz, CDCl
.16 (2H, br s), 3.65 (1H, d, J = 12 Hz), 3.79 (1H, d, J = 12 Hz), 4.33
To a stirred solution of cyclopentenol 10 (520 mg, 2.79 mmol)
in dry DMF (12 mL), imidazole (951 mg, 13.96 mmol) was added
at 0 °C. To this solution TBDPSCl (2.2 mL, 8.40 mmol) was added
dropwise at 0 °C and the reaction mixture was stirred at room tem-
perature for 24 h. Solvent was removed in vacuo and the reaction
mixture was partitioned between water and diethyl ether. The com-
bined organic layer was washed with brine, dried over anhydrous
1
3
): δ 1.39 (3H, s), 1.47 (3H, s),
(
5
1H, d, J = 8 Hz), 4.73 (1H, d, J = 8 Hz), 5.26 (3H, td, J = 12 Hz, 4 Hz),
.54 (1H, d, J = 16 Hz), 6.05–6.16 (2H, m); 1 C NMR (100 MHz, CDCl
3
3
):
δ 26.3, 28.1, 62.3, 72.7, 80.2, 84.4, 108.7, 116.7, 118.2, 132.7, 136.4;
HRMS (ESI) (m/z): calcd for C11
+
H
18
O
4
[M + Na] 237.1102; found
2
37.0995.
2 4
Na SO , filtered and solvent was removed in vacuo to give the crude
product which was purified by silica gel column chromatography
using hexane and ethyl acetate (10:0.1) as eluent to give the di-
TBDPS protected product 16 (1.798g, 96%) as a colourless viscous
4
.5. (+)-(3aS,4S,6aR)-3a-(Hydroxymethyl)-2,2-dimethyl-4,6a-
ldihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (10)
2
5
oil; [α]
D
3 f
−19.697 (c 0.06, CHCl ); R 0.7 (hexane:EtOAc, 9:1); IR
−
1
To the stirred solution of diene 15 (5.95 g, 27.76 mmol), in dry
methylene chloride (60 mL) was added Grubbs’ second genera-
tion catalyst (235 mg, 1 mol %) at room temperature. The reaction
mixture was stirred for 24 h and evaporated in vacuo to give a brown
residue. This residue was directly applied to silica gel column chro-
matography and purified by using hexane and ethyl acetate (3:1)
as the eluent to give the cyclopentenol 10 (4.85 g, 93%) as a white
crystalline solid; mp 50.4–53.2 °C; [α]
R
2
(film)vmax/cm : 3070, 3051, 2957, 2932, 2892, 2858, 1468, 1427,
1364, 1243, 1211, 1190, 1110, 1060, 1005; H NMR (400 MHz, CDCl
1
3
):
δ 0.94 (9H, s), 1.11 (9H, s), 1.46 (3H, s); 1.55 (3H, s); 3.48 (1H, d,
J = 8 Hz); 3.61 (1H, d, J = 6 Hz); 4.56 (1H, s); 4.91 (1H, s); 5.72 (1H,
d, J = 8 Hz); 5.93 (1H, d, J = 4 Hz); 7.24–7.44 (12H, m); 7.52 (2H, d,
13
J = 8 Hz); 7.61(2H, d, J = 4 Hz); 7.74(4H, s); C NMR (100 MHz, CDCl
3
): δ 19.2, 19.3, 26.8, 26.9, 28.8, 29.1, 65.4, 76.3, 85.9, 89.2, 113.3,
127.58, 127.63, 127.67, 129.7, 132.6, 133.2, 133.3, 133.7, 134.3, 135.6,
2
5
D
3
+20.833 (c 0.09, CHCl );
−
1
f
0.5 (hexane:EtOAc, 1:1); IR (KBr)vmax/cm : 3418, 3062, 2990, 2936,
875, 1458, 1376, 1351, 1312, 1239, 1217, 1179, 1099, 1048; H NMR
135.7, 135.9, 136.1, 137.1; HRMS (ESI) (m/z): calcd for C41
[M + Na] 685.3145; found 685.3138.
H
50
O
4
Si
2
1
+
(
(
400 MHz, CDCl
3
): δ 1.37 (3H, s), 1.43 (3H, s), 3.01 (2H, br s), 3.73
13
2H, s), 4.41 (1H, s), 4.90 (1H, s), 5.89 (2H, s); C NMR (100 MHz,
4.9. (+)-(1R,2R,5S)-5-(tert-Butyldiphenylsilyloxy)-1-
CDCl
3
): δ 28.8, 29.1, 64.4, 75.4, 85.8, 89.4, 113.4, 132.7; HRMS (ESI)
((tert-butyldiphenylsilyloxy)methyl) cyclopent-3-ene-1,2-diol (19)
+
(m/z): calcd for C
9
H
14
O
4
[M + Na] 209.0789; found 209.0786.
To a stirred suspension of compound 16 (3.63 g, 5.48 mmol) in
THF (4 mL) was added water (3 mL) followed by dropwise addi-
tion of trifluoroacetic acid (5 mL) at 0 °C and stirred for 1.5 h. The
solution was neutralized by addition of sodium bicarbonate at 0 °C
and partitioned between water and ethyl acetate. The organic layer
4
.6. (−)-(3aR,6aR)-3a-(Hydroxymethyl)-2,2-dimethyl-3aH-
cyclopenta[d][1,3]dioxol-4(6aH)-one (17)
To a stirred solution of cyclopentenol 10 (330 mg, 1.77 mmol)
in dry toluene was added activated MnO
2
powder (4.80 g,
2 4
was washed with brine, dried over anhydrous Na SO , filtered and
4
6.93 mmol) at room temperature under inert atmosphere and re-
solvent was removed in vacuo to give the crude product which was
purified by silica gel column chromatography using hexane and ethyl
acetate (5:0.25) as eluent to give the di-TBDPS protected product
fluxed for 24 h at 90 °C. The reaction mixture was filtered in a celite
pad and the filtrate was evaporated in vacuo to give the crude
product. It was then applied on silica gel column chromatography
and purified by using hexane and ethyl acetate (4:1) as the eluent
to give the cyclopentenone 17 (250 mg, 77%) as a white crystalline
25
19 (3.2 g, 93%) as a white crystalline solid; mp 87–91.5 °C; [α]
+1.814 (c 0.32, CHCl ); R 0.5 (hexane:EtOAc, 10:1); IR (film)vmax
D
3
f
/
−1
cm : 3483, 3070, 3051, 2957, 2932, 2892, 2859, 1783, 1468, 1427,
2
5
1
solid; mp 67.7–69.6 °C; [α]
hexane:EtOAc, 1:1); IR (KBr)vmax/cm : 3423, 2991, 2937, 1723, 1587,
459, 1374, 1346, 1274, 1245, 1215, 1168, 1123, 1073; 1H NMR
400 MHz, CDCl ): δ 1.28 (3H, s), 1.40 (3H, s), 2.50 (1H, s), 3.80 (2H,
t, J = 12 Hz), 5.19 (1H, d, J = 4 Hz), 6.25 (1H, d, J = 8 Hz), 7.64 (1H, dd,
D
−18.568 (c 0.1, CHCl
3
); R
f
0.5
1391, 1362, 1336, 1171, 1111, 1053, 1002; H NMR (400 MHz, CDCl
3
):
−1
(
1
(
δ 0.96 (9H, s), 1.10 (9H, s), 2.79 (1H, br s); 3.62 (1H, d, J = 12 Hz);
3.73 (1H, d, J = 8 Hz); 4.58 (1H, s); 4.85 (1H, s); 5.48 (1H, d, J = 8 Hz);
5.87 (1H, d, J = 4 Hz); 7.32–7.48 (12H, m); 7.59 (4H, dd, J = 8 Hz,
3
1
3
3
12 Hz); 7.68 (4H, t, J = 4 Hz); C NMR (100 MHz, CDCl ): δ 19.25,
1
3
J = 4 Hz, 8 Hz); C NMR (100 MHz, CDCl
3
): δ 28.5, 28.7, 61.5, 81.4,
19.34, 26.8, 26.9, 64.4, 75.2, 79.4, 127.7, 127.8, 127.9, 128.0, 129.7,
129.8, 130.1, 130.2, 132.2, 132.4, 133.1, 133.2, 135.61, 135.64, 135.8,
84.5, 115.4, 134.8, 160.9, 204.9; HRMS (ESI) (m/z): calcd for C H O
9 12 4
+
46 4 2
135.2, 136.0; HRMS (ESI) (m/z): calcd for C38H O Si
[M + Na]+
[
M + Na] 207.0633; found 207.0628.
645.2832; found 645.2828.
4.7. (+) Pentenomycin I (18)
4.10. (+)-(4S,5S)-4-(tert-Butyldiphenylsilyloxy)-5-
To the compound 17 (140 mg, 0.76 mmol) in H
2
O (1 mL)
((tert-butyldiphenylsilyloxy)methyl)-5-hydroxycyclopent-2-enone
(20)
trifluoroacetic acid (2 mL) was added dropwise at 0 °C and stirred
at room temperature for 30 min. Then TFA was removed in vacuo
under reduced pressure to give a colourless syrup and it was pu-
rified by column chromatography using methylene chloride and
methanol (9:1) as eluent to give (+) pentenomycin I 18 (90 mg, 82%)
To a stirred solution of diol 19 (232 mg, 0.372 mmol) in
dichloromethane (10 mL) was added pyridinium dichromate
(560 mg, 1.48 mmol) and 4 Å molecular sieves (500 mg) at room tem-
perature and stirred under inert atmosphere for 5 h. The reaction
mixture was filtered in celite pad and the filtrate was dried under
vacuo to give the crude product. It was then purified by silica gel
column chromatography using hexane and ethyl acetate (5:0.2) as
eluent to give the cyclopentenone 20 (150 mg, 65%) as a colourless
25
14b
as a colourless syrup; [α]
D
D
+21.8 (c 0.35, MeOH) (lit. [α] +30.1
−
1
(
2
1
(
(
(
c 0.1, EtOH); R
f
0.3 (CH
2
Cl
2 3
:CH OH, 10:1); IR (KBr)vmax/cm : 3417,
929, 2851, 1750, 1715,1643, 1405, 1344, 1147, 1114, 1073, 1039,
1
026; H NMR (400 MHz, D
2
O): δ 3.63 (2H, dd, J = 12 Hz, 24 Hz), 4.73
13
1H, s), 6.35 (1H, d, J = 8 Hz), 7.75 (2H, dd, J = 4 Hz, 8 Hz); C NMR
2
5
100 MHz, D
m/z): calcd for C
2
O): δ 63.2, 71.6, 76.2, 133.4, 164.5, 209.8; HRMS (ESI)
viscous oil; [α]
D
+8.653 (c 0.08, CHCl
3
); R
f
0.6 (hexane:EtOAc, 10:1);
+
−1
6
H
8
O
4
[M + Na] 167.0320; found 167.0313.
IR (film)vmax/cm : 3492, 3070, 2956, 2929, 2857, 1729, 1467, 1427,

S. Das et al./Carbohydrate Research 416 (2015) 24–31
29
1
1
363, 1338, 1110, 1054, 1002; H NMR (400 MHz, CDCl
s), 1.07 (9H, s), 3.50 (1H, d, J = 8 Hz); 3.53 (1H, s); 3.97 (1H, d, J = 4 Hz);
.99 (1H, q, J = 4 Hz); 6.26 (1H, dd, J = 4 Hz, 8 Hz); 7.03 (1H, d, J = 4 Hz);
3
): δ 0.78 (9H,
CDCl
3
): δ 19.2, 26.7, 28.5, 28.6, 63.1, 82.1, 84.2, 115.3, 127.8, 127.9,
129.92, 129.94, 132.3, 132.9, 135.3, 135.5, 135.7, 160.2, 204.7;
HRMS (ESI) (m/z): calcd for C25
445.1806.
4
7
30 4
H O Si [M + Na]+ 445.1811; found
1
3
.25–7.49 (16H, m); 7.64 (2H, d, J = 8 Hz); 7.67 (2H, d, J = 4 Hz);
NMR (100 MHz, CDCl ): δ 19.2, 19.4, 26.7, 27.0, 64.9, 73.8, 74.3, 127.9,
28.3, 128.3, 129.89, 129.94, 130.7, 131.8, 132.6, 132.8, 132.9, 135.0,
C
3
1
1
C
35.6, 135.7, 135.8, 135.9, 160.6, 206.5; HRMS (ESI) (m/z): calcd for
4.14. (+)-(3aR,6aR)-3a-((tert-Butyldiphenylsilyloxy)methyl)-5-
iodo-2,2-dimethyl-3aH-cyclopenta[d][1,3]dioxol-4(6aH)-one (24)
+
38
H
44
O
4
Si
2
[M + Na] 643.2675; found 643.2684.
To a stirred solution of cyclopentenone 22 (1.5 g, 3.54 mmol) in
THF (15 mL) was added iodine (1.35 g, 5.31 mmol) at room tem-
perature under inert atmosphere. To this solution, pyridine (0.286 mL,
4
.11. (−) Pentenomycin I (4)
A buffered solution was prepared by addition of glacial acetic
3.54 mmol) was added at 0 °C and the reaction mixture was stirred
acid (0.03 mL, 0.587 mmol) to a solution of TBAF (0.340 mL,
.17 mmol). Then a stirred solution of cyclopentenone 20 (731 mg,
.17 mmol) in THF (10 mL) was treated with the previously pre-
at rt for 2 h. The reaction mixture was diluted with water. The organic
layer was extracted with methylene chloride, washed with brine,
dried over anhydrous Na SO , filtered and solvent was evaporated
2 4
1
1
pared buffer solution at 0 °C and stirred at rt for 1.5 h. Solvent was
removed in vacuo and the crude product was directly applied to silica
gel column chromatography and it was purified by using methy-
lene chloride and methanol (9:1) as eluent to give 4 (110 mg, 65%)
to give the crude product. It was then purified by silica gel column
chromatography using hexane and ethyl acetate (5:0.2) as eluent
to give the iodo substituted cyclopentenone 24 (1.75 g, 90%) as a
2
5
25
14b
colourless viscous oil; [α]
D
3 f
+27.442 (c 0.2, CHCl ); R 0.8
as a colourless syrup; [α]
c 0.29, EtOH); R 0.3 (CH
D
−23.396 (c 0.27, MeOH) (lit. [α]
D
−30.2
O):
−1
1
(hexane:EtOAc, 20:1); IR (film)vmax/cm : 3070, 2991, 2932, 2858,
(
f
Cl
2 2
:CH
3
OH, 10:1); H NMR (400 MHz, D
2
1
740, 1570, 1466, 1427, 1376, 1316, 1260, 1212, 1108, 1043, 1009;
δ 3.63 (2H, dd, J = 12 Hz, 24 Hz), 4.73 (1H, s), 6.35 (1H, d, J = 8 Hz),
.75 (2H, dd, J = 4 Hz, 8 Hz).
1
H NMR (400 MHz, CDCl
.79 (1H, d, J = 8 Hz); 4.12 (1H, d, J = 8 Hz); 5.19 (1H, d, J = 4 Hz); 7.38–
.45 (6H, m); 7.56–7.61 (4H, m); 8.06 (1H, d, J = 4 Hz); 13C NMR
100 MHz, CDCl ): δ 19.2, 26.7, 28.2, 28.4, 63.5, 81.9, 83.3, 106.4, 115.5,
3
): δ 0.97 (9H, s); 1.29 (3H, s), 1.35 (3H, s);
7
3
7
(
4
2
.12. (+)-(3aS,4S,6aR)-3a-((tert-Butyldiphenylsilyloxy)methyl)-
,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (21)
3
1
27.9, 129.9, 132.0, 135.5, 135.7, 165.3, 199.5; HRMS (ESI) (m/z): calcd
+
for C25
H
29IO
4
Si[M + Na] 571.0777; found 571.0772.
To a stirred solution of cyclopentenol 10 (1.54 g, 8.3 mmol) in
dichloromethane (15 mL) was added triethyl amine (3 mL, 20 mmol)
dropwise at 0 °C under inert atmosphere. Then TBDPSCl solution
4
.15. (+)-(3aR,6aR)-3a-(Hydroxymethyl)-5-iodo-2,2-dimethyl-3aH-
(2.39 mL, 9.13 mmol) was added dropwise at 0 °C followed by a cata-
cyclopenta[d][1,3]dioxol-4(6aH)-one (26)
lytic amount of DMAP and stirred for 24 h at rt. The reaction mixture
was partitioned between water and ethyl acetate, organic layer was
washed with brine, dried over anhydrous Na SO , filtered and solvent
2 4
A buffer solution was prepared by addition of acetic acid (0.05 mL,
.9 mmol) to TBAF (1M solution in THF, 1.82 mL, 1.82 mmol). To a
0
was removed under reduced pressure to provide the crude product.
It was then purified by silica gel column chromatography and it was
purified by using hexane and ethyl acetate (5:0.25) as eluent to give
a the mono-TBDPS protected product 21 (3.29 g, 93%) as a colourless
stirred solution of the compound 24 (1 g, 1.82 mmol) was added the
previously prepared buffer solution dropwise at 0 °C and stirred at
room temperature for 2.5 h. Solvent was removed in vacuo and the
crude product was directly applied to silica gel column chroma-
tography. Then it was purified by using hexane and ethyl acetate
2
5
viscous oil; [α]
D
3 f
+11.799 (c 0.1, CHCl ); R 0.3 (hexane:EtOAc, 9:1);
−
1
IR (film)vmax/cm : 3449, 3069, 2932, 2858, 1467, 1427, 1374, 1110;
(4:1) as eluent to give the iodocyclopentenone 26 (382 mg, 68%) as
1
H NMR (400 MHz, CDCl
3
): δ 1.03 (9H, s), 1.36 (9H, s), 1.38 (1H, s);
25
a yellow viscous oil; [α]
6
1
D
−1
3 f
+23.622 (c 0.1, CHCl ) R 0.3 (hexane:EtOAc,
2
.68 (1H, br s); 3.77 (2H, s); 4.59 (1H, s); 5.03 (1H, s); 5.92 (2H, q,
:1); IR (film)vmax/cm : 3450, 3065, 2990, 2935, 2875, 1733, 1568,
13
J = 4 Hz); 7.36–7.44 (m, 6H); 7.63–7.65 (4H, m); C NMR (100 MHz,
CDCl ): δ 19.5, 26.9, 29.0, 29.3, 64.5, 75.0, 86.1, 89.3, 113.4, 127.9,
457, 1377, 1318, 1243, 1213, 1159, 1111, 1078, 1054; 1H NMR
3
(
(
(
400 MHz, CDCl
3
): δ 1.31 (3H, s); 1.45 (3H, s); 2.49 (1H, br s); 3.88
1
30.01, 130.03, 132.9, 133.1, 133.3, 135.75, 135.81, 137.4; HRMS (ESI)
13
2H, q, J = 12 Hz); 5.22 (1H, d, J = 4 Hz); 8.07 (1H, d, J = 4 Hz); C NMR
100 MHz, CDCl ): δ 28.3, 28.6, 61.5, 82.4, 105.4, 115.7, 166.0, 199.3;
3
+
(m/z): calcd for C25
H
32
O
4
Si [M + Na] 447.1967; found 447.1965.
HRMS (ESI) (m/z): calcd for C
9
H
11IO
4
[M + Na]+ 332.9599; found
4
2
.13. (−)-(3aR,6aR)-3a-(((tert-Butyldiphenylsilyl)oxy)methyl)-
,2-dimethyl-3aH-cyclopenta[d][1,3]dioxol-4(6aH)-one (22)
332.9594.
To a stirred solution of the cyclopentenol 21 (250 mg, 0.588 mmol)
4.16. (+) Iodopentenenomycin I (28)
in dichloromethane was added pyridinium dichromate (886 mg,
.35 mmol) and 4 Å molecular sieves (100 mg) at room tempera-
2
The compound 26 (380 mg, 1.22 mmol) was treated with THF,
water and trifluoroacetic acid in 1:1:2 proportion at 0 °C and stirred
at rt for 2 h. Then TFA was removed in vacuo under reduced pres-
sure to give a colourless syrup and it was purified by column
chromatography using methylene chloride and methanol (20:1) as
ture and stirred under inert atmosphere for overnight. The reaction
mixture was filtered in celite pad and the filtrate was dried under
vacuo to give the crude product. It was then purified by silica gel
column chromatography using hexane and ethyl acetate (5:0.15)
as eluent to give the cyclopentenone 22 (197 mg, 79%) as a
eluent to give (+) iodopentenomycin I 28 (195 mg, 60%) as a yellow
2
5
25
colourless viscous oil; [α]
(
D
−0.671 (c 0.30, CHCl
3
); R
f
0.7
crystalline solid; mp 87.0–92.7 °C; [α]
0.4 (CH Cl :CH
D
+15.714 (c 0.07, MeOH);
−
1
−1
hexane:EtOAc, 10:1); IR (film)vmax/cm : 3071, 3050, 2995, 2957,
R
f
2
2
3
OH, 10:1); IR (film)vmax/cm : 3282, 2931, 2879,
2
1
932, 2891, 2858, 1731, 1589, 1471, 1427, 1381, 1372, 1343, 1270,
245, 1214, 1180, 1111, 1046; 1H NMR (500 MHz, CDCl
): δ 1.01
1730, 1632, 1570, 1447, 1402, 1371, 1266, 1193, 1159, 1096, 1065,
1
3
1003; H NMR (400 MHz, D
d, J = 12 Hz); 4.78 (1H, d, J = 4 Hz); 8.25 (1H, d, J = 4 Hz); C NMR
2
O): δ 3.66 (1H, d, J = 12 Hz); 3.75 (1H,
13
(
9H, s); 1.35 (3H, s); 1.39 (3H, s); 3.83 (1H, d, J = 10 Hz); 4.10 (1H,
d, J = 10 Hz); 5.32 (1H, s); 6.39 (1H, d, J = 5 Hz) 7.40–7.48 (6H, m);
.63–7.67 (4H, m); 7.72 (1H, dd, J = 5 Hz, 10 Hz); 13C NMR (125 MHz,
(100 MHz, D
(m/z): calcd for C
2
O): δ 63.3, 72.9, 74.7, 102.8, 169.9, 204.8; HRMS (ESI)
+
7
6 7
H O
4
I [M + Na] 292.9286; found 292.9274.

30
S. Das et al./Carbohydrate Research 416 (2015) 24–31
4
.17. (+)-(3aR,6aR)-5-Chloro-3a-(hydroxymethyl)-2,2-dimethyl-
filtered and solvent was removed under reduced pressure to provide
the crude product. It was then purified by silica gel column chro-
matography using hexane and ethyl acetate (3:1) as eluent to give
the diol 30 (652 mg, 64% (bsr)) as a white crystalline solid; mp 55.7–
3aH-cyclopenta[d][1,3]dioxol-4(6aH)-one (25)
To a stirred solution of cyclopentenone 17 (287 mg, 1.558 mmol)
2
5
in dichloromethane (10 mL) were added bis-acetoxyiodobenzene
602.2 mg, 1.87 mmol) and pyridinium hydrochloride (432.1 mg,
.74 mmol) at room temperature and stirred for 6 h. Pyridine was
57.2 °C; [α]
D
3 f
+11.682 (c 0.1, CHCl ); R 0.5 (hexane:EtOAc, 4:1); IR
−1
(
3
(film)vmax/cm : 3372, 3074, 3036, 3012, 2958, 2936, 2894, 2860,
1
1721, 1592; H NMR (500 MHz, CDCl
3
): δ 1.02 (9H, s); 3.05 (1H, s);
removed in vacuo and after the addition of water, the mixture was
extracted with methylene chloride. The combined organic layer was
3.41 (1H, s); 3.74 (1H, d, J = 10 Hz); 3.85 (1H, d, J = 10 Hz); 4.85 (1H,
s); 6.36 (1H, d, J = 5 Hz); 7.39–7.48 (6H, m); 7.60–7.65(4H, m); 7.68
1
3
washed with brine, dried over anhydrous Na
2
4
SO , filtered and evapo-
(1H, dd, J = 5 Hz, 10 Hz); C NMR (125 MHz, CDCl
3
): δ 19.2, 26.7,
rated under reduced pressure to give a crude product. It was then
purified by silica gel column chromatography using hexane and ethyl
acetate (6:1) as eluent to give the chloro derivative 25 (51 mg, 15%)
65.3, 72.5, 74.7, 127.85, 127.89, 130.0, 132.3, 132.6, 133.9, 135.57,
26 4
135.62, 162.8, 206.4; HRMS (ESI) (m/z): calcd for C22H O
Si [M + Na]+
405.1498; found 405.1499.
2
5
as a colourless viscous oil; [α]
D
3 f
+23.952 (c 0.16, CHCl ); R 0.8
−1
(hexane:EtOAc, 1:1); IR (film)vmax/cm : 3472, 3075, 2992, 2938, 2878,
4.21. (+)-(3aR,6aR)-3a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-
1
740, 1592, 1458, 1376, 1321, 1269, 1243, 1215,1164, 1096, 1053;
dimethyl-3aH-cyclopenta[d][1,3]dioxol-4(6aH)-one (31)
1
H NMR (400 MHz, CDCl
3
3
): δ 1.34 (3H, s), 1.47 (3H, s); 1.99 (1H, s);
13
.89 (2H, s); 5.24 (1H, d, J = 4 Hz); 7.58 (1H, d, J = 4 Hz); C NMR
To a stirred solution of the cyclopentenol 30 (976.9 mg,
(
1
100 MHz, CDCl
96.7; HRMS (ESI) (m/z): calcd for C
3
): δ 28.5, 28.7, 61.6, 78.9, 84.4, 115.7, 137.9, 153.4,
2
.553 mmol) in dichloromethane were added pyridinium dichro-
+
9
H
11
O
4
Cl [M + Na] 241.0243;
mate (3.843 g, 10.21 mmol) and 4 Å molecular sieves (100 mg) at
room temperature and stirred under inert atmosphere for 5 h. The
reaction mixture was filtered in celite pad and the filtrate was dried
under vacuo to give the crude product. It was then purified by silica
gel column chromatography using hexane and ethyl acetate (3:1)
found 241.0242.
.18. (+) Chloropentenenomycin I (27)
The compound 25 (100 mg, 0.457 mmol) was treated with
4
as eluent to give the cyclopentenone 31 (368.9 mg, 38%) as a yellow
THF, water and trifluoroacetic acid in 1:1:2.5 proportion at 0 °C
and stirred at rt for 12 h. Then TFA was removed in vacuo under
reduced pressure to give a colourless syrup and it was purified by
column chromatography using methylene chloride and methanol
25
crystalline solid; mp 129.9–131.4 °C; [α]
R
f
D
3
+2.077 (c 0.09, CHCl );
−1
0.5 (hexane:EtOAc, 3:1); IR (KBr)vmax/cm : 3482, 3063, 3028, 2957,
2
928, 2892, 2858, 1756, 1708, 1465, 1427, 1385, 1360, 1331, 1117;
1
H NMR (500 MHz, CDCl
3
): δ 0.91 (9H, s); 3.01 (1H, d, J = 10 Hz); 3.84
(
20:1) as eluent to give (+) chloropentenomycin I 27 (22 mg, 27%)
13
(2H, s); 7.35–7.43 (6H, m); 7.45 (2H, s); 7.49–7.51 (4H, m); C NMR
25
as a colourless viscous oil; [α]
(
D
f
+25.714 (c 0.07, MeOH); R 0.8
(
1
4
3
125 MHz, CDCl ): δ 19.1, 26.6, 63.5, 74.1, 127.9, 130.1, 131.8, 135.5,
−
1
CH
2
Cl
2
:CH
3
OH, 10:1); IR (film)vmax/cm : 3417, 1727, 1637,
276, 1073; H NMR (400 MHz, D
Si [M + Na]+
49.7, 202.5; HRMS (ESI) (m/z): calcd for C22H O
24 4
1
1
3
2
O): δ 3.70 (1H, d, J = 12 Hz);
03.1341; found 403.1340.
.79 (1H, d, J = 12 Hz); 4.82 (1H, d, J = 4 Hz); 7.81(1H, d, J = 4 Hz);
13
C NMR (100 MHz, D
2
O): δ 63.4, 69.7, 76.3, 136.4, 157.5, 201.9;
4.22. Dehydropentenomycin (5)
+
HRMS (ESI) (m/z): calcd for C
6
H
7
O
4
Cl [M + Na] 200.9930; found
2
00.9925.
A buffered solution was prepared by addition of glacial acetic
acid (0.022 mL, 0.383 mmol) to a solution of TBAF (0.228 mL,
4.19. (+)-(1R,2S,3S)-2-(((tert-Butyldiphenylsilyl)oxy)methyl)
0.784 mmol). Then a stirred solution of cyclopentenone 31 (300 mg,
cyclopent-4-ene-1,2,3-triol (29)
0.788 mmol) in THF (10 mL) was treated with the previously pre-
pared buffer solution at 0 °C and stirred at rt for 4.5 h. Solvent was
removed in vacuo and the crude product was directly applied to
silica gel column chromatography and it was purified by using
methylene chloride and methanol (8:1) as eluent to give
dehydropentenomycin 5 (95 mg, 85%) as a yellow viscous liquid;
The cyclopentenol 21 (3.29 g, 7.74 mmol) was treated with THF,
water and trifluoroacetic acid in 3:3:4 proportion at 0 °C and stirred
for 1.5–2 h. The reaction mixture was neutralized by addition of
NaHCO
bined organic layer was washed with brine, dried over anhydrous
Na SO , filtered and solvent was removed under reduced pressure
3
and partitioned between water and ethyl acetate. The com-
−1
R
f
0.5 (CH
2
Cl
2
:CH
3
OH, 10:1); IR (film)vmax/cm : 3384, 2937, 1754,
2
4
1
1
707, 1638, 1331, 1126, 1055, 1033; H NMR (400 MHz, acetone-
to provide the crude product. It was then purified by silica gel column
chromatography and it was purified by using hexane and ethyl
acetate (3:1) as eluent to give the triol 29 (3.29 g, 93%) as a white
d
6
): δ 3.79 (2H, d, J = 5.2 Hz); 4.28 (1H, t, J = 5.2 Hz); 5.17 (1H, s);
13
7
.51(2H, s); C NMR (100 MHz, acetone-d
HRMS (ESI) (m/z): calcd for C
[M + Na]+ 165.0163; found
65.0154.
6
): δ 63.6, 74.1, 149.6, 205.2;
6 4
H O
2
5
6
crystalline solid; mp 110.4–111.6 °C; [α]
D
−
3 f
+0.744 (c 0.1, CHCl ); R
1
1
0
.3 (hexane:EtOAc, 1:1); IR (film)vmax/cm : 3468, 3390, 3132, 3052,
1
2
955, 2923, 2892, 2857, 2745, 2713; H NMR (400 MHz, CDCl
3
): δ
Acknowledgements
1
.06 (9H, s); 2.68 (2H, br s); 3.74 (2H, s); 4.48 (2H, s); 5.84 (2H, s);
13
3
7.36–7.44 (6H, m); 7.64–7.66 (4H, m); C NMR (100 MHz, CDCl ):
This work is partially supported by Prof. G. N. Mohapatra award,
Utkal University, Bhubaneswar Dev-I/R&D-50/8770/12. The authors
thank CIF NMR facility, IIT Bhubaneswar. A junior research fellow-
ship to SD from Department of Science and Technology (DST-
INSPIRE /2012/517), New Delhi is gratefully acknowledged.
δ 19.4, 27.1, 66.8, 76.3, 79.9, 128.0, 130.1, 133.1, 134.3, 135.8; HRMS
+
28 4
(ESI) (m/z): calcd for C22H O Si [M + Na] 407.1654; found 407.1651.
4.20. (+)-(4R,5R)-5-(((tert-Butyldiphenylsilyl)oxy)methyl)-4,5-
dihydroxycyclopent-2-enone (30)
The cyclopentenone 22 (2.58 g, 6.1 mmol) was treated with THF,
water and trifluoroacetic acid in 1:1:3 proportion at 0 °C and stirred
Appendix: Supplementary material Spectral data and X-ray
crystallographic data
for 3.5 h. The reaction mixture was neutralized by addition of NaHCO
and partitioned between water and ethyl acetate. The combined
4
organic layer was washed with brine, dried over anhydrous Na SO ,
3
Supplementary data to this article can be found online at
doi:10.1016/j.carres.2015.08.003.
2

S. Das et al./Carbohydrate Research 416 (2015) 24–31
31
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