Synthesis of fused pyran-carbahexopyranoses as glycosidase inhibitors

Article abstract of DOI:10.1016/j.carres.2009.01.017

Synthesis of polyhydroxylated oxabicyclo[4,4,0]decanes, which constitute a new family of annulated carbasugars, has been accomplished in a stereoselective manner by employing readily available 1,2-anhydro-3,4,6-tri-O-benzyl-α-d-glycopyranoses.

Full text of DOI:10.1016/j.carres.2009.01.017

Carbohydrate Research 344 (2009) 606–612
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of fused pyran-carbahexopyranoses as glycosidase inhibitors
*
Venkata Ramana Doddi, Pavan K. Kancharla, Y. Suman Reddy, Amit Kumar, Yashwant D. Vankar
Department of Chemistry, Indian Institute of Technology Kanpur, 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis of polyhydroxylated oxabicyclo[4,4,0]decanes, which constitute a new family of annulated
carbasugars, has been accomplished in a stereoselective manner by employing readily available 1,2-
Received 16 September 2008
Received in revised form 16 January 2009
Accepted 18 January 2009
anhydro-3,4,6-tri-O-benzyl-
a
-
D-glycopyranoses.
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 23 January 2009
Keywords:
Carbasugars
Hybrid sugars
Glycosidase inhibitors
OH
1. Introduction
O
A
O
OH
OH
OH
OH
HO
OH
OH
HO
HO
HO
HO
B
Carbasugars, also called as pseudosugars 11,2 (Fig. 1), have struc-
tural similarities with monosaccharides except that the ring oxy-
gen is replaced by a methylene group. Carbasugars, especially
pseudo-b-fructopyranoses, have been found to be useful as artifi-
cial sweeteners,1–3 and they also occur in nature as part of the
structure of antibiotics validamycins.1a,e,f More importantly, they
act as glycosidase inhibitors,1a,4 molecules of high current interest5
both from synthetic and medicinal points of view. For example,
OH
OH
OH
OH
HO
OH
2
1
HO
OH
OH
OH
OH
HO
OH
OH
OH
OH
OH
acarbose,5 a tetrasaccharide and an
a-glucosidase inhibitor that
5
4
3
is being used as an antidiabetic drug, contains a carba-amino sugar
moiety as its integral and active part. More recently,6 the synthetic
carbasugar derivative oseltamivir, popularly known as Tamiflu, is
being used as a drug against influenza. Because of these important
developments, it is desirable to synthesize derivatives of carbasu-
gars for improved/or selective activity as glycosidase inhibitors. Ef-
forts in this direction are already underway,1,4 including the recent
notable reports by Shing et al.7 on the synthesis of carbasugar
derivatives as potent glycosidase inhibitors.
Figure 1.
2. Results and discussion
Our synthesis emanated from 1,2-anhydro-3,4,6-tri-O-benzyl-
-D-glucopyranose (7), which can be easily obtained from tri-O-
a
benzyl-glucal 6, by reaction with in situ generated dimethyldioxi-
rane (DMDO) using a known procedure developed by Dondoni
et al.11 A regio- and stereospecific ring opening of oxirane 7 with
allyl magnesium chloride in THF at 0 °C gave an alcohol 8 as a sin-
gle diastereomer.12 Alcohol 8 was oxidized with DMSO–Ac2O to af-
ford ketone 9,13 which was subjected to a Grignard reaction with
allyl magnesium bromide in THF affording a separable mixture of
In continuation of our ongoing program8 on synthesizing new
glycosidase inhibitors, we report in this paper the synthesis of a
new class of fused pyran-carbahexopyranoses (2, Fig. 1) as glycosi-
dase inhibitors. These compounds can be considered as a hybrid9 of
a normal sugar A (Fig. 1) and a carbasugar derivative B.10 The three
fused pyran-carbahexopyranoses 17, 19 and 29 have been synthe-
sized from oxiranes 7 (Scheme 1) and 22 (Scheme 2) and they
show moderate inhibitions of glycosidases.
tertiary alcohols 10 and 11 (9:1 ratio, 65%) in favor of the D-manno
configured isomer 10. The major diene 10 has the allyl group at C-2
equatorially oriented and it is trans to the anomeric allyl group, as
expected,14 and it is characterized by 1H NMR and nOe spectral
analysis. Its 1H NMR spectrum showed a clean doublet at d 3.55
with J = 9.0 Hz indicating that proton H-4 couples only with H-5
* Corresponding author. Fax: +91 512 259 0007.
E-mail address: vankar@iitk.ac.in (Y.D. Vankar).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.01.017

V. R. Doddi et al. / Carbohydrate Research 344 (2009) 606–612
607
OBn
O
OBn
O
OBn
O
Ref 12
Cl
DMSO
Ac2O
BnO
BnO
BnO
BnO
BnO
BnO
Mg,THF, 0 o
C
OH
O
6
8
7
OBn
OBn
O
OBn
7
OH
O
10
8
OH
BnO
BnO
BnO
BnO
Grubbs' catalyst
Br
2
O
BnO
10
THF, -78 oC
9
4
DCM
89%
BnO
Mg,
O
12
13
H
11
60%
+
H
9
12
(5%)
10
13
OBn
OR
O
H11
O
BnO
H5
OBn
12
OR
BnO
BnO
OSO4, NMO
86% (4:1)
BnO
BnO
O
BnO
BnO
10
OR
2
8
OR
4
9
OH
11
OR
OR
13 R=H
14
R=H 15
R=Ac 16
Ac2O,
Et3N
92%
Ac2O,
Et3N
94%
R=Ac
OAc
OAc
O
OH
OBn
OH
OH
3
Ac2O, Et3N
DMAP
93%
Pd(OH)2/C
O
HO
HO
AcO
AcO
O
BnO
BnO
8a
5 atm, H2,
EtOH, 98%
4a
4
7
AcO
HO
OH
HO
OH
OAc
OH
18
17
13
OAc
H8a H7
OH
O
4
OAc
OAc
8
2
4a
OH
AcO
5
OH
OAc
4
OAc
OH
OH
O
OAc
OAc
H8a H7
Pd(OH)2/C
OAc
3
Ac2O, Et3N
OH
O
4
OAc
OAc
HO
HO
15
O
OAc
8
AcO
AcO
2
5 atm, H2,
EtOH, 98%
OH
8
DMAP
91%
8a
OAc
4a
20
4a
6
AcO
6
OAc
19
OAc
OH
OH
HO
OH
5
Scheme 1.
and thus must be trans diaxial to each other. Proton H-11 appeared
as a doublet of doublets at d 2.67 with J = 14.1, 7.3 Hz, and proton
H-12 appeared as a multiplet at d 5.66–5.55. In an nOe experiment,
when the signal for proton H-11 was irradiated, the signal for H-4
was enhanced along with the signals for H-110and H-12 suggesting
that the C-2 allyl group is in the equatorial position. When H-12
proton was irradiated, signals corresponding to H-4 and H-2 were
enhanced along with the signals for H-11 and H-13, which further
confirmed that the C-2 allyl group of the major compound 10 is in
equatorial position.
Likewise, the structure of the minor compound 11 was estab-
lished on the basis of its spectral data (cf. Supplementary data)
including COSY and nOe experiments. All protons were identified
based on the 1H NMR and COSY spectral data. As expected, its 1H
NMR spectrum showed a doublet for proton H-4 at d 3.54 with
J = 9.7 Hz indicating that H-4, being coupled only with H-5, must
be trans diaxial to each other. Proton H-5 appeared at d 3.64 as a
doublet of doublets with J = 9.7, 10.8 Hz, and the allylic proton H-
11 of C-2 allyl group appeared at d 2.64-2.62 as a multiplet. In an
nOe experiment, when the signal for proton H-11 was irradiated
the signal for H-5 was enhanced, and there was no enhancement
of signals corresponding to H-4 and H-2 suggesting that C-2 allyl
group is in axial position. The signal corresponding to H-2 ap-
peared at d 3.27 as a doublet of doublet with J = 9.0, 2.2 Hz. Irradi-
ation of the H-2 proton signal resulted in the enhancement of
signals corresponding to H-4 and H-6, but there was no enhance-
ment of signals corresponding to H-11 and H-12. This further con-
firmed that the C-2 allyl group of the minor compound 11 is in
axial position.
Ring closing metathesis of diene 10 using the first-generation
Grubbs’ catalyst (1 mol %)15 at ambient temperature afforded the
expected cyclized product 12 in 89% yield (Scheme 1). The pres-

608
V. R. Doddi et al. / Carbohydrate Research 344 (2009) 606–612
OBn
O
BnO
BnO
BnO
BnO
BnO
BnO
OBn
O
OBn
O
Ref 12
DMSO
Cl
Ac2O
69%
Mg,THF, 0 oC
72%
OH
O
21
23
22
Br
OBn
BnO
OBn
BnO
BnO
7
OBn
O
OH
O
BnO
BnO
OH
10
8
5
BnO
Grubbs' catalyst
THF, -78 o
61%
C
O
Mg,
2
DCM
89%
4
9
12
13
O
11
H
H
24
26
25
OBn
OH
O
OBn
OH
BnO
BnO
BnO
BnO
O
OSO4, NMO
86%
Ac2O,
Et3N
94%
HO
AcO
OH
28
OAc
27
OH
OH
O
OAc
OH
OAc
HO
HO
AcO
3
H8a H7
8
Ac2O, Et3N
O
4
OAc
OAc
2
Pd(OH)2/C
O
2
8a
8a
4a
OH
8
7
27
DMAP
90%
AcO
5 atm, H2,
EtOH, 98%
4a
4
5
AcO
5
HO
AcO
OH
29
OAc
OAc
30
OH
OH
HO
4
OH
Scheme 2.
ence of only two olefinic protons at d 5.68 as a broad singlet for two
protons in its 1H NMR spectrum confirmed the formation of the ex-
pected cyclized product. Dihydroxylation of 12 was performed
using a catalytic amount of OsO4 in the presence of N-methylmor-
pholine-N-oxide (NMO), which afforded a diastereomeric mixture
of triols 13 and 15 in 4:1 ratio in 86% yield. These triols were char-
acterized as their triacetates 14 and 16, respectively. The absolute
stereochemistry of the newly generated stereocenters C-6 and C-7
of compounds 13 and 15 was confirmed from the nOe experiments
of the hexaacetates 18 and 20, respectively, which were obtained
later.
Bicyclic triols 13 and 15 were subjected to debenzylation on
treatment with 20% Pd(OH)2–C in methanol at 5 atm H2 to give
the hybrid molecules 17 and 19, both in 98% yield. The annulated
carbasugars 17 and 19 were further characterized as their perace-
tates 18 and 20, which were obtained in 93% and 91% yields,
respectively. The stereochemistry of the major isomer 18 was de-
duced from the absence of nOe correlation between protons H-7
and H-8a showing the anti-relationship between them, which fur-
ther suggested that dihydroxylation of the olefin 12 had taken
place selectively at the lower face of the double bond present in
the carbasugar moiety. Interestingly, the proton H-8a appeared
as a broad singlet at d 4.48, although it should have appeared as
a doublet of doublet with a coupling constant typical for a diaxial
and axial–equatorial coupling if the ring was in chair conforma-
tion. Clearly, the conformation is distorted, and does not permit
such couplings. At this stage, however, the identity of conforma-
tion is unclear. The stereochemistry of the minor isomer 20 was
confirmed from the observed nOe correlation between protons
with 3-deoxy-b-
way follows the same sequence as was used for the synthesis of
hybrids 17 and 19 from 3,4,6-tri-O-benzyl- -galactal 6. Thus, oxi-
rane 23 upon reaction with allyl magnesium chloride led to the for-
mation of the known16 olefinic alcohol 23 in 72% yield. Oxidation
of the alcohol 23 with DMSO–Ac2O led to the formation of the
ulose 24, which upon treatment with allyl magnesium bromide
in THF at ꢀ78 °C formed alcohol 25 as a single diastereomer, which
could be isolated in 61% yield after chromatography. The assigned
D-manno-carbasugar analog 4. The synthetic path-
D
structure of the tertiary alcohol 25 (D-talo configured) was con-
firmed by 1H NMR and nOe spectral analysis (Scheme 2). Chemical
shifts of protons were identified based on the 1H NMR and COSY
spectral data. The 1H NMR spectrum of compound 25 showed a
clean doublet at d 3.34 with J = 2.6 Hz indicating that H-4 that
can have coupling with only H-5 must have axial, equatorial rela-
tionship between them. In an nOe experiment, when the signal for
proton H-4 was irradiated the signals for H-2, H-11 and H-12 were
enhanced along with those for H-6 and H-13 confirming that C-2
allyl group is in equatorial position. Diene 25 was then dihydroxyl-
ated using OsO4/NMO which gave a single diastereomer 27, which
was characterized as the diacetate 28, obtained in 94% yield. The
stereochemistry of the newly generated stereocenters was, how-
ever, established by nOe analysis of the pentaacetate, which was
obtained later. Debenzylation of 28 with Pd(OH)2–C and hydrogen
gave the desired target molecule 29 in 98% yield, which was char-
acterized from its spectral data (see experimental section). Per-
acetylation of hybrid 29 under standard acetylation conditions
afforded the pentaacetate 30 in 90% yield instead of the expected
hexaacetate, as confirmed from its mass spectrum, in addition to
other spectral data, which showed HRMS [M+H]+ peak at
461.1659 (calculated 461.1654). This may be attributed to the fact
that the tertiary alcohol was not acetylated due to developing 1,3-
diaxial steric hindrance in the galactal ring. The stereochemistry of
compound 30 was deduced from the absence of an nOe correlation
between protons H-7 and H-8a showing an anti-relationship be-
tween them. These data further suggested that dihydroxylation
H-7 and H-8a. Compound 17 represents a hybrid of
and 3-deoxy-b-
-manno-carbasugar analog 411 (Fig. 1 and Scheme
1), the diastereomeric bicyclic carbasugar 19 represents a hybrid of
-mannose and 3-deoxy-
-gluco derivative 511 as shown in
Scheme 1.
Likewise, compound 29 (Scheme 2) was synthesized from 3,4,6-
tri-O-benzyl- -galactal 21, and it represents a hybrid of -talose
D-mannose
D
D
a-D
D
D

V. R. Doddi et al. / Carbohydrate Research 344 (2009) 606–612
609
Table 1
solution was further stirred for 30 min at ambient temperature
to give a solution of allylmagnesium bromide in THF. This freshly
prepared reagent was added to a solution of ketone (472 mg, 1
mmol) in THF (5 mL) at ꢀ78 °C and stirred at the same tempera-
ture for 1 h. The reaction mixture was quenched by the addition
of a satd aq soln of NH4Cl (15 mL). The aq layer was extracted with
ether (2 ꢁ 15 mL), and the combined organic extracts were washed
with brine (15 mL), dried over MgSO4, and concentrated in vacuo,
and the crude product was purified by silica gel chromatography.
IC50 (mM) values for compounds 17, 19, and 29a
Enzyme
-Glucosidase (yeast)
b-Glucosidase (almonds)
-Galactosidase (coffee beans)
b-Galactosidase (bovine)
17
19
29
a
NI
NI
NI
NI
NI
NI
NI
NI
0.73 mM
NI
NI
NI
1.68 mM
1.20 mM
NI
a
a-Mannosidase (Jack beans)
a
Inhibition studies were carried out at millimolar concentration, optimal pH of
the enzymes, and at 37 °C. NI: no inhibition at 5 mM concentration of the inhibitor.
3.3. General procedure (B): ring closing metathesis reaction
of olefin 26 had taken place only at the a-face of the double bond
present in the carbasugar part as shown in Scheme 2.
To a stirred solution of diene (514 mg, 1 mmol) in dry CH2Cl2 at
room temperature was added Grubbs’ first-generation catalyst
(6 mg, 1 mol %). The mixture was stirred for 5 h and after comple-
tion of the reaction (TLC monitoring), the solvent was evaporated
under reduced pressure, and the crude product was purified by col-
umn chromatography to give the desired cyclized compound.
2.1. Enzyme inhibition studies
In summary, we have synthesized three new polyhydroxylated
oxabicyclo[4,4,0]decanes 17, 19, and 29, which represent hybrids
of
D-mannose and D-talose with 3-deoxy-carbasugar analogs (4
and 5). These compounds are found to be moderate glycosidase
inhibitors. It is possible to improve the inhibition activity by appro-
priately changing the structural features of these molecules.
Preliminary screening of the three annulated carbasugars 17,
3.4. General procedure (C): dihydroxylation using OsO4–NMO
To a stirred solution of olefin (486 mg, 1 mmol) in a mixture of
acetone, water, and t-BuOH (1:1:0.4, 5 mL) at room temperature
were added NMOꢂH2O (162 mg, 1.2 mmol) and a catalytic amount
19, and 29 was carried out against five common glycosidases:
a-
glucosidase (EC 3.2.1.20), b-glucosidase (EC 3.2.1.21),
dase (EC 3.2.1.22), b-galactosidase (EC 3.2.1.23), and
a
a
-galactosi-
-mannosi-
of OsO4 (10 lL of 2% t-BuOH solution). The reaction mixture was
stirred for 24 h, and then it was treated with Na2S2O5 (228 mg,
1.2 mmol). The reaction mixture was stirred for further 1 h and ex-
tracted with EtOAc (2 ꢁ 15 mL). The combined organic extracts
were washed with 1 N HCl (10 mL), water, and finally with brine,
and the organic layer dried over Na2SO4. Removal of the solvent
under reduced pressure gave a residue that was purified by column
chromatography to obtain the dihydroxylated product.
dase (EC 3.2.1.24), which accept the corresponding p-nitrophenyl
glycosides as their substrates.17 Hybrid 17 exhibited no significant
inhibition against these enzymes even at 5 mM concentration.
However, annulated carbasugar 19 showed moderate inhibition
only against b-galactosidase at a concentration of 0.73 mM (Table
1). Compound 29 showed less inhibition against
a-galactosidase
at a concentration of 1.68 mM and against b-galactosidase at a con-
centration of 1.20 mM as shown in Table 1. This suggests further
screening to be carried out against a wider range of glycosidases
to assess the potential of these compounds.
3.5. General procedure (D): deprotection of benzyl groups
The cyclized product (260 mg, 0.5 mmol) was dissolved in
10 mL of MeOH, 20% Pd(OH)2–C (100 mg) was added, and this mix-
ture was shaken under 5 atm H2 for 30–35 h at room temperature.
The catalyst was filtered through Celite, and the mixture was con-
centrated in vacuo to obtain the target hybrid molecules.
3. Experimental
3.1. General methods
IR spectra were recorded with an FTIR as a thin film or by using
3.6. General procedure (E): acetylation of alcohols
KBr pellets, and are expressed in cmꢀ1 1H (400 or 500 MHz) and
.
13C (100 or 125 MHz) NMR spectra were recorded using CDCl3 as a
solvent. The stereochemistry of the compounds was assigned with
the help of nOe experiments. Chemical shifts are reported in ppm
downfield to tetramethylsilane. Coupling constants are reported
and expressed in Hertz; splitting patterns are designated as br
(broad), s (singlet), d (doublet), dd (double doublets), ddd (doublet
of a doubletof doublets), and m(multiplet). Elementalanalyseswere
carriedouton a ThermoquestCE-instruments EA-1110C, H, N, S ana-
lyzer. Rotation values were recorded on Autopol II automatic polar-
imeter at the wavelength of sodium D-line (589 nm) at 25 °C. All
reactions were carried out using freshly distilled and dry solvents.
The visualization of spots on TLC plates was effected by exposure
to iodine or by spraying with 10% H2SO4 and charring. Column chro-
matography was performed over silica gel (100–200 Mesh) using
hexane and ethyl acetate as eluent. The mass spectra were recorded
on a Micromass Quattro II Triple Quadrupole Mass Spectrometer.
An alcohol was subjected to acetylation with excess of triethyl-
amine, Ac2O (1:1, 2 mL), and a catalytic amount of N,N-dimethyl-4-
aminopyridine (DMAP) at room temperature for 10 h. Removal of
the solvent under reduced pressure gave a residue that was puri-
fied by column chromatography to obtain an acetylated product.
3.7. Allylation of compound 9
2-Ulose 9 (472 mg, 1 mmol) was allylated with allylmagnesium
bromide using the general procedure A to give 10 (308 mg, 60%)
and 11 (26 mg, 5%) as a separable mixture of diastereomers (9:1).
3.7.1. (2S,3R,4S,5R,6R)-2,3-Diallyl-4,5-bis(benzyloxy)-6-
(benzyloxymethyl) tetra-hydro-2H-pyran-3-ol (10)
(Yield: 60%). Rf = 0.6 (hexane–EtOAc 9:1). Colorless oil, aD28
ꢀ36.3 (c 0.5, CH2Cl2). IR (CH2Cl2)
m
max: 3550, 3062, 3028, 2868,
;
1638, 1110, 1049, 913, 753, 698 cmꢀ1
1H NMR (400 MHz, CDCl3):
3.2. General procedure (A): allylation of 2-uloses with Grignard
reagents
d 7.36–7.17 (m, 15H, Ar-H), 6.00–5.90 (m, 1H, H-9), 5.66–5.55 (m,
1H, H-12), 5.14–4.96 (m, 4H, H-10, H-100, H-13, H-130), 4.99 (d, 1H,
J = 10.9 Hz, –OCH2Ph), 4.76 (d, 1H, J = 10.7 Hz, –OCH2Ph), 4.74 (d,
1H, J = 10.7 Hz, –OCH2Ph), 4.66–4.55 (m, 3H, –OCH2Ph), 3.87 (dd,
1H, J = 9.5, 9.0 Hz, H-5), 3.76 (dd, 1H, J = 11.0, 1.9 Hz, H-7), 3.70
(dd, 1H, J = 11.0, 4.8 Hz, H-70), 3.55 (d, 1H, J = 9.0 Hz, H-4), 3.37
To a stirred mixture of THF (5 mL), Mg (58.3 mg, 2.4 m atom)
and a catalytic amount of I2 at 0 °C was added allyl bromide
(0.1 mL, 1.2 mmol). After disappearance of the color of iodine, the

610
V. R. Doddi et al. / Carbohydrate Research 344 (2009) 606–612
(ddd, 1H, J = 9.5, 4.6, 1.7 Hz, H-6), 3.32 (dd, 1H, J = 9.7, 2.6 Hz, H-2),
2.67 (dd, 1H, J = 14.1, 7.3 Hz, H-11), 2.52–2.32 (m, 2H, H-8, H-80),
2.26 (dd, 1H, J = 14.1, 7.3 Hz, H-110); 13C NMR (100 MHz, CDCl3):
d 138.3, 138.1, 138.0, 135.8, 132.1, 128.4–127.4 (m), 119.0, 116.2,
82.4, 79.6, 79.4, 77.8, 76.1, 75.3, 74.8, 73.4, 69.1, 39.2, 32.4. ESMS:
m/z 537 [M+Na]+. Anal. Calcd for C33H38O5: C, 77.01; H, 7.44.
Found: C, 77.03; H, 7.42.
2.62–2.57 (m, 1H, H-50), 2.55 (dd, 1H, J = 1.2, 1.0 Hz, H-8), 2.35
(dd, 1H, J = 8.0, 1.0 Hz, H-5), 2.09 (s, 3H, –COCH3), 1.99 (s, 3H,
–COCH3), 1.99–1.95 (m, 1H, H-80), 1.91 (s, 3H, –COCH3); 13C NMR
(125 MHz, CDCl3): d 170.2, 170.0, 169.9, 138.4, 138.1, 137.9,
128.3–127.5 (m), 82.7, 82.3, 79.3, 77.9, 75.1, 74.9, 73.3, 72.9,
68.8, 67.4, 67.3, 29.6, 26.6, 22.4, 21.2, 21.0. ESMS: m/z 669
[M+Na]+. Anal. Calcd for C37H42O10: C, 68.71; H, 6.55. Found: C,
68.69; H, 6.58.
3.7.2. (2S,3S,4S,5R,6R)-2,3-Diallyl-4,5-bis(benzyloxy)-6-
(benzyloxymethyl)tetra-hydro-2H-pyran-3-ol (11)
3.9.2. (2R,3R,4S,4aR,6S,7R,8aS)-3,4-Bis(benzyloxy)-2-
(benzyloxymethyl)octahydro-2H-chromene-4a,6,7-triyl
triacetate (16)
(Yield: 5%). Rf = 0.55 (hexane–EtOAc 9:1). Colorless oil. aD28
ꢀ18.3 (c 0.5, CH2Cl2). IR (CH2Cl2)
m
max: 3552, 3064, 3029, 2920,
2860, 1640, 1496, 1108, 1049, 913, 753, 697 cmꢀ1
;
1H NMR
(Yield: 92%). Rf = 0.38 (hexane–EtOAc, 4:1). Colorless oil. aD28
(400 MHz, CDCl3): d 7.39–7.13 (m, 15H, Ar-H), 6.12–6.01 (m, 1H,
H-12), 5.96–5.83 (m, 1H, H-9), 5.17–5.01 (m, 4H, H-10, H-100, H-
13, H-130), 4.90 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.79 (d, 1H,
J = 11.7 Hz, –OCH2Ph), 4.77 (d, 1H, J = 10.9 Hz, –OCH2Ph), 4.64 (d,
1H, J = 12.0 Hz, –OCH2Ph), 4.54 (d, 1H, J = 12.0 Hz, –OCH2Ph), 4.49
(d, 1H, J = 10.9 Hz, –OCH2Ph), 3.79–3.63 (m, 2H, H-7, H-70), 3.64
(dd, 1H, J = 9.7, 10.8 Hz, H-5), 3.54 (d, 1H, J = 9.7 Hz, H-4), 3.50–
3.48 (m, 1H, H-6), 3.27 (dd, 1H, J = 9.0, 2.2 Hz, H-2), 2.64–2.62
(m, 1H, H-11), 2.44–2.40 (m, 1H, H-8, H-110), 2.29–2.21 (m, 1H,
H-80); 13C NMR (100 MHz, CDCl3): d 138.9, 138.2, 138.0, 135.9,
134.7, 128.4–127.6 (m), 118.9, 116.3, 90.1, 86.6, 82.8, 80.5, 80.2,
80.0, 79.3, 69.1, 68.6, 34.6, 33.4. ESMS: m/z 537 [M+Na]+. Anal.
Calcd for C33H38O5: C, 77.01; H, 7.44. Found: C, 77.05; H, 7.42.
ꢀ9.2 (c 0.5, CH2Cl2). IR (CH2Cl2)
mmax: 2924, 2854, 1737, 1648,
1496, 1453, 1400, 1235, 1141, 1109, 1046, 1027, 738, 698 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 7.34–7.14 (m, 15H, Ar-H), 5.16–5.15
(m, 2H, H-6, H-7), 4.82–4.75 (m, 3H, –OCH2Ph, H-3, H-4), 4.66 (d,
1H, J = 11.0 Hz, –OCH2Ph), 4.62 (d, 1H, J = 11.5 Hz, –OCH2Ph),
4.56–4.45 (m, 3H, –OCH2Ph), 3.75–3.68 (m, 3H, H-8a, H-9, H-90),
3.48 (br d, 1H, J = 10.0 Hz, H-2), 2.35–2.20 (m, 3H, H-8, H-5, H-
50), 2.03 (s, 3H, –COCH3), 1.94 (s, 3H, –COCH3), 1.92 (s, 3H, –COCH3),
1.74 (br d, 1H, J = 16.0 Hz, H-80); 13C NMR (125 MHz, CDCl3): d
171.2, 170.5, 170.2, 138.5, 138.1, 128.5–127.8 (m), 85.9, 81.7,
79.4, 78.1, 75.1, 75.0, 73.5, 70.4, 69.2, 68.2, 67.4, 28.7, 21.1, 22.3,
21.2, 21.1. ESMS: m/z 669 [M+Na]+. Anal. Calcd for C37H42O10: C,
68.71; H, 6.55. Found: C, 68.70; H, 6.54.
3.8. (2R,3R,4S,4aR,8aS)-3,4-Bis(benzyloxy)-2-(benzyloxymeth-
yl)-3,4,4a,5,8,8a-hexahydro-2H-chromen-4a-ol (12)
3.10. (2R,3S,4S,4aS,6R,7S,8aS)-2-(Hydroxymethyl)octahydro-2H-
chromene-3,4,4a,6,7-pentaol (17)
Diene 10 (514 mg, 1 mmol) was subjected to ring closing
metathesis using the general procedure B to give 12 (436 mg,
89%) as a colorless thick liquid. Rf = 0.5 (hexane–EtOAc 9:1). aD28
Compound 13 (260 mg, 0.5 mmol) was subjected to global
deprotection using the general procedure D to give 17 (124 mg,
98%) as a thick liquid. Rf = 0.45 (MeOH–EtOAc 1:9). a2D8 ꢀ16.4 (c
0.2, H2O). 1H NMR (400 MHz, D2O): d 3.92 (br s, 1H, J = 3.9 Hz),
3.79 (br d, 1H, J = 11.9 Hz), 3.68 (d, 1H, J = 11.9 Hz), 3.51 (dd, 1H,
J = 11.7, 5.1 Hz), 3.41 (br s, 1H), 3.24–3.18 (m, 3H), 1.97–1.84 (m,
2H), 1.73 (dd, 1H, J = 8.5, 4.8 Hz), 1.58 (br d, 1H, J = 13.6 Hz); 13C
NMR (100 MHz, CDCl3): d 81.1, 80.1, 79.2, 73.8, 70.0, 69.2, 67.4,
61.8, 30.2, 28.7. HRMS calcd for C10H17O7 [MꢀH]ꢀ 249.0974, found
249.0975.
+22.3 (c 0.5, CH2Cl2); IR (CH2Cl2)
m
max: 3062, 2903, 2861, 1604,
1495, 1453, 1417, 1209, 1109, 1027, 736, 698 cmꢀ1
;
1H NMR
(400 MHz, CDCl3): d 7.38–7.13 (m, 15H, Ar-H), 5.68 (br s, 2H, H-
6, H-7), 4.91 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.87 (d, 1H,
J = 11.4 Hz, –OCH2Ph), 4.80 (d, 1H, J = 10.7 Hz, –OCH2Ph), 4.59 (d,
1H, J = 12.2 Hz, –OCH2Ph), 4.51 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.48
(d, 1H, J = 10.2 Hz, OCH2Ph), 3.72–3.60 (m, 4H, H-9, H-90, H-3, H-
4), 3.53–3.50 (m, 1H, H-2), 3.38 (d, 1H, J = 4.3 Hz, H-8a), 2.54–
2.39 (m, 2H, H-8, H-80), 2.30–2.20 (m, 2H, H-5, H-50), 1.85 (s, 1H,
OH); 13C NMR (100 MHz, CDCl3): d 138.9, 138.2, 138.1, 128.5-
127.5 (m), 123.7, 122.1, 88.6, 79.8, 78.0, 75.5, 75.4, 75.0, 73.3,
72.1, 69.2, 29.4, 27.7. ESMS: m/z 509 [M+Na]+. Anal. Calcd for
C31H34O5: C, 76.52; H, 7.04. Found: C, 76.50; H, 7.05.
3.11. (2R,3S,4S,4aS,6S,7R,8aS)-2-(Hydroxymethyl)octahydro-2H-
chromene-3,4,4a,6,7-pentaol (19)
Compound 15 (60 mg, 0.12 mmol) was subjected to global
deprotection using the general procedure D to give 19 (28 mg,
98%) as a thick liquid. Rf = 0.43 (MeOH–EtOAc 1:9). a2D8 ꢀ13.6 (c
1.0, H2O). 1H NMR (400 MHz, D2O): d 3.77–3.76 (m, 2H), 3.70
(dd, 1H, J = 12.4, 2.2 Hz), 3.54 (dd, 1H, J = 12.4, 5.8 Hz), 3.37–3.28
(m, 3H), 3.40 (dd, 1H, J = 7.3, 6.3 Hz), 1.92–1.91 (m, 2H), 1.70 (dd,
1H, J = 10.6, 4.4 Hz), 1.54 (t, 1H, J = 12.6 Hz); 13C NMR (100 MHz,
CDCl3): d 83.2, 82.3, 78.9, 76.8, 71.3, 70.8, 69.6, 63.3, 32.5, 30.1.
HRMS calcd for C10H17O7 [MꢀH]ꢀ 249.0974, found 249.0972.
3.9. Dihydroxylation of compound 12
Olefin 12 (486 mg, 1 mmol) was subjected to dihydroxylation
using the general procedure C to give 13 (358 mg, 69%) and 15
(88 mg, 17%) as a separable mixture of diastereomers (4:1), which
were further subjected to acetylation using the general procedure
E to give 14 (Yield: 94%) and 16 (Yield: 92%), respectively.
3.12. (2R,3R,4S,4aR,6R,7S,8aS)-2-(Acetoxymethyl)octahydro-2H-
3.9.1. (2R,3R,4S,4aR,6R,7S,8aS)-3,4-Bis(benzyloxy)-2-
(benzyloxymethyl)octahydro-2H-chromene-4a,6,7-triyl
triacetate (14)
chromene-3,4,4a,6,7-pentayl pentaacetate (18)
Compound 17 (50 mg, 0.2 mmol) was acetylated using the gen-
eral procedure E to give 18 (93 mg, 93%) as a colorless oil. Rf = 0.5
(Yield: 94%). Rf = 0.4 (hexane–EtOAc 4:1). White solid. a2D8 +24.5
(c 0.8, CH2Cl2). IR (CH2Cl2)
1496, 1453, 1400, 1237, 1135, 1098, 1048, 1028, 798, 738,
698 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.34–7.12 (m, 15H, Ar-
m
max: 3030, 2923, 2854, 1738, 1648,
(hexane–EtOAc 1:1). a2D8 ꢀ91.6 (c 1.0, CH2Cl2). IR (CH2Cl2) mmax
:
2923, 2853, 1743, 1369, 1235, 1144, 1038, 680 cmꢀ1 1H NMR
;
;
(400 MHz, CDCl3): d 5.69 (d, 1H, J = 9.5 Hz, H-4), 5.40–5.41 (m,
1H, H-6), 5.18 (td, 1H, J = 8.2, 4.1, H-7), 5.02 (dd, 1H, J = 10.5,
9.5 Hz, H-3), 4.48 (br s, 1H, H-8a), 4.17–4.08 (m, 2H, H-9, H-90),
3.70 (ddd, 1H, J = 10.5, 2.6, 2.2 Hz, H-2), 2.88 (br d, 1H,
J = 15.8 Hz, H-5), 2.22–2.19 (m, 1H, H-8), 2.09–1.98 (m, 2H, H-80,
H), 5.36 (d, 1H, J = 3.1 Hz, H-6), 5.24 (td, 1H, J = 12.7, 3.9 Hz, H-7),
4.76–4.64 (m, 5H, –OCH2Ph, H-3, H-4), 4.59 (d, 1H, J = 12.7 Hz,
–OCH2Ph), 4.54 (d, 1H, J = 12.4 Hz, –OCH2Ph), 4.49 (d, 1H,
J = 10.7 Hz, –OCH2Ph), 3.66–3.55 (m, 4H, H-9, H-90, H-8a, H-2),

V. R. Doddi et al. / Carbohydrate Research 344 (2009) 606–612
611
H-50), 2.10 (s, 3H, –COCH3), 2.07 (s, 3H, –COCH3), 2.05 (s, 3H,
–COCH3), 2.01 (s, 3H, –COCH3), 2.00 (s, 3H, –COCH3), 1.99 (s, 3H,
–COCH3); 13C NMR (100 MHz, CDCl3): d 170.9, 170.6, 170.3,
170.2, 169.7, 83.2, 76.2, 72.5, 71.2, 68.1, 67.7, 67.2, 62.5, 28.3,
26.9, 22.2, 21.1, 20.8, 20.7, 20.6. HRMS calcd for C22H31O13
[M+H]+ 503.1759, found 503.1765.
(d, 1H, J = 10.2 Hz, H-100), 4.92 (d, 1H, J = 12.2 Hz, –OCH2Ph), 4.90
(d, 1H, J = 11.7 Hz, –OCH2Ph), 4.59 (d, 1H, J = 11.9 Hz, –OCH2Ph),
4.50 (d, 1H, J = 12.2 Hz, –OCH2Ph), 4.41 (d, 1H, J = 11.9 Hz,
–OCH2Ph), 4.36 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.27 (d, 1H,
J = 2.4 Hz, H-4), 4.15 (d, 1H, J = 2.4 Hz, H-2), 3.92 (dd, 1H, J = 6.1,
5.8 Hz, H-5), 3.81 (dd, 1H, J = 7.0, 4.8 Hz, H-6), 3.57-3.47 (m, 2H,
H-7, H-70), 2.61–2.36 (m, 2H, H-8, H-80); 13C NMR (100 MHz,
CDCl3): d 172.5, 138.6, 138.0, 137.8, 135.0, 128.5–126.9 (m),
116.8, 83.7, 80.9, 79.1, 74.4, 73.5, 71.9, 69.9, 68.6, 33.0. ESMS: m/
z 495 [M+Na]+. Anal. Calcd for C30H32O5: C, 76.25; H, 6.83. Found:
C, 76.23; H, 6.85.
3.13. (2R,3R,4S,4aR,6S,7R,8aS)-2-(Acetoxymethyl)octahydro-2H-
chromene-3,4,4a,6,7-pentayl pentaacetate (20)
Compound 19 (30 mg, 0.12 mmol) was acetylated using the
general procedure E to give 20 (61 mg, 91%) as a colorless oil.
Rf = 0.5 (hexane–EtOAc 1:1). a2D8 ꢀ70.3 (c 1.0, CH2Cl2). IR (CH2Cl2)
3.16. (2S,3R,4S,5S,6R)-2,3-Diallyl-4,5-bis(benzyloxy)-6-
(benzyloxymethyl)tetra-hydro-2H-pyran-3-ol (25)
m
max: 2924, 2853, 1744, 1430, 1370, 1253, 1037 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d 5.39–5.37 (m, 1H, H-3), 5.27–5.25 (m, 1H, H-
6), 4.83 (td, 1H, J = 4.9, 8.5 Hz, H-7), 4.78 (d, 1H, J = 12.2 Hz, H-4),
4.16–4.13 (m, 2H, H-9, H-90), 3.96–3.93 (m, 1H, H-2), 3.43 (dd,
1H, J = 11.9, 3.8 Hz, H-8a), 2.45–2.31 (m, 2H, H-8, H-5), 1.99–1.95
(m, 1H, H-80), 1.36 (brd, 1H, J = 13.7 Hz, H-50), 2.08 (s, 3H, –COCH3),
2.07 (s, 3H, –COCH3), 2.05 (s, 3H, –COCH3), 2.04 (s, 3H, –COCH3),
2.03 (s, 3H, –COCH3), 2.00 (s, 3H, –COCH3); 13C NMR (100 MHz,
CDCl3): d 170.7, 170.5, 170.2, 170.0, 169.6, 83.1, 77.3, 76.1, 72.4,
71.1, 68.0, 67.5, 67.1, 62.4, 28.2, 26.8, 22.1, 21.0, 20.7, 20.6. HRMS
calcd for C22H31O13 [M+H]+ 503.1759, found 503.1764.
2-Ulose 24 (472 mg, 1 mmol) was allylated with allylmagne-
sium bromide using the general procedure
A to give 25
(313 mg, 61%) as a colorless oil. Rf = 0.45 (hexane–EtOAc 9:1).
a2D8 ꢀ21.9 (c 1.0, CH2Cl2). IR (CH2Cl2)
m
max: 2923, 2869, 1601,
1495, 1452, 1272, 1095, 1026, 917, 738, 699 cmꢀ1
;
1H NMR
(400 MHz, CDCl3): d 7.39–7.22 (m, 15H, Ar-H), 5.85–5.83 (m,
1H, H-9), 5.36–5.32 (m, 1H, H-12), 5.04–4.93 (m, 4H, H-10, H-
100, H-13, H-130), 4.88 (d, 1H, J = 10.8 Hz, –OCH2Ph), 4.74 (d, 1H,
J = 11.4 Hz, –OCH2Ph), 4.50–4.46 (m, 3H, –OCH2Ph), 4.42 (d, 1H,
J = 11.7 Hz, –OCH2Ph), 4.09 (br s, 1H, H-5), 3.63–3.56 (m, 2H, H-
7, H-70), 3.47 (dd, 1H, J = 6.8, 5.6 Hz, H-6), 3.34 (d, 1H, J = 2.6 Hz,
H-4), 3.20 (dd, 1H, J = 10.0, 2.4 Hz, H-2), 2.84 (dd, 1H, J = 14.0,
7.7 Hz, H-11), 2.45–2.41 (m, 1H, H-8), 2.29–2.27 (m, 1H, H-80),
2.10 (dd, 1H, J = 14.1, 7.5 Hz, H-110); 13C NMR (100 MHz, CDCl3):
3.14. (2S,3S,4R,5S,6R)-2-Allyl-4,5-bis(benzyloxy)-6-
(benzyloxymethyl)tetrahydro-2H-pyran-3-ol (23)
To a solution of epoxide 22 (864 mg, 2 mmol) in THF (30 mL)
was added allylmagnesium chloride (2 mL of 2.0 M solution in
THF, 4 mmol) dropwise at 0 °C, and then the reaction mixture
was allowed to stir at ambient temperature. After 30 min, the reac-
tion mixture was quenched by the addition of a satd aq soln of
NH4Cl (25 mL), and the aq phase was extracted with ether
(3 ꢁ 20 mL). The combined organic extracts were washed with
brine (15 mL), dried over Na2SO4, and concentrated in vacuo, and
the crude product was purified by silica gel chromatography to
give 23 (Yield: 685 mg, 72%) as a white solid. Rf = 0.5 (hexane–
d
138.0, 137.6, 137.6, 136.1, 132.7, 128.5-127.8 (m), 118.5,
115.9, 81.7, 77.5, 75.6, 75.2, 73.7, 73.6, 73.5, 71.2, 68.7, 37.4,
32.4; ESMS: m/z 537 [M+Na]+. Anal. Calcd for C33H38O5: C,
77.01; H, 7.44. Found: C, 77.05; H, 7.42.
3.17. (2R,3S,4S,4aR,8aS)-3,4-Bis(benzyloxy)-2-(benzyloxymeth-
yl)-3,4,4a,5,8,8a-hexahydro-2H-chromen-4a-ol (26)
Diene 25 (514 mg, 1 mmol) was subjected to ring closing
metathesis using the general procedure B to give 26 (432 mg,
89%) as a colorless thick liquid. Rf = 0.4 (hexane–EtOAc 9:1). aD28
EtOAc 9:1). aD28 ꢀ39.4 (c 0.8, CH2Cl2). IR (CH2Cl2)
m
;
max: 2923,
2854, 1737, 1601, 1453, 1101, 1020, 698 cmꢀ1
1H NMR
(400 MHz, CDCl3): d 7.34–7.25 (m, 15H, Ar-H), 5.95–5.88 (m, 1H,
H-9), 5.10 (d, 1H, J = 17.0 Hz, H-10), 5.03 (d, 1H, J = 10.2 Hz, H-
100), 4.84 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.74 (d, 1H, J = 11.9 Hz,
–OCH2Ph), 4.62 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.54–4.44 (m, 3H,
–OCH2Ph), 4.02 (s, 1H, H-4), 3.80 (dd, 1H, J = 9.5, 8.0 Hz, H-5),
3.59 (br s, 3H, H-3, H-7, H-70), 3.38 (dd, 1H, J = 7.0, 2.4 Hz, H-6),
3.24 (dd, 1H, J = 8.5, 5.8 Hz, H-2), 2.60–2.59 (m, 1H, H-8), 2.34–
2.29 (m, 2H, H-80, OH); 13C NMR (100 MHz, CDCl3): d 138.6,
138.0, 137.8, 135.0, 128.6–127.5 (m), 116.6, 84.2, 79.6, 74.3, 73.6,
72.7, 71.6, 70.4, 68.9, 36.3. ESMS: m/z 497 [M+Na]+. Anal. Calcd
for C30H34O5: C, 75.92; H, 7.22. Found: C, 76.93; H, 7.24.
+26.8 (c 0.5, CH2Cl2). IR (CH2Cl2)
m
max: 3063, 2904, 2865, 1605,
1455, 1207, 1106, 1023, 739, 698 cmꢀ1
;
1H NMR (400 MHz,
CDCl3): d 7.35–7.19 (m, 15H, Ar-H), 5.49–5.44 (m, 2H, H-6, H-
7), 4.93 (d, 1H, J = 11.0 Hz, –OCH2Ph), 4.74 (d, 1H, J = 12.2 Hz,
–OCH2Ph), 4.51 (d, 1H, J = 11.0 Hz, –OCH2Ph), 4.03 (m, 1H, H-3),
3.55–3.53 (m, 3H, H-4, H-9, H-90), 3.35 (dd, 1H, J = 10.2, 6.0 Hz,
H-2), 3.14 (d, 1H, J = 2.4 Hz, H-8a), 2.56 (dd, 1H, J = 17.8, 3.9 Hz,
H-8), 2.35–2.29 (m, 1H, H-50), 2.15-2.10 (m, 1H, H-5), 1.70 (br
d, 1H, J = 17.8 Hz, H-80). 13C NMR (100 MHz, CDCl3): d 137.8,
137.6, 128.4–127.8 (m), 123.8, 123.3, 80.9, 78.2, 78.1, 75.1,
73.5, 71.6, 71.4, 71.2, 68.8, 35.1, 27.3. ESMS: m/z 509 [M+Na]+.
Anal. Calcd for C31H34O5: C, 76.52; H, 7.04. Found: C, 76.50; H,
7.01.
3.15. (2S,4S,5S,6R)-2-Allyl-4,5-bis(benzyloxy)-6-
(benzyloxymethyl)dihydro-2H-pyran-3(4H)-one (24)
3.18. (2R,3S,4S,4aR,6R,7S,8aS)-3,4-Bis(benzyloxy)-2-
(benzyloxymethyl)-4a-hydroxy-octahydro-2H-chromene-6,7-
diyl diacetate (28)
A solution of alcohol 23 (474 mg, 1 mmol) in a mixture of
DMSO–Ac2O (2:1 24 mL) was stirred for 5 h under N2 atmosphere.
The reaction mixture was quenched by the addition of ice-cold
water (100 mL), and the aq phase was extracted with ether
(3 ꢁ 30 mL). The combined organic extracts were washed with
brine (15 mL), dried over Na2SO4, concentrated in vacuo, and puri-
fied by silica gel chromatography to give 24 (Yield: 327 mg, 69%) as
a white solid. Rf = 0.6 (hexane–EtOAc 9:1). a2D8 ꢀ40.2 (c 0.8, CH2Cl2).
Olefin 26 (486 mg, 1 mmol) was subjected to dihydroxylation
using the general procedure C to give 27 (447 mg, 86%), which
was further subjected to acetylation using the general procedure
E to give 28 (Yield: 484 mg, 94%) as a white solid. Rf = 0.5 (hex-
ane–EtOAc 4:1). aD28 +96.3 (c 0.8, CH2Cl2). IR (CH2Cl2)
m
max: 3087,
IR (CH2Cl2)
465 cmꢀ1
H), 5.84–5.77 (m, 1H, H-9), 5.08 (d, 1H, J = 17.3 Hz, H-10), 5.01
m
max: 2923, 2854, 1729, 1601, 1382, 1095, 1021, 698,
3062, 2927, 1743, 1496, 1264, 1100, 1028, 737, 698 cmꢀ1 1H
;
;
1H NMR (400 MHz, CDCl3): d 7.32–7.21 (m, 15H, Ar-
NMR (500 MHz, CDCl3): d 7.39–7.24 (m, 15H, Ar-H), 5.41 (br s,
1H, H-6), 5.23–5.20 (m, 1H, H-7), 4.94 (d, 1H, J = 11.0 Hz, –OCH2Ph),

612
V. R. Doddi et al. / Carbohydrate Research 344 (2009) 606–612
4.75 (d, 1H, J = 11.9 Hz, –OCH2Ph), 4.58 (d, 1H, J = 11.9 Hz,
–OCH2Ph), 4.53 (d, 1H, J = 11.0 Hz, –OCH2Ph), 4.54 (d, 1H,
J = 11.7 Hz, –OCH2Ph), 4.52 (d, 1H, J = 11.7 Hz, –OCH2Ph), 4.34 (d,
1H, J = 2.1 Hz, H-4), 4.05 (d, 1H, J = 2.6 Hz, H-3), 3.61–3.56 (m,
3H, H-9, H-90, OH), 3.44 (dd, 1H, J = 11.7, 4.4 Hz, H-2), 3.27 (d,
1H, J = 2.6 Hz, H-8a), 2.36 (dd, 1H, J = 11.4, 4.4 Hz, H-50), 2.18–
2.14 (m, 1H, H-80), 1.88–1.85 (m, 1H, H-5), 2.06 (s, 3H, –COCH3),
1.96 (s, 3H, –COCH3), 1.46–1.44 (m, 1H, H-8); 13C NMR (125 MHz,
CDCl3): d 170.0, 169.8, 137.6, 137.4, 137.3, 128.5–127.9 (m), 80.0,
77.9, 76.3, 75.2, 73.7, 73.6, 72.8, 71.8, 69.1, 68.7, 68.2, 32.1, 29.4,
21.1, 20.9. ESMS: m/z 627 [M+Na]+. Anal. Calcd for C35H40O9: C,
69.52; H, 6.67. Found: C, 69.56; H, 6.65.
thanks the Council of Scientific and Industrial Research, New Delhi,
and P.K.K. thanks UGC, Government of India, for a senior research
fellowship.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2009.01.017.
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3.19. (2R,3R,4S,4aS,6R,7S,8aS)-2-(Hydroxymethyl)octahydro-
2H-chromene-3,4,4a,6,7-pentaol (29)
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tection using the general procedure D to give 29 (249 mg, 98%) as a
thick liquid. Rf = 0.5 (MeOH–EtOAc 1:4). a2D8 ꢀ19.2 (c 0.2, H2O). 1H
NMR (400 MHz, D2O): d 3.94 (br s, 1H, J = 3.9 Hz), 3.77–3.74 (m,
2H), 3.63 (dd, 1H, J = 11.5, 4.0 Hz), 3.61 (d, 1H, J = 5.0 Hz), 3.57–
3.44 (m, 2H), 3.41 (d, 1H, J = 2.5 Hz), 3.35 (d, 1H, J = 2.5 Hz), 1.95
(dd, 1H, J = 13.0, 4.0 Hz), 1.88–1.85 (m, 2H), 1.40 (dd, 1H, J = 13.0,
12.5 Hz); 13C NMR (100 MHz, CDCl3): d 80.0, 75.0, 73.8, 71.6, 69.6,
68.8, 66.7, 61.4, 30.0, 30.7. HRMS calcd for C10H17O7 [MꢀH]ꢀ
249.0974, found 249.0974.
3.20. (2R,3S,4S,4aR,6R,7S,8aS)-2-(Acetoxymethyl)-4a-
hydroxyoctahydro-2H-chromene-3,4,6,7-tetrayl tetraacetate
(30)
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Compound 29 (50 mg, 0.2 mmol) was acetylated using the
general procedure E to give 30 (82 mg, 90%) as a colorless oil.
Rf = 0.5 (hexane–EtOAc, 1:1). a2D8 +6.2 (c 1.0, CH2Cl2); IR (CH2Cl2)
m
max: 2926, 2851, 1746, 1237, 1141, 1039, 680 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d 5.43 (m, 1H, H-7), 5.39 (d, 1H, J = 2.9 Hz,
H-3), 5.19–5.17 (m, 1H, H-6), 4.19 (d, 1H, J = 3.5 Hz, H-4),
4.13–4.11 (m, 2H, H-9, H-90), 3.96 (dd, 1H, J = 6.6, 2.9 Hz, H-2),
3.67 (dd, 1H, J = 11.9, 4.8 Hz, H-8a), 2.90 (br s, 1H, OH), 2.16–
2.15 (m, 1H, H-8), 2.11–2.07 (m, 2H, H-80, H-5), 1.65–1.62 (m,
1H, H-50), 2.16 (s, 3H, –COCH3), 2.11 (s, 3H, –COCH3), 2.09 (s,
3H, –COCH3), 2.05 (s, 3H, –COCH3), 1.97 (s, 3H, –COCH3); 13C
NMR (100 MHz, CDCl3):
d 170.5, 170.4, 170.0, 169.9, 169.3,
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76.2, 75.3, 72.1, 71.1, 68.6, 67.7, 67.6, 61.6, 31.3, 29.2, 21.0,
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We thank the Department of Science and Technology, New Del-
hi, for financial support to one of us (Y.D.V.) in the form of Raman-
na Fellowship (Grant No. SR/S1/RFOC-04/2006). V.R.D. and Y.S.R.