Synthesis of spiro carbon linked disaccharides from D-glucose, D- and L-arabinose

Article abstract of DOI:10.1016/S0040-4020(02)00319-8

The synthesis of new spiro carbon linked disaccharides from D-glucose, D- and L-arabinose is described. In the present study furan is used as a masked sugar synthon, while chirality is transferred from the sugar derived chiral templates.

Full text of DOI:10.1016/S0040-4020(02)00319-8

TETRAHEDRON
Pergamon
Tetrahedron 58 ?2002) 3801±3812
Synthesis of spiro carbon linked disaccharides from d-glucose,
d- and l-arabinoseq
G. V. M. Sharma,a,p V. Goverdhan Reddy,a Palakodety Radha Krishna,a A. Ravi Sankarb
and A. C. Kunwarb
aDiscovery Laboratory D-211, Organic Chemistry Division III, Indian Institute Of Chemical Technology, Hyderabad 500 007, India
bCenter for Nuclear Magnetic Resonance, Indian Institute Of Chemical Technology, Hyderabad 500 007, India
Received 26February 2001; revised 18 February 2002; accepted 14 March 2002
AbstractÐThe synthesis of new spiro carbon linked disaccharides from d-glucose, d- and l-arabinose is described. In the present study
furan is used as a masked sugar synthon, while chirality is transferred from the sugar derived chiral templates. q 2002 Elsevier Science Ltd.
All rights reserved.
1. Introduction
This has led to interest in the synthesis of glycosyl
mimics such as C-glycosides, C-saccharides,12 aza-sugars13
etc. Notwithstanding these advances, no attempt has
ever been made to synthesize spiro-C-disaccharides in
which the sugars are attached through a `spiro' carbon
atom. Due to the rigidity of the spiro system, these systems
should hold the hydroxy substituents in a precisely de®ned
fashion and hence should have potential for speci®c
interactions. Our continued interest on the use of carbo-
hydrate derived chiral templates for the synthesis of new
glycosubstances as well as glycosyl mimics,14±18 prompted
the synthesis of the new `spiro carbon linked disaccharides'
?Fig. 1).
Bio-active glycosubstances, over the years, have received
great attention in chemical, medicinal and pharmaceutical
research.1±4 As a consequence, the design and implementa-
tion of stereoselective strategies for preparing them by using
readily available homochiral precursors constituted promi-
nent issue of a number of laboratories5±9 Among the various
means with which a carbohydrate unit can be assembled,
methodologies involving carbon-carbon bond formation
between an enantiopure `short' precursor and a homo-
logative manipulable reactant constitute
subject in the modern synthetic chemistry panorama.10,11
a
leading
Figure 1.
q IICT Communication No. 4717.
Keywords: carbohydrates; glycosyl mimics; furan; spiro carbon liked disaccharides.
Corresponding author. Fax: 191-40-717-3387; e-mail: esmvee@iict.ap.nic.in
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020?02)00319-8

3802
G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
Scheme 1.
2. Results and discussion
the majority of the starting material being recovered. On the
other hand, osmylation of acetate 8 was completed in 16h
and gave the diol 16 in 87% yield. The diols 15 and 16 were
independently subjected to acetylation with Ac2O±Et3N to
furnish the spiro disaccharides 1 ?74%) and 2 ?77%),
respectively.
2.1. Synthesis and conformational analysis of spiro
carbon linked disaccharides from d-glucose
The construction of spiro disaccharides 1 and 2 was
attempted according to the retrosynthetic analysis shown
in Scheme 1. Accordingly, allyl acetates 7 and 8 were
envisaged as late stage precursors for 1 and 2, while 7 and
8 in turn would be derived from the enone 9. Oxidative ring
opening of furan in the furyl sugar 10, which was envisaged
from `diacetone glucose', would easily make the enone 9.
Thus overall, in the present study on synthesis of spiro
carbon linked disaccharides 1 and 2, furan was utilized as
a four carbon masked sugar synthon, while the requisite
chirality would be de®ned by chiral building block 11
derived from `diacetone glucose'.
The 1H and 2D-NOESY experiments unambiguously deter-
mined the structures of both the disaccharides 1 and 2, and
further con®rmations were made from other spectral data
like mass and HRMS analysis. Compound 1 has shown
characteristic nOe cross-peak between H8 and H10, while
in compound 2, no nOe was observed between H8 and H10
indicating epimeric nature of stereocentre at C10. Presence
Accordingly, 1,2:5,6-di-O-isopropylidine-a-d-glucofurano-
3-ulose ?11) prepared19,20 from d-glucose was subjected to
alkylation ?Scheme 2) with 2-furyl lithium21 in THF at
2408C to afford the 3-C-furanyl-d-allose derivative 1022
in 75% yield. The stereochemical outcome at the C-3 center
is a consequence of steric hindrance of the 1,2-O-isopropyl-
idine group on the a-face.22 Oxidative ring opening23 of the
furan in 10 with NBS in aqueous THF at 258C gave an
anomeric mixture of lactols 9, which were subsequently
converted into an inseparable mixture of the a,b-O-methyl
pyranosides 12 using Ag2O±MeI, in 3:2 ratio ?76%). Stereo-
selective reduction of 12 under Luche's24,25 reaction
conditions using CeCl3´7H2O±NaBH4 in methanol and
chromatographic puri®cation afforded allylic alcohols 13
and 14 with complete facial selectivity.26
Alcohols 13 and 14 were acetylated independently using
Ac2O±Et3N to give the corresponding acetates 7 ?87%)
and 8 ?81%), respectively. Having made the allylic acetates
7 and 8, these were submitted to catalytic osmylation27,28
using OsO4±NMO in acetone±water ?4:1) to afford the diols
15 and 16 respectively with diastereofacial control, i.e. anti
relative to the ±OAc group. A key observation made during
the osmylation of allylic acetates 7 and 8 was that the
a-anomer 7 underwent osmylation at a very slow rate result-
ing in trace amounts of the diol 15, even after 15 days with

G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
3803
Scheme 2. Reagents: ?a) Furan, n-BuLi, THF, 2408C; ?b) NBS, THF±H2O ?4:1), 258C; ?c) Ag2O, MeI, CH2Cl2, RT; ?d) CeCl3´7H2O, NaBH4, MeOH, 08C; ?e)
Ac2O, Et3N, CH2Cl2; ?f) OsO4, NMO, acetone±water ?4:1).
of nOe cross peaks between H1-Me ?A) and H2-Me ?A)
implies an envelope conformation for the isopropylidine
group. Relative orientation of both the sugar rings is
con®rmed by the nOe cross peaks between H8 and H2
and H7 and H5. The NMR data is in agreement with the
energy minimized structures obtained by using SYBYL
program.
l-arabinose. As described earlier, the 1,2-O-isopropylidine
group of furanoses play a crucial role in dictating the stereo-
chemical outcome at the spiro centre as evidenced by
complete facially selective attack of the furyl lithium on
the prochiral ketonic functionality. Thus, the study on d-
and l-arabinose should result in the enantiomeric spiro
carbon linked disaccharides.
Accordingly, compounds 17 and 18 ?Scheme 3) on treat-
ment with PDC and Ac2O in CH2Cl2 at re¯ux temperature
gave ketones 19 and 20, respectively, in 75% yield, which
on C-alkylation with furan and n-BuLi in THF at 2408C
furnished 3-C-furanyl derivatives 21 ?65%) and 22 ?57%),
respectively.
2.2. Synthesis and conformational analysis of
enantiomeric spiro carbon linked disaccharides from d-
and l-arabinoses
In the preceding discussion, a new methodology was
described for the synthesis of spiro carbon linked disacchar-
ides, a new class of glycosubstances. Having developed a
methodology for the synthesis of new class of disaccharides
from d-glucose, it was next aimed at extension of the same
study for the synthesis of enantiomeric spiro carbon linked
disaccharides 3 and 4 from d-arabinose, 5 and 6 from
Compound 21 ?Scheme 4) was subjected to oxidative ring
opening with NBS in aqueous THF at 258C to afford the
lactols 23 ?85%), which on treatment with Ag2O and MeI in
CH2Cl2 gave a chromatographically separable mixture of

3804
G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
Scheme 3. Reagents: ?a) PDC, Ac2O, CH2Cl2, re¯ux; ?b) Furan, n-BuLi, THF, 2408C.
pyranosides 24 and 25. Similarly, 22 on reaction with NBS
gave 26 ?85%), which on methylation gave 27 ?62%) as an
inseparable mixture.
Stereoselective reduction of enones 24 and 25 ?Scheme 5)
using CeCl3´7H2O±NaBH4 in MeOH afforded 28 ?80%) and
31 ?76%), which on acetylation ?Ac2O and Et3N) afforded
the acetates 29 ?70%) and 32 ?87%), respectively. Acetates
29 and 32 were subjected to osmylation ?OsO4±NMO) in
acetone±water ?4:1) for one week to give the diols 30 ?60%)
and 33 ?33%). Finally, acetylation of 30 and 33 with Ac2O
and Et3N in CH2Cl2 afforded the spiro carbon linked
disaccharides 3 ?65%) and 4 ?72%), respectively.
The structures of these disaccharides were unambiguously
assigned from their spectral analysis and NOESY
experiments. nOe between H7 and H9 supports their diaxial
disposition in compound 3, whereas in compound 4 no nOe
was observed between H7 and H9, indicating that C9 center
is epimeric. These observations in combination with the
other couplings in the six membered rings suggest a chair
conformation for hexose. The relative orientation of the
sugar rings is con®rmed, by the nOe cross peaks between
H2 and H6in compounds 3 and 4 along with the nOe
between H4 and H9 in compound 3. The structures obtained
from the diagnostic data derived from the measurements of
interproton coupling constants and detection of speci®c
Scheme 4. Reagents: ?a) NBS, THF±H2O ?4:1), 258C; ?b) Ag2O, MeI, CH2Cl2, RT.

G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
3805
Scheme 5. Reagents: ?a) CeCl3´7H2O, NaBH4, MeOH, 08C; ?b) Ac2O, Et3N, CH2Cl2; ?c) OsO4, NMO, acetone±water ?4:1).
nOe's were further supported by molecular modeling
calculations using SYBYL program.
other spectral data such as 2D-NOESY spectra. Large
vicinal coupling between H6and H7 of 8.5 Hz and nOe
cross peak between H7 and H9 support their their diaxial
disposition in compound 5 and one large vicinal coupling
J6,7 of 10.8 Hz was observed in compound 6. These
observations in combination with the other couplings in
the six membered ring suggest a chair conformation for
hexose. The relative orientation of the sugar rings is
con®rmed by the nOe cross peaks between H7 and H2
and H6and H5 0. The structures obtained from the diagnostic
data derived from the measurements of interproton coupling
constants and detection of speci®c nOe's were further
supported by molecular modeling calculations using
Similarly, the inseparable mixture of 27 ?Scheme 6) was
subjected to reduction with CeCl3´7H2O±NaBH4 to afford
the alcohols 34 and 35, which were chromatographically
separable. Acetylation of 34 and 35 and osmylation of the
resultant acetates 36 and 37 gave diols 38 ?60%) and 39
?39%), respectively. Finally diols 38 and 39 on acetylation
afforded the spiro carbon linked disaccharides 5 ?80%) and
6 ?76%).
The structures of 5 and 6 were assigned from 1H NMR and
Scheme 6. Reagents: ?a) CeCl3´7H2O, NaBH4, MeOH, 08C; ?b) Ac2O, Et3N, CH2Cl2; ?c) OsO4, NMO, acetone±water ?4:1).

3806
G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
1
SYBYL program. The H NMR and optical rotation data
clearly indicate that the spiro disaccharides derived from d-
and l-arabinose were enantiomeric.
scopy ?NOESY) experiments. All the experiments were
carried out in the phase sensitive mode using the procedure
of States et al.29 The spectra were acquired with 2£192 free
induction decays ?FID) containing 8±16transients with
the relaxation decay of 1.5 s. The NOESY were per-
formed with mixing time of 0.5 s. The two dimensional
data were processed with gaussian apodization in both the
dimensions.
All molecular mechanical calculations were carried out
using SYBYL 6.8 program on a silicon graphics O2 work-
station. The Tripos force ®eld with default parameters was
used through out the simulations. Minimization's were done
®rst with Steepest Decent, followed by Conjugate Gradient
methods for a maximum of 1000 iterations or RMS devia-
tion of 0.005 kcal mol21, whichever was earlier. The energy
minimized molecules were then subjected to MOPAC. The
new geometrical structures thus obtained were again mini-
mized using the above mentioned energy minimization
protocol.
Optical rotations were measured with a JASCO DIP-370
instrument, and [a]D-values are in units of
1021 deg cm2 g21. IR spectra were taken with a Perkin±
Elmer 1310 spectrometer. Mass spectra were recorded on
CEC-21-11013 or Finnigan Mat 1210 double focussing
mass spectrometers operating at a direct inlet system and
FABMS and HRMS were measured using VG AUTOSPEC
mass spectrometers at 5 or 7 K resolution using per¯uoro-
kerosene as an internal reference. Nomenclature mentioned
in this section was adopted from ACD/Name Version 1.0 b,
Advanced Chemistry Development Inc., Toronto, Canada.
Organic solutions were dried over anhydrous Na2SO4 and
concentrated below 408C in vacuo.
3. Conclusion
Thus, in conclusion the ®rst synthesis of spiro carbon linked
disaccharides as a new class of glycosubstances has been
achieved by using a 3-keto sugar resulting in the spiro
carbon center on sugar templates. The presence of the 1,2-
O-isopropylidine group on the a- and b-faces determines
the entry of the furan moiety on nucleophilic addition,
thereby determining the course of spiro carbon linked
disaccharide generation. Overall, the chirality is induced
from the sugar template, while d- and l-arabinose gave
access to a new class of enantiomeric spiro carbon linked
disaccharides. The methodology developed in the present
study would be of immense utility in the synthesis of new
glycosubstances and the thus made new disaccharides might
®nd potential use biologically.
4.1.1. 5-+2,2-Dimethyl-+4R)-1,3-dioxolan-4-yl)-6-+2-furyl)-
2,2-dimethyl-+3aR,5R,6R,6aR)-perhydrofuro-[2,3-d][1,3]-
dioxol-6-ol +10). To a stirred solution of furan ?1.48 mL,
20.3 mmol) in dry THF ?15 mL), n-BuLi ?13.5 mL,
20.3 mmol, 1.5 M solution in hexane) was added dropwise
at 2408C. After 1 h, ketone 11 ?3.5 g, 13.56mmol) in dry
THF ?8 mL) was added dropwise at the same temperature
over 10 min and the reaction mixture warmed slowly to
room temperature over a period of 30 min. The reaction
mixture was treated with saturated aqueous NH4Cl solution
?20 mL), diluted with water ?40 mL) and extracted with
ether ?3£50 mL). The ethereal solution was washed with
water ?40 mL), brine ?35 mL), dried ?Na2SO4) and concen-
trated to the crude. The residue was puri®ed by column
chromatography ?Si-gel, 60±120 mesh, 6% EtOAc±hexane)
to afford 5--2,2-dimethyl--4R)-1,3-dioxolan-4-yl)-6--2-
furyl)-2,2-dimethyl--3aR,5R,6R,6aR)-perhydrofuro-[2,3-
d][1,3]dioxol-6-ol ?10, 3.3 g, 75%) as a colorless syrup.
4. Experimental
4.1. General
All moisture sensitive reactions were performed under
nitrogen atmosphere using ¯ame-dried glassware. Solvents
were dried over standard drying agents and freshly distilled
prior to use. NMR spectra were recorded on Varian Gemini
FT-200 MHz, Unity-400 MHz ?218C) and Inova-500 MHz
?308C) spectrometers, with 7±10 mM solutions in appro-
priate solvents using TMS as internal standard. 13C NMR
spectra were recorded with complete proton decoupling.
The assignments were carried out with the help of two-
dimensional Double Quantum Filtered Correlation Spectro-
scopy ?DQFCOSY) and Nuclear Overhauser Effect Spectro-
27
[a]D ˆ121.6? c 0.72, CHCl3); dH ?200 MHz, CDCl3),
7.38 ?1H, br s, H-10), 6.38 ?2H, br s, H-8,9), 5.95 ?1H, d,
J1,2ˆ4.0 Hz, H-1), 4.52 ?1H, d, J1,2ˆ5.0 Hz, H-2), 4.05 ?1H,
d, J4,5ˆ5.8 Hz, H-4), 3.80±3.72 ?1H, m, H-5), 3.70±3.60
?1H, m, H-60), 3.50±3.40 ?1H, m, H-6), 3.05 ?1H, br s,
OH), 1.22, 1.38, 1.60 ?12H, 3s, CH3); dC ?50 MHz,
CDCl3), 152.4, 142.2, 113.1, 110.5, 109.0, 107.4, 104.6,
82.6, 82.2, 79.0, 74.0, 65.4, 26.7, 26.6 ?2C), 25.1; m/z:
311 ?EIMS, M1215), 196, 110; HRMS: ?EIMS, M1215),
found 311.1129. C15H19O7 requires 311.1131.

G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
3807
4.1.2. 5-+2,2-Dimethyl-+4R)-1,3-dioxolan-4-yl)-60-meth-
oxy-2,2-dimethyl-+3aR,5R,60R,6aR)spiro[perhydrofuro-
[2,3-d][1,3]-dioxole-6,20-+60H-pyran)]-30-one +12). A solu-
tion of 10 ?2.0 g, 6.13 mmol) in THF±water ?10 mL, 4:1)
was cooled to 258C and NBS ?1.09 g, 6.13 mmol) added in
portions. After 5 min, the reaction mixture was neutralized
with saturated NaHCO3 solution ?5 mL), diluted with water
?20 mL) and extracted with ethylacetate ?3£30 mL). The
combined organic layers were washed with water
?2£30 mL), brine ?30 mL), dried ?Na2SO4) and concentrated
to afford the lactols 9 ?1.78 g, 85%) as a syrup.
H 7.19. C17H26O8 requires C 56.98, H 7.26%; dH ?200 MHz,
CDCl3), 6.20 ?1H, dd, J8,9ˆ12.5 Hz, J7,8ˆ7.0 Hz, H-8), 5.85
?1H, br d, J8,9ˆ12.5 Hz, H-9), 5.68 ?1H, d, J1,2ˆ4.4 Hz,
H-1), 5.32 ?1H, br s, H-10), 4.65 ?1H, dd, J7,8ˆ7.0 Hz,
J7,OHˆ8.5 Hz, H-7), 4.18 ?1H, d, J1,2ˆ4.4 Hz, H-2), 4.10±
3.90 ?3H, m, H-4,6,60), 3.70±3.55 ?1H, m, H-5), 3.48 ?3H, s,
OCH3), 3.0 ?1H, br d, OH), 1.60,1.40, 1.30, 1.29 ?12H, 4s,
CH3); IR ?neat): 3440, 2942, 2895, 1100 cm21; m/z: ?EIMS,
M1215), 343.
4.1.4. 5-+2,2-Dimethyl-+4R)-1,3-dioxolan-4-yl)-60-meth-
oxy-2,2-dimethyl-+30R,3aR,5R,60R,60S,6aR)-spiro[per-
hydrofuro[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-3-yl
acetate +7). A solution of 13 ?0.07 g, 0.19 mmol) and Et3N
?0.05 mL, 0.38 mmol) in CH2Cl2 ?5 mL) was treated with
Ac2O ?0.04 mL, 0.39 mmol) in presence catalytic DMAP at
08C. After stirring for 1hr, it was neutralized with saturated
aqueous NaHCO3 solution and extracted with CH2Cl2
?2£10 mL). Combined organic layers were washed with
water ?20 mL), dried ?Na2SO4) and concentrated to the
crude, which on puri®cation by column chromatography
?Si-gel, 10% EtOAc±hexane) gave 5--2,2-dimethyl--4R)-
1,3-dioxolan-4-yl)-60-methoxy-2,2-dimethyl--30R,3aR,5R,
60R,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,60H-pyran)]-3-yl acetate ?7, 0.068 g, 87%) as a syrup.
Analysis found: C 56.82; H 6.93. C19H28O9 requires C
56.99; H 7.05%; IR ?neat, cm21): 2930, 2885, 1710, 1050;
A solution of the above lactols 9 ?1.5 g, 4.38 mmol) in
CH2Cl2 ?10 mL) was treated with MeI ?0.62 mL,
8.77 mmol) in the presence of Ag2O ?1.0 g, 4.38 mmol)
for 12 h. The reaction mixture was ®ltered through celite
and washed with CH2Cl2 ?3£50 mL). The organic layer was
evaporated and the crude puri®ed by column chromato-
graphy ?Si-gel, 10% EtOAc±hexane) to afford an anomeric
mixture of O-methyl glycosides 5--2,2-dimethyl--4R)-1,3-
dioxolan-4-yl)-60-methoxy-2,2-dimethyl--3aR,5R,60R,6aR)-
spiro[perhydrofuro-[2,3-d][1,3]-dioxole-6,20--60H-pyran)]-
30-one ?12, 1.18 g, 76%) as a syrup in 3:2 ratio. dH
?200 MHz, CDCl3), 6.86±6.15 ?2H, m, H-8,9), 5.81 ?1H,
d, J1,2ˆ4.0 Hz, H-1), 5.45 ?0.4H, d, J9,10ˆ2.7 Hz, H-10),
5.20 ?0.6H, d, J9,10ˆ4.5 Hz, H-10), 4.38 ?1H, d,
J1,2ˆ4.0 Hz, H-2), 4.16±4.05 ?1H, m, H-5), 4.00±3.80
?3H, m, H-4,6,60), 3.58, 3.54 ?3H, 2s, OCH3), 1.60, 1.40,
1.30, 1.20 ?12H, 4s, CH3), IR ?neat): 2930, 2885, 1694,
1052 cm21; m/z: 341 ?EIMS, M1215); HRMS: M1215,
found 341.1246. C16H21O8 requires 341.1236.
27
[a]D ˆ1133.5 ?c 1.3, CHCl3); dH ?200 MHz, CDCl3), 6.15
?1H, dd, J7,8ˆ5.4 Hz, J8,9ˆ1.7 Hz, H-8), 6.00 ?1H, d,
J8,9ˆ1.7 Hz, H-9), 5.60 ?1H, d, J1,2ˆ4.2 Hz, H-1), 5.05
?1H, s, H-10), 4.74 ?1H, d, J7,8ˆ5.4 Hz, H-7), 4.36?1H, q,
J0ˆ10.8 Hz, H-5), 4.29 ?1H, d, J1,2ˆ4.2 Hz, H-2), 4.15 ?1H,
d, J4,5ˆ5.7 Hz, H-4), 3.82±4.0 ?2H, m, H-6,60), 3.45 ?3H, s,
OCH3), 2.10 ?3H, s, CH3), 1.60, 1.45, 1.31, 1.29 ?12H, 4s,
CH3), dc ?50 MHz, CDCl3), 169.7, 130.9, 124.0, 112.5,
109.3, 102.7, 84.9, 82.1, 81.2, 80.7, 73.6, 67.0, 64.4, 55.4,
26.78, 26. 7 ?2C), 25.4, 20.9; m/z: ?EIMS, M1215), 385.
4.1.3. Reduction of enones 12. To a solution of 12 ?0.3 g,
0.84 mmol) in methanol ?6mL), was added CeCl 3´7H2O
?0.47 g, 1.26mmol) and stirred at room temperature for
10 min. The reaction mixture was cooled to 08C, treated
with NaBH4 ?0.046g, 1.26mmol) in portions over a period
of 5 min. and methanol was removed under vacuum. The
reaction mixture was quenched with ice-cold water ?10 mL)
and extracted with ethylacetate ?3£25 mL). The organic
layer was washed with water ?2£25 mL), brine ?30 mL),
dried ?Na2SO4) and concentrated to the crude. The crude
containing a mixture of anomers 13 and 14 was separated
by column chromatography ?Si-gel, 15% EtOAc±hexane).
4.1.5. 5-+2,2-Dimethyl-+4R)-1,3-dioxolan-4-yl)-60-meth-
oxy-2,2-dimethyl-+30R,3aR,5R,60R,60R,6aR)-spiro[per-
hydrofuro[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-3-yl
acetate +8). A solution of 14 ?0.07 g, 0.19 mmol) and Et3N
?0.05 mL, 0.38 mmol) in CH2Cl2 ?5 mL) was treated with
Ac2O ?0.04 mL, 0.39 mmol) in presence catalytic DMAP at
08C and worked up as described for 7 to afford 5--2,2-
dimethyl--4R)-1,3-dioxolan-4-yl)-60-methoxy-2,2-dimethyl-
-30R,3aR,5R,60R,60R,6aR)-spiro [perhydrofuro[2,3-d][1,3]-
dioxole-6,20--30H,60H-pyran)]-3-yl acetate ?8, 0.06 3 g,
81%) as a syrup. Analysis found: C 56.80; H 6.87.
First eluted was 5--2,2-dimethyl--4R)-1,3-dioxolan-4-yl)-60-
methoxy-2,2-dimethyl--30R,3aR,5R,60R, 60S,6aR)-spiro[-
perhydrofuro[2,3-d][1,3]dioxole-6,20--30H,60H-pyran)]-30-
27
ol ?13; 0.11 g, 37%) as a syrup, [a]D ˆ163.9 ?c 1.1,
27
CHCl3); dH ?200 MHz, CDCl3), 6.18 ?1H, dd, J8,9ˆ7.8 Hz,
J7,8ˆ7.0 Hz, H-8), 5.90 ?1H, dd, J8,9ˆ7.8 Hz, J9,10ˆ2.0 Hz,
C19H28O9 requires C 56.99; H 7.05%; [a]D ˆ113.7 ?c
1.5, CHCl3); dH ?200 MHz, CDCl3), 6.16, 6.10 ?1H, 2d,
J7,8ˆ5.4 Hz, J8,9ˆ1.6Hz, H-8), 5.98, 5.90, ?1H, 2d,
J9,10ˆ1.8 Hz, J8,9ˆ1.6Hz, H-9), 5.69 ?1H, d, J1,2ˆ4.5 Hz,
H-1), 5.32 ?1H, d, J9,10ˆ1.8 Hz, H-10), 4.74 ?1H, d,
J7,8ˆ5.4 Hz, H-7), 4.58±4.50 ?1H, m, H-5), 4.25 ?1H, d,
J1,2ˆ4.5 Hz, H-2), 4.06±3.83 ?3H, m, H-4,6,6 0), 3.50 ?3H,
s, OCH3), 2.10 ?3H, s, CH3), 1.30, 1.40, 1.60 ?12H, 3s, CH3);
m/z: ?EIMS, M1215), 385.
H-9), 5.60 ?1H, d, J1,2ˆ4.4 Hz, H-1), 4.96?1H, d, J9,10
ˆ
2.0 Hz, H-10), 4.65 ?1H, dd, J7,OHˆ8.5 Hz, J7,8ˆ7.0 Hz,
H-7), 4.23 ?1H, d, J1,2ˆ4.4 Hz, H-2), 4.15±4.05 ?2H, m,
H-4,60), 3.98±3.89 ?1H, m, H-6), 3.70±3.53 ?1H, m, H-5),
3.45 ?3H, s, 3H, OCH3), 2.67 ?1H, br d, OH), 1.60, 1.47,
1.32, 1.30 ?12H, 4s, CH3); m/z: ?EIMS, M1215), 343.
Second eluted was 5--2,2-dimethyl--4R)-1,3-dioxolan-4-yl)-
60-methoxy-2,2-dimethyl--30R,3aR,5R,60R, 60R,6aR)-spiro-
[perhydrofuro[2,3-d][1,3]dioxole-6,20--30H,60H-pyran)]-
30-ol ?14; 0.09 g, 30%) as a colorless solid, mp: 1438C;
[a]D ˆ159.1 ?c 0.61, CHCl3); Analysis found: C 56.81,
4.1.6. 5-+2,2-Dimethyl-+4R)-1,3-dioxolan-60-methoxy-2,2-
dimethyl-+30R,3aR,40R,5R,50R,60S,60S,6aR)-spiro[per-
hydrofuro[2,3-d][1,3]dioxole-6,20-+30H,40H,50H,60H-
pyran)]-3-yl acetate +1). To a stirred solution of 7 ?0.041 g,
27

3808
G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
0.10 mmol) in acetone±water ?5 mL, 4:1), were added
sequentially NMO ?0.023 g, 0.20 mmol) and OsO4 ?2 drops,
1.0 M solution in toluene) at room temperature. After 15 days,
the reaction mixture was quenched with aqueous NaHSO3
solution and acetone was evaporated on rotary evaporator.
The reaction mixture was diluted with water ?20 mL) and
extracted with ethylacetate ?2£15 mL). The organic layer
was washed with water ?15 mL), brine ?20 mL), dried
?Na2SO4) and concentrated to the crude, which on puri®cation
by column chromatography ?Si-gel, 60±120 mesh, 60%
EtOAc±hexane) furnished 15 ?5 mg) as a syrup.
CH2Cl2 ?50 mL), were added PDC ?5.27 g, 14.0 mmol),
Ac2O ?catalytic) and heated at re¯ux temperature for 3 h.
Reaction mixture was evaporated and the residue dissolved in
ether. Ethereal solution was ®ltered through silica gel, washed
with ether and the combined ethereal layers were concen-
trated below 258C to afford 19 ?2.24 g, 75%) as a syrup.
To a stirred solution of furan ?0.52 mL, 7.74 mmol) in dry
THF ?10 mL), n-BuLi ?5.16mL, 7.74 mmol, 1.5 M solution
in hexane) was added dropwise at 2408C. After 1 h, ketone
19 ?2.2 g, 5.16mmol) in dry THF ?6mL) was added drop-
wise at the same temperature over 10 min and the reaction
mixture was worked up as described for 10 and puri®ed by
column chromatography ?Si-gel, 60-±120 mesh, 3% ethyl-
acetate in hexane) to afford 5-t-butyldiphenylsilyloxymethyl-
6--2-furyl)-2,2-dimethyl--3aS,5R,6S,6aS)-perhydrofuro-
[2,3-d][1,3]dioxol-6-ol ?21, 1.65 g, 65%) as a syrup.
The above diol 15 ?5 mg, 0.01 mmol) in CH2Cl2 ?5 mL) was
treated with Et3N ?2 drops) and Ac2O ?2 drops) and worked
up as described for 7 to afford 5--2,2-dimethyl--4R)-1,3-
dioxolan-60-methoxy-2,2-dimethyl--30R,3aR,40R,5R,50R,
60S,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-3-yl acetate ?1, 4 mg, 74%) as a
27
[a]D ˆ220.6? c 1.32, CHCl3); dH ?200 MHz, CDCl3),
27
syrup. [a]D ˆ28.0 ?c 0.25, CHCl3); dH ?200 MHz,
7.80±7.60 ?5H, m, Ph), 7.46±7.25 ?6H, m, H-8, Ph), 6.32
?2H, br s, H-6,7), 5.80 ?1H, d, J1,2ˆ4.0 Hz, H-1), 4.70 ?1H,
CDCl3), 5.75 ?1H, d, J1,2ˆ4.05 Hz, H-1), 5.40 ?1H, dd,
J8,9ˆ5.3 Hz, J7,8ˆ1.9 Hz, H-8), 5.09 ?1H, dd, J8,9ˆ5.3 Hz,
J9,10ˆ3.7 Hz, H-9), 5.02 ?1H, d, J9,10ˆ3.7 Hz, H-10), 4.85
?1H, d, J7,8ˆ1.9 Hz, H-7), 4.50 ?1H, d, J1,2ˆ4.05 Hz, H-2),
4.48±4.36?1H, m, H-5), 4.15 ?1H, d, J4,5ˆ4.5 Hz, H-4),
3.95±3.80 ?2H, m, H-6,60), 3.55 ?3H, s, OCH3), 2.18,
2.12, 2.02 ?9H, 3s, OAc), 1.60, 1.45, 1.35, 1.25 ?12H, 4s,
CH3); m/z: ?FABMS), 519 ?M111), 503 ?M1215).
d, J1,2ˆ4.0 Hz, H-2), 4.25 ?1H, t, Jˆ4.8 Hz, H-4), 4.07 ?1H,
0
0
dd, J5,5 ˆ11.0 Hz, J4,5ˆ4.8 Hz, H-5 ), 3.92 ?1H, dd,
0
J5,5 ˆ11.0 Hz, J4,5ˆ4.8 Hz, H-5), 3.50 ?1H, br s. OH),
1.60, 1.45 ?6H, 2s, CH3), 1.10, 1.02 ?9H, 2s, CH3); dC
NMR ?50 MHz, CDCl3), 142.4, 135.65, 135.6 ?2C), 134.7,
129.6 ?3C), 127.6 ?4C), 115.4, 110.3, 106.5, 104.6, 85.2,
84.4, 75.9, 62.7, 27.3, 27.2, 26.7 ?3C), 26.5 ?2C), 19.1;
m/z: ?FABMS), 517 ?M1123), 437, 419; HRMS found:
517.2021. C28H34O6NaSi ?M1123) requires 517.2022.
4.1.7. 5-+2,2-Dimethyl-+4R)-1,3-dioxolan-4-yl)-60-meth-
oxy-2,2-dimethyl-30,40-di+methylcarbonyl-oxy)-+30R,
3aR,40R,5R,50R,60S,60R,6aR)-spiro[perhydrofuro[2,3-
d][1,3]dioxole-6,20-+30H,40H,50H,60H-pyran)]-5-yl ace-
tate +2). To a stirred solution of 8 ?0.041 g, 0.14 mmol) in
acetone±water ?5 mL, 4:1) were added sequentially NMO
?0.032 g, 0.27 mmol) and OsO4 ?2 drops) at room tempera-
ture. After 16h ?monitered by TLC), it was worked up as
described for 15 to afford 16 ?0.038 g, 87%) as a syrup.
4.1.9. Ring opening of 21. A solution of 21 ?1.4 g,
2.82 mmol) in THF±water ?10 mL, 4:1) was cooled to
258C and NBS ?0.5 g, 2.82 mmol) added in portions.
After 5 min, the reaction mixture was worked up as
described for 9 and concentrated to afford a mixture of the
lactols 23 ?1.22 g) in 85% yield.
A mixture of the above lactols 23 ?1.22 g, 2.39 mmol) in
CH2Cl2 ?10 mL) was treated with MeI ?0.34 mL,
4.78 mmol) in the presence of Ag2O ?0.55 g, 2.39 mmol)
for 12 h. The reaction mixture was worked up as described
for 12 and puri®ed by column chromatography ?Si-gel, 60±
120 mesh, 7% EtOAc±hexane).
The above diol 16 ?0.03 g, 0.07 mmol) in CH2Cl2 was
treated with Et3N ?0.024 mL, 0.17 mmol) and Ac2O
?0.01 mL, 0.1 mmol) and worked up as described for 7 to
afford 5--2,2-dimethyl--4R)-1,3-dioxolan-4-yl)-60-methoxy-
2,2-dimethyl-30,40-di-methylcarbonyl-oxy)-30R,3aR,40R,5R,
50R,60S,60R,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20--30H,40H,50H,60H-pyran)]-5-yl acetate ?2, 0.027 g,
First eluted was: 5-t-butyldiphenylsilyloxymethyl-60-meth-
oxy-2,2-dimethyl--3aS,5R,60S,60S,6aS)-spiro[perhydrofuro-
27
77%) as a colorless solid. Mp 117±1198C; [a]D ˆ127.9
?c 0.91, CHCl3); dH ?200 MHz, CDCl3), 5.61 ?1H, d,
J1,2ˆ4.5 Hz, H-1), 5.48 ?1H, dd, J7,8ˆ5.4 Hz, J8,9ˆ4.5 Hz,
H-8), 5.16?1H, dd, J9,10ˆ9.1 Hz, J8,9ˆ4.5 Hz, H-9), 5.10
?1H, d, J9,10ˆ9.1 Hz, H-10), 4.86?1H, d, J7,8ˆ5.4 Hz,
H-7), 4.80 ?1H, d, J1,2ˆ4.5 Hz, H-2), 4.70±4.59 ?1H, m,
H-5), 4.20 ?1H, d, J4,5ˆ4.5 Hz, H-4), 4.19±3.80 ?2H, m,
H-6,60), 3.55 ?3H, s, OCH3), 2.19, 2.12, 2.10 ?9H, 3s,
OCOCH3), 1.62, 1.49, 1.39 ?1£6H, 2£3H, 3s, CH3); dC
?50 MHz, CDCl3), 169.6 ?2C), 168.9, 112.9 ?2C), 108.8,
102.9, 98.1, 82.8, 82.2, 73.5, 69.2, 68.8, 66.9, 65.8, 56.6,
29.6, 26.7 ?2C), 26.4, 25.5, 20.7 ?2C); m/z: 519 ?FABMS,
M111), 503 ?M215); HRMSFAB: found 503.1763.
C22H31O13 ?M1215) requires 503.1765.
[2,3-d][1,3]dioxole-6,20--30H,60H-pyran)]-30-one
?24,
27
0.45 g, 36%) as a syrup, [a]D ˆ235.35 ?c 1.68, CHCl3);
dH ?200 MHz, CDCl3) 7.80±7.60 ?4H, m, Ph), 7.50±7.30
?6H, m, Ph), 6.88 ?1H, dd, J7,8ˆ11.5 Hz, J8,9ˆ1.4 Hz, H-8),
6.18 ?1H, d, J7,8ˆ11.5 Hz, H-7), 5.90 ?1H, br s, H-9), 5.78
?1H, d, J1,2ˆ4.3 Hz, H-1), 4.62 ?1H, d, J1,2ˆ4.3 Hz, H-2),
0
4.45 ?1H, dd, J4,5ˆ3.8 Hz, J4,5 ˆ3.7 Hz, H-4), 3.78 ?1H, dd,
J4,5 ˆ3.7 Hz, J5,5 ˆ10.4 Hz, H-50), 3.72 ?1H, dd,
0
0
0
J4,5ˆ3.8 Hz, J5,5 ˆ10.4 Hz, H-5), 3.56?3H, s, OCH 3),
1.41, 1.32, 1.03, 1.0 ?15H, 4s, CH3), IR ?neat, cm21):
2925, 2885, 1690, 1060; m/z: ?FABMS), 547 ?M1123),
467, 435; HRMS found: 523.2128. C29H35O7Si ?M121)
requires 523.2152.
4.1.8. 5-t-Butyldiphenylsilyloxymethyl-6-+2-furyl)-2,2-
dimethyl-+3aS,5R,6S,6aS)-perhydrofuro-[2,3-d][1,3]-
dioxol-6-ol +21). To a solution of 17 ?3.0 g, 7.0 mmol) in
Second eluted was: 5-t-butyldiphenylsilyloxymethyl-60-
methoxy-2,2-dimethyl--3aS,5R,60R,60S,6aS)-spiro [perhydro-
furo[2,3-d][1,3]dioxole-6,20--30H,60H-pyran)]-30-one ?25,

G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
3809
27
0.41 g, 33%) as a syrup, [a]D ˆ216.66 ?c 1.2, CHCl3); dH
J6,7ˆ3.2 Hz, H-6), 5.40 ?1H, br s, H-9), 4.55 ?1H, d,
J1,2ˆ3.9 Hz, H-2), 4.14±4.0 ?2H, m, H-4,50), 3.95±3.85
?1H, m, H-5), 3.23 ?3H, s, OCH3), 2.12 ?3H, s, COCH3),
1.40, 1.32, 1.26, 1.05 ?15H, 4s, CH3); dC ?50 MHz, CDCl3)
169.6, 135.7 ?2C), 135.6 ?2C), 129.4 ?2C), 128.9 ?2C), 127.5
?4C), 113.7, 105.5, 95.5, 84.9, 82.5, 81.4, 69.1, 63.0, 54.1,
26.8 ?5C), 26.7 ?2C), 20.9, 19.1; m/z: ?FABMS), 591
?M1123); HRMSFAB found: 568.6484. C31H40O8Si ?M1)
requires 568.6517.
?200 MHz, CDCl3) 7.80±7.60 ?4H, m, Ph), 7.50±7.30 ?6H,
m, Ph), 6.82 ?1H, dd, J7,8ˆ12.2 Hz, J8,9ˆ3.4 Hz, H-8), 6.16
?1H, d, J7,8ˆ12.2 Hz, H-7), 5.72 ?1H, d, J1,2ˆ4.0 Hz, H-1),
5.12 ?1H, d, J8,9ˆ3.4 Hz, H-9), 4.45 ?1H, d, J1,2ˆ4.0 Hz, H-
0
2), 4.19 ?1H, dd, J4,5ˆ5.2 Hz, J4,5 ˆ5.3 Hz, H-4), 3.90±3.70
?2H, m, H-5,50), 3.47 ?3H, s, OCH3), 1.40, 1.25, 1.02, 1.0
?15H, 4s, CH3); m/z: ?FABMS), 547 ?M1123), 467, 435.
HRMS found: 523.2143. C29H35O7Si ?M121) requires
523.2152.
4.1.13. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+30S,3aS,5R,60S,60R,6aS)-spiro[perhydrofuro-
4.1.10. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+30S,3aS,5R,60S,60S,6aS)-spiro[perhydrofuro-
[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-30-ol +28). To a
solution of 24 ?0.3 g, 0.57 mmol) in methanol ?5 mL),
CeCl3´7H2O ?0.21 g, 0.57 mmol) and NaBH4 ?21 mg,
0.57 mmol) were added sequentially at 08C and worked up
as described for 13 to afford 5-t-butyldiphenylsilyloxy-
methyl-60-methoxy-2,2-dimethyl-30S,3aS,5R,60S,60S,6aS)-
spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20--30H,60H-
[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-3-yl
acetate
+32). A solution of 31 ?0.2 g, 0.35 mmol) and Et3N
?0.12 mL, 0.88 mmol) in CH2Cl2 ?5 mL) was treated with
Ac2O ?0.06mL, 0.57 mmol) in presence of catalytic DMAP
at 08C and worked up as described for 7 to afford 5-t-butyl-
diphenylsilyloxymethyl-60-methoxy-2,2-dimethyl--30S,3aS,
5R,60S,60R,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20--30H,60H-pyran)]-3-yl acetate ?32, 0.18 g, 87%) as a
27
27
pyran)]-30-ol ?28, 0.24 g, 80%) as a syrup. [a]D ˆ219.8 ?c
syrup. [a]D ˆ18.08 ?c 0.94, CHCl3); dH ?200 MHz,
1.0, CHCl3); IR ?neat, cm21): 3445, 2942, 2880, 1050; dH
?200 MHz, CDCl3) 7.80±7.60 ?4H, m, Ph), 7.48±7.30 ?6H,
m, Ph), 5.90 ?1H, br s, H-8), 5.75±5.88 ?1H, m, H-7), 5.69
?1H, d, J1,2ˆ4.4 Hz, H-1), 5.32 ?1H, br s, H-9), 4.54 ?1H, d,
J1,2ˆ4.4 Hz, H-2), 4.26?1H, brs, H-6), 4.20±3.95 ?3H, m,
H-4,5,50), 3.25 ?3H, s, OCH3), 1.40, 1.25, 1.20, 1.06?15H,
4s, CH3); m/z: ?FABMS), 549 ?M1123), 469, 437; HRMS
found: 526.2384. C29H38O7Si requires 526.2387.
CDCl3) 7.80±7.60 ?4H, m, Ph), 7.45±7.30 ?6H, m, Ph),
5.90±5.75 ?2H, m, H-7,8), 5.65 ?1H, d, J1,2ˆ4.1 Hz, H-1),
5.55 ?1H, d, J6,7ˆ2.5 Hz, H-6), 4.89 ?1H, br s, H-9), 4.42
?1H, d, J1,2ˆ4.1 Hz, H-2), 4.22±4.10 ?2H, m, H-4,50), 3.92±
3.80 ?1H, m, H-5), 3.24 ?3H, s, OCH3), 2.13 ?3H, s,
COCH3), 1.26, 1.25, 1.05 ?15H, 3s, CH3); dC ?50 MHz,
CDCl3) 169.8, 135.7 ?3C), 129.4 ?2C), 128.0, 127.8,
127.57 ?3C), 111.9, 105.8, 94.7, 87.9, 79.9, 78.6, 70.9,
64.2, 56.0, 29.7, 26.8 ?4C), 26.4 ?2C), 26. 0 ?2C), 21.0,
19.2; m/z: ?FABMS), 591 ?M1123). HRMSFAB found:
568.6495. C31H40O8Si ?M1) requires 568.6517.
4.1.11. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+30S,3aS,5R,60R,60S,6aS)-spiro[perhydrofuro-
[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-30-ol +31). To a
stirred solution of 25 ?0.32 g, 0.61 mmol) in methanol
?5 mL), CeCl3´7H2O ?0.22 g, 0.61 mmol) and NaBH4
?23 mg, 0.61 mmol) were added sequentially at 08C and
worked up as described for 13 to afford 5-t-butyldiphenyl-
silyloxymethyl-60-methoxy-2,2-dimethyl--30S,3aS,5R,60R,
60S,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20--30H,
4.1.14. 5-t-Butyldiphenylsilyloxymethyl-40,50-dihydroxy-
60-methoxy-2,2-dimethyl-+30S,3aS,40S,5R,50S,60S,60R,
6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-+30H,40,
50H,60H-pyran)]-3-yl acetate +30). To a stirred solution of
29 ?0.15 g, 0.26mmol) in acetone±water ?5 mL, 4:1) were
added sequentially NMO ?31 mg, 0.26mmol) and OsO 4 ?2
drops) at room temperature. After completion of reaction ?1
week, monitered by TLC), the reaction mixture was worked
up as described for 15 and puri®ed by column chromato-
graphy ?Si-gel, 60±120 mesh, 30% EtOAc±hexane) to
afford 5-t-butyldi-phenylsilyloxymethyl-40,50-dihydroxy-60-
methoxy-2,2-dimethyl--30S,3aS,40S,5R,50S,60S,60R,6aS)-
spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20--30H,40H,50H,
60H-pyran)]-3-yl acetate ?30, 0.095 g, 60%) as a syrup.
Analysis found: C 61.59; H 6.91. C31H42O10Si requires C
60H-pyran)]-30-ol ?31, 0.24 g, 76%) as
a
syrup.
27
[a]D ˆ15.53 ?c 1.3, CHCl3); dH ?200 MHz, CDCl3)
7.85±7.50 ?4H, m, Ph), 7.50±7.30 ?6H, m, Ph), 6.02±5.83
?2H, m, H-7, 8), 5.73 ?1H, d, J1,2ˆ4.0 Hz, H-1), 4.90 ?1H, br
s, H-9), 4.60 ?1H, d, J1,2ˆ4.0 Hz, H-2), 4.27 ?1H, br s, H-6),
4.20±3.98 ?3H, m, H-4,5,50), 3.35 ?3H, s, OCH3), 1.40, 1.32,
1.31, 1.10 ?15H, 4s, CH3); m/z: ?FABMS), 549 ?M1123),
437. Analysis found: C 65.97; H 7.14. C29H38O7Si requires
C 66.13; H 7.27.
27
61.77; H 7.02%; [a]D ˆ214.6? c 0.5, CHCl3); dH
4.1.12. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+30S,3aS,5R,60S,60S,6aS)-spiro[perhydrofuro-
[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-3-yl
?200 MHz, CDCl3) 7.76±7.65 ?5H, m, Ph), 7.42±7.30
?5H, m, Ph), 5.60 ?1H, d, J1,2ˆ4.0 Hz, H-1), 5.39 ?1H, br
d, J6,7ˆ9.6Hz, H-6), 4.53 ?1H, br s, H-9), 4.46 ?1H, d,
J1,2ˆ4.0 Hz, H-2), 4.31±4.10 ?2H, m, H-7,8), 4.0±3.85
?3H, m, H-4,5,50), 3.45 ?3H, s, OCH3), 2.15 ?3H, s,
COCH3), 1.25, 1.20, 1.04 ?15H, 3s, CH3); m/z: ?FABMS),
625 ?M1123), 551, 545.
acetate
+29). A solution of 28 ?0.2 g, 0.38 mmol) and Et3N
?0.13 mL, 0.95 mmol) in CH2Cl2 ?5 mL) was treated with
Ac2O ?0.06mL, 0.57 mmol) in presence of catalytic DMAP
at 08C and worked up as described for 7 to afford 5-t-butyl-
diphenylsilyloxymethyl-60-methoxy-2,2-dimethyl--30S,3aS,
5R,60S,60S,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20--30H,60H-pyran)]-3-yl acetate ?29, 0.15 g, 70%) as a
4.1.15. 5-t-Butyldiphenylsilyloxymethyl-40,50-dihydroxy-
60-methoxy-2,2-dimethyl-+30S,3aS,40S,5R,50S,60R,60R,
6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-+30H,
40H,50H,60H-pyran)]-3-yl acetate +33). To a stirred
solution of 32 ?0.1 g, 0.17 mmol) in acetone±water ?5 mL,
4:1) were added sequentially NMO ?21 mg, 0.17 mmol) and
syrup. [a]D ˆ10.27 ?c 1.44, CHCl3); IR ?neat, cm21):
27
2940, 2885, 1720, 1060; dH ?200 MHz, CDCl3) 7.80±7.60
?4H, m, Ph); 7.45±7.30 ?6H, m, Ph), 5.95±5.75 ?2H, m,
H-7,8), 5.69 ?1H, d, J1,2ˆ3.9 Hz, H-1), 5.55 ?1H, d,

3810
G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
OsO4 ?2 drops) at room temperature. After completion of
reaction ?1 week, monitered by TLC), the reaction
mixture was worked up as described for 15 and puri®ed
by column chromatography ?Si-gel, 60±120 mesh, 30%
EtOAc±hexane) to afford 5-t-butyldi- phenylsilyloxy-
methyl-4 0,5 0-dihydroxy-6 0-methoxy-2,2-dimethyl-
-30S,3aS,40S,5R, 50S,60R,60R,6aS)-spiro[perhydrofuro[2,3-
d][1,3]dioxole-6,20--30H,40H,50H,60H-pyran)]-3-yl acetate
?33, 0.035 g, 33%) as a syrup. Analysis found: C 61.62; H
4.1.18. 5-t-Butyldiphenylsilyloxymethyl-6-+2-furyl)-2,2-
dimethyl-+3aR,5S,6R,6aR)-perhydrofuro[2,3-d][1,3]-
dioxol-6-ol +22). To a solution of 18 ?3.0 g, 7.0 mmol) in
CH2Cl2 was added PDC ?5.2 g, 14.0 mmol), Ac2O ?cataly-
tic) and heated at re¯ux temperature for 3 h. Usual work up
as described for 19 gave 20 ?2.23 g, 75%) as a syrup.
To a stirred solution of furan ?0.52 mL, 7.74 mmol) in dry
THF ?10 mL), n-BuLi ?5.16mL, 7.74 mmol, 1.5 M solution
in hexane) was added dropwise at 2408C. After 1 h, ketone
20 ?2.2 g, 5.16mmol) in dry THF ?6mL) was added drop-
wise at the same temperature over 10 min and the reaction
mixture was worked up as described for 10 and puri®ed by
column chromatography ?Si-gel, 60±120 mesh, 3% ethyl-
acetate in hexane) to afford 5-t-butyldiphenylsilyloxymethyl-
6--2-furyl)-2,2-dimethyl--3aR,5S,6R,6aR)-perhydrofuro-
[2,3-d][1,3]dioxol-6-ol ?22, 1.45 g, 57%) as a syrup.
27
6.87. C31H42O10Si requires C 61.77; H 7.02%; [a]D ˆ17.5
?c 0.64, CHCl3); dH ?200 MHz, CDCl3) 7.80±7.60 ?5H, m,
Ph), 7.51±7.30 ?5H, m, Ph), 5.52 ?1H, d, J1,2ˆ4.0 Hz, H-1),
5.48 ?1H, d, J6,7ˆ4.7 Hz, H-6), 4.98 ?1H, d, J8,9ˆ7.3 Hz, H-
9), 4.85 ?1H, d, J1,2ˆ4.0 Hz, H-2), 4.05±3.95 ?2H, m, H-
7,8), 3.90±3.70 ?2H, m, H-4,50), 3.52 ?3H, s, OCH3), 3.50±
3.40 ?1H, m, H-5), 2.19 ?3H, s, COCH3), 1.48, 1.40, 1.04
?15H, 3s, CH3); m/z: ?FABMS), 625 ?M1123), 551, 545.
27
[a]D ˆ23.4 ?c 1.8, CHCl3); dH ?200 MHz, CDCl3) 7.80±
4.1.16. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di+methylcarbonyloxy)-+30S,3aS,40S,5R,
50S,60S,60R,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20-+30H,40H,50H,60H-pyran)]-5-yl acetate +3). A solution
of the diol 30 ?0.03 g, 0.05 mmol) in CH2Cl2 ?5 mL) was
treated with Et3N ?0.017 mL, 0.12 mmol) and Ac2O
?0.01 mL, 0.1 mmol) and worked up as described for 7
to afford 5-t-butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di-methylcarbonyloxy) -30S,3aS,40S,5R,50S,
60S,60R,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-5-yl acetate ?3, 0.022 g, 65%) as
7.60 ?5H, m, Ph), 7.41±7.25 ?6H, m, H-8, Ph), 6.32 ?2H, br
s, H-6,7), 5.79 ?1H, d, J1,2ˆ3.9 Hz, H-1), 4.68 ?1H, d,
J1,2ˆ3.9 Hz, H-2), 4.28±4.01 ?2H, m, H-4,50), 3.89 ?1H,
0
dd, J4,5ˆ5.5 Hz, J5,5 ˆ11.0 Hz, H-5), 3.50 ?1H, br s. OH),
1.51, 1.32 ?6H, 2s, CH3), 1.01, 0.09 ?9H, 2s, CH3); dC
?50 MHz, CDCl3) 142.0, 135.6?2C), 135.5 ?2C), 134.7
?2C), 129.5 ?2C), 127.6 ?4C), 110.3, 106.4, 104.5, 85.1,
84.4, 62.7, 41.5, 27.2, 27.1, 26.7 ?2C), 26.5 ?2C), 23.2,
19.0; m/z: ?FABMS), 517 ?M1123), 437, 419; HRMS
found: 517.2016. C28H34O6NaSi ?M1123) requires 517.2022.
a syrup. [a]D ˆ121.14 ?c 1.05, CHCl3); IR ?neat, cm21):
4.1.19. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+3aR,5S,60R,6aR)-spiro[perhydrofuro[2,3-d]-
[1,3]dioxole-6,20-+30H,60H-pyran)]-30-one +27). A solution
of 22 ?1.4 g, 2.83 mmol) in THF±water ?10 mL, 4:1) was
cooled to 258C and NBS ?0.5 g, 2.83 mmol) was added in
portions. After 5 min, the reaction mixture was worked up
as described for 9 to afford the lactols 26 ?1.22 g, 85%, 3:2)
as a syrup.
27
2930, 2885, 1700, 1725, 1050; dH ?400 MHz, CDCl3) 7.76±
7.65 ?5H, m, Ph), 7.42±7.30 ?5H, m, Ph), 5.61±5.52 ?2H, m,
H-1,6), 5.40 ?1H, dd, J7,8ˆ3.4 Hz, J8,9ˆ2.9 Hz, H-8), 5.19
?1H, t, Jˆ3.4 Hz, H-7), 4.63 ?1H, d, J8,9ˆ2.9 Hz, H-9), 4.58
?1H, d, J1,2ˆ4.1 Hz, H-2), 4.30±4.10 ?2H, m, H-4,50), 3.73
0
?1H, dd, J5,5 ˆ11.2 Hz, J4,5ˆ5.6Hz, H-5), 3.42 ?3H, s, OC H3),
2.15, 2.10, 2.01 ?9H, 3s, COCH3), 1.28, 1.20, 1.05 ?15H, 3s,
CH3); m/z: ?FABMS), 709 ?M1123); HRMSFAB found:
709.2644. C35H46O12NaSi ?M1123) requires 709.2656.
A mixture of the above lactols 26 ?1.22 g, 2.39 mmol) in
CH2Cl2 ?10 mL) was treated with MeI ?0.34 mL,
4.78 mmol) in the presence of Ag2O ?0.55 g, 2.39 mmol)
for 12 h. The reaction mixture was worked up as described
for 10 to afford an anomeric mixture of O-methyl glycosides
5-t-butyldiphenylsilyloxymethyl-60-methoxy-2,2-dimethyl-
-3aR,5S,60R,6aR)-spiro[perhydrofuro[2,3-d][1,3]di -oxole-
6,20--30H,60H-pyran)]-30-one ?27, 0.77 g, 62%) as a syrup.
Trace of the b-anomer was separated by column chromato-
graphy. b-anomer: dH ?200 MHz, CDCl3) 7.80±7.60 ?5H,
m, Ph), 7.50±7.32 ?5H, m, Ph), 6.16 ?1H, dd, J7,8ˆ9.3 Hz,
H-8), 6.05 ?1H, dd, J7,8ˆ9.3 Hz, H-7), 5.85 ?1H, s, H-9),
5.72 ?1H, d, J1,2ˆ4.2 Hz, H-1), 4.60 ?1H, d, J1,2ˆ4.2 Hz,
4.1.17. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di+methylcarbonyloxy)-+30S,3aS,40S,5R,
50S,60R,60R,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20-+30H,40H,50H,60H-pyran)]-5-yl acetate +4). A solution
of the diol 33 ?30 mg, 0.05 mmol) in CH2Cl2 ?5 mL) was
treated with Et3N ?0.017 mL, 0.12 mmol) and Ac2O
?0.01 mL, 0.1 mmol) and worked up as described for 7
to afford 5-t-butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di-methylcarbonyloxy)--30S,3aS,40S,5R,50S,
60R,60R,6aS)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-5-yl acetate ?4, 24 mg, 72%) as a
27
0
syrup. [a]D ˆ229.2 ?c 0.9, CHCl3); dH ?500 MHz, CDCl3)
H-2), 4.40 ?1H, dd, J4,5ˆ5.3 Hz, J4,5 ˆ10.5 Hz, H-4), 4.10
7.65±7.76 ?5H, m, Ph), 7.30±7.42 ?5H, m, Ph), 5.69 ?1H,
dd, J8,9ˆ3.3 Hz, J7,8ˆ3.1 Hz, H-8), 5.60 ?1H, d,
J1,2ˆ4.0 Hz, H-1), 5.23 ?1H, d, J8,9ˆ3.3 Hz, H-9), 5.18
?1H, d, J6,7ˆ8.5 Hz, H-6), 4.99 ?1H, d, J1,2ˆ4.0 Hz, H-2),
4.88 ?1H, dd, J6,7ˆ8.5 Hz, J7,8ˆ3.1 Hz, H-7), 4.04 ?1H, dd,
?1H, t, Jˆ10.5 Hz, H-50), 3.82±3.70 ?1H, m, H-5), 3.52 ?3H,
s, OCH3), 1.60, 1.42, 1.27, 1.0 ?15H, 4s, CH3); m/z:
?FABMS), 547 ?M1123), 467, 435; HRMS found:
523.2149. C29H35O7Si ?M121) requires 523.2152.
0
J5,5 ˆ10.1 Hz, J4,5ˆ6.05 Hz, H-5), 3.85 ?1H, dd,
4.1.20. Reduction of enone 27. To a solution of 27 ?0.6g,
1.14 mmol) in methanol ?5 mL), CeCl3´7H2O ?0.42 g,
1.14 mmol) and NaBH4 ?42 mg, 1.14 mmol) were added
sequentially and it was worked up as described for 7 and
puri®ed by column chromatography ?Si-gel, 60±120 mesh,
10% EtOAc±hexane).
0
J4,5ˆ6.0 Hz, J4,5 ˆ10.1 Hz, H-4), 3.80 ?1H, t, Jˆ10.1
0
0
J5,5 ˆ10.1 Hz, H-5 ), 3.44 ?3H, s, OCH3), 2.19, 2.05, 2.02
?9H, 3s, CH3), 1.49, 1.40 ?6H, 2s, CH3), 1.20, 1.02 ?9H, 2s,
CH3), m/z: ?FABMS), 709 ?M1123); HRMSFAB found:
709.2652. C35H46O12NaSi ?M1123) requires 709.2656.

G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
3811
First eluted was: 30-t-butyldiphenylsilyloxy-60-methoxy-2,2-
dimethyl--30R,3aR,5S,60S,60R,6aR)-spiro [perhydrofuro[2,
3-d][1,3]dioxole-6,20--30H,60H-pyran)]-5-ylmethanol ?34,
?5H, m, Ph), 5.88±5.70 ?2H, m, H-7,8), 5.60 ?1H, d,
J1,2ˆ4.0 Hz, H-1), 5.52 ?1H, d, J6,7ˆ2.5 Hz, H-6), 4.89
?1H, s, H-9), 4.40 ?1H, d, J1,2ˆ4.0 Hz, H-2), 4.22±4.09
?2H, m, H-4,50), 3.92±3.80 ?1H, m, H-5), 3.21 ?3H, s,
OCH3), 2.12 ?3H, s, COCH3), 1.24, 1.20 ?6H, 2s, 6H,
CH3), 1.02 ?9H, s, CH3), 13C NMR ?50 MHz, CDCl3):
169.7, 135.6 ?3C), 135.4, 129.3 ?2C), 128.0, 127.8 ?2C),
127.4 ?3C), 111.8, 105.7, 94.7, 87.8, 79.8, 78.5, 70.9,
64.2, 56.0, 29.6, 26.8 ?4C), 26.3, 26.0, 20.9, 19.1;
FABMS: 591 ?M1123).
27
0.20 g, 33%), [a]D ˆ219.8 ?c 1.0, CHCl3); dH
?200 MHz, CDCl3) 7.70±7.55 ?5H, m, Ph), 7.35±7.22
?5H, m, Ph), 5.82 ?1H, dd, J7,8ˆ7.2 Hz, H-8), 5.66 ?1H,
dd, J7,8ˆ7.2 Hz, H-7), 5.60 ?1H, d, J1,2ˆ3.8 Hz, H-1), 5.29
?1H, br s, H-9), 4.49 ?1H, d, J1,2ˆ3.8 Hz, H-2), 4.20 ?1H, br
s, H-6), 4.12±3.82 ?3H, m, H-4,5,50), 3.18 ?3H, s, OCH3),
1.30, 1.23, 1.20, 1.0 ?15H, 4s, CH3), m/z: ?FABMS), 549
?M1123), 469, 437; HRMS found: 526.2383. C29H38O7Si
requires 526.2386.
4.1.23. 5-t-Butyldiphenylsilyloxymethyl-40,50-dihydroxy-
60-methoxy-2,2-dimethyl-+30R,3aS,40R,5S,50R,60S,60S,
6aR)spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-+30H,
40H,50H,60H-pyran)]-3-yl acetate +38). To a stirred solu-
tion of 36 ?0.15 g, 0.26mmol) in acetone±water ?5 mL, 4:1)
were added sequentially NMO ?31 mg, 0.26mmol) and
OsO4 ?2 drops) at room temperature. After completion of
reaction ?1 week, monitored by TLC), the reaction mixture
was worked up as described for 15 and puri®ed by column
chromatography ?Si-gel, 60±120 mesh, 30% EtOAc±
hexane) to afford 5-t-butyldiphenylsilyloxymethyl-40,50-
dihydroxy-60-methoxy-2,2-dimethyl--30R,3aS,40R,5S,50R,
60S,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-3-yl acetate ?38, 0.095 g, 60%)
as a syrup. Analysis found: C 61.56; H 6.82. C31H42O10Si
Second eluted was: 30-t-butyldiphenylsilyloxy-60-methoxy-
2,2-dimethyl--30R,3aR,5S,60R,60R,6aR)-spiro[perhydro-
furo[2,3-d][1,3]dioxole-6,20--30H,60H-pyran)]-5-ylmetha-
nol ?35, 0.21 g, 35%) as a syrup, Analysis found: C 65.97; H
27
7.03. C29H38O7Si requires C 66.13; H 7.27%; [a]D ˆ10.42
?c 0.6, CHCl3); dH ?200 MHz, CDCl3) 7.80±7.67 ?5H, m,
Ph), 7.45±7.30 ?5H, m, Ph), 5.99 ?1H, dd, J7,8ˆ7.8 Hz, H-8),
5.82 ?1H, dd, J7,8ˆ7.8 Hz, J6,7ˆ4.6Hz, H-7), 5.70 ?1H, d,
J1,2ˆ4.2 Hz, H-1), 4.89 ?1H, br s, H-9), 4.53 ?1H, d,
J1,2ˆ4.2 Hz, H-2), 4.20 ?1H, d, J6,7ˆ4.6Hz, H-6), 4.16±
3.90 ?3H, m, H-4,5,50), 3.29 ?3H, s, OCH3), 1.28, 1.24,
1.21, 1.05 ?15H, 4s, CH3); m/z: ?FABMS), 549 ?M1123),
469, 437.
27
requires C 61.77; H 7.02%; [a]D ˆ118.5 ?c 1.3, CHCl3);
4.1.21. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+30R,3aR,5S,60R,60S,6aR)spiro[perhydrofuro-
dH ?200 MHz, CDCl3) 7.80±7.65 ?5H, m, Ph), 7.46±7.30
?5H, m, Ph), 5.60 ?1H, d, J1,2ˆ3.8 Hz, H-1), 5.20 ?1H, d,
J6,7ˆ4.7 Hz, H-6), 4.95 ?1H, d, J1,2ˆ3.8 Hz, H-2), 4.90 ?1H,
d, J8,9ˆ7.2 Hz, H-9), 4.40 ?1H, t, Jˆ4.4 Hz, H-4), 4.05±
3.95 ?2H, m, H-7,8), 3.90±3.80 ?1H, m, H-50), 3.80±3.68
?1H, m, H-5), 3.50 ?3H, s, OCH3), 2.15 ?3H, s, COCH3),
1.41, 1.25, 1.02 ?15H, 3s, CH3); FABMS: 625 ?M1123).
[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-3-yl
acetate
+36). A solution of 34 ?0.2 g, 0.38 mmol) and Et3N
?0.13 mL, 0.95 mmol) in CH2Cl2 ?5 mL) was treated with
Ac2O ?0.06mL, 0.57 mmol) in presence of catalytic DMAP
at 08C and worked up as described for 7 afforded 5-t-butyl-
diphenylsilyloxymethyl-60-methoxy-2,2-dimethyl--30R,3aR,
5S,60R,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20--30H,60H-pyran)]-3-yl acetate ?36, 0.15 g, 70%) as a
syrup. Analysis found: C 65.32; H 6.87. C31H40O8Si requires
4.1.24. 5-t-Butyldiphenylsilyloxymethyl-40,50-dihydroxy-
60-methoxy-2,2-dimethyl-+30R,3aR,40R,5S,50R,60R,60S,
6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-+30H,
40H,50H,60H-pyran)]-3-yl acetate +39). To a stirred solu-
tion of 37 ?0.1 g, 0.17 mmol) in acetone±water ?5 mL, 4:1)
were added sequentially NMO ?21 mg, 0.17 mmol) and
OsO4 ?2 drops) at room temperature. After completion of
reaction ?1 week, monitered by TLC), the reaction mixture
was worked up as described for 15 and puri®ed by column
chromatography ?Si-gel, 60±120 mesh, 30% EtOAc±
hexane) to afford 5-t-butyldiphenylsilyloxymethyl-40,50-
dihydroxy-60-methoxy-2,2-dimethyl--30R,3aR,40R,5S,50R,
60R,60S,6aR)-spiro[perhydrofuro[2,3-d]-[1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-3-yl acetate ?39, 0.035 g, 39%)
as a syrup. Analysis found: C 61.52; H 6.88. C31H42O10Si
27
C 65.47; H 7.09%; [a]D ˆ135.5 ?c 0.25, CHCl3); dH
?200 MHz, CDCl3) 7.75±7.60 ?5H, m, Ph), 7.42±7.30
?5H, m, Ph), 5.93±5.88 ?2H, m, H-7,8), 5.80 ?1H, d,
J1,2ˆ4.1 Hz, H-1), 5.58 ?1H, d, J6,7ˆ2.2 Hz, H-6), 5.42
?1H, br s, H-9), 4.53 ?1H, d, J1,2ˆ4.1 Hz, H-2), 4.12±4.0
?2H, m, H-4,50), 3.94±3.87 ?1H, m, H-5), 3.21 ?3H, s,
OCH3), 2.12 ?3H, s, COCH3), 1.40, 1.39, 1.22, 1.02 ?15H,
4s, CH3); dC ?50 MHz, CDCl3) 169.5, 135.7 ?2C), 135.6
?2C), 133.5, 129.4 ?2C), 128.9 ?2C), 127.5 ?3C), 113.7,
105.5, 95.5, 84.9, 82.5, 81.4, 69.1, 63.0, 54.1, 29.3, 26.8
?4C), 26.7 ?2C), 20.9, 19.1; m/z: ?FABMS), 591 ?M1123).
27
4.1.22. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-+30R,3aR,5S,60R,60R,6aR)-spiro[perhydrofuro-
requires C 61.77; H 7.02%; [a]D ˆ215.7 ?c 2.2, CHCl3);
dH ?200 MHz, CDCl3) 7.76±7.65 ?5H, m, Ph), 7.42±7.30
?5H, m, Ph), 5.60 ?1H, d, J1,2ˆ4.0 Hz, H-1), 5.39 ?1H, br d,
J6,7ˆ9.6Hz, H-6), 4.53 ?1H, br s, H-9), 4.46?1H, d, J1,2ˆ
4.0 Hz, H-2), 4.31±4.10 ?2H, m, H-7,8), 4.0±3.85 ?3H, m,
H-4,5,50), 3.35 ?3H, s, OCH3), 2.15 ?3H, s, COCH3), 1.25,
1.20, 1.05 ?15H, 3s, CH3), FABMS: 625 ?M1123).
[2,3-d][1,3]dioxole-6,20-+30H,60H-pyran)]-3-yl
acetate
+37). A solution of 35 ?0.2 g, 0.38 mmol) and Et3N
?0.13 mL, 0.95 mmol) in CH2Cl2 ?5 mL) was treated with
Ac2O ?0.06mL, 0.57 mmol) in presence of catalytic DMAP
at 08C and worked up as described for 8 to afford 5-t-butyl-
diphenylsilyloxymethyl-60-methoxy-2,2-dimethyl--30R,3aR,
5S,60R,60R,6aR)-spiro-[perhydrofuro[2,3-d][1,3]dioxole-
6,20--30H,60H-pyran)]-3-yl acetate ?37, 0.11 g, 55%) as a
syrup. Analysis found: C 65.37; H 6.91. C31H40O8Si requires
4.1.25. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di+methylcarbonyloxy)-+30R,3aR,40R,5S,
50R,60S,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20-+30H,40H,50H,60H-pyran)]-5-yl acetate +5). A solution
of the diol 38 ?30 mg, 0.05 mmol) in CH2Cl2 ?5 mL) was
27
C 65.47; H 7.09; [a]D ˆ218.5 ?c 1.5, CHCl3); dH
?200 MHz, CDCl3) 7.76±7.60 ?5H, m, Ph), 7.45±7.30

3812
G. V. M. Sharma et al. / Tetrahedron 58 -2002) 3801±3812
3. Carbohydrates. Synthetic Methods Applications in Medicinal
Chemistry, Ogura, H., Hasegawa, A., Suami, T., Eds.;
Kodansha: Tokyo, 1992.
treated with Et3N ?0.017 mL, 0.12 mmol) and Ac2O
?0.01 mL, 0.1 mmol) and worked up as described for 7 to
afford 5-t-butyl diphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di-methylcarbonyloxy)--30R,3aR,40R,5S,50R,
60S,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-5-yl acetate ?5, 27 mg, 80%) as a
4. Ager, D. J.; East, M. B. Tetrahedron 1993, 49, 5683.
5. Hanessian, S. The Total Synthesis of Natural Products: the
Chiron Approach; Pergamon: Oxford, 1983.
6. Casiraghi, G.; Rasu, G. Synthesis 1995, 607.
7. Casiraghi, G.; Rasu, G. Aspects of Modern Higher Carbon
Sugar Synthesis. Studies in Natural Product Chemistry;
Atta-ur-Rahman, T., Ed.; Elsevier: Amsterdam, 1992; Vol.
11, p. 429.
27
syrup. [a]D ˆ132.2 ?c 0.7, CHCl3); dH ?500 MHz, CDCl3)
7.76±7.65 ?5H, m, Ph), 7.42±7.30 ?5H, m, Ph), 5.69 ?1H, t,
Jˆ3.1 Hz, H-8), 5.60 ?1H, d, J1,2ˆ4.0 Hz, H-1), 5.22 ?1H, d,
J8,9ˆ3.1 Hz, H-9), 5.18 ?1H, d, J6,7ˆ8.5 Hz, H-6), 4.99 ?1H,
d, J1,2ˆ4.0 Hz, H-2), 4.88 ?1H, dd, J6,7ˆ8.46Hz,
0
8. Baggett, N.; Kennedy, J. F. Synthesis of Monosaccharides by
Chain Extension. In Carbohydrate Chemistry, Kennedy, J. F.,
Ed.; Clarendon: Oxford, 1988.
J7,8ˆ3.1 Hz, H-7), 4.04 ?1H, dd, J4,5 ˆ10.16Hz,
J4,5ˆ6.05 Hz, H-4), 3.84±3.78 ?2H, m, H-5,50), 3.44 ?3H,
s, OCH3), 2.19, 2.05, 2.02 ?9H, 3s, CH3), 1.49, 1.40 ?6H, 2s,
CH3), 1.20, 1.02 ?9H, 2s, CH3); FABMS: 709 ?M1123).
HRMSFAB found: 709.2655. C35H46O12NaSi requires
709.2656.
9. Hanessian, S.; Franco, J.; Larouche, B. Pure Appl. Chem.
1990, 62, 1887.
10. Casiraghi, G.; Rasu, G. Chemtracts-Org. Chem. 1993, 6, 336.
11. ?a) Rouzaud, D.; Sinay, P. J. Chem. Soc., Chem. Commun.
1983, 1353. ?b) Neuman, A.; Longchambon, F.; Abbes, O.;
Gillier-Pandraud, H.; Perez, S.; Rouzaud, D.; Sinay, P.
Carbohydr. Res. 1990, 195, 2209.
4.1.26. 5-t-Butyldiphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di+methylcarbonyloxy)-+30R,3aR,40R,5S,
50R,60R,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-
6,20-+30H,40H,50H,60H-pyran)]-5-yl acetate +6). A solution
of the diol 39 ?30 mg, 0.05 mmol) in CH2Cl2 ?5 mL) was
treated with Et3N ?0.017 mL, 0.12 mmol) and Ac2O
?0.01 mL, 0.1 mmol) and worked up as described for 7 to
afford 5-t-butyl diphenylsilyloxymethyl-60-methoxy-2,2-
dimethyl-30,40-di-methylcarbonyloxy)--30R,3aR,40R,5S,50R,
60R,60S,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,20-
-30H,40H,50H,60H-pyran)]-5-yl acetate ?6, 25 mg, 76%) as a
12. Levy, D.; Tang, C. The Chemistry of C-Glycosides; Elsevier:
New York, 1995.
13. Bols, M. Acc. Chem. Res. 1998, 31, 1.
14. Sharma, G. V. M.; Hymavathi, L.; Radhakrishna, P.
Tetrahedron Lett. 1997, 38, 6929.
15. Sharma, G. V. M.; Chander, A. S.; Krishnudu, K.;
Radhakrishna, P. Tetrahedron Lett. 1997, 38, 9051.
16. Sharma, G. V. M.; Chander, A. S.; Krishnudu, K.;
Radhakrishna, P. Tetrahedron Lett. 1998, 39, 6957.
17. Sharma, G. V. M.; Reddy, V. G.; Radhakrishna, P.
Tetrahedron Lett. 1999, 40, 1783.
27
syrup. [a]D ˆ220.7 ?c 0.75, CHCl3); dH ?500 MHz,
CDCl3) 7.76±7.65 ?5H, m, Ph), 7.42±7.30 ?5H, m, Ph),
5.62 ?1H, d, J6,7ˆ10.8 Hz, H-6), 5.59 ?1H, d, J1,2ˆ3.7 Hz,
H-1), 5.45 ?1H, dd, J7,8ˆ3.2 Hz, J6,7ˆ10.8 Hz, H-7), 5.22
?1H, dd, J7,8ˆ3.2 Hz, J8,9ˆ1.9 Hz, H-8), 4.64 ?1H, d,
J8,9ˆ1.9 Hz, H-9), 4.61 ?1H, d, 1H, J1,2ˆ3.7 Hz, H-2),
4.30±4.10 ?2H, m, H-4,50), 3.73 ?1H, dd, J5,5ˆ11.2 Hz,
J4,5ˆ5.6Hz, H-5), 3.42 ?3H, s, OCH 3), 2.15, 2.10, 2.01
?9H, 3s, COCH3), 1.28, 1.20, 1.05 ?15H, 3s, CH3);
FABMS: 709 ?M1123). HRMSFAB found: 709.2679.
C35H46O12NaSi ?M1123) requires 709.2656.
18. Sharma, G. V. M.; Chander, A. S.; Reddy, V. G.; Krishnudu,
K.; Ramana Rao, M. H. V.; Kunwar, A. C. Tetrahedron Lett.
2000, 41, 1997.
19. Yoshimura, J.; Sato, K.; Hoshimoto, H. Chem. Lett. 1977,
1327.
20. Herscovici, J.; Antonakis, K. J. Chem. Soc., Chem. Commun.
1980, 561.
21. Mukaiyama, T.; Suzuki, K.; Yamada, T.; Tabusa, F.
Tetrahedron 1990, 46, 265.
22. Kakinuma, K.; Li, H.-Y. Tetrahedron Lett. 1989, 30, 4157.
23. Georgeiadis, M. P.; Couladouros, E. A. J. Org. Chem. 1986,
51, 2725.
Acknowledgements
Mr V. G. Reddy and A. Ravi Sankar are thankful to CSIR,
New Delhi, India, for ®nancial assistance. G. V. M. Sharma
is thankful to CSIR for the ®nancial support from CSIR
Young Scientist Award Grant.
24. Luche, J. L.; Rodriguez-Hahn, L.; Crabbe, P. J. Chem. Soc.,
Chem. Commun. 1978, 601.
25. Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748.
26. Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett. 1983, 24,
3943.
27. Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40,
2247.
References
28. Bouzide, A.; Sauve, G. Tetrahedron Lett. 1997, 38, 5945.
29. States, D. J.; Haber Korn, R. A.; Ruber, D. J. J. Magn. Reson.
1982, 48, 286.
1. Casiraghi, G.; Zanardi, F. Chem. Rev. 1995, 95, 1677.
2. Garegg, P. J. Acc. Chem. Res. 1992, 25, 575.