Synthesis of an adenine nucleoside containing the (8′ R) epimeric carbohydrate core of amipurimycin and its biological study

Article abstract of DOI:10.1021/jo102193q

The (8′R) epimeric carbohydrate core 2 of amipurimycin was synthesized from d-glucose derived allylic alcohol 3 in 11 steps and 13% overall yield. The key steps involve an acid-catalyzed acetonide ring opening of 9 with concomitant formation of an unprece

Full text of DOI:10.1021/jo102193q

NOTE
pubs.acs.org/joc
Synthesis of an Adenine Nucleoside Containing the (80R) Epimeric
Carbohydrate Core of Amipurimycin and Its Biological Study
Rajendra S. Mane,†,^ Sougata Ghosh,‡ Balu A. Chopade,‡ Oliver Reiser,§ and Dilip D. Dhavale*,†
†Department of Chemistry, Garware Research Centre, and ‡Institute of Bioinformatics and Biotechnology, University of Pune, Pune 411
007, India
§Institut f€ur Organische Chemie, Universit€at Regensburg, Universit€atstrasse 31, 93053 Regensburg, Germany
S Supporting Information
b
ABSTRACT: The (80R) epimeric carbohydrate core 2 of amipurimy-
cin was synthesized from D-glucose derived allylic alcohol 3 in 11 steps
and 13% overall yield. The key steps involve an acid-catalyzed
acetonide ring opening of 9 with concomitant formation of an
unprecedented pyranose ring skeleton to give 2,7-dioxabicyclo-
[3.2.1]octane 10. The R-orientation of the furan ring in 10 readily
allows the stereoselective β-glycosylation and opening of the furanose
ring that on removal of protecting groups affords the pyranosyl adenine nucleoside 2. The antifungal and anticancer activities of 2
were studied.
he peptidyl nucleoside antibiotic amipurimycin 1 (Figure 1),
isolated from Streptomyces novoguineensis sp. nov., shows
in 3 using 30% HClO4 in THF gave triol 4, which on treatment
with NaIO4 afforded aldehyde 5. Reduction of aldehyde func-
tionality in 5 with NaBH4 gave diol 6, which on protection using
benzyl bromide and sodium hydroxide afforded dibenzylated
product 7.7 Dihydroxylation of the double bond in 7 using
T
activity against Pyricularia oryzae, a causative agent for rice blast
disease.1 On the basis of the chemical degradation, Goto et al.2
have assigned the primary structure of amipurimycin that in-
cludes (a) a unique carbohydrate ring skeleton having a qua-
ternary center at C-30 bearing a hydroxy group and a branched
1,2-dihydroxyethyl side chain, (b) a glycosidic β-linked purine
nucleobase at the anomeric carbon, and (c) an amino acid at C-50
attached at its N-terminus to cis-pentacin with undefined abso-
lute configurations at C-60 and in the aminocyclopentane ring.3
Different strategies for the synthesis of pyranosyl sugar cores of
amipurimycin with/without C-30 side chain, nucleobase, and
peptidyl region at C-60 are known.4 As a part of our continuing
efforts in the sugar chemistry,5 we are now reporting the synthe-
sis of the hitherto unknown (80R) epimeric pyranosyl adenine
nucleoside analogue 2, representing a carbohydrate core of
amipurimycin with C-30 dihydroxyethyl side chain, and the study
of its antifungal and anticancer activity.
Our retrosynthetic analysis (Scheme 1) suggested that acety-
lated 2,7-dioxabicyclo[3.2.1]octane A would allow the stereo-
selective β-glycosylation with concomitant opening of the furan
ring to give pyranosyl nucleoside 2. We envisaged the formation
of the bridged bicyclic system A upon opening of the 1,2-
acetonide functionality in B under acidic conditions, followed
by addition of the alkoxy side chain at C-3 to the in situ generated
oxocarbenium ion intermediate. Intermediate B could be ob-
tained from the D-glucose derived homoallylic alcohol 3 by
dihydroxylation, oxidation, and reduction protocol.
K2OsO4 2H2O (5 mol %) and N-methylmorpholine-N-oxide
3
(NMO) as co-oxidant followed by oxidative cleavage of the
intermediate diol with NaIO4 gave aldehyde 8. Reduction of 8
using NaBH4 followed by hydrolysis of 1,2-acetonide group in 9
with TFA/water (3:1) provided 10 with the desired 2,7-
dioxabicyclo[3.2.1]octane framework as a single product
(overall 34% yield from 3). Acetylation of 10 using Ac2O and
pyridine gave monoacetyl derivative 11. The chemical shift
1
assignments and coupling constant values in the H NMR of
1
11 were obtained from the decoupling experiments. In the H
NMR spectrum of 11, the H-1 and H-2 protons appeared as two
singlets at δ 5.26 and δ 4.95, respectively. The absence of vicinal
coupling constant between H-1 and H-2 requires the dihedral
angle between these protons to be approximately 90ꢀ. As the
absolute configuration (R) at the C-2 in 9 is retained in the
bicyclic system 10, the H-2 was given the axial position, and
therefore the H-1 was assigned the equatorial orientation. This is
in agreement with the attack of primary hydroxyl side chain at
C-3 from the β-face forcing the H-1 into the equatorial position.
The little twist in the chair conformation, due to the bridged
system, arranges the dihedral angle between the H-1 and H-2
close to 90ꢀ accounting for the absence of a coupling constant.
The formation of anomeric anhydro sugar 10 can be explained
as follows. Under acidic conditions, opening of the 1,2-acetonide
As shown in Scheme 2, D-glucose was converted to the known
alcohol 3 having a well-defined quaternary center and requisite
hydroxyl and allyl groups.6 Selective 5,6-acetonide deprotection
Received: November 3, 2010
Published: March 07, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo102193q J. Org. Chem. 2011, 76, 2892–2895
|

The Journal of Organic Chemistry
NOTE
Scheme 2. Synthesis of 11 and 14
Figure 1. Structures of amipurimycin 1, cis-pentacin, and pyranosyl
nucleoside 2.
Scheme 1. Retrosynthesis of 2
structure of 14, it was alternatively obtained from the previously
synthesized 10 by hydrogenation (10% Pd/C, 80 psi, methanol)
(Scheme 2). Alternatively, hydrogenation of 13 with 10% Pd-
(OH)2 in methanol under balloon pressure afforded the fully
deprotected pyranosyl nucleoside 2 in 77% yield.
functionality in 9 results in the generation of an oxocarbenium
ion Y (Scheme 3), which could be attacked either reversibly by
water to give rise to a hemiacetal or irreversibly by the primary
alcohol to yield 10. We suggest that the attack of the primary
alcohol to the C-1 position of the oxocarbenium ion Y in an
intramolecular and irreversible manner gives rise to a stable
pyranose ring shifting the equilibrium in favor of the bridged
bicyclic system 10.
The antifungal activity of the pyranosyl nucleoside 2 against
seven different pathogenic fungi, Candida tropicalis, Candida
albicans, Fusarium oxysporum, Phoma exigua, Aspergillus oryzae,
Helminthosporium graminium, Trichoderma resei, and Cladospor-
ium herbarum, was determined. Nystatin, a known antifungal
drug, was used as reference.10 Compound 2 did not exhibit
significant antifungal activity against any of the fungal pathogens
as compared to Nystatin, pointing toward the cis-pentacin core as
the active principle for the antifungal activity found in 1. Indeed,
cis-pentacin has pronounced antifungal activity3 and has been an
important lead structure for the development of novel antifungal
agents. The in vitro cytotoxicity of the pyranosyl nucleoside 2
against HeLa (human epithelial cervical cancer) cell lines was
determined at a concentration range of 2.5ꢀ100 μΜ at different
times (24ꢀ96 h).11 The 3-(4,5-dimethyl-thiazol-2-yl)-2,5-di-
phenyl-tetrazolium bromide (MTT) colorimetric assay was used
to determine growth inhibition12 and percentage of inhibition
was calculated and statistically analyzed.5a As shown in Figure 2,
compound 2 exhibited maximum activity during 96 h, highest
being 72.8 ( 1.7% at 100 μΜ. Our results were compared with
the Mitomycin C, a known anticancer drug as standard reference,
which showed 50% inhibition at 5 μM. As compound 2 showed
52.63% inhibition at 20 μΜ, it was found to be four times less
active than the Mitomycin C.
In the next step, the acetyl derivative 11 was glycosylated using
a protocol developed by Zou and Robins8 (Scheme 4). This one-
pot process involves the stereoselective formation of the β-
oriented adenine nucleoside with concomitant opening of the
furan ring unmasking the 1,2-dihydroxyethyl side chain to give
12. The large coupling constant between the H-10 and H-20 (J =
1
8.4 Hz) in the H NMR spectrum of 12 indicated their diaxial
orientation, confirming the stereoselective opening of the
bridged system by the attack of the adenine nucleobase from
the β-face, which is being assisted either by the R-orientated
furanose ring at C-30 or by the acetoxy group at C-20.
In the final steps, hydrolysis of the acetyl and N-benzoyl
protecting groups in 12 using 1 N NaOH yielded nucleoside 13
in good yield. Hydrogenation of 13 with 10% Pd/C at 80 psi in
methanol at room temperature for 12 h unexpectedly afforded
compound 14 (Scheme 2) and not the desired pyranosyl nucleo-
side 2. This one-pot three-step process involves cleavage of the
benzyl groups and restoration of the bridged bicyclic system 14
with concurrent cleavage of the glycosidic bond.9 To confirm the
In conclusion, we have exploited the carbon skeleton of D-
glucose to construct the pyranose ring skeleton with a C-3
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NOTE
Scheme 3. Formation of 10
mmol) in TFAꢀwater (5 mL, 3:1) was stirred for 3 h at 0 ꢀC to rt. TFA
was coevaporated with toluene. Purification by column chromatography
(n-hexane/ethyl acetate = 7/3) furnished 10 (0.30 g, 83%) as a viscous
liquid: Rf 0.61 (n-hexane/ethyl acetate = 3/2); [R]25 þ8.1 (c 0.5,
D
1
CHCl3); IR (CHCl3) 3500ꢀ3000 (br) cmꢀ1; H NMR (300 MHz,
CDCl3) δ 1.60 (br s, 1H), 1.77 (dd, J = 13.2, 4.8 Hz, 1H), 2.05ꢀ2.20 (m,
1H), 3.75ꢀ3.96 (m, 5H), 4.40ꢀ4.45 (m, 1H), 4.48 (d, J = 11.4 Hz, 1H),
4.58 (ABq, J = 12.0 Hz, 2H), 4.63 (d, J = 11.4 Hz, 1H), 5.24 (s, 1H),
7.20ꢀ7.40 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 29.3, 59.0, 66.7,
67.5, 73.3, 80.0, 80.1, 81.2, 102.6, 127.4 (strong), 127.6 (strong), 127.7
(strong), 128.0 (strong), 128.4 (strong), 128.6 (strong), 137.8, 137.9.
Anal. Calcd for C21H24O5: C, 70.77; H, 6.79. Found: C, 70.92; H, 6.93.
(1S,5R,6R,8R)-5-O-Benzyl-6-benzyloxymethyl-8-acetoxy-
2,7-dioxabicyclo[3.2.1]octane (11)14. To a solution of 10 (0.20 g,
0.56 mmol) in pyridine (2 mL) was added Ac2O (0.10 mL, 1.12 mmol),
and the mixture was stirred for 6 h. After concentration, residue was
purified by column chromatography (n-hexane/ethyl acetate = 9/1) to
give 11 (0.18 g, 82%) as a solid: mp 72ꢀ74 ꢀC; Rf 0.81 (n-hexane/ethyl
1H NMR (300 MHz, CDCl3) δ 1.76 (dd, J = 12.9, 4.8 Hz, 1H), 2.10 (s,
3H), 2.24ꢀ2.38 (m, 1H), 3.70ꢀ4.00 (m, 4H), 4.42ꢀ4.48 (m, 1H), 4.43
(ABq, J = 11.1, 2H), 4.56 (ABq, J = 12.3, 2H), 4.95 (s, 1H), 5.26 (s, 1H),
7.18ꢀ7.38 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 20.7, 29.8, 58.8,
67.0, 67.2, 73.2, 76.0, 80.0, 80.6, 101.1, 127.2 (strong), 127.5 (strong),
127.6 (strong), 128.2 (strong), 137.7, 169.8. Anal. Calcd for C23H26O6:
C, 69.33; H, 6.58. Found: C, 69.58; H, 6.76.
Scheme 4. Synthesis of 2
acetate = 7/3); [R]25D þ15.5 (c 1.4, CHCl3); IR (CHCl3) 1739 cmꢀ1
.
Pyranosyl Nucleoside (12). N,O-Bis(trimethylsilyl)acetamide
(0.74 mL, 3.01 mmol) was added to a solution of N-benzoyl adenine
(0.25 g, 1.05 mmol) in dry acetonitrile (4 mL), the reaction mixture was
stirred for 20 min and cooled to 0 ꢀC, a solution of 11 (0.40 g, 1.00
mmol) in dry acetonitrile (3 mL) and TMSOTf (0.19 mL, 1.00 mmol)
was added dropwise at 0 ꢀC, and the resulting solution was stirred for 10
h at 50 ꢀC. The reaction mixture was cooled to 0 ꢀC, and chloroform
(10 mL) and then saturated aq NaHCO3 solution (5 mL) were added.
The reaction mixture was extracted with chloroform (20 mL ꢁ 3), and
the combined organic layers were extracted with brine and concentrated.
Purification by column chromatography (n-hexane/ethyl acetate = 1/4)
gave nucleoside 12 (0.47 g, 73%) as a viscous oil: Rf 0.56 (n-hexane/
ethyl acetate = 1/9); [R]25D þ12.2 (c 0.2, CHCl3); IR (CHCl3) 3300
(br), 1745 cmꢀ1 1H NMR (300 MHz, CDCl3) δ 1.77 (s, 3H),
;
1.80ꢀ2.00 (br s, 1H), 2.10ꢀ2.23 (m, 1H), 2.23ꢀ2.35 (m, 1H), 3.55
(dd, J = 9.9, 6.3 Hz, 1H), 3.90 (dd, J = 9.9, 2.4 Hz, 1H), 3.95ꢀ4.07 (m,
1H), 4.28ꢀ4.65 (m, 6H), 5.76 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 8.4 Hz,
1H), 7.08ꢀ7.38 (m, 10H), 7.42ꢀ7.67 (m, 3H), 8.02 (d, J = 7.2 Hz, 2H),
8.25 (s, 1H), 8.82 (s, 1H), 9.11 (br s, 1H) ; 13C NMR (75 MHz, CDCl3)
δ 20.4, 30.0, 63.6, 64.5, 71.6, 72.7, 73.3, 75.0, 77.5, 81.4, 122.4, 127.5
(strong), 127.6 (strong), 127.7 (strong), 128.3 (strong), 128.7 (strong),
132.6, 133.7, 137.8, 141.1, 149.3, 151.8, 152.8, 164.5, 169.2. Anal. Calcd
for C35H35N5O7: C, 65.92; H, 5.53. Found: C, 66.07; H, 5.66.
Figure 2. Anti-proliferative activity of compound 2 against HeLa cells
incubated with different concentrations at different times (24ꢀ96 h).
The data are expressed as a percentage of the control MTT reduction
(always taken as 100%) and represent the average ( SEM (n = 3). *
denotes more significant value (P < 0.05).13
Pyranosyl Nucleoside (13). A solution of nucleoside 12 (0.5 g,
0.78 mmol) in ethanolꢀwater (7:3, 10 mL) and NaOH (0.12 g, 3.13
mmol) was stirred at room temperature. After 24 h, the reaction mixture
was neutralized with 1 N HCl, and the volume of the reaction mixture
was reduced to half by evaporation at reduced pressure. The mixture was
extracted with chloroform (10 mL ꢁ 3), and the combined organic
layers were concentrated. Purification of the residue by column chro-
matography (n-hexane/ethyl acetate = 1/9) gave nucleoside 13 (0.32 g,
dihydroxyethyl side chain. A unique feature of our strategy is (a)
the acid-catalyzed closing of the pyran ring utilizing a hydro-
xyethyl residue of the sugar furanose ring in 9 to get the bicyclic
ring system 10 and (b) β-selective opening of the sugar furanose
ring in 10 with adenine nucleobase, giving the (80R) epimeric
carbohydrate core 2 of amipurimycin. The pyranosyl adenine
nucleoside 2 showed potent anticancer activity against HeLa
cells.
84%) as a white solid: mp 94ꢀ96 ꢀC; Rf 0.38 (ethyl acetate); [R]25
D
ꢀ36.7 (c 0.5, CHCl3); IR 3650ꢀ3050 (br) (CHCl3) cmꢀ1; 1H NMR
(300 MHz, CDCl3) δ 1.95ꢀ2.18 (m, 1H), 2.20ꢀ2.38 (br d, J = 12.9 Hz,
1H), 3.68ꢀ3.82 (m, 1H), 3.90ꢀ4.10 (m, 2H), 4.22ꢀ4.40 (m, 1H),
4.48ꢀ4.72 (m, 4H), 4.75ꢀ4.94 (m, 2H), 5.40ꢀ6.00 (br s, 2H), 6.12 (br
s, 2H), 6.29 (d, J = 8.7 Hz, 1H), 7.18ꢀ7.38 (m, 10H), 7.79 (s, 1H), 8.12
(s, 1H); 13C NMR (75 MHz, CDCl3) δ 31.6, 64.0, 65.3, 70.0, 72.1, 73.3,
’ EXPERIMENTAL SECTION
(1S,5R,6R,8R)-5-O-Benzyl-6-benzyloxymethyl-8-hydroxy-
2,7-dioxabicyclo[3.2.1]octane (10)14. A solution of 9 (0.40 g, 0.94
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NOTE
73.9, 78.1, 84.0, 118.3, 127.1 (strong), 127.3, 127.7, 127.8 (strong),
128.3 (strong), 128.4 (strong), 137.8, 138.8, 139.4, 149.3, 152.8, 154.6.
Anal. Calcd for C26H29N5O5: C, 63.53; H, 5.95. Found: C, 63.79;
H, 6.16.
(2) (a) Goto, T.; Toya, Y.; Ohgi, T.; Kondo, T. Tetrahedron Lett.
1982, 23, 1271–1274.
(3) (a) Iwamoto, T.; Tsujii, E.; Ezaki, M.; Fujie, A.; Hashimoto, S.;
Okuhara, M.; Kohsaka, M.; Imanaka, H.; Kawabata, K. J. Antibiot. 1990,
43, 1–7. (b) Kawabata, K.; Inamoto, Y.; Sakane, K.; Iwamoto, T.;
Hashimoto, S. J. Antibiot. 1990, 43, 513–518.
(1S,5R,6R,8R)-5,8-Dihydroxy-6-hydroxymethyl-2,7-dioxa-
bicyclo[3.2.1]octane (14)14. To a solution of 10 (0.50 g, 1.40 mmol)
in methanol (15 mL) was added 10% Pd/C (0.20 g), and the solution
was hydrogenated at 80 psi for 12 h. The catalyst was filtered off and
washed with methanol, and the filtrate was concentrated. Purification by
column chromatography (methanol/chloroform = 3/2) furnished 14
(0.17 g, 70%) as a viscous liquid: Rf 0.31 (methanol); [R]25D þ6.9 (c 0.2,
MeOH); IR (neat) 3500ꢀ2900 (br) cmꢀ1; 1H NMR (300 MHz, D2O)
δ 1.88ꢀ2.08 (m, 2H), 3.72 (s, 1H), 3.84ꢀ3.95 (m, 3H), 4.03 (dd, J =
12.3, 9.0 Hz, 1H), 4.22 (br d, J = 8.4 Hz, 1H), 5.28 (s, 1H).; 13C NMR
(75 MHz, D2O) δ 31.6, 58.6, 59.3, 75.2, 77.8, 80.5, 101.9. Anal. Calcd for
C7H12O5: C, 47.72; H, 6.87. Found: C, 47.97; H, 6.96.
Pyranosyl Nucleoside (2). To a stirred solution of nucleoside 13
(0.4 g, 0.80 mmol) in dry methanol (10 mL) was added 10% Pd(OH)2
on carbon (0.05 g). The reaction mixture was flushed with hydrogen
three times and stirred under a hydrogen atmosphere at balloon
pressure. After 12 h, the catalyst was filtered through Celite, the filtrate
was evaporated under reduced pressure, and the residue was purified by
column chromatography (methanol/chloroform = 4/1) to give nucleo-
(4) (a) Stauffer, C. S.; Datta, A. J. Org. Chem. 2008, 73, 4166–4174.
(b) Xue, J.; Guo, Z. J. Carbohydr. Chem. 2007, 27 (2), 51–69. (c) Bhaket,
P.; Stauffer, C. S.; Datta, A. J. Org. Chem. 2004, 69, 8594–8601. (d)
Garner, P.; Yoo, J. U.; Sarabu, R.; Kennedy, V. O.; Youngs, W. J.
Tetrahedron 1998, 54, 9303–9316. (e) Czernecki, S.; Franco, S.; Valery,
J.-M. J. Org. Chem. 1997, 62, 4845–4847. (f) Czernecki, S.; Valery, J.-M.;
Wilkens, R. Bull. Chem. Soc. Jpn. 1996, 69, 1347–1351. (g) Rauter, A. P.;
Fernandes, A. C.; Czernecki, S.; Valery, J.-M. J. Org. Chem. 1996,
61, 3594–3598. (h) Casiraghi, G.; Colombo, L.; Rassu, G.; Spanu, P. J.
Org. Chem. 1991, 56, 6523–6527. (i) Hara, K.; Fujimoto, H.; Sato, K. I.;
Hashimoto, H.; Yoshimura, J. Carbohydr. Res. 1987, 159, 65–79.
(5) (a) Sanap, S. P.; Ghosh, S.; Jabgunde, A. M.; Pinjari, R. V.; Gejji,
S. P.; Singh, S.; Chopade, B. A.; Dhavale, D. D. Org. Biomol. Chem. 2010,
14, 3307–3315. (b) Jadhav, V. H.; Bande, O. P.; Pinjari, R. V.; Gejji, S. P.;
Puranik, V. G.; Dhavale, D. D. J. Org. Chem. 2009, 74, 6486–6494. (c)
Bhujbal, N. N.; Bande, O. P.; Dhavale, D. D. Carbohydr. Res. 2009,
344, 734–738. (d) Bande, O. P.; Jadhav, V. H.; Puranik, V. G.; Dhavale,
D. D. Synlett 2009, 12, 1959–1963. (e) Bande, O. P.; Jadhav, V. H.;
Puranik, V. G.; Dhavale, D. D. Tetrahedron lett 2009, 50, 6906–6908.
(6) (a) Mane, R. S.; Ajish Kumar, K. S.; Dhavale, D. D. J. Org. Chem.
2008, 73, 3284–3287. (b) Hotha, S.; Maurya, S. K.; Gurjar, M. K.
Tetrahedron Lett. 2005, 46, 5329–5332.
side 2 (0.18 g, 77%) as a viscous liquid: Rf 0.15 (methanol); [R]25
D
ꢀ13.7 (c 0.3, H2O); IR (neat) 3600ꢀ2900 (br) cmꢀ1; 1H NMR (300
MHz, D2O) δ 1.94ꢀ2.05 (m, 1H), 2.36 (br d, J = 14.4 Hz, 1H), 3.78
(dd, J = 11.7, 8.1 Hz, 1H), 3.98ꢀ4.10 (m, 2H), 4.15 (br d, J = 10.8 Hz,
1H), 4.20 (dd, J = 8.1, 2.4 Hz, 1H), 4.32 (d, J = 9.3 Hz, 1H), 6.16 (d, J =
9.3 Hz, 1H), 8.21 (s, 1H), 8.38 (s, 1H); 13C NMR (75 MHz, D2O) δ
35.6, 65.2, 66.1, 74.7, 76.6, 77.8, 85.5, 121.0, 143.1, 151.3, 155.2, 158.0.
Anal. Calcd for C12H17N5O5: C, 46.30; H, 5.50. Found: C, 46.57;
H, 5.95.
(7) Wengel et al. have reported the synthesis of compound 7 using
different methodology; see: Nielsen, P.; Pfundheller, H. M.; Olsen, C.;
Wengel, J. J. Chem. Soc., Perkin Trans. 1 1997, 3423–3433.
(8) Zou, R.; Robins, M. J. Can. J. Chem. 1987, 65, 1436–1437.
(9) (a) Analogous results were obtained with 10% Pd/C or 10%
Pd(OH)2, ammonium formate, methanol reflux conditions. (b) Wengel
et al. have also observed glycosidic bond cleavage under various
debenzylation methods (20% Pd(OH)2)/C, H2, ethanol; 10% Pd/C,
H2, methanol; 10% Pd/C, 1,4-cyclohexadiene, methanol; BCl3, dichlor-
omethane, hexane; 20% Pd(OH)2, ammonium formate, methanol;
BBr3, dichloromethane; sodium, ethanol; CrO3/CH3COOH;
iodotrimethylsilane); see: Singh, S. K.; Kumar, R.; Wengel, J. J. Org.
Chem. 1998, 63, 6078–6079.
’ ASSOCIATED CONTENT
S
Supporting Information. General experimental meth-
b
ods, experimental procedure, spectral and analytical data for
compounds 4, 5, 6, 7, 8, and 9 and copies of 1H and 13C NMR
spectrum of compounds 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 2.
This material is available free of charge via the Internet at http://
pubs.acs.org.
(10) (a) Gazim, Z. C.; Rezende, C. M.; Fraga, S. R.; Svidzinski,
T. I. E.; Cortez, D. A. G. Braz. J. Microbiol. 2008, 39, 61–63. (b)
Kumbhar, A. S.; Padhye, S. B.; Saraf, A. P.; Mahajani, H. B.; Chopade,
B. A.; West, D. K. Biometals 1991, 4, 141–143.
(11) (a) Liu, Y.; Xing, H.; Han, X.; Shi, X.; Liang, F.; Cheng, G.; Lu,
Y.; Ma, D. J. Huazhong Univ. Sci. Technolog. Med. Sci. 2008, 28, 197–199.
(12) Mosmann, T. J. Immunol. Meth. 1983, 65, 55–63.
(13) The general procedure and statistical analysis for anticancer
assay is discussed in Supporting Information.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: ddd@chem.unipune.ac.in.
(14) The names of the sugars 10, 11, and 14 are given according to
the von Baeyer nomenclature; however, the assignments of the protons
and carbons in the figures follow standard carbohydrate nomenclature.
DISCLOSURE
^Part of this work was carried out with Prof. Oliver Reiser,
Institut fur Organische Chemie, Universit€at Regensburg, 93053
Regensburg, Germany under the INDIGO programme.
’ ACKNOWLEDGMENT
We are grateful to Prof. M. S. Wadia for helpful discussions. R.
S.M. is thankful to the UGC, New Delhi and the DAAD/BASF
(INDIGO programme, Germany) for the fellowships and CSIR
Project No. 01(2343)/09/EMR-II) for financial assistance.
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