A synthesis of new coumarin C-glycosyl derivatives

Full text of DOI:10.1021/jo981868z

J . Org. Chem. 1999, 64, 1715-1719
1715
the synthesis of the hitherto unknown coumarin C-
glycosyl compounds, wherein the coumarin ring is at C-5
of the pyranose and the anomeric center of the sugar is
free. A large number of coumarin derivatives including
some with O-glycosidic linkages occur naturally.5 How-
ever, the coumarin C-glycosides are rare in nature, and
only two examples, namely dauroside D6a and mulber-
roside6b having spasmolytic and hypotensive activities
but with mild toxicity, are known.7 The first synthesis
of coumarin C-glycosides was reported by Schmidt and
Mahling.8 However, no report of the C-glycosyl com-
pounds with the coumarin ring at C-5 of the pyranose,
with a free anomeric center, is known. To our visualiza-
tion, the â-keto ester appendage at C-4 in 1, with
electrophilic and nucleophilic sites, appeared to be suit-
able for the construction of a coumarin ring at this end.
The polyoxygenated carbon framework, with multiple
avenues of chirality, would then portray the glycosidic
part.
A Syn th esis of New Cou m a r in C-Glycosyl
Der iva tives†
Nabendu N. Saha, Vijaya N. Desai, and
Dilip D. Dhavale*
Department of Chemistry, Garware Research Centre,
University of Pune, Pune-411 007, India
Received September 15, 1998
The use of C-glycosyl compounds as chiral intermedi-
ates in the synthesis of aryl C-glycosides and more
complex natural products is an ongoing interest over the
years.1 This has resulted into a number of synthetic
strategies for the C-C bond formation that link the
aliphatic or aromatic moiety with the sugar substrate.
In general, there are two main streams of synthetic
sequences. The first route involves stereoselective intro-
duction of an alkyl or aryl moiety (R or â) at the anomeric
carbon of the sugar substrate, while the second makes
use of a preexisting alkyl appendage, at C-1 or C-4 of
the furanose/C-5 of the pyranose, for the construction of
the required moiety. Although a number of stereocon-
trolled syntheses of the former type are reported,2 only
stray cases of the latter type are known.3 With the sugar
â-keto esters 1 and 2 in hand,4 we were interested in the
second approach. We describe herein a methodology for
Resu lts a n d Discu ssion
The sugar â-keto esters 1 and 2 were easily prepared
from R-D-xylo-pentodialdo-1,4-furanose and R-D-ribo-
pentodialdo-1,4-furanose derivatives, respectively, by the
BF3‚etherate-catalyzed reaction with ethyl diazoacetate
as described by us earlier.4 One-pot Knoevenagel con-
densation9 of the sugar â-keto esters 1 with 2-hydroxy
benzaldehydes 3a -e and 2 with 3a -c, in ethanol using
piperidine as a base, led to concomitant cyclization
affording the corresponding coumarin sugar derivatives
4a -e and 5a -c in 55-65% yield (Scheme 1).10 A char-
acteristic feature, as in 3-acyl coumarin,11 was observed
* To whom correspondence should be addressed. Fax: 0091-20-353
899. E-mail: ddd@chem.unipune.ernet.in.
† Dedicated to Prof. N. S. Narasimhan on the occasion of his 70th
birthday.
(1) For recent reviews on aryl C-glycosides, see: (a) Daves, G. D.,
J r. Acc. Chem. Res. 1990, 23, 201-206. (b) Postema, M. H. D.
Tetrahedron 1992, 48, 8545-8599. (c) Rahman, A. U. Studies in
Natural Products Chemistry; Elsevier: Amsterdam, 1992; Vol. 10, pp
337-403. (d) J aramillo, C.; Knapp, S. Synthesis 1994, 1-20 and
references therein. (e) Schmidt, R. R. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21-123. (f) Beau, J .-M.; Gallagher, T. Top. Curr. Chem. 1997,
187, 1-54. (g) Nicotra, F. Top. Curr. Chem. 1997, 187, 55-83. (g) Togo,
H.; He, W.; Waki, Y.; Yokoyama, M. Synlett 1998, 700-717. (h) Du,
Y.; Linhardt, R. J . Tetrahedron 1998, 54, 9913-9959.
1
in the H NMR spectra of 4 and 5 wherein the chemical
(3) (a) Kraus, G. A.; Shi, J . J . Org. Chem. 1990, 55, 4922-4925. (b)
Yamaguchi, M.; Horiguchi, A.; Ikeura, C.; Minami, T. J . Chem. Soc.,
Chem. Commun. 1992, 434-436. (c) Kozikowski, A. P.; Cheng, X.-M.
J . Chem. Soc., Chem. Commun. 1987, 680-683. (d) Pulley, S. R.; Carey,
J . P. J . Org. Chem. 1998, 63, 5275-5279.
(4) (a) Dhavale, D. D.; Bhujbal, N. N.; J oshi, P.; Desai, S. G.
Carbohydr. Res. 1994, 263, 303-307. (b) Dhavale, D. D.; Saha, N. N.;
Desai, V. N. J . Org Chem. 1997, 62, 7482-7484.
(5) For references of coumarin compounds see: (a) Murray, R. D.
H., Mendez, J ., Brown, S. A., Eds. The Natural Coumarins, Occurrence,
Chemistry and Biochemistry; J ohn Wiley: New York, 1982. (b) Murray,
R. D. H. Naturally Occurring Plant Coumarins. In Progress in the
Chemistry of Organic Natural Products; Herz, W., Kirby, G. W.,
Steglich, W., Tamm, Ch., Eds.; Springer-Verlag: New York, 1991; Vol.
58, 83-316 and references therein.
(6) (a) Baturen, D.; Batirov, E. Kh.; Malikov, V. M. Khim. Prir.
Soedin. 1982, 650-651; Chem. Abstr. 1983, 98, 86226m. (b) Hirakura,
K.; Saida, I.; Fukai, T.; Nomura, T. Heterocycles 1985, 23, 2239-2242.
(7) Aminov, S. D.; Vakhabov, A. A. Dokl. Akad. Nauk USSR 1985,
44-45; Chem. Abstr. 1986, 104, 122600g.
(8) Mahling, J .-A.; Schmidt, R. R. Liebigs Ann., 1995, 467-469.
(9) J ones, G. Organic Reactions; Wiley: New York, 1967; Vol. 15,
pp 204-599.
(10) The benzylidene adduct was isolated in ∼20-25% yield as a
mixture of E and Z isomers. Attempts to improve the yield of 4/5 by
making use of KF or weak bases such as Et3N, isopropylamine, Cs2-
CO3, pyrrolidine, or DBU in different proportions under a variety of
temperature and solvent conditions were unsuccessful. The solid-
supported reactions using either silica gel or alumina or cadmium
iodide also did not improve the yield. (a) Brillon, D.; Sauve, G. J . Org.
Chem. 1992, 57, 1838-1842. (b) Kabalka, G. W.; Pagni, R. M.
Tetrahedron 1997, 53, 7999-8065 and references therein. (c) Prajapati,
D.; Sandhu, J . S. J . Chem. Soc., Perkin Trans. 1 1993, 739-740.
(11) In 3-acyl coumarin the olefinic proton appears at δ 8.5 and the
methyl at δ 2.6. (a) Dimitrova, E.; Anghelova, Y. Synth. Commun. 1986,
16(10), 1195-1205. (b) Clinging, R.; Dean. F. M.; Houghton, L. E. J .
Chem. Soc. C 1970, 897-902.
(2) (a) Hauser, F. M.; Adams, T. C., J r. J . Org. Chem. 1984, 49,
2296-2297. (b) Nicotra, F.; Perego, R.; Ronchetti, F.; Russo, G.; Toma,
L. Gazz. Chim. Ital. 1984, 114, 193-195. (c) Narasaka, K.; Ichikawa,
Y.-I.; Kubota, H. Chem. Lett. 1987, 2139-2142. (d) Nicotra, F.; Panza,
L.; Russo, G. J . Org. Chem. 1987, 52, 5627-5630. (e) Wu, T.-C.;
Goekjian, P. G.; Kishi, Y. J . Org. Chem. 1987, 52, 4819-4823. (f)
Goekjian, P. G.; Wu, T.-C.; Kang, H.-Y.; Kishi, Y. J . Org. Chem. 1987,
52, 4823-4825. (g) Babirad, S. A.; Goekjian, P. G.; Kishi, Y. J . Org.
Chem. 1987, 52, 4825-4827. (h) Cai, M.-S.; Qui, D.-X. Carbohydr. Res.
1989, 191, 125-129. (i) Gracia Martin, M. De G.; Horton, D. Carbohydr.
Res. 1989, 191, 223-229. (j) Matsumuto, T.; Katsuki, M..; J ona, H.;
Suzuki, K. Tetrahedron. Lett. 1989, 45, 6185-6188. (k) Matsumuto,
T.; Hosoya, T.; Suzuki, K. Tetrahedron. Lett. 1990, 32, 4629-4632. (l)
Matsumoto, T.; Hosoya, T.; Suzuki, K. Synlett 1991, 709-711. (m) Hart,
D. J .; Leroy, V.; Merriman, G. J .; Young, D. G. J . J . Org. Chem. 1992,
57, 5670-5680. (n) Polt, R.; Szabo, L.; Trieiberg, J .; Li Y.; Hruby, V.
J . J . Am. Chem. Soc. 1992, 114, 10249-10258. (o) Parker, K. A.; Koh,
Y.-H. J . Am. Chem. Soc. 1994, 116, 11149-11150 (p) Parker, K. A.;
Coburn, C. A.; Koh, Y.-H. J . Org. Chem. 1995, 60, 2938-2941. (q)
Mcdonald, F. E.; Zhu, H. Y. H.; Holmquist, C. R. J . Am. Chem. Soc.
1995, 117. 6605-6606. (r) Furster, A.; Muller, T. J . Org. Chem. 1998,
63, 424-425. (s) Crich, D.; Sun, S. J . Am. Chem. Soc. 1998, 120, 435-
436. (t) Douglas, N. L.; Ley, S. V.; Lucking, U.; Warriner, S. L. J . Chem.
Soc., Perkin Trans. 1 1998, 51-65. (u) Fiecchi, A.; Cighetti, G.; Muir,
M.; Scala, A.; Tyman, J . J . Chem. Soc., Perkin Trans. 1 1998, 575-
582. (v) Moineau, C.; Bolitt, V.; Sinou, D. J . Org. Chem. 1998, 63, 582-
591. (w) Furstner, A.; Muller, T. J . Org. Chem. 1998, 63, 424-425 and
references therein. (x) Crich, D.; Sun, S. J . Am. Chem. Soc. 1998, 120,
435-436. (y) Douglas, N. L.; Ley, S. V.; Lucking, U.; Warriner, S. L.
J . Chem. Soc., Perkin Trans. 1 1998, 51-65. (z) Fiecchi, A.; Cighetti,
G.; Muir, M.; Scala, A.; Tyman, J . J . Chem. Soc., Perkin Trans. 1 1998,
575-582. Moineau, C.; Bolitt, V.; Sinou, D. J . Org. Chem. 1998, 63,
582-591 and references therein.
10.1021/jo981868z CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/13/1999

1716 J . Org. Chem., Vol. 64, No. 5, 1999
Notes
Sch em e 1
Sch em e 2a
shifts of the olefinic protons in 4a -e (δ ∼8.4) and in 5a -c
(δ ∼8.2) were downfield in contrast to that in the
unsubstituted coumarin (δ ∼7.7). This fact defined an
S-cis conformation for the enone moiety leading to the
structures 4 and 5 as shown in Scheme 1. In agreement
with this, the chemical shifts of the H-4 of the furanose
in 4 and 5 were deshielded, resonating at δ ∼5.9 and
∼5.4, respectively, as compared to the related sugar
compounds appearing at δ ∼4.3.3a,4
a
Reaction conditions: (a) NaBH4, methoxyethanol, -78 °C, 30
min; (b) NaBH4-CeCl3, MeOH, -78 °C, 30 min; (c) 3 N HCl/THF,
70 °C, 2 h; (d) Ac2O, pyridine, DMAP, 25 °C; 20 h; (e) 10% Pd/C,
ethanol-acetic acid, H2, 1 atm, 24 h.
of structurally analogous compounds. It is known that,
for a given pair of C-5 epimeric carbinols, derived from
R-D-gluco-furanose, the chemical shift of H-3 is reported
to be diagnostic such that in the L-idoconfiguration the
H-3 resonates significantly upfield (δ ∼3.6) as compared
to that in the D-glucoconfiguration (δ ∼4.0).16 In carbinol
7a , H-3 appeared considerably downfield at δ 4.17
supporting the D-glucoconfiguration at C-5.17 The ob-
served good diastereoselectivity in favor of the erythro-
carbinol 7a could be explained on the basis of Felkin-
Anh’s model.18a In case of CeCl3-mediated reduction
processes, the Ce3+ enhances the formation of nonchela-
tion-controlled products.18b Therefore, for compound 4a ,
two conformations A and B (Scheme 3) were considered.
In conformation A, the electron-withdrawing C-O group
of furanose, whereas in B the largest C-3-benzyloxy
substituent, both at CR to the carbonyl, was placed at a
right angle to the CdO group. Although conformation A
is preferred18c over B, the attack of the hydride from the
opposite face of the C-O group (Re face) is disfavored by
the C-3-benzyloxy substituent explains why threo-
Aiming toward coumarin C-glycosyl derivatives, we
chose 4a as a model compound. In the next step, the
reduction of the C-5 keto group in 4a with NaBH4 (0.5
equiv) in MeOH or in MeOH-THF,12 at different tem-
peratures, was attempted. This yielded a mixture of
products from which two compounds were isolated. The
spectral data revealed the reduction of the coumarin Cd
C as well as the C-5 keto group. However, when 4a was
reduced with NaBH4 (0.5 equiv) in methoxyethanol at
-78 °C the dihydrocoumarin 6 was isolated in 80% yield
in which the CdC bond had been chemoselectively
reduced, keeping the C-5 keto group intact (Scheme 2).
1
The H NMR spectrum of 6 exhibited the ABX pattern
for the methine and the methylene protons of the
dihydrocoumarin. The methine proton appeared at δ 4.39
as a doublet of doublet with J ) 12.5, 6.4 Hz. This
indicated the pseudoaxial-axial and pseudoaxial-equa-
torial relationship of the methine proton with the meth-
ylene protons. The preferential 1,4 reduction13 of the Cd
C, over the CdO group, could be due to the increased
reactivity of the CdC that is substituted at the same end
by the C-5 keto group and the lactone carbonyl group.
In another reaction, compound 4a was reduced with
NaBH4-CeCl3 in methanol at -78 °C.14 This afforded
carbinols 7a and 7b as a diastereomeric mixture in a
ratio of 89:11, which on chromatography furnished the
desired D-glucodiastereomer 7a in 78% yield (Scheme 2).15
The assignment of the configuration at C-5 in carbinol
(16) (a) Cornia, M.; Casiraghi, G. Tetrahedron 1989, 45, 2869-2874.
(b) Prakash, K. R. C.; Rao, S. P. Tetrahedron 1993, 49, 1505-1510. (c)
Hauser, F. M.; Adams, T. C. J . Org. Chem. 1984, 49, 2296-2297. (d)
Gesson, J .-P.; J acquesy, J .-C.; Mondon, M. Tetrahedron 1989, 45,
2627-2640.
(17) In the 1H NMR spectrum of 7a , the H-4 of furanose appeared
at the usual value of δ 4.5, indicating the absence of the diamagnetic
deshielding effect of a lactone carbonyl. Probably, the intramolecular
hydrogen bonding with -OH at C-5 holds the coumarin ring as shown
in conformational structure 7a .
1
7a was based on a comparison of its H NMR with those
(18) (a) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
2199-2204. Anh, N. T.; Einsenstein, O. Nouv. J . Chim. 1977, 1, 61.
(b) Marcantoni, E.; Cingolani, S.; Bartoli, G.; Bosco, M.; Sambri, L. J .
Org. Chem. 1998, 63, 3624-3630. (c) Conformation A has less steric
impedance of the substituents than B. In addition, the nucleophilic
attack in A seeks the LUMO of the carbonyl, which is stabilized
through the mixing of the π* CdO orbital with the lowest energy σ*
orbital associated with the electronegative oxygen of the furanose;
see: Houk, K. N.; Paddon-Row: M. N.; Rondan, N. G.; Wu, Y.-D.;
Brown, F. K.; Spellmeyer, D. C.; Metz, J . T.; Li, Y.; Loncharich, R. J .
Science 1986, 231, 1108-1117. We are thankful to one of the reviewers
for his comments.
(12) Varma, R. S.; Kabalka, G. W. Synth. Commun. 1985, 15, 985-
990.
(13) (a) Brown, H. C.; Krishnamurthy, S. Tetrahedron 1979, 35,
567-607. (b) Wigfield, D. C. Tetrahedron 1979, 35, 449-462. (c)
Raucher, S.; Hwang, K.-J . Synth. Commun. 1980, 10(2), 133-137.
(14) Gemal, A. L.; Luche, J .-L. J . Am. Chem. Soc. 1981, 103, 5454-
5459 and references therein.
(15) The isolation of 7a was possible due to the higher Rf value of
7a than 4a ; however, our attempts to isolate 7b in pure form were
unsuccessful.

Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1717
Sch em e 3
triplets for H-3 and H-4, with large coupling constants,
indicated that the substituents at C-2, C-3, and C-4 of
the pyranose, in compounds 8-11, were equatorially
4
oriented with a C1 conformation for the pyranose ring.
In conclusion, we have developed a convenient ap-
proach for the synthesis of the unnatural C-5 coumarin
glycosyl compounds by making use of the sugar â-keto
ester 1. The three-step simple reaction sequence of
Knoevenagel condensation and lactonization, the hydride
reduction of the ketone, and the acid-mediated acetal
exchange forms a practical strategy. The freely available
anomeric position in these compounds could be used as
a handle for further conversion to O-/C-glycosides, C-
nucleosides, and disaccharides. Work in this direction is
in progress.
Exp er im en ta l Section
1H NMR (300 MHZ, 500 MHz) and 13C NMR (75 MHz, 125
MHz) spectra were recorded using CDCl3 as a solvent unless
otherwise stated. Chemical shifts are reported in ppm (δ) relative
to internal standard Me4Si. IR spectra of samples were measured
as thin films in Nujol mull on KBr plates. Optical rotations were
recorded at ambient temperature. Whenever required, the
reactions were carried out in oven-dried glassware under dry
N2. On workup, the solvents were evaporated at reduced
pressure with a rotary evaporator. Thin-layer chromatography
was performed on 0.25 mm precoated silica gel, and flash
chromatography was carried out on silica gel (200-400 mesh).
The organic solvents such as n-hexane, THF, diethyl ether,
methylene chloride, petroleum ether (pet. ether, 60-70 °C
fraction), ethyl acetate, pyridine, and acetic anhydride were
purified and dried before use. Piperidine, anhydrous cerous
chloride, DMAP, sodium borohydride, and phosphorus oxychlo-
ride were purchased from Aldrich and/or Fluka. Ethyl-3-O-
benzyl-6-deoxy-1,2-O-isopropylidene-R-D-xylo-heptofuranuronate-
5-ulose 1 and ethyl-3-O-benzyl-6-deoxy-1,2-O-isopropylidene-R-
D-ribo-heptofuranuronate-5-ulose 2 were prepared from D-glucose
in 70% and 65% yield, respectively, as reported previously.4
4-Methoxy-2-hydroxy benzaldehyde, 5-methyl-2-hydroxy benzal-
dehyde, 3-methoxy-2-hydroxy benzaldehyde, and 4,6-dimethoxy-
2-hydroxy benzaldehyde were prepared from reported proce-
dures.24
carbinol 7b is obtained as a minor product. However, in
the alternate conformation B, the hydride addition from
the opposite face of the bulky C-3-benzyloxy group (Si
face) is strongly favored due to the minimized steric
nonbonded interactions, leading to the preferential for-
mation of the erythro-carbinol 7a as the major product.
In the next step, the hydrogenolysis of 7a using H2/
Pd-C was attempted, which resulted in a mixture of
products.19 Alternately, when 7a was hydrolyzed with 3
N HCl-THF at 70 °C for 2 h, the 3-O-benzyl-5-C-(3-
coumarin)-D-xylo-pyranose 8 (R:â ) 3:2) was isolated as
a pale brown solid in 80% yield. The compound 8 on
acetylation and separation of the anomeric mixture gave
the triacetate derivatives 9R and 9â as pale yellow solids.
Hydrogenolysis of 8, using H2-Pd/C in EtOH-AcOH at
1 atm for 24 h, afforded an anomeric mixture of 5-C-(3-
coumarin)-D-xylo-pyranose 10 as a solid in 79% yield. The
acetylation of 10 gave the tetraacetate derivative 11,
which was characterized by spectroscopic techniques.
The configurations at the anomeric carbon and at C-5
Gen er a l P r oced u r e for th e Kn oeven a gel Con d en sa tion
a n d Cycliza tion for Com p ou n d s 4a -d a n d 5a -c. The
reaction procedure given for 4a is representative:
1
in 8-11 were assigned on the basis of the H NMR data
of the glycosidic part. The anomers with low J 1,2 (3.0-
4.0 Hz) were assigned the R-configuration, while those
with high J 1,2 (8.0-9.0 Hz) were assigned the â-config-
uration.20 This assignment was supported by the greater
deshielding of the H-1 in the R-anomers as compared to
the â-anomers.21 In fixing the configuration at C-5, the
crucial factor was the coupling constant between H-5 and
H-4.22 The H-5 proton in 8R-11R appeared as a doublet
at δ ∼5.0 with J 4,5 ≈ 9.7 Hz and in 8â-11â at δ ∼5.14
with J 4,5 ≈ 10.0 Hz. The large value of the J 4,5 was in
accordance with the axial-axial relationship of the H-5
and H-4. This confirmed the equatorial orientation of the
coumarin ring in 8-11.23 The presence of two sets of
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-xylo-p en tofu -
r a n -5-u lose)]-2H-1-ben zop yr a n -2-on e (4a ). To a solution of
sugar â-keto ester 1 (1.0 g, 2.75 mmol), piperidine (0.28 g, 3.3
mmol), and molecular sieves (1.0 g) in ethanol (6 mL) at 25 °C
was added 2-hydroxy benzaldehyde 3a (0.40 g, 3.3 mmol) in
ethanol (4 mL) over a 10 min period, and the reaction was heated
at 70 °C for 20 min in an oil bath. On cooling, the reaction
mixture was neutralized with 2 N HCl (2 mL), concentrated,
and extracted with Et2O (5 × 20 mL). The combined extract was
washed with water and brine and dried (Na2SO4). Removal of
the solvent followed by chromatography (elution with pet. ether/
EtOAc ) 8/2) gave 4a as a pale yellow solid (0.753 g, 65%): mp
123-124 °C; Rf ) 0.56 (hexane/EtOAc ) 2/3); [R]D ) -80.34 (c
0.42, CHCl3); IR (cm-1) 1710, 1690, 1595; 1H NMR (500 MHz) δ
1.36 (s, 3H), 1.55 (s, 3H), 4.25 (d, J ) 12.0 Hz, 1H), 4.57 (d, J )
12.0 Hz, 1H), 4.56 (d, J ) 3.7 Hz, 1H), 4.69 (d, J ) 4.2 Hz, 1H),
5.89 (d, J ) 4.2 Hz, 1H), 6.16 (d, J ) 3.7 Hz, 1H), 6.90-7.21 (m,
5H), 7.32 (dd, J ) 8.2, 1.5 Hz, 1H), 7.36 (dt, J ) 7.6, 1.5 Hz,
1H), 7.60 (dd, J ) 7.6, 1.5 Hz, 1H), 7.68 (dt, J ) 8.2, 1.5 Hz,
1H), 8.46 (s, 1H); 13C NMR (125 MHz) δ 26.9, 27.5, 72.1, 82.5,
83.0, 85.8, 105.7, 112.8, 116.9, 118.5, 123.0, 125.3, 128.1, 128.3,
128.5, 130.5, 134.8, 136.5, 148.6, 155.3, 158.8, 190.8. Anal. Calcd
for C24H22O7: C, 68.24; H, 5.25. Found: C, 68.02; H, 5.35.
(19) Debenzylation in glucofuranose derivatives require high pres-
sure under which CdC was found to be reduced. Starting compound
was recovered even after 48 h at 4 bar.
(20) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; J ames, K. J . Am.
Chem. Soc. 1975, 97, 4056-4062.
(21) The chemical shifts of H-1: 8R/10R ≈ δ 5.2, J 1,2 ≈ 3.3 Hz; 8â/
10â ≈ δ 5.1, J 1,2 ≈ 9.0 Hz. For acetates 9R/11R ≈ δ 6.4, J 1,2 ≈ 3.7 Hz;
9â/11â ≈ δ 5.8, J 1,2 ≈ 8.2 Hz).
(22) Lemieux, R. U.; Howard, J . Can. J . Chem. 1963, 41, 308-316.
The characterization of structures 8-11 supported our earlier assign-
ment for the carbinol 7a with the D-gluco configuration at C-5.
(23) The 1H NMR data for all these compounds and in particular
for 9â thus confirms the D-gluco configuration of 7a . The H-5 appeared
as a doublet with a coupling constant of ∼9.7 Hz, indicating the axial-
axial relation with H-4.
(24) (a) Ray, P. J . Chem. Soc. 1926, 941. (b) Godfrey, J . M.; Sargent,
M. V.; Eliy, J . A. J . Chem. Soc., Perkin Trans. 1 1974, 1353-1354. (c)
Nakazawa, K.; Matsuura, S. J . Pharm. Soc. J pn. 1953, 73, 751; Chem.
Abstr. 1954, 48, 7007a.

1718 J . Org. Chem., Vol. 64, No. 5, 1999
Notes
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-xylo-p en tofu -
r a n -5-u lose)]-6-m eth yl-2H-1-ben zop yr a n -2-on e (4b). The
reaction of 1 (1.0 g, 2.75 mmol) and 2-hydroxy-5-methylbenzal-
dehyde 3b (0.449 g, 3.3 mmol) using piperidine (0.28 g, 3.3 mmol)
and molecular sieves (1.0 g) in ethanol (10 mL) gave 4b as a
yellow solid (0.743 g, 62%): mp 81-82 °C; Rf ) 0.58 (hexane/
EtOAc ) 2/3); [R]D ) -66.06 (c 0.44, CHCl3); IR (cm-1) 1720,
1698, 1616; 1H NMR (300 MHz) δ 1.37 (s, 3H), 1.56 (s, 3H), 2.45
(s, 3H), 4.26 (d, J ) 12.1 Hz, 1H), 4.58 (d, J ) 12.1 Hz, 1H),
4.67 (d, J ) 3.9 Hz, 1H), 4.70 (d, J ) 4.1 Hz, 1H), 5.90 (d, J )
4.1 Hz, 1H), 6.17 (d, J ) 3.9 Hz, 1H), 6.90-7.05 (m, 5H), 7.23
(d, J ) 8.9 Hz, 1H), 7.41 (d, J ) 1.5 Hz, 1H), 7.49 (dd, J ) 8.9,
1.5 Hz, 1H), 8.45 (s, 1H); 13C NMR (75 MHz) δ 20.8, 26.8, 27.3,
71.9, 82.3, 82.8, 85.6, 105.5, 112.6, 116.4, 118.1, 122.7, 127.9,
128.1, 128.3, 129.9, 134.9, 135.9, 136.4, 148.5, 153.4, 158.9, 190.7.
Anal. Calcd for C25H24O7: C, 68.80; H, 5.54. Found: C, 68.52;
H, 5.76.
NMR (75 MHz)) δ 26.9, 27.2, 72.5, 78.6, 79.5, 82.4, 105.2, 113.9,
116.8, 118.1, 124.9, 125.4, 127.9, 128.0, 128.3, 129.8, 134.3, 137.3,
146.9, 155.0, 158.5, 196.2. Anal. Calcd for C24H22O7: C, 68.24;
H, 5.25. Found: C, 68.12; H, 5.40.
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-r ibo-p en tofu -
r a n -5-u lose)]-6-m eth yl-2H-1-ben zop yr a n -2-on e (5b). The
reaction of 2 (1.0 g, 2.75 mmol) and 2-hydroxy-5-methylbenzal-
dehyde 3b (0.449 g, 3.3 mmol) using piperidine (0.28 g, 3.3 mmol)
and molecular sieves (1.0 g) in ethanol (10 mL) gave 5b as a
yellow solid (0.682 g, 57%): mp 95-96 °C; Rf ) 0.58 (hexane/
EtOAc ) 2/3); [R]D ) -6.79 (c 0.21, CHCl3); IR (cm-1) 1720, 1690,
1610; 1H NMR (300 MHz) δ 1.39 (s, 3H), 1.66 (s, 3H), 2.42 (s,
3H), 4.34 (dd, J ) 8.6, 4.0 Hz, 1H), 4.61 (d, J ) 12.1 Hz, 1H),
4.63 (dd, J ) 4.0, 3.3 Hz, 1H), 4.75 (d, J ) 12.1 Hz, 1H), 5.41 (d,
J ) 8.6 Hz, 1H), 5.83 (d, J ) 3.3 Hz, 1H), 7.22-7.40 (m, 7H),
7.43-7.46 (dd, J ) 8.6, 2.0 Hz 1H), 8.20 (s, 1H);13C NMR (75
MHz) δ 20.7, 26.9, 27.2, 72.5, 78.6, 79.5, 82.5, 105.2, 113.9, 116.5,
117.9, 126.0, 127.9, 128.1, 128.3, 129.4, 134.8, 135.5, 137.3, 147.1,
153.1, 158.2, 196.4. Anal. Calcd for C25H24O7: C, 68.80; H, 5.54.
Found; C, 68.91; H, 5.78.
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-xylo-fu r a n -5-
u lose)]-7-m eth oxy-2H-1-ben zop yr a n -2-on e (4c). The reaction
of 1 (1.0 g, 2.75 mmol) and 2-hydroxy-4-methoxybenzaldehyde
3c (0.502 g, 3.3 mmol) using piperidine (0.28 g, 3.3 mmol) and
molecular sieves (1.0 g) in ethanol (10 mL) gave 4c as a yellow
solid (0.664 g, 62%): mp 142-143 °C; Rf ) 0.48 (hexane/EtOAc
) 2/3); [R]D ) -103.54 (c 0.45, CHCl3); IR (cm-1) 1710, 1680,
1590; 1H NMR (500 MHz) δ 1.34 (s, 3H), 1.53 (s, 3H), 3.91 (s,
3H), 4.24 (d, J ) 12.1 Hz, 1H), 4.55 (d, J ) 12.1 Hz, 1H), 4.66
(d, J ) 3.7 Hz, 1H), 4.68 (d, J ) 4.1 Hz, 1H), 5.87 (d, J ) 4.1 Hz,
1H), 6.15 (d, J ) 3.7 Hz, 1H), 6.76 (d, J ) 2.0 Hz, 1H), 6.90 (dd,
J ) 8.7, 2.0 Hz, 1H), 6.92-7.15 (m, 5H), 7.50 (d, J ) 8.7 Hz,
1H), 8.45 (s, 1H); 13C NMR (125 MHz) δ 26.9, 27.4, 56.4, 72.1,
82.4, 83.1, 85.7, 100.5, 105.7, 112.4, 112.7, 114.1, 119.9, 127.9,
128.3, 128.5, 131.9, 136.8, 148.9, 158.8, 159.2, 165.7, 190.5. Anal.
Calcd for C25H24O8: C, 66.36; H, 5.35. Found: C, 66.19; H, 5.06.
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-xylo-p en tofu -
r a n -5-u lose)]-8-m eth oxy-2H-1-ben zop yr a n -2-on e (4d ). The
reaction of 1 (1.0 g, 2.75 mmol) and 2-hydroxy-3-methoxyben-
zaldehyde 3d (0.502 g, 3.3 mmol) using piperidine (0.28 g, 3.3
mmol) and molecular sieves (1.0 g) in ethanol (10 mL) gave 4d
as a yellow solid (0.675 g, 63%): mp 105-106 °C; Rf ) 0.49
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-r ibo-p en tofu -
r a n -5-u lose)]-7-m eth oxy-2H-1-ben zop yr a n -2-on e (5c). The
reaction of 2 (1.0 g, 2.75 mmol) and 2-hydroxy-4-methoxyben-
zaldehyde 3c (0.502 g, 3.3 mmol) using piperidine (0.28 g, 3.3
mmol) and molecular sieves (1.0 g) in ethanol (10 mL) gave 5c
as a yellow solid (0.621 g, 58%): mp 99-101 °C; Rf ) 0.48
(hexane/EtOAc ) 2/3); [R]D ) -19.65 (c 0.20, CHCl3); IR (cm-1
)
1720, 1690, 1600; 1H NMR (300 MHz) δ 1.39 (s, 3H), 1.67 (s,
3H), 3.90 (s, 3H), 4.28 (dd, J ) 8.6, 4.2 Hz, 1H), 4.6 (d, J ) 12.1
Hz, 1H), 4.65 (dd, J ) 4.2, 3.5 Hz, 1H), 4.75 (d, J ) 12.1 Hz,
1H), 5.50 (d, J ) 8.6 Hz, 1H), 5.84 (d, J ) 3.5 Hz, 1H), 6.81 (d,
J ) 1.9 Hz, 1H), 6.87-6.91 (dd, J ) 8.8, 1.9 Hz, 1H), 7.20-7.34
(m, 5H), 7.50 (d, J ) 8.8 Hz, 1H), 8.24 (s, 1H); 13C NMR (75 MHz)
δ 26.9, 27.2, 56.1, 72.5, 78.6, 79.5, 81.9, 84.2, 100.4, 105.2, 111.9,
113.8, 120.9, 127.9, 128.0, 128.3, 131.2, 137.4, 147.8, 157.6, 158.5,
165.3, 195.5. Anal. Calcd for C25H24O8: C, 66.36; H, 5.35.
Found: C, 66.28; H, 5.29.
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-xylo-p en tofu -
r a n -5-u lose)]-3,4-d ih yd r o-2H-1-ben zop yr a n -2-on e (6). To a
stirred solution of 4a (1.0 g, 2.37 mmol) in methoxymethanol
(20 mL) at -78 °C was added NaBH4 (0.044 g, 1.18 mmol) in
three portions. The reaction mixture was further stirred at -78
°C for 30 min, quenched with 2 N HCl (2 mL), and concentrated.
The residue was extracted with Et2O (5 × 20 mL), and the
combined extract was washed with water and brine and dried
(Na2SO4). Removal of the solvent afforded a yellow solid which
was crystallized (pet. ether/EtOAc ) 4/1) to give 6 as a pale
yellow solid (0.804 g, 80%): mp 148-150 °C; Rf ) 0.42 (hexane/
(hexane/EtOAc ) 2/3); [R]D ) -101.0 (c 0.42, CHCl3); IR (cm-1
)
1715, 1700, 1610; 1H NMR (300 MHz) δ 1.37 (s, 3H), 1.56 (s,
3H), 4.0 (s, 3H), 4.26 (d, J ) 12.1 Hz, 1H), 4.56 (d, J ) 12.1 Hz,
1H), 4.65 (d, J ) 3.9 Hz, 1H), 4.71 (d, J ) 4.2 Hz, 1H), 5.92 (d,
J ) 4.2 Hz, 1H), 6.16 (d, J ) 3.9 Hz, 1H), 6.90-7.10 (m, 5H),
7.14-7.35 (m, 3H), 8.40 (s, 1H); 13C NMR (75 MHz) δ 26.8, 27.3,
56.4, 72.0, 82.6, 82.8, 85.6, 105.5, 106.5, 112.6, 116.1, 118.9,
121.4, 124.9, 127.8, 127.9, 128.2, 128.4, 136.4, 147.0, 148.6, 158.2,
190.7. Anal. Calcd for C25H24O8: C, 66.36; H, 5.35. Found: C,
66.48; H, 5.40.
EtOAc ) 3/2); [R]D ) -31.3 (c 0.02, CHCl3, after 48 h);25 IR (cm-1
)
1755, 1720, 1450; 1H NMR (300 MHz) δ 1.33 (s, 3H), 1.49 (s,
3H), 2.61 (dd, J ) 16.1, 6.4 Hz, 1H), 3.31 (dd, J ) 16.1, 12.5 Hz,
1H), 4.32 (d, J ) 3.6 Hz, 1H), 4.39 (dd, J ) 12.5, 6.4 Hz, 1H),
4.41 (d, J ) 11.2 Hz, 1H), 4.58 (d, J ) 11.2 Hz, 1H), 4.62 (d, J
) 3.6 Hz, 1H), 4.91 (d, J ) 3.6 Hz, 1H), 6.07 (d, J ) 3.6 Hz, 1H),
6.88-7.42 (m, 9H). 13C NMR (75 MHz) 25.2, 26.5, 27.1, 47.3,
72.7, 81.5, 84.5, 85.6, 106.3, 112.8, 116.7, 121.8, 124.5, 124.7,
128.1, 128.3, 128.4, 128.6, 136.6, 151.5, 165.8, 203.8. Anal. Calcd
for C24H24O7: C, 67.91; H, 5.70. Found: C, 67.73; H, 5.62. The
1H and 13C NMR spectra showed additional signals (<5%)
corresponding to the enol form and/or other isomer.
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-xylo-fu r a n -5-
u lose)]-5,7-d im eth oxy-2H-1-ben zop yr a n -2-on e (4e). The re-
action of 1 (1.0 g, 2.75 mmol) and 2-hydroxy-4,6-dimethoxyben-
zaldehyde 3e (0.601 g, 3.3 mmol) using piperidine (0.28 g, 3.3
mmol) and molecular sieves (1.0 g) in ethanol (10 mL) gave 4e
as a yellow solid (0.821 g, 62%): mp 182-183 °C; Rf ) 0.26
(hexane/EtOAc ) 1/1); [R]D ) -49.13 (c 1.245, CHCl3); IR (cm-1
)
1718, 1691, 1588; 1H NMR (300 MHz) δ 1.37 (s, 3H), 1.56 (s,
3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.27 (d, J ) 12.08 Hz, 1H), 4.57
(d, J ) 12.08 Hz, 1H), 4.64 (d, J ) 3.84 Hz, 1H), 4.69 (d, J )
4.03 Hz, 1H), 5.89 (d, J ) 4.03 Hz, 1H), 6.17 (d, J ) 3.84 Hz,
1H), 6.29 (d, J ) 2.01 Hz, 1H), 6.38 (d, J ) 2.01 Hz, 1H), 7.00-
7.05 (m, 5H), 8.85 (s, 1H); 13C NMR (75 MHz) δ 26.84, 27.31,
56.23, 71.90, 82.34, 83.05, 85.48, 92.62, 95.21, 104.51, 105.52,
112.49, 116.85, 127.71, 128.11, 128.28, 136.80, 144.56, 158.52,
159.35, 166.90, 190.12. Anal. Calcd for C26H26O9: C, 64.72; H,
5.43. Found: C, 64.57; H, 5.33.
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-r ibo-p en tofu -
r a n -5-u lose)]-2H-1-ben zop yr a n -2-on e (5a ). The reaction of 2
(1.0 g, 2.75 mmol) and 2-hydroxybenzaldehyde 3a (0.40 g, 3.3
mmol) using piperidine (0.28 g, 3.3 mmol) and molecular sieves
(1.0 g) in ethanol (10 mL) gave 5a as a pale yellow solid (0.637
3-[5-(1,2-O-Isop r op ylid en e-3-O-ben zyl-r-D-glu co-p en to-
fu r a n ose)]-2H-1-ben zop yr a n -2-on e (7a ). To a stirred solution
of 4a (1.0 g, 2.37 mmol) and anhydrous cerous chloride (1.17 g,
4.74 mmol) in methanol (30 mL) at -78 °C was added NaBH4
(0.143 g, 3.79 mmol) in three portions. After being stirred for
30 min at -78 °C, the solution was quenched with 2 N HCl (2
mL) and concentrated. The residue was extracted with ether (5
× 20 mL), and the combined extract was washed with water
and brine and dried (Na2SO4). Removal of the solvent and
chromatography (elution with pet. ether/EtOAc ) 9/1) gave 7a
as a pale yellow solid (0.804 g, 80%): mp 75-76 °C; Rf ) 0.64
(hexane/EtOAc ) 1/1); [R]D ) +5.92 (c 0.51, CHCl3); IR (cm-1
)
g, 55%): mp 87-88 °C; Rf ) 0.51 (hexane/EtOAc ) 2/3); [R]D
)
-37.5 (c 0.11, CHCl3); IR (cm-1) 1718, 1695, 1598; 1H NMR (300
MHz) δ 1.39 (s, 3H), 1.66 (s, 3H), 4.32 (dd, J ) 8.8, 4.4 Hz, 1H),
4.61 (d, J ) 12.1 Hz, 1H), 4.64 (dd, J ) 4.4, 3.3 Hz, 1H), 4.76 (d,
J ) 12.1 Hz, 1H), 5.42 (d, J ) 8.8 Hz, 1H), 5.83 (d, J ) 3.3 Hz,
1H), 7.20-7.42 (m, 6H), 7.60-7.73 (m, 2H), 8.20 (s, 1H); 13C
(25) Compound 6 in chloroform solution showed keto-enol tautom-
erism that resulted in a change in the optical rotation value. The 1H
and 13C NMR spectra showed <5% signals corresponding to enol
tautomer.

Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1719
3440-3425, 1730, 1607; 1H NMR (300 MHz) δ 1.30 (s, 3H), 1.48
(s, 3H), 4.03 (d, J ) 8.4 Hz, 1H, disappears on D2O exchange),
4.17 (d, J ) 2.9 Hz, 1H), 4.57-4.66 (m, 3H), 4.73 (d, J ) 11.5
Hz, 1H), 4.98 (dd, J ) 8.4, 8.1 Hz, after D2O exchange appears
as a doublet with J ) 8.1 Hz), 5.95 (d, J ) 3.6 Hz, 1H), 7.26-
7.56 (m, 9H), 7.72 (s, 1H); 13C NMR (75 MHz) δ 26.3, 26.8, 69.5,
72.7, 79.8, 82.3, 82.5, 105.2, 112.1, 116.5, 119.1, 124.6, 127.1,
127.9, 128.1, 128.6, 131.6, 137.2, 140.8, 153.2, 161.5. Anal. Calcd
for C24H24O7: C, 67.91; H, 5.70. Found: C, 68.02; H, 5.88.
3-[5-(3-O-Ben zyl-r,â-D-glu co-h exop yr a n ose)]-2H -1-b en -
zop yr a n -2-on e (8). A solution of 7a (1.82 g, 4.74 mmol) in
THF/3 N HCl (1/1, 20 mL) was heated at 70 °C for 2 h. After
being cooled, the reaction mixture was neutralized with satu-
rated Na2CO3 solution to pH 7 and concentrated. The residue
was extracted with EtOAc (5 × 20 mL), and the combined extract
was dried (Na2SO4) and evaporated to give an oil that on
chromatography (first elution with chloroform and then with
CHCl3/MeOH ) 99/1) afforded a pale brown solid (1.44 g, 80%):
mp 72-74 °C; Rf ) 0.34 (CHCl3/MeOH ) 9/1); [R]D ) +10.97 (c
1.01 g, CHCl3, after 16 h); IR (cm-1) 3600, 2300, 1710, 1607; 1H
NMR (300 MHz) δ 1.40-1.80 (broad, 2H, exchanges with D2O,
R- and â-anomer), 2.35-2.45 (broad, exchanges with D2O, R- and
â-anomer), 3.51-4.90 (m, R- and â-anomer), 4.62 (d, J ) 9.7 Hz,
R-anomer), 4.80 (d, J ) 7.8 Hz, â-anomer), 4.92 (AB quartet, J
) 11.4 Hz, R- and â-anomer), 5.11 (d, J ) 9.1, â-anomer), 5.36
(d, J ) 3.1 Hz, R-anomer), 7.20-7.82 (m, R- and â-anomer), 7.88
(s, R-anomer), 7.92 (s, â-anomer). The 1H NMR showed an
anomeric ratio of R/â ) 3:2. Anal. Calcd for C21H20O7‚2H2O: C,
59.99; H, 5.75. Found: C, 59.30; H, 5.60.
8.3 Hz, 1H), 7.21-7.34 (m, 7H), 7.49-7.54 (m, 2H), 7.91 (s, 1H);
13C NMR (125 MHz) δ 21.0, 21.0, 21.1, 70.3, 71.1, 72.6, 74.3,
74.9, 80.2, 92.6, 117.2, 119.0, 124.8, 127.6, 128.4, 129.1, 129.4,
131.9, 137.9, 153.7, 160.6, 169.2, 169.5, 170.0. Anal. Calcd for
C27H26O10: C, 63.52; H, 5.13. Found: C, 63.45, H, 4.80.
3-[5-(r,â-D-glu co-H exop yr a n ose)]-2H -1-b en zop yr a n -2-
on e (10). A solution of 8 (0.20 g, 0.521 mmol) and 10% Pd/C
(100 mg) in ethanol/AcOH (15 mL, 14.5/0.5) was hydrogenated
at 1 atm for 24 h. The solution was filtered on Celite, washed
with ethanol, and concentrated to afford a viscous liquid.
Chromatographic purification (elution first with CHCl3/MeOH
) 9/0.1 and then with CHCl3/MeOH ) 9/1) afforded an anomeric
mixture of 10 as a pale yellow solid (0.124 g, 79%): mp 148-
151 °C; Rf ) 0.34 (CHCl3/MeOH ) 8/2); [R]D ) +9.5 (c 1.22 g,
CHCl3, after 18 h); IR (cm-1) 3665-2700, 1715; 1H NMR (300
MHz, CD3OD) δ 3.41-3.85 (m, 3H, R- and â-anomer), 4.49 (d, J
) 9.7 Hz, R-anomer), 4.64 (d, J ) 7.8 Hz, â-anomer), 4.70-4.95
(broad, -OH), 5.01 (d, J ) 9.8, â-anomer), 5.20 (d, J ) 3.6 Hz,
R-anomer), 7.30-7.40 (m, R- and â-anomer), 7.55-7.75 (m, R-
and â-anomer), 8.03 and 8.04 (s, R- and â-anomer). The 1H NMR
showed an anomeric ratio of R/â ) 3:2. Anal. Calcd for C14H14O7‚
2H2O: C, 50.90; H, 5.45. Found: C, 51.40; H, 5.58.
3-[5-(1,2,3,4-Tetr a -O-a cetyi-r,â-D-glu co-h exop yr a n osid e]-
2H-1-ben zop yr a n -2-on e (11). To a solution of 10 (1.48 g, 3.85
mmol) in pyridine (6.91 mL, 73.22 mmol) cooled to 0 °C was
added acetic anhydride (10 mL, 123.33 mmol) for a period of 30
min followed by DMAP (5.0 mg, 0.041 mmol). The reaction
mixture was allowed to warm to room temperature and stirred
for 15 h. The solution was poured into ice-water (10 mL), and
the aqueous mixture was extracted with CHCl3 (5 mL). The
organic extracts were combined and successively washed with
water (10 mL), cold hydrochloric acid 3% (6 × 5 mL), and
saturated NaHCO3 (5 mL). The removal of solvent gave a
residue. Purification by chromatography (first elution with pet.
ether/EtOAc ) 4/1) gave 11 as an inseparable anomeric mixture
as a white foamy solid (1.31 g, 56%): mp 50-53 °C; Rf ) 0.75
(hexane/EtOAc ) 1/1); IR (cm-1) 1743, 1713, 1631, 1608; 1H
NMR δ 1.95, 1.97, 2.02, 2.03, 2.05, 2.06, 2.12, 2.23 (s), 4.97 (d, J
) 9.8 Hz), 5.15-5.34 (m), 5.43 (dd, J ) 9.5, 9.3 Hz), 5.63-5.72
(m), 5.87 (d, J ) 8.2 Hz, â-anomer), 6.42 (d, J ) 3.7 Hz,
R-anomer), 7.00-7.60 (m), 7.89, 7.91 (s, 1H). The 1H NMR
showed an anomeric ratio of R:â ) 3/2. Anal. Calcd for
3-[5-(1,2,4-Tr i-O-a cetyl-3-O-ben zyl-r-D-glu co-h exop yr a -
n osid e)]-2H-1-ben zop yr a n -2-on e (9r) a n d 3-[5-(1,2,4-Tr i-O-
a cet yl-3-O-b en zyl-â-D-glu co-h exop yr a n osid e)]-2H -1-b en -
zop yr a n -2-on e (9â). To a solution of 8 (1.48 g, 3.85 mmol) in
pyridine (6.91 mL, 73.22 mmol) cooled to 0 °C were added acetic
anhydride (10 mL, 123.33 mmol) dropwise for a period of 30 min
and DMAP (5.0 mg, 0.041 mmol). The reaction mixture was
allowed to warm to room temperature, stirred for 15 h, and
concentrated. Chromatographic purification by eluting first with
pet. ether/Et2O ) 2/3 gave 9R as a pale yellow solid (1.317 g,
67%): mp 220-221 °C; Rf ) 0.46 (hexane/EtOAc ) 1/1); [R]D
)
+45.05 (c 0.2, CHCl3); IR (cm-1) 1743, 1713, 1631, 1608; 1H NMR
(500 MHz) δ 1.92 (s, 3H), 2.02 (s, 3H), 2.20 (s, 3H), 4.16 (dd, J
) 9.8, 9.4 Hz, 1H), 4.69-4.73 (AB quartet, J ) 11.8 Hz, 2H),
5.10-5.17 (m, 3H), 6.41 (d, J ) 3.7 Hz, 1H), 7.23-7.53 (m, 9H),
7.94 (s, 1H); 13C NMR (125 MHz) δ 20.8, 21.0, 21.2, 67.5, 68.2,
72.1, 74.1, 75.0, 89.5, 89.8, 116.4, 119.0, 125.2, 127.3, 128.1,
128.3, 129.0, 129.4, 133.0, 138.2, 141.9, 153.6, 160.9, 169.2, 170.0.
The 1H and 13C NMR spectra showed additional signals (<5%)
corresponding to the â-anomer. Anal. Calcd for C27H26O10; C,
63.52; H, 5.13. Found: C, 63.28, H, 5.03.
C
22H22O11: C, 57.14; H, 4.76. Found: C, 56.32, H, 5.53.
Ack n ow led gm en t. We are thankful to RSIC and
TIFR Bombay for NMR spectra and to CSIR New Delhi
for financial support and senior research fellowship to
N.N.S.. We are grateful to Prof. M. S. Wadia and Prof.
N. S. Narasimhan, for helpful discussions.
Further elution with dichloromethane afforded 9â as a white
solid (0.45 g, 23%): mp 244-246 °C; Rf ) 0.43 (hexane/EtOAc
) 1:1); [R]D ) +25.00 (c 0.22, CHCl3); IR (cm-1) 1737, 1712, 1632,
1607; 1H NMR (500 MHz) δ 1.91 (s, 3H), 1.99 (s, 3H), 2.10 (s,
3H), 3.93 (dd, J ) 9.1, 8.8 Hz, 1H), 4.64 (d, J ) 11.8 Hz, 1H),
4.67 (d, J ) 11.8 Hz, 1H), 4.89 (d, J ) 9.7 Hz, 1H), 5.17 (dd, J
) 9.7, 9.1 Hz, 1H), 5.26 (dd, J ) 8.8, 8.3 Hz, 1H), 5.78 (d, J )
Su p p or tin g In for m a tion Ava ila ble: 1H NMR (300 MHz/
500 MHz) spectra of 4a -e, 5a -c, 6, 7a , and 8-11 are
provided. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O981868Z