Epimerization of 2'-carbonylalkyl-C-glycosides via enolation, beta-elimination and intramolecular cycloaddition.

Article abstract of DOI:10.1021/jo034446k

Treatment of 2'-carbonyl-alpha-C-glycopyranosides of gluco, galacto, manno, 2-deoxy, and 2-azido sugars with 4% NaOMe resulted in anomeric epimerization to give their respective beta-anomers in good to excellent yields. The epimerization of the 2'-aldehyd

Full text of DOI:10.1021/jo034446k

Ep im er iza tion of 2′-Ca r bon yla lk yl-C-Glycosid es via En ola tion ,
â-Elim in a tion a n d In tr a m olecu la r Cycloa d d ition
Zerong Wang, Huawu Shao, Edith Lacroix, Shih-Hsiung Wu,† Harold J . J ennings, and
Wei Zou*
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa,
Ontario K1A 0R6, Canada, and Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
wei.zou@nrc.ca
Received April 8, 2003
Treatment of 2′-carbonyl-R-C-glycopyranosides of gluco, galacto, manno, 2-deoxy, and 2-azido sugars
with 4% NaOMe resulted in anomeric epimerization to give their respective â-anomers in good to
excellent yields. The epimerization of the 2′-aldehyde of R-C-galactopyranoside (10) in deuterium
methanol, which afforded the â-anomer with exclusive deuterium replacements at the 1′-position,
excluded the possibility of the exo-glycal as being involved as an intermediate. When 2′-aldehyde
(36) and 2′-ketone (41) of 2,3-di-O-benzyl-R/â-L-C-arabinofuranoside were used as substrates we
were able to obtain the respective equatorial R-C-arabinopyranosides (37 and 42). These observations
confirmed that the epimerization involves an acyclic R,â-unsaturated aldehyde or ketone, which is
formed by the enolation of 2′-carbonyl-R-C-glycoside with subsequent â-elimination. Thereafter an
intramolecular hetero-Michael cycloaddition occurs, leading to the formation of thermodynamically
controlled stable products, which were exclusively the equatorial C-glycopyranosides, except in
the case of 2′-carbonyl-C-furanosides, where a mixture of two anomers was obtained.
The development of synthetic methodology for C-
glycosides is largely stimulated by their occurrence as
building blocks in a variety of biologically important
natural products1 and by the fact that they may serve
as promising biological tools and potential therapeutics.2
A number of recent reviews have been devoted to this
subject.3 The formation of C-glycosides is based on
various types of reactions at the anomeric carbon includ-
ing (1) nucleophilic substitution of glycosyl halides,
lactones, glycals, and 1,2-anhydrosugars using carbon-
anion reagents, including Lewis acid catalyzed alkyla-
tions with stannane and silane reagents to O-glycosides
or 1-O-acetates; (2) electrophilic substitution of anomeric
anionic intermediates; (3) radical alkylations activated
by samarium, tin, and other reagents; and (4) the de novo
synthesis. In general, these methods do provide a certain
degree of stereoselectivity, but the observed stereoselec-
tivity depends on both the anomeric configuration and
the neighboring group at the 2-O-position of the sugar
substrates as well as the reaction conditions. The syn-
thesis of â-C-mannosides are more difficult because they
have 1,2-cis configurations. For example, reactions using
samarium-based approaches result in the formation of
1,2-trans-C-glycosides (gluco and galacto â-C-glycosides
and manno R-C-glycosides).4 The Wittig reactions to
sugar lactols after intramolecular cyclization selectively
afforded gluco and galacto â-C-glycosides, but a mixture
of anomers (1:1) for the manno C-glycosides.5 Reactions
of various nucleophiles to sugar lactones may yield â-C-
glycosides but are sometimes problematic to produce
* To whom correspondence should be addressed. Tel.: 613-991-0855.
Fax: 613-952-9092.
† Institute of Biological Chemistry, Academia Sinica.
(1) See the following for examples. Polytoxin: (a) Moore, R. E.;
Scheuer, P. J . Science 1971, 172, 495-498. (b) Moore, R. E.; Bartolini,
G. J . J . Am. Chem. Soc. 1981, 103, 2491-2494. (c) Usami, M.; Satake,
M.; Ishida, S.; Inoue, A.; Kan, Y.; Yasumoto, T. J . Am. Chem. Soc. 1995,
117, 5389-5390. (d) Suh, E. M.; Kishi, Y. J . Am. Chem. Soc. 1994,
116, 11205-11206. Polyether macrolides: (e) Hirata, Y.; Uemura, D.
Pure Appl. Chem. 1986, 58, 701-710. (f) Litaudon, M.; Hickford, S. J .
H.; Lill, R. E.; Lake, R. J .; Blunt, J . W.; Munro, M. H. G. J . Org. Chem.
1997, 62, 1868-1871. Polyketides: (g) Trefzer, A.; Hoffmeister, D.;
Ku¨nzel, E.; Stockert, S.; Weitnauer, G.; Westrich, L.; Rix, U.; Fuchser,
J .; Bindseil, K. U.; Rohr, J .; Bechthold, A. Chem. Biol. 2000, 7, 133-
142 and references therein.
(2) (a) Sears, P.; Wang, C.-H. Proc. Natl. Acad. Sci. U.S.A. 1996,
93, 12086-12093. (b) Witczak, Z. J . Curr. Med. Chem. 1995, 1, 392-
405. (c) Beau, J .-M.; Vauzeilles, B.; Skrydstrup, T. In Glycoscience:
Chemistry and Chemical Biology; Fraser-Reid, B., Tatsuta, K., Thiem,
J ., Eds.; Springer: Heidelberg, 2001; Vol. 3, pp 2679-2724.
(3) For leading reviews on C-glycoside synthesis: (a) Du, Y.;
Linhardt, R. J .; Vlahov, I. R. Tetrahedron 1998, 54, 9913-9959. (b)
Togo, H.; He, W.; Waki, Y.; Yokoyama, M. Synlett 1998, 700-717. (c)
Beau, J .-M.; Gallagher, T. Top. Curr. Chem. 1997, 187, 1-54. (d)
Nicotra, F. Top. Curr. Chem. 1997, 187, 55-583. (e) Praly, J .-P. Adv.
Carbohydr. Chem. Biochem. 2000, 56, 115-126. (f) Postema, M. H. D.
C-Glycoside Synthesis; CRC Press: London, 1995. (g) Levy, D. E.; Tang,
C. The Chemistry of C-Glycosides; Elsevier: Tarrytown, NY, 1995; Vol.
13.
(4) (a) Skrydstrup, T.; J arreton, O.; Mazeas, D.; Urban, D.; Beau,
J .-M. Chem. Eur. J . 1998, 4, 655-671. (b) Miquel, N.; Doisneau, G.;
Beau, J .-M. Angew. Chem., Int. Ed. 2000, 39, 4111-4113. (c) Huang,
S.-C.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996, 35, 2671-2674.
(d) Huang, S.-C.; Wong, C.-H. Tetrahedron Lett. 1996, 37, 4903-4906.
(e) Mazeas, D.; Skrydstrup, T.; Beau, J .-M. Angew. Chem., Int. Ed.
Engl. 1995, 34, 909-912.
(5) (a) Dheilly, L.; Frechou, C.; Beaupere, D.; Uzan, R.; Demailly,
G. Carbohydr. Res. 1992, 224, 301-306. (b) Dawe, R. D.; Fraser-Reid,
B. J . Org. Chem. 1984, 49, 522-528. (c) Pougny, J . R.; Nassr, M. A.
M.; Sinay¨, P. J . Chem. Soc., Chem. Commun. 1981, 375-376. (d) Orhui,
H.; J ones, G. H.; Moffat, J . G.; Maddox, M. L.; Christensen, A. T.;
Byram, S. K. J . Am. Chem. Soc. 1975, 97, 4602-4613. (e) Hanessian,
S.; Ogawa, T.; Guindon, Y. Carbohydr. Res. 1974, 38, C12-14.
10.1021/jo034446k CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/13/2003
J . Org. Chem. 2003, 68, 8097-8105
8097

Wang et al.
SCHEME 1
H2SO4-Ac2O. Allyl 2-azido-R-C-mannopyranoside (7) was
prepared from 1 in three steps: (1) Zemple´n de-O-
acetylation, (2) trifluromethylsulfonation (Tf2O/py), and
(3) SN2 replacement by NaN3 in DMF. The overall yield
(41%) was low because of competing elimination. Under
the same conditions we failed to obtain respective allyl
2-azido-3,4,6-tri-O-benzyl-R-C-glucopyranoside;13 instead,
allyl 3,4,6-tri-O-benzyl-2-deoxy-R-D-erythro-C-hex-2-eno-
pyanoside14 formed from elimination was isolated as the
major product (70-80%). The allyl R-C-glycoside of
N-acetylglucosamine (8) was prepared by a previously
reported procedure.15
manno and N-Ac-manno â-C-glycosides.6 The methods
currently available for the stereoselective syntheses of
manno â-C-glycosides include an intramolecular delivery
reported by Beau et al.,7 in which a silicon-tethered
unsaturated group was placed at the 2-O position and
an intramolecular radical reaction led to the 1,2-cis
C-glycosides; a modified Keck reaction described by Praly
et al.,8 in which a halo C-glycoside formed from glycosyl
dihalide was reduced from axial direction; a reaction of
mannopyranose with a sulfur ylide to form an epoxide
followed by intramolecular cyclization; 9 and a Ramberg-
Ba¨cklund rearrangement of S-glycosides developed by
Taylor and Franck.10
In addition to these aforementioned methods we re-
cently reported an effective epimerization that converts
2′-carbonyl-R-C-glycopyranosides to their â-anomers in-
cluding gluco, galacto, and manno â-C-glycosides as
illustrated in Scheme 1.11 Since the preliminary report
we have extended this epimerization to 2-deoxy and
2-azido sugars and investigated the mechanism using
various sugar substrates. The evidence supports a mech-
anism in which the epimerization was initiated by the
enolation of 2′-carbonyl-R-C-glycoside, followed by â-
elimination to form an acyclic R,â-unsaturated aldehyde
or ketone. Thereafter, an intramolecular hetero-Michael
addition led to the formation of â-C-glycopyranoside. The
evidence also indicates that the stereochemistry observed
is entirely controlled by the thermostability of the
products.
With these allyl R-C-glycosides in hand we performed
ozonolysis (O3/CH2Cl2 at -78 °C) on 1-8, respectively,
followed by reduction of ozonides with either Zn/HOAc
(overnight) or dimethyl sulfide (2 days). Respective 2′-
carbonyl-R-C-glycosides (9-15) were obtained in good
yields. However, no expected 2′-aldehyde was obtained
from 8 by the same procedure. To prepare 2′-ketone-R-
C-glycosides, aldehyde 10 obtained above was further
subjected to Grignard reactions with MeMgBr and Al-
lylMgBr, respectively, to afford alcohols 16 and 17.
Neither reaction was stereoselective, and two diastere-
omers were obtained in ca. 1:1 ratio based on NMR
assignment. Further oxidation of alcohols (16 and 17)
using DMSO/Ac2O led to 2′-ketones (18 and 19) in 30-
45% yield and significant amount of byproducts; thio-
methoxymethyl ethers16 were also isolated in both cases.
Ep im er iza tion . During the preliminary study the
epimerization was first performed on gluco and galacto
R-C-glycopyranosides (9 and 10). When they were treated
overnight with 4% NaOMe and Zn(OAc)2, â-C-glycosides
were obtained as respective acetylated products (20 and
21) after reduction with NaBH4, followed by acetylation
(Ac2O/Py). Without reduction and acetylation, 2′-alde-
hyde-â-C-galactoside (22) was obtained from 10. Under
the same conditions manno R-C-glycosides (11-13) were
also converted smoothly to respective â-C-glycosides (23-
25) with good to excellent yields (see Table 1). Appar-
ently, the 2-O-substitution and configuration do not deter
the â-stereoselectivity. Thus, this epimerization provides
effective access to manno 2′-carbonyl-â-C-glycosides.
The utility of this epimerization may also be extended
to the synthesis of 2′-carbonyl-â-C-glycosides of 2-deoxy,
2-azido, and 2-acetamido sugars, which are important
structural elements in some natural products. When 2′-
carbonyl-2-deoxy-R-C-glycoside (14) obtained from 6 was
subjected to the base treatment with and without
Zn(OAc)2, 2′-carbonyl-â-C-glycoside (26) was obtained in
over 90% yield. Similarly, 2′-carbonyl-2-azido-â-C-man-
nopyranoside (27) was also obtained in good yield from
15 and the stereochemistry at C2-position was not
Syn th esis of 2′-Ca r bon yl-r-C-glycosid es. Allyl R-C-
glycosides (1-4 and 6) were prepared from either methyl
O-glycosides or glycosyl 1-O-acetates and allyltrimeth-
ylsilane by Lewis acid (TMS triflate) catalyzed alkyla-
tions.12 6-O-Acetylated allyl R-C-mannoside (5) was de-
rived from 3 by selective 6-O-acetolysis using 0.05%
(6) (a) Molina, A.; Czernecki, S.; Xie, J . Tetrahedron Lett. 1998, 39,
7507-7510. (b) Xie, J .; Molina, A.; Czernecki, S. J . Carbohydr. Chem.
1999, 18, 481-498. (c) Yang, W. B.; Wu, C. Y.; Chang, C. C.; Wang, S.
H.; Teo, C. F.; Lin, C. H. Tetrahedron Lett. 2001, 42, 6907-6910.
(7) (a) Skrydstrup, T.; Beau, J .-M.; Elmouchir, M.; Mazeas, D.; Riche,
C.; Chiaroni, A. Chem. Eur. J . 1997, 3, 1342-1356. (b) Mazeas, D.;
Skrydstrup, T.; Doumeix, O.; Beau, J .-M. Angew. Chem., Int. Ed. Engl.
1994, 33, 1383-1386.
(8) Praly, J .-P.; Chen, G.-R.; Gola, J .; Hetzer, G.; Raphoz, C.
Tetrahedron Lett. 1997, 47, 8185-8188.
(9) (a) Frechou, C.; Dheilly, L.; Beaupere, D.; Demailly, R. U.
Tetrahedron Lett. 1992, 33, 5067-5070. (b) Lo´pez-Herrera, F. J .;
Sarabia-Garc´ıa, F.; Heras-Lo´pez, A.; Pino-Gonza´lez, M. S. J . Org.
Chem. 1997, 62, 6056-6059.
(10) (a) Taylor, R. J . K. Chem. Commun. 1999, 217-228 and
references therein. (b) Campbell, A. D.; Paterson, D. E.; Raynham, T.
M.; Taylor, R. J . K. Chem. Commun. 1999, 1599-1600. (c) Belica, P.
S.; Franck, R. W. Tetrahedron Lett. 1998, 39, 8225-8228.
(11) Shao, H.; Wang, Z.; Laroix, E.; Wu, S.-H.; J ennings, H. J .; Zou,
W. J . Am. Chem. Soc. 2002, 124, 2130-2131.
(12) (a) Giannis, A.; Sandhoff, K. Tetrahedron Lett. 1985, 26, 1479-
1482. (b) Allevi, P.; Anastasia, M.; Ciuffreda, P.; Fiecchi, A.; Scala, A.
J . Chem. Soc., Chem. Commun. 1987, 1245-1246. (c) Bombard, S.;
Maillet, M.; Capmau, M.-L. Carbohydr. Res. 1995, 275, 433-440. (d)
T. G. Marron, T. G.; Woltering, T. J .; Weitz-Schmidt, G.; Wong, C.-H.
Tetrahedron Lett. 1996, 37, 9037-9040. (e) McDevitt, J . P.; Lansbury,
P. T. J . Am. Chem. Soc, 1996, 118, 3818-3828. (f) Zou, W.; Wang, Z.;
Laroix, E.; Wu, S.-H.; J ennings, H. J . Carbohydr. Res. 2001, 334, 223-
231.
(13) The same replacement on allyl C-galactoside derivative also
failed; see Cipolla, L.; Ferla, B. L.; Lay, L.; Peri, F.; Nicotra, F.
Tetrahedron: Asymmetry 2000, 11, 295-303.
(14) 1H NMR (CDCl3) δ 2.28 and 2.51 (m and m, 1H each, CH2CHd
CH2), 3.55 (dd, 1H, H-6, J ) 10.0, 4.4 Hz), 3.65 (dd, 1H, H-6′, J )
10.0, 5.6 Hz), 4.00 (d, 1H, H-4, J ) 5.2 Hz), 4.13 (m, 1H, H-5), 4.31 (m,
1H, H-1), 4.48-4.82 (m, 6H, 3 × CH2Ph), 4.84 (d, 1H, H-2, J ) 2.8
Hz), 5.06-5.11 (m, 2H, CHdCH2), 5.87 (m, 1H, CHdCH2), 7.24-7.36
(m, 15H, 3 × Ph).
(15) Roe, B. A.; Boojamra, C. G.; Griggs, J . L.; Bertozzi, C. R. J .
Org. Chem. 1996, 61, 6442-6445.
(16) J ones, G. H.; Moffatt, J . G. Methods Carbohydr. Chem. 1972,
6, 315-322.
8098 J . Org. Chem., Vol. 68, No. 21, 2003

Epimerization of 2′-Carbonylalkyl-C-Glycosides
TABLE 1. Ep im er iza tion of 2′-Ca r bon yla lk yl-r-C-glycop yr a n osid esa
a
For reaction conditions see General Procedures for Epimerization in Supporting Information.
affected.17 Disappointingly, however, we were unable to
SCHEME 2
test the epimerization on 2-acetamido sugars because of
our failure to obtain 2′-aldehyde of 2-acetamido-R-C-
glucopyranoside form 8.
2′-Ketone-R-C-glycosides were also investigated, and
both 18 and 19 were epimerized to the â-C-glycosides (28
and 29) under same conditions. The more stable R,â-
conjugated 29 resulted from double bound migration
under basic conditions, and a further 1,4-addition by
MeO- to 29 afforded 30 as a major product.
With the successful conversion of 2′-carbonyl-R-C-
glycopyranosides to their â-anomers we then attempted
this epimerization on C-glycofuranosides. After ozonolysis
of the C-furanosides indicates that they have similar
of 31 (R/â 1:1), we were able to isolate a small amount of
pure â-C-glycofuranoside 32 by chromatography and a
mixture of two anomers (32 and 33 R/â 8:10). When 32
was treated with 4% NaOMe overnight a mixture of 2′-
carbonyl-R/â-L-arabinosides (32 and 33) with a ratio of
R/â ca.1:1 was obtained as determined by NMR analysis.
The same R/â ratio was also observed when a mixture of
32/33 was used as substrates. These experiments sug-
gested that equilibrium was likely reached between two
anomers and that epimerization was a thermodynamic
process. A similar observation in Wittig reaction to
furanose lactol was previously reported by Fraser-Reid
et al.18 The almost equal distribution of the two anomers
thermostabilities.
Contrary to our previous hypothesis the new experi-
ments indicate that the presence of additional ions is not
essential to the epimerization, because without the
addition of Zn2+ ion we obtained similar yields and
stereoselectivity on 22, 26, and 27. Furthermore, no
obvious kinetic difference was observed with additional
Zn2+ on the epimerization of 11, which we were able to
monitor because two anomers were separable by TLC.
Both anomers of C-glycosides were well characterized
by various 1D and 2D NMR experiments. In general the
chemical shifts of equatorial anomeric protons in R-C-
glycopyranosides are between 4.5 and 4.8 ppm, whereas
(17) C2 epimerization was encountered in Horner-Emmons nuce-
lophilic addition to N-Ac-sugar lactol; see Werner, R. M.; Williams, L.
M.; Davis, J . T. Tetrahedron Lett. 1998, 39, 9135-9138.
(18) Sun, K. M.; Dawe, R. D.; Fraser-Reid, B. Carbohydr. Res. 1987,
171, 36-47.
J . Org. Chem, Vol. 68, No. 21, 2003 8099

Wang et al.
SCHEME 3
SCHEME 4
F IGURE 1. The epimerization via enolation, â-elimination,
and 1,4-cycloaddition.
Although this epimerization resembles the mechanism
of Wittig-type reactions to sugar lactol, the generality and
excellent stereoselectivity of the method could be very
useful particularly for the synthesis of manno and
2-azido-manno 2′-carbonyl-â-C-glycopyranosides.
On the basis of the above observations we conclude that
the stereochemistry of the epimerization is dictated by
the difference in thermostability between equatorial and
axial C-glycosides. The mechanism of the reaction in-
volves enolation and subsequent â-elimination to an
acyclic R,â-unsaturated aldehyde (or ketone), followed by
an intramolecular 1,4-addition in a ring-closure step.
Cycloaddition and â-elimination are reversible reactions
and eventually lead to more stable products (see Figure
1). As a result of the absence of an anomeric effect, the
C-glycopyranosides with an equatorial substitution are
more stable than the axial substituted anomers. How-
ever, in C-furanosides, such differences are less apparent
and the distribution of the anomers depends on their
relative thermostability.
these of the â-anomers in axial configuration are found
in the range of 3.3-3.9 ppm. However, direct evidence
on the stereochemistry was determined by the NOEs
observed in the â-anomers among H-1, H-3, and H-5 in
4
a C1 conformation adopted by the â-C-glycopyranosides.
Mech a n ism of Ep m er iza tion . Many syntheses of
C-glycosides involve the formation of exo-glycal interme-
diates, such as in the nucleophilic additions to sugar
lactones6 and Ramberg-Ba¨cklund rearangement.10 How-
ever, the exo-glycal-type intermediate in this epimeriza-
tion was ruled out because the only product isolated,
when the reaction was performed on 10 in CD3OD, was
compound 34, in which both protons at the 1′-position
were replaced by deuteriums (see Scheme 3). This was
indicated by the disappearance of resonance of 1′-protons
at 1.8 and 2.2 ppm in the 1H NMR spectrum and the
absence of D-substitution at the anomeric proton (H-1).
The intermediate we propose is an open chain R,â-
unsaturated aldehyde or ketone resulted from â-elimina-
tion, similar to that formed in Wittig reaction to sugar
lactol. An intramolecular hetero-Michael addition in a
ring-closure step leads to a more stable â-C-glycoside. The
substrates such as 5-hydroxy-L-C-arabinofuranosides 36
and 41 should then produce an intermediate after
â-elimination with two hydroxy groups, which may
compete in the cycloaddition to form either pyranoside
or furanoside. Considering the thermodynamic nature of
the reaction and knowing that pyranoside is more stable
than furanoside, we expected the equatorial R-L-C-
arabinopyranosides to be the major products. Thus,
treatment of 36, a mixture of two anomers (R/â 1:1), with
NaOMe afforded 37 as predicted in 54% yield. In addi-
tion, we also synthesized 2′-ketone 41 from 36 (see
Scheme 4) by Grignard reaction (MeMgBr), protection,
oxidation, and deprotection procedures. Similarly, after
treatment of 41 (R/â 1:1) with base, C-pyranoside 42 was
isolated as major product (61%) and a mixture of C-
furanosides (R/â ca. 1:1) remained as minor products
(22%). It is noteworthy that equilibrium was likely
reached because the prolonged reaction did not result in
further transformation.
Exp er im en ta l Section
3-(6-O-Acetyl-2,3,4-tr i-O-ben zyl-r-D-m a n n op yr a n osyl)-
p r op en e (5). To a solution of 3 (10 g, 17.7 mmol) in Ac2O (57
mL) at 0 °C was added a solution of 1% H2SO4-Ac2O (3 mL).
The mixture was stirred for 16 h while the temperature was
slowly warmed to room temperature. The mixture was diluted
by the addition of EtOAc (200 mL) and aqueous NaHCO3 (50
mL). The organic phase was subsequently washed with aque-
ous NaHCO3 and water, dried, and concentrated to a residue.
Purification by chromatography (hexane/EtOAc 5:1) gave 5 (6.4
g, 70%) as a syrup: 1H NMR (CDCl3) δ 2.03 (s, 3H, OAc), 2.26-
2.35 (m, 2H, CH2CHdCH2), 3.63 (dd, 1H, H-2, J ) 4.0, 2.4
Hz), 3.75-3.82 (m, 3H, H-3, 4, 5), 4.07 (m, 1H, H-1), 4.25 (dd,
1H, H-6, J ) 12.0, 2.8 Hz), 4.40 (dd, 1H, H-6′, J ) 12.0, 6.4
Hz), 4.51-4.73 (m, 6H, 3 × CH2Ph), 4.76-5.04 (m, 2H, CHd
CH2), 5.78 (m, 1H, CHdCH2), 7.24-7.36 (m, 15H, 3 × Ph);
13C NMR (CDCl3) δ 21.3 (CH3CO), 34.8 (CH2CHdCH2), 63.6
(C-6), 71.9 (CH2Ph), 72.4 (C-5), 72.5 (CH2Ph), 72.6 (CH2Ph),
74.3 (C-1), 75.1 (C-2), 75.4 (C-3), 77.3 (C-4), 117.6 (CHdCH2),
127.6, 128.0, 128.2, 128.3, 128.6, 128.7, 129.2 (3 × Ph), 134.3
(CHdCH2), 138.2, 138.4 (3 × Ph), 171.1 (CdO); HRFABMS
anal. calcd for C32H37O6 [M + H] 517.2590, found 517.2873.
3-(3,4,6-Tr i-O-ben zyl-2-d eoxy-r-D-glu cop yr a n osyl)-p r o-
p en e (6). To a solution of methyl 3,4,6-tri-O-benzyl-2-deoxy-
R-D-glucopyanoside (2.7 g, 6.2 mmol) in dry MeCN (20 mL)
were added allyltrimethylsilane (1.4 g, 12.3 mmol) and TMS
8100 J . Org. Chem., Vol. 68, No. 21, 2003

Epimerization of 2′-Carbonylalkyl-C-Glycosides
triflate (0.53 mL, 3.1 mmol) at -40 °C. The mixture was stirred
overnight while the temperature was slowly warmed to room
temperature. The mixture was diluted by the addition of ethyl
acetate (60 mL), and the organic phase was subsequently
washed with aqueous NaHCO3 and water, dried, and concen-
trated to a residue. Purification by chromatography (hexane/
EtOAc 6:1-4:1) afforded 6 (2.43 g, 86%) as a syrup: 1H NMR
(CDCl3) δ 1.76 (m, 1H, H-2ax), 1.99 (m, 1H, H-2eq), 2.22 and
2. 45 (m and m, 1H each, CH2CHdCH2), 3.54 (dd, 1H, H-4, J
) 7.2, 6.8 Hz), 3.66 (dd, 1H, H-6, J ) 12.4, 5.2 Hz), 3.74-3.82
(m, 3H, H-6′, 5, 3), 4.04 (m, 1H, H-1), 4.51 (d, 1H, CH2Ph, J )
12.4 Hz), 4.53 (d, 1H, CH2Ph, J ) 11.2 Hz), 4.56 (d, 1H, CH2-
Ph, J ) 10.4 Hz), 4.60 (d, 2H, CH2Ph, J ) 12.0 Hz), 4.78 (d,
1H, CH2Ph, J ) 11.2 Hz), 5.02-5.06 (m, 2H, CHdCH2), 5.76
(m, 1H, CHdCH2), 7.20-7.34 (m, 15H, 3 × Ph); 13C NMR
(CDCl3) δ 32.6 (C-2), 37.0 (CH2CHdCH2), 69.2 (C-6), 70.8 (C-
1), 71.5 (CH2Ph), 73.0 (C-5), 73.6 (CH2Ph), 74.3 (CH2Ph), 76.6
(C-3), 77.1 (C-4), 117.2 (CH)CH2), 127.7, 127.8, 128.0, 128.1,
128.5, 128.5 (3 × Ph), 134.8 (CHdCH2), 138.4, 138.5, 138.6 (3
× Ph); HRFABMS anal. calcd for C30H35O4 [M + H] 459.2535,
found 459.2587.
3-(2-Azid o-3,4,6-tr i-O-ben zyl-2-d eoxy-r-D-m a n n op yr a -
n osyl)-p r op en e (7). A solution of 1 (300 mg, 0.58 mmol) in
0.1% NaOMe (3 mL) was kept at room temperature for 2 h
and was neutralized by the addition of Dowex-50 (H+). The
filtrate was concentrated to a residue. To this residue in dry
CH2Cl2 (5 mL) and pyridine (103 µL, 1.27 mmol) was added
trifluoromethanesulfonic anhydride (230 mg, 0.82 mmol) at
-30 °C. The reaction was allowed to proceed at 0 °C for 1 h.
Ice-water was added, and the organic phase was subsequently
washed with water, cold 1 N HCl, and brine, dried, and
concentrated to an oil. Without further purification, a solution
of the above crude in DMF (5 mL) was treated with sodium
azide (152 mg 2.34 mmol) for 6 days at 70 °C. Water was
added, and the aqueous solution was extracted with ether. The
ether extracts were washed with brine, dried, and concentrated
to oil. Purification by chromatography (hexane/EtOAc 10:1-
4:1) afforded 7 (120 mg, 41%) as oil: 1H NMR (CDCl3) δ 2.27
(dd, 2H, CH2CHdCH2, J ) 6.4, 6.0 Hz), 3.35 (m, 1H, H-1),
3.45 (m, 1H, H-5), 3.63-3.67 (m, 2H, H-3, 4), 3.68-3.75 (m,
2H, H-6, 6′), 4.56 (d, 2H, CH2Ph, J ) 12.0 Hz), 4.62 (d, 1H,
CH2Ph, J ) 12.4 Hz), 4.66 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.79
(d, 1H, CH2Ph, J ) 12.8 Hz), 4.82 (d, 1H, CH2Ph, J ) 11.6
Hz), 4.91 (m, 1H, H-2), 5.03-5.09 (m, 2H, CHdCH2), 5.85 (m,
1H, CHdCH2), 7.17-7.34 (m, 15H, 3 × Ph); 13C NMR (CDCl3)
δ 31.2 (CH2CHdCH2), 69.1 (C-6), 73.5 (CH2Ph), 73.9 (C-2), 75.2
(CH2Ph), 75.4 (CH2Ph), 77.7 (C-1), 78.6 (C-4), 79.4 (C-5), 84.8
(C-3), 117.2 (CH)CH2), 127.7, 127.9, 128.2, 128.6 (3 × Ph),
134.1 (CHdCH2), 138.1, 138.5, 138.4 (3 × Ph); HRFABMS
anal. calcd for C30H34O4N3 [M + H] 500.2549, found 500.2553.
3.65 (dd, 1H, H-6, J ) 10.5, 5.0 Hz), 3.69 (dd, 1H, H-3, J )
7.0, 2.0 Hz), 3.78 (m, 1H, H-2), 3.84 (dd, 1H, H-6′, J ) 10.5,
7.5 Hz), 3.99 (dd, 1H, H-4, J ) 3.0, 2.0 Hz), 4.03 (m, 1H, H-5),
4.46 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.47 (d, 1H, CH2Ph, J )
11.5 Hz), 4.50 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.52 (m, 1H, H-1),
4.56 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.58 (d, 1H, CH2Ph, J )
11.5 Hz), 4.61 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.69 (d, 2H, CH2-
Ph, J ) 11.5 Hz), 7.22-7.34 (m, 20H, 4 × Ph), 9.67 (s, 1H,
CHO); 13C NMR (CDCl3) δ 42.8 (CH2CHO), 66.9 (C-1, 6), 72.9
(CH2Ph), 73.1 (CH2Ph), 73.2 (C-5), 73.3 (CH2Ph), 73.7 (C-4),
76.1 (C-2), 76.7 (C-3), 127.5, 127.6, 127.659, 127.7, 127.8 (2),
127.9, 128.1, 128.3, 128.4 (3), 137.7, 138.2, 138.3 (2), 200.6
(CHO); HRFABMS anal. calcd for C36H39O6 [M + H] 567.2747,
found 567.2849.
2-(2,3,4,6-Tetr a-O-ben zyl-r-D-m an n opyr an osyl)-eth yl Al-
d eh yd e (11). This compound was obtained from 3 by ozonoly-
sis and purified by chromatography (hexane/EtOAc 5:1): 1H
NMR δ 2.72 (ddd, 1H, CH2CHO, J ) 16.0, 8.0, 2.0 Hz), 2.76
(ddd, 1H, CH2CHO, J ) 16.0, 8.0, 2.0 Hz), 3.71(d, 1H, H-2, J
) 7.5 Hz), 3.80-3.95 (m, 4H, H-3, 4, 6, 6′), 4.10 (m, 1H, H-5),
4.51-4.64 (m, 9H, H-1 and 4 × CH2Ph), 7.31-7.42 (m, 20H, 4
× Ph), 9.78 (t, 1H, CHO, J ) 2.5 Hz); 13C NMR (CDCl3) δ 45.5
(CH2CHO), 66.2 (C-1), 68.2 (C-6), 71.3 (CH2Ph), 72.4 (CH2Ph),
72.5 (CH2Ph), 73.2 (CH2Ph), 74.1 (C-4), 74.2 (C-3), 74.4 (C-5),
75.7 (C-2), 127.6, 127.7, 127.7, 127.8, 127.9 (2), 128.0, 128.1,
128.3, 128.4 (2), 137.7, 137.9, 138.0, 138.2, 200.5 (CHO);
HRFABMS anal. calcd for C36H39O6 [M + H] 567.2747, found
567.2898.
2-(2-O-Acetyl-3,4,6-tr i-O-ben zyl-r-D-m a n n op yr a n osyl)-
eth yl Ald eh yd e (12). This compound was obtained from 4
by ozonolysis and purified by chromatography (hexane/EtOAc
4:1): 1H NMR (CDCl3) δ 1.97 (s, 3H, AcO), 2.63 (dd, 1H, CH2-
CHO, J ) 16.0, 5.5 Hz), 2.75 (ddd, 1H, CH2CHO, J ) 16.0,
8.5, 2.5 Hz), 3.64 (d, 1H, H-6, J ) 8.0 Hz), 3.67-3.74 (m, 3H,
H-4, 5, 6′), 3.77 (dd, 1H, H-3, J ) 8.5, 7.5 Hz), 4.48 (d, 1H,
CH2Ph, J ) 12.0 Hz), 4.50 (d, 1H, CH2Ph, J ) 11.0 Hz), 4.58
(d, 1H, CH2Ph, J ) 12.0 Hz), 4.69 (d, 1H, CH2Ph, J ) 11.0
Hz), 4.71 (d, 1H, CH2Ph, J ) 10.5 Hz), 4.74 (d, 1H, CH2Ph, J
) 11.0 Hz), 4.78 (m, 1H, H-1), 5.08 (dd, 1H, H-2, J ) 7.5, 5.5
Hz), 7.16-7.34 (m, 15H, 3 × Ph), 9.72 (s, 1H, CHO); 13C NMR
δ 20.8 (CH3CO), 42.3 (CH2CHO), 67.2 (C-1), 68.4 (C-6), 71.7
(C-2), 73.1 (C-5), 73.4 (CH2Ph), 74.4 (CH2Ph), 74.5 (CH2Ph),
76.5 (C-4), 79.1 (C-3), 127.6, 127.7, 127.8 (3), 127.9, 128.3, 128.4
(2), 137.8, 137.9, 138.0, 169.9 (COCH3), 199.2 (CHO); HR-
FABMS anal. calcd for C31H35O7 [M + H] 519.2383, found
519.2609.
2-(6-O-Acetyl-3,4,6-tr i-O-ben zyl-r-D-m a n n op yr a n osyl)-
eth yl Ald eh yd e (13). This compound was obtained from 5
by ozonolysis and purified by chromatography (hexane/EtOAc
4:1): 1H NMR (CDCl3) δ 2.04 (s, 3H, AcO), 2.55 (ddd, 1H, CH2-
CHO, J ) 16.0, 8.0, 2.5 Hz), 2.70 (dd, 1H, CH2CHO, J ) 16.0,
4.5 Hz), 3.60-3.62 (m, 2H, H-2, 4), 3.80 (dd, 1H, H-3, J ) 4.0,
3.5 Hz), 3.97 (dd, 1H, H-5, J ) 8.0, 4.0 Hz), 4.08 (dd, 1H, H-6,
J ) 12.0, 4.0 Hz), 4.45 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.49 (d,
1H, CH2Ph, J ) 12.0 Hz), 4.50 (d, 3H, CH2Ph, J ) 12.0 Hz),
4.54-4.57 (m, 1H, H-1), 4.60 (d, 1H, CH2Ph, J ) 12.5 Hz),
4.67 (dd, 1H, H-6′, J ) 12.0, 8.5 Hz), 7.21-7.35 (m, 15H, 3 ×
Ph), 9.70 (s, 1H, CHO); 13C NMR (CDCl3) δ 20.8 (CH3CO), 45.5
(CH2CHO), 61.8 (C-6), 65.7 (C-1), 71.5 (CH2Ph), 72.5 (CH2Ph),
72.9 (CH2Ph), 73.6 (C-5), 73.6 (C-3), 74.5 (C-2), 75.7 (C-4),
127.8, 127.9, 128.1, 128.5 (2), 137.6 (2), 137.7, 170.8 (COCH3),
200.6 (CHO). FABMS for C31H34O7 (518.61): 535 (M + NH3),
518 (M), 459 (M - OAc), 455, 427, 411.
2-(2-O-Acet yl-3,4,6-t r i-O-b en zyl-r-D-glu cop yr a n osyl)-
eth yl Ald eh yd e (9). This compound was obtained from 1 by
ozonolysis and purified by chromatography (hexane/EtOAc
4:1): 1H NMR (CDCl3) δ 1.97 (s, 3H, AcO), 2.63 (dd, 1H, CH2-
CHO, J ) 16.5, 5.5 Hz), 2.75 (ddd, 1H, CH2CHO, J ) 16.5,
8.5, 2.5 Hz), 3.63 (d, 1H, H-6, J ) 8.0 Hz), 3.67-3.74 (m, 3H,
H-4, 5, 6), 3.77 (dd, 1H, H-3, J ) 8.0, 7.0 Hz), 4.48 (d, 1H,
CH2Ph, J ) 12.0 Hz), 4.50 (d, 1H, CH2Ph, J ) 11.0 Hz), 4.58
(d, 1H, CH2Ph, J ) 12.0 Hz), 4.69 (d, 1H, CH2Ph, J ) 11.0
Hz), 4.71 (d, 1H, CH2Ph, J ) 11 Hz), 4.74 (d, 1H, CH2Ph, J )
11.0 Hz), 4.78 (m, 1H, H-1), 5.08 (dd, 1H, H-2, J ) 8.0, 5.5
Hz), 7.16-7.34 (m, 15H, 3 × Ph), 9.72 (s, 1H, CHO); 13C NMR
(CDCl3) δ 20.8 (CH3CO), 42.3 (CH2CO), 67.2 (C-1), 68.4 (C-6),
71.7 (C-2), 73.1 (C-5), 73.5 (CH2Ph), 74.4 (CH2Ph), 74.5 (CH2-
Ph), 76.5 (C-4), 79.1 (C-3), 127.6, 127.7, 127.8, 127.8, 127.8,
127.9, 128.4, 128.4, 128.4, 137.8, 137.9, 138.0, 169.9 (COCH3),
199.2 (CHO); HRFABMS anal. calcd for C31H35O7 [M + H]
519.2383, found 519.2609.
2-(3,4,6-Tr i-O-ben zyl-2-d eoxy-r-D-glu cop yr a n osyl)-eth -
yl Ald eh yd e (14). This compound was obtained from 6 by
ozonolysis and purified by chromatography (hexane/EtOAc 10:
1-4:1): 1H NMR (CDCl3) δ 1.82 (ddd, 1H, H-2ax, J ) 13.6,
7.6, 4.0 Hz), 1.94 (ddd, 1H, H-2eq, J ) 13.6, 5.6, 4.4 Hz), 2.44
(ddd, 1H, CH2CHO, J ) 16.4, 5.6, 2.0 Hz), 2.74 (ddd, 1H, CH2-
CHO, J ) 16.4, 11.0, 2.4 Hz), 3.54 (dd, 1H, H-4, J ) 6.0, 6.0
Hz), 3.66 (dd, 1H, H-6, J ) 10.4, 4.0 Hz), 3.74 (m, 1H, H-3),
3.79 (dd, 1H, H-6′, J ) 10.4, 5.2 Hz), 3.86 (m, 1H, H-5), 4.46-
2-(2,3,4,6-Tetr a -O-ben zyl-r-D-ga la ctop yr a n osyl)-eth yl
Ald eh yd e (10). This compound was obtained from 2 by
ozonolysis and purified by chromatography (hexane/EtOAc
5:1): 1H NMR (CDCl3) δ 2.63 (d, 2H, CH2CHO, J ) 6.0 Hz),
J . Org. Chem, Vol. 68, No. 21, 2003 8101

Wang et al.
4.57 (m, 6H, H-1 and 2.5 × CH2Ph), 4.70 (d, 1H, CH2Ph, J )
11.2 Hz), 7.21-7.33 (m, 15H, 3 × Ph), 9.72 (dd, 1H, CHO, J )
2.4, 1.6 Hz); 13C NMR (CDCl3) δ 32.7 (C-2), 47.1 (CH2CHO),
65.0 (C-1), 68.6 (C-6), 71.5 (CH2Ph), 73.4 (CH2Ph), 73.5 (CH2-
Ph), 73.7 (C-5), 75.1 (C-4), 75.3 (C-3), 127.7, 127.8, 127.9, 128.0,
128.5 (2), 138.3 (3), 200.6 (CHO); HRFABMS anal. calcd for
(2), 128.4 (2), 138.0, 138.3, 138.4 (2), 206.8 (CH3COCH2);
HRFABMS anal. calcd for C37H41O6 [M + H] 581.2903, found
581.2941.
1-(2,3,4,6-Tetr a -O-ben zyl-r-D-ga la ctop yr a n osyl)-4-p en t-
en -2-on e (19). A solution of 17 (0.3 g, 0.49 mmol) in DMSO-
Ac2O (2:1, 5 mL) was kept at room temperature overnight.
Routine workup and purification by chromatography (hexane/
EtOAc 2:1) gave 19 (0.1 g, 33%) and thiomethoxymethyl ether
(0.12 g): 1H NMR (CDCl3) δ 2.64 (dd, 1H, CHHCO, J ) 16.0,
6.0 Hz), 2.71 (dd, 1H, CHHCO, J ) 16.0, 7.0 Hz), 3.10 (dd,
1H, CH2COCHHCHdCH2, J ) 16.5, 7.5 Hz), 3.15 (dd, 1H,
CH2COCHHCHdCH2, J ) 16.5, 7.0 Hz), 3.65 (dd, 1H, H-6, J
) 11.0, 5.0 Hz), 3.68 (dd, 1H, H-3, J ) 7.2, 3.0 Hz), 3.80-3.84
(m, 2H, H-2, 6), 3.98 (dd, 1H, H-4, J ) 3.0, 3.0 Hz), 4.01 (m,
1H, H-5), 4.43 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.44 (d, 1H, CH2-
Ph, J ) 12.0 Hz), 4.51 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.54 (m,
1H, H-1), 4.55 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.56 (d, 1H, CH2-
Ph, J ) 12.0 Hz), 4.63 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.68 (d,
1H, CH2Ph, J ) 12.0 Hz), 4.69 (d, 1H, CH2Ph, J ) 11.5 Hz),
5.05-5.13 (m, 2H, CHdCH2), 5.84 (m, 1H, CH2CHdCH2),
7.24-7.34 (m, 20H, 4 × Ph); 13C NMR (CDCl3) δ 41.3 (CH2-
CO), 48.1 (COCH2CHdCH2), 67.3 (C-6), 67.8 (C-1), 72.8, 73.0,
73.2, 73.3 (CH2Ph, C-5), 73.8 (C-4), 76.1 (C-2, C-3), 118.8
(CH)CH2), 127.5 (2), 127.6 (2), 127.8 (2), 127.9, 128.1, 128.3
(3), 128.4, 130.4 (CHdCH2), 137.9, 138.3, 138.4, 206.5 (COCH3);
HRFABMS anal. calcd for C39H43O6 [M + H] 607.3060, found
607.3137.
2-(2-O-Acet yl-3,4,6-t r i-O-b en zyl-â-D-glu cop yr a n osyl)-
eth yl Aceta te (20). See epimerization Procedure A (Support-
ing Information). 1H NMR (CDCl3) δ 1.75-1.84 (m, 2H,
CH2CH2OAc), 1.94 (s, 3H, AcO), 2.03 (s, 3H, AcO), 3.37 (dd,
1H, H-1, J ) 9.5, 3.5 Hz), 3.41 (dd, 1H, H-5, J ) 10.0, 3.0 Hz),
3.64 (dd, 1H, H-3, J ) 9.5, 9.0 Hz), 3.68-3.73 (m, 3H, H-4, 6,
6′), 4.14-4.24 (m, 2H, CH2OAc), 4.53 (d, 1H, CH2Ph, J ) 12.0
Hz), 4.56 (d, 1H, CH2Ph, J ) 10.5 Hz), 4.61 (d, 1H, CH2Ph, J
) 12.0 Hz), 4.67 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.78 (d, 1H,
CH2Ph, J ) 10.5 Hz), 4.82 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.88
(dd, 1H, H-2, J ) 9.5, 9.5 Hz), 7.17-7.33 (m, 15H, 3 × Ph);
13C NMR (CDCl3) δ 21.2 (2 × CH3), 30.9 (CH2CHO), 60.8 (CH2-
OAc), 68.7 (C-6), 73.5, 73.7 (C-2), 74.7 (C-1), 74.9, 75.1, 78.2
(C-4), 79.1 (C-5), 84.4 (C-3), 127.6, 127.7, 127.8, 127.9, 128.0,
128.1, 128.3, 128.4, 128.6, 138.1 (2), 138.4 (2), 169.8 (COCH3),
171.2 (COCH3); HRFABMS anal. calcd for C33H39O8 [M + H]
563.2645, found 563.2675.
C
29H33O5 [M + H] 461.2328, found 461.2241.
2-(2-Azid o-3,4,6-tr i-O-ben zyl-2-d eoxy-r-D-m a n n op yr a -
n osyl)-eth yl Ald eh yd e (15). This compound was obtained
from 7 by ozonolysis and purified by chromatography (hexane/
EtOAc 6:1-4:1) (33%): 1H NMR (CDCl3) δ 2.62 (ddd, 1H, CH2-
CHO, J ) 16.4, 5.6, 1.6 Hz), 2.75 (ddd, 1H, CH2CHO, J ) 16.4,
8.4, 2.8 Hz), 3.62-3.74 (m, 4H, H-6, H-4, H-6′, H-5), 3.77 (dd,
1H H-3, J ) 8.0, 7.6 Hz), 4.48 (d, 1H, CH2Ph, J ) 12.0 Hz),
4.50 (d, 1H, CH2Ph, J ) 10.8 Hz), 4.58 (d, 1H, CH2Ph, J )
12.0 Hz), 4.70 (d, 1H, CH2Ph, J ) 10.8 Hz), 4.72 (d, 1H, CH2-
Ph, J ) 11.6 Hz), 4.75 (d, 1H, CH2Ph, J ) 11.6 Hz), 4.77 (ddd,
1H, H-1, J ) 10.8, 5.6, 5.6 Hz), 5.08 (dd, 1H, H-2, J ) 8.0, 5.2
Hz), 7.13-7.38 (m, 15H, 3 × Ph), 9.72 (dd, 1H, CHO, J ) 2.8,
1.6 Hz); 13C NMR (CDCl3) δ 42.5 (CH2CHO), 67.5 (C-1), 68.6
(C-6), 71.9 (C-2), 73.3 (C-5), 73.7 (CH2Ph), 74.8 (2 × CH2Ph),
76.7 (C-4), 79.3 (C-3), 128.0, 128.6, 138.0, 199.3 (CHO);
HRFABMS anal. calcd for C29H31O5N3 [M] 501.2264, found
501.2251.
1-(2,3,4,6-Tetr a -O-ben zyl-r-D-ga la ctop yr a n osyl)-2-p r o-
p a n ol (16). To a solution of 10 (1.0 g, 1.76 mmol) in ether (50
mL) was added MeMgBr (3.0 M in ether, 1.5 mL) at -78 °C,
and the mixture was stirred overnight. Water (50 mL) was
added to the mixture, and the aqueous solution was extracted
with EtOAc (50 mL × 2), dried, and concentrated. Purification
by chromatography (hexane/EtOAc 2:1) afforded 16 (0.85 g,
83%) as a mixture of two distereomers (ca. 1:1): 1H NMR
(CDCl3) δ 1.17 (d, J ) 4.5 Hz, 3H), 1.18 (d, J ) 6.0 Hz, 3H),
1.41 and 1.90 (m and m, 1H each, CH2CHOH), 1.55 and 1.83
(m and m, 1H each, CH2CHOH), 4.19 (m, 1H, H-1), 4.26 (m,
1H, H-1) 4.43-4.80 (m, 16H, 8 × CH2Ph), 7.20-7.35 (m, 40H,
4 × Ph); 13C NMR (CDCl3) δ 23.0 (23.5) (CH3), 64.6, 68.3, 71.2,
73.1, 73.2, 73.3, 73.4, 74.0, 74.2, 76.9, 127.5-128.4, 138.0,
138.3, 138.4.
1-(2,3,4,6-Tetr a -O-ben zyl-r-D-ga la ctop yr a n osyl)-4-p en t-
en -2-ol (17). To a solution of 10 (0.53 g, 0.94 mmol) in ether
(20 mL) was added allyl-MgBr (1.0 M in ether, 3 mL) at -50
°C, and the mixture was stirred overnight. Similar workup
and purification by chromatography (hexane/EtOAc 2:1) af-
forded 17 (0.45 g, 79%) as a mixture of two distereomers (ca.
1:1): 1H NMR (CDCl3) δ 1.43 and 1.90 (m and m, 1H each,
CH2CHOH), 1.59 and 1.82 (m and m, 1H each, CH2CHOH),
4.16 (m, 1H, H-1), 4.27 (m, 1H, H-1) 4.46-4.72 (m, 16H, 8 ×
CH2Ph), 5.06-5.10 (m, 4H, 2 × CH2CHdCH2), 5.79 (m, 2H, 2
× CH2CHdCH2), 7.23-7.32 (m, 40H, 4 × Ph); 13C NMR
(CDCl3) δ 41.7 (41.9), 117.0 (117.1) (CHdCH2), 135.1 (135.2)
(CHdCH2).
2-(2,3,4,6-Tet r a -O-b en zyl-â-D-ga la ct op yr a n osyl)-et h yl
Aceta te (21). See epimerization Procedure A (Supporting
1
Information). H NMR (CDCl3) δ 1.79 (m, 1H, CHHCH2OAc),
2.03 (s, 3H, AcO), 2.22 (m, 1H, CHHCH2OAc), 3.36 (dd, 1H,
H-1, J ) 9.0, 8.5 Hz), 3.53-3.58 (m, 3H, H-5, 6, 6′), 3.62 (dd,
1H, H-3, J ) 9.5, 2.0 Hz), 3.71 (dd, 1H, H-2, J ) 9.5, 9.0 Hz),
4.02 (s, 1H, H-4), 4.17 and 4.26 (m and m, 1H each, CH2OAc),
4.43 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.48 (d, 1H, CH2Ph, J )
11.5 Hz), 4.65 (d, 2H, CH2Ph, J ) 11.0 Hz), 4.69 (d, 1H, CH2-
Ph, J ) 10.5 Hz), 4.78 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.96 (d,
1H, CH2Ph, J ) 10.0 Hz), 4.98 (d, 1H, CH2Ph, J ) 10.5 Hz),
7.28-7.40 (m, 20 H, 4 × Ph); 13C NMR (CDCl3) δ 21.2 (CH3),
31.2 (CH2CH2O), 61.4 (CH2OAc), 69.0 (C-6), 72.4, 73.7, 73.8
(C-4), 74.7, 75.7, 76.5 (C-1), 77.2 (C-5), 79.0 (C-2), 85.0 (C-3),
127.7, 127.8, 127.9, 128.0 (2), 128.1, 128.3, 128.4 (2), 128.6 (3),
138.1, 138.4, 138.5, 138.9, 171.3 (COCH3).
1-(2,3,4,6-Te t r a -O-b e n zyl-r-D-ga la ct op yr a n osyl)-a c-
eton e (18). A solution of 16 (0.27 g, 0.46 mol) in DMSO/Ac2O
(2:1, 5 mL) was kept at room temperature overnight. The
mixture was diluted by the addition of EtOAc (50 mL), washed
subsequently with water, aqueous NaHCO3, and water, dried,
and concentrated. Purification by chromatography (hexane/
EtOAc 2:1) gave 18 (0.12 g, 33%) and thiomethoxymethyl ether
(0.13 g): 1H NMR (CDCl3) δ 2.08 (s, 3H, AcO), 2.61 (dd, 1H,
CHHCOCH3, J ) 16.0, 5.5 Hz), 2.71 (dd, 1H, CHHCOCH3, J
) 16.0, 8.0 Hz), 3.65 (dd, 1H, H-6, J ) 10.5, 4.5 Hz), 3.68 (dd,
1H, H-3, J ) 7.5, 3.0 Hz), 3.80-3.84 (m, 2H, H-2, 6), 3.98 (dd,
1H, H-4, J ) 3.5, 3.0 Hz), 4.01 (m, 1H, H-5), 4.44 (d, 2H, CH2-
Ph, J ) 12.0 Hz), 4.51 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.53 (m,
1H, H-1), 4.56 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.58 (d, 1H, CH2-
Ph, J ) 12.0 Hz), 4.63 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.69 (d,
2H, CH2Ph, J ) 12.0 Hz), 7.22-7.34 (m, 20H, 4 × Ph); 13C
NMR (CDCl3) δ 30.5 (CH3CO), 42.6 (CH3COCH2), 67.3 (C-6),
67.9 (C-1), 72.8, 73.1, 73.2 (C-5), 73.2, 73.3, 73.9 (C-4), 76.2
(C-2), 76.3 (C-3), 127.5, 127.6 (3), 127.8 (2), 127.9, 128.1, 128.3
2-(2,3,4,6-Tet r a -O-b en zyl-â-D-ga la ct op yr a n osyl)-et h yl
Ald eh yd e (22). See epimerization Procedure B (Supporting
Information). 1H NMR (CDCl3) δ 2.58 (ddd, 1H, CH2CHO, J
) 16.2, 7.8, 2.5 Hz), 2.72 (ddd, 1H, CH2CHO, J ) 16.2, 3.5,
2.5 Hz), 3.52 (d, 2H, H-6, 6′, J ) 6.0 Hz), 3.59 (dd, 1H, H-5, J
) 7.0, 6.0 Hz), 3.63 (dd, 1H, H-3, J ) 9.0, 2.5 Hz), 3.73 (dd,
1H, H-2, J ) 9.0, 9.0 Hz), 3.77-3.81 (m, 1H, H-1), 4.01 (dd,
1H, H-4, J ) 1.5, 1.0 Hz), 4.40 (d, 1H, CH2Ph, J ) 11.5 Hz),
4.45 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.59 (d, 1H, CH2Ph, J )
10.5 Hz), 4.61 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.67 (d, 1H, CH2-
Ph, J ) 11.5 Hz), 4.76 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.93 (d,
1H, CH2Ph, J ) 12.0 Hz), 4.93 (d, 1H, CH2Ph, J ) 10.5 Hz),
8102 J . Org. Chem., Vol. 68, No. 21, 2003

Epimerization of 2′-Carbonylalkyl-C-Glycosides
7.24-7.37 (m, 20H, 4 × Ph), 9.69 (bs, 1H, CHO); 13C NMR
(CDCl3) δ 46.3 (CH2CHO), 68.7 (C-6), 72.1, 73.5, 73.6 (C-4),
74.5, 74.8 (C-1), 75.2, 77.3 (C-5), 77.9 (C-2), 84.6 (C-3), 127.5,
127.6, 127.7, 127.8, 127.9 (2), 128.1, 128.2, 128.3, 128.4,
128.430, 128.5, 137.8, 137.9, 138.0, 138.5, 200.4 (CHO).
FABMS for C36H38O6 (566.69): 567.2 (M), 475.1.
15H, 3 × Ph), 9.79 (dd, 1H, CHO, J ) 2.4, 1.6 Hz); 13C NMR
(CDCl3) δ 37.0 (C-2), 49.3 (CH2CHO), 69.4 (C-6), 70.9 (C-1),
71.7 (CH2Ph), 73.6 (CH2Ph), 75.3 (CH2Ph), 78.2 (C-4), 79.3 (C-
5), 80.8 (C-3), 127.8, 128.1, 128.5, 128.6, 138.2, 138.5, 200.6
(CHO); HRFABMS anal. calcd for C29H33O5 [M + H] 461.2328,
found 461.2232.
2-(2,3,4,6-Tetr a-O-ben zyl-â-D-m an n opyr an osyl)-eth yl Ac-
eta te (23). See epimerization Procedure A (Supporting Infor-
mation). H NMR (CDCl3) δ 1.69 (m, 1H, CHHCH2O), 2.04 (s,
2-(2-Azid o-3,4,6-tr i-O-ben zyl-2-d eoxy-â-D-m a n n op yr a -
n osyl)-eth yl Ald eh yd e (27). See epimerization Procedure C
(Supporting Information). H NMR (CDCl3) δ 2.65 (ddd, 1H,
1
1
3H, AcO), 2.10 (m, 1H, CHHCH2O), 3.39-3.43 (m, 2H, H-1,
H-5), 3.63 (dd, 1H, H-3, J ) 9.5, 3.0 Hz), 3.68-3.76 (m, 3H,
H-2, 6, 6′), 3.94 (dd, 1H, H-4, J ) 10.0, 10.0 Hz), 4.05 (m, 2H,
CH2CH2O), 4.54 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.57 (d, 1H, CH2-
Ph, J ) 10.5 Hz), 4.63 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.68 (d,
1H, CH2Ph, J ) 11.5 Hz, 1H), 4.74 (d, 1H, CH2Ph, J ) 12.0
Hz), 4.79(d, 1H, CH2Ph, J ) 12.0 Hz), 4.88 (d, 1H, CH2Ph, J
) 10.5 Hz), 5.03 (d, 1H, CH2Ph, J ) 11.5 Hz), 7.18-7.39 (m,
20H, 4 × Ph); 13C NMR (CDCl3) δ 20.9 (CH3CO), 30.9 (CH2-
CH2O), 61.6 (CH2OAc), 69.8 (C-6), 72.8 (CH2Ph), 73.7 (CH2-
Ph), 74.5 (CH2Ph), 75.2 (C-1), 75.4 (CH2Ph), 75.6 (C-2), 75.6
(C-4), 80.1 (C-5), 85.5 (C-3), 127.6, 127.7, 127.8, 127.9, 128.1,
128.2, 128.4 (2), 128.5, 128.6, 128.7, 138.6 (2), 138.8 (2), 179.5
(COCH3); HRFABMS anal. calcd for C38H43O7 [M + H]
611.3008, found 611.2953.
2-(2-O-Acetyl-3,4,6-tr i-O-ben zyl-â-D-m a n n op yr a n osyl)-
eth yl Aceta te (24). See epimerization Procedure A (Support-
ing Information). 1H NMR (CDCl3) 1.77 and 1.96 (m and m,
1H each, CH2CH2OAc), 2.03 (s, 3H, AcO), 2.17 (s, 3H, AcO),
3.43 (d, 1H, H-5, J ) 10.0 Hz), 3.59 (dd, 1H, H-1, J ) 8.8, 4.0
Hz), 3.67 (dd, 1H, H-3, J ) 9.0, 2.5 Hz), 3.73-3.74 (m, 2H,
H-6, 6′), 3.776 (ddd, 1H, H-4, J ) 9.8, 9.2, 1.5 Hz), 4.14-4.24
(m, 2H, CH2OAc), 4.49 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.50 (d,
1H, CH2Ph, J ) 10.0 Hz), 4.52 (d, 1H, CH2Ph, J ) 11.0 Hz),
4.64 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.75 (d, 1H, CH2Ph, J )
11.0 Hz), 4.86 (d, 1H, CH2Ph, J ) 10.5 Hz), 5.47 (d, 1H, H-2,
J ) 3.0 Hz), 7.16-7.35 (m, 15H, 3 × Ph); 13C NMR (CDCl3) δ
20.8 (CH3CO), 20.9 (CH3CO), 30.4 (CH2CH2OAc), 60.9 (CH2-
OAc), 69.1 (C-2), 69.2 (C-6), 71.5, 73.4, 73.6 (C-1), 74.3 (C-4),
75.0, 79.3 (C-5), 81.7 (C-3), 127.4, 127.5, 127.6, 127.7, 127.8,
128.0, 128.2 (2), 128.3, 137.7, 138.1, 138.2, 170.6 (CdO), 170.8
(CdO); HRFABMS anal. calcd for C33H39O8 [M + H] 563.2645,
found 563.2635.
CHHCHO, J ) 16.4, 8.0, 2.8 Hz), 2.83 (ddd, 1H, CHHCHO, J
) 16.4, 4.0, 1.6 Hz), 3.36 (m, 1H, H-2), 3.46-3.72 (m, 3H, H-4,
6, 6′), 3.76 (m, 1H, H-1), 4.52 (d, 1H, CH2Ph, J ) 12.0 Hz),
4.59 (d, 1H, CH2Ph, J ) 10.8 Hz), 4.60 (d, 1H, CH2Ph, J )
12.0 Hz), 4.71 (d, 1H, CH2Ph, J ) 11.6 Hz), 4.80 (d, 1H, CH2-
Ph, J ) 10.8 Hz), 4.98 (d, 1H, CH2Ph, J ) 11.6 Hz), 7.19-
7.37 (m, 15H, 3 × Ph), 9.78 (dd, 1H, CHO, J ) 2.4, 2.0 Hz);
13C NMR (CDCl3) δ 46.5 (CH2CHO), 68.8 (C-6), 73.6 (CH2Ph),
73.7 (C-2), 74.7 (C-1), 75.1 (CH2Ph), 75.5 (CH2Ph), 78.3 (C-4),
79.5 (C-3), 86.6 (C-5), 128.0, 128.1, 128.2, 128.6, 128.9, 138.0,
138.5, 200.7 (CHO); HRFABMS anal. calcd for C29H32O5N3 [M
+ H] 502.2342, found 502.2328.
1-(2,3,4,6-Te t r a -O-b e n zyl-â-D-ga la ct op yr a n osyl)-a c-
eton e (28). See epimerization Procedure B (Supporting In-
formation). 1H NMR (CDCl3) δ 2.10 (s, 3H, CH3), 2.60 (dd, 1H,
CHHCO, J ) 16.0, 8.5 Hz), 2.71 (dd, 1H, CHHCO, J ) 16.0,
2.5 Hz), 3.51 (d, 2H, H-6, 6′, J ) 5.5 Hz, 2H), 3.58 (dd, 1H,
H-5, J ) 6.5, 6.0 Hz), 3.62 (dd, 1H, H-3, J ) 9.5, 1.5 Hz), 3.68
(dd, 1H, H-2, J ) 9.5, 9.0 Hz), 3.75 (ddd, 1H, H-1, J ) 9.0, 8.8,
2.5 Hz), 4.00 (d, 1H, H-4, J ) 1.0 Hz), 4.39 (d, 1H, CH2Ph, J
) 12.0 Hz), 4.44 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.60 (d, 1H,
CH2Ph, J ) 11.5 Hz), 4.61 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.65
(d, 1H, CH2Ph, J ) 11.5 Hz), 4.74 (d, 1H, CH2Ph, J ) 13.0
Hz), 4.92 (d, 1H, CH2Ph, J ) 13.0 Hz), 4.95 (d, 1H, CH2Ph, J
) 11.5 Hz), 7.23-7.36 (m, 20H, 4 × Ph); 13C NMR (CDCl3) δ
30.7 (CH3), 46.2 (CH2COCH3), 68.6 (C-6), 72.1, 73.4, 73.7 (C-
4), 74.5, 75.1, 75.9 (C-1), 77.0 (C-5), 78.0 (C-2), 84.7 (C-3), 127.5,
127.6 (2), 127.7 (2), 127.8, 128.0, 128.1, 128.2, 128.3, 128.4 (2),
137.8, 138.1, 138.2, 138.6, 206.7 (CdO); HRFABMS anal. calcd
for C37H41O6 [M + H] 581.2903, found 581.2984.
1-(2,3,4,6-Tetr a -O-ben zyl-r-D-ga la ctop yr a n osyl)-3-p en t-
en -2-on e (29) a n d 1-(2,3,4,6-Tetr a -O-ben zyl-â-D-ga la cto-
p yr a n osyl)-4-m eth oxy-p en ta n -2-on e (30). See epimeriza-
tion Procedure B (Supporting Information). For 29: 1H NMR
(CDCl3) δ 1.81 (d, 3H, CH3, J ) 7.0 Hz), 2.72 (dd, 1H, CHHCO,
J ) 15.8, 8.0 Hz), 2.78 (dd, 1H, CHHCO, J ) 15.8, 2.5 Hz),
3.48-3.54 (m, 2H, H-6, 6′), 3.58 (dd, 1H, H-5, J ) 6.5, 6.0 Hz),
3.64 (dd, 1H, H-3, J ) 9.5, 2.0 Hz), 3.70 (dd, 1H, H-2, J ) 9.5,
9.0 Hz), 3.83 (ddd, 1H, H-1, J ) 9.0, 8.5, 2.5 Hz), 4.01 (s, 1H,
H-4), 4.38 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.44 (d, 1H, CH2Ph, J
) 11.5 Hz), 4.62 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.63 (d, 1H,
CH2Ph, J ) 11.0 Hz), 4.66 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.75
(d, 1H, CH2Ph, J ) 12.0 Hz), 4.93 (d, 1H, CH2Ph, J ) 11.5
Hz), 4.96 (d, 1H, CH2Ph, J ) 11.0 Hz), 6.08 (d, 1H, COCHdC,
J ) 15.5 Hz), 6.69-6.76 (m, 1H, CdCHCH3), 7.26-7.36 (m,
20H, 4 × Ph); 13C NMR (CDCl3) δ 18.2 (CH3), 42.6 (CH2CO),
68.6 (C-6), 72.1, 73.4, 73.8 (C-4), 74.6, 75.0, 75.8 (C-1), 76.7
(C-5), 78.1 (C-2), 84.8 (C-3), 127.5, 127.6 (2), 127.7, 127.9, 128.0,
128.1, 128.2, 128.3, 128.4 (2), 132.2 (dCHCH3), 138.0, 138.2,
138.3, 138.7, 142.8 (COCHd), 197.6 (CdO); HRFABMS anal.
calcd for C39H42O6 [M] 606.2981, found 606.2770. For 30: a
mixture of R and S (ca. 1:1); 1H NMR (CDCl3) δ 1.08 (dd, 3H,
CH3, J ) 9.5 Hz), 2.38 (ddd, 1H, CH3CHOMeCHH, J ) 16.5,
7.5, 7.5 Hz), 2.60 (dd, 1H, CH3CHOMeCHH, J ) 16.0, 8.5 Hz),
2.68 (dd, 1H, COCHH, J ) 16.0, 7.0 Hz), 2.73 (ddd, 1H,
COCHH, J ) 16.0, 3.5, 3.0 Hz), 3.22 (s, 3H, OMe), 3.48-3.54
(m, 2H, H-6, 6′), 3.57 (dd, 1H, H-5, J ) 6.5, 6.5 Hz), 3.62 (dd,
1H, H-3, J ) 7.0, 2.0 Hz), 3.67 (dd, 1H, H-2, J ) 9.5, 3.5 Hz),
3.70-3.74 (m, 1H, CH3CHOMe), 3.77 (m, 1H, H-1), 3.98 (s,
1H, H-4), 4.38 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.43 (d, 1H, CH2-
Ph, J ) 12.0 Hz), 4.61 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.62 (d,
1H, CH2Ph, J ) 12.0 Hz), 4.65 (d, 1H, CH2Ph, J ) 12.0 Hz),
4.74 (d, 1H, CH2Ph, J ) 11.5 Hz), 4.92 (d, 1H, CH2Ph, J )
2-(6-O-Acetyl-3,4,6-tr i-O-ben zyl-â-D-m a n n op yr a n osyl)-
eth yl Aceta te (25). See epimerization Procedure A (Support-
1
ing Information). H NMR (CDCl3) δ 1.66 (m, 1H, CHHCH2-
OAc), 2.02 (s, 3H, AcO), 2.04 (s, 3H, AcO), 2.07 (m, 1H,
CHHCH2OAc), 3.40 (dd, 1H, H-1, J ) 8.8, 4.5 Hz), 3.45 (dd,
1H, H-5, J ) 9.5, 6.5 Hz), 3.65 (dd, 1H, H-3, J ) 9.5, 2.0 Hz),
3.74 (bs, 1H, H-2), 3.87 (dd, 1H, H-4, J ) 9.5, 9.5 Hz), 4.05
(dd, 2H, CH2OAc, J ) 6.0, 6.0 Hz), 4.22 (dd, 1H, H-6, J ) 11.5,
6.5 Hz), 4.34 (d, 1H, H-6′, J ) 11.5 Hz), 4.60 (d, 1H, CH2Ph, J
) 11.0 Hz), 4.67 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.74 (d, 1H,
CH2Ph, J ) 12.0 Hz), 4.80 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.93
(d, 1H, CH2Ph, J ) 11.0 Hz), 5.02 (d, 1H, CH2Ph, J ) 12.0
Hz), 7.22-7.39 (m, 15 H, 3 × Ph); 13C NMR (CDCl3) δ 20.9
(CH3CO), 21.0 (CH3CO), 30.6 (CH2CH2OAc), 61.2 (CH2OAc),
64.0 (C-6), 72.5, 74.3, 75.0 (C-1), 75.1 (C-4), 75.2, 75.3 (C-2),
77.5 (C-5), 85.1 (C-3), 127.5, 127.6, 127.7, 127.8, 127.9, 128.0,
128.1, 128.2, 128.4 (2), 128.5, 138.0, 138.1, 138.4, 170.6 (2)
(COCH3). FABMS for C33H38O8 (562.66): 563 (M), 503 (M -
OAc), 455.
2-(3,4,6-Tr i-O-ben zyl-2-d eoxy-â-D-glu cop yr a n osyl)-eth -
yl Ald eh yd e (26). See epimerization Procedure C (Supporting
Information). 1H NMR (CDCl3) δ 1.47 (dd, 1H, H-2ax, J ) 24.0,
11.2 Hz), 2.20 (ddd, 1H, H-2eq, J ) 12.8, 5.2, 1.6 Hz), 2.54
(ddd, 1H, CHHCHO, J ) 16.8, 5.2, 1.6 Hz), 2.77 (ddd, 1H,
CHHCHO, J ) 16.8, 7.6, 2.4 Hz), 3.42 (ddd, 1H, H-5, J ) 9.6,
3.2, 2.8 Hz), 3.52 (dd, 1H, H-4, J ) 9.2, 9.2 Hz), 3.69 (m, 3H,
H-6′, 3, 6), 3.90 (m, 1H, H-1), 4.52 (d, 1H, CH2Ph, J ) 12.4
Hz), 4.55 (d, 1H, CH2Ph, J ) 9.6 Hz), 4.60 (d, 1H, CH2Ph, J )
9.6 Hz), 4.62 (d, 1H, CH2Ph, J ) 8.4 Hz), 4.69 (d, 1H, CH2Ph,
J ) 11.6 Hz), 4.90 (d, 1H, CH2Ph, J ) 10.8 Hz), 7.18-7.34 (m,
J . Org. Chem, Vol. 68, No. 21, 2003 8103

Wang et al.
12.0 Hz), 4.95 (d, 1H, CH2Ph, J ) 11.5 Hz), 7.22-7.35 (m, 20H,
4 × Ph); 13C NMR (CDCl3) δ 19.2 (19.3) (CH3), 45.9 (46.1)
(CH2CdO), 50.1 (50.4) (COCH2), 56.0 (56.1) (OMe), 68.5 (68.6)
(C-6), 72.1, 72.7 (72.76) (CHOMe), 73.4, 73.7 (C-4), 74.5, 75.0
(75.1), 75.7 (C-1), 76.9 (C-5), 77.8 (77.9) (C-2), 84.6 (84.7) (C-
3), 127.5, 127.6, 127.7, 127.8, 127.9, 128.00, 128.1, 128.2, 128.3,
128.4, 137.8, 138.1, 138.2, 138.6, 206.9 (207.0) (CdO). FABMS
for C40H46O7 (638.8): 639 (M), 607, 547.
1H, CH2Ph, J ) 12.0 Hz), 4.47 (m, 1 H, H-1R), 4.50-4.59 (m,
7H, 3.5 × CH2Ph), 4.57 (m, 1H, H-1â), 7.24-7.38 (m, 20H, 4
× Ph), 9.75 (t, 1H, CHO, J ) 1.6 Hz), 9.78 (t, 1H, CHO, J )
1.2 Hz); 13C NMR (CDCl3) δ 21.1 (COCH3), 43.5, 47.2, 64.5,
64.8, 71.9, 72.0, 72.1, 72.2, 76.7, 78.1, 81.3, 81.7, 82.7, 83.8,
84.8, 86.5, 127.8, 127.9, 128.1, 128.2, 128.6, 128.7, 137.3, 137.4,
137.5, 170.9 (COCH3), 200.9 (CHO); HRFABMS anal. calcd for
C23H26O6 [M + H] 399.1808, found 399.2169.
2-(2, 3-Di-O-ben zyl-r-L-a r a bin op yr a n osyl)-eth yl Ald e-
h yd e (37). See epimerization Procedure C (Supporting Infor-
mation). 1H NMR (CDCl3) δ 2.51 (bs, 1H, 4-OH), 2.56 (ddd,
1H, CH2CHO, J ) 16.4, 8.0, 2.4 Hz), 2.74 (ddd, 1H, CH2CHO,
J ) 16.4, 4.0, 2.0 Hz), 3.48 (bd, 1H, H-5ax, J ) 12.8 Hz), 3.57
(dd, 1H, H-2, J ) 9.2, 9.1 Hz), 3.64 (dd, 1H, H-3, J ) 9.2, 3.2
Hz), 3.69 (ddd, 1H, H-1, J ) 9.2, 8.0, 4.0 Hz), 4.01-4.05 (m,
2H, H-4, 5eq) 4.60 and 4.91 (d and d, 1H each, CH2Ph, J )
11.2 Hz), 4.69 and 4.74 (d and d, 1 H each, CH2Ph, J ) 11.6
Hz), 7.27-7.36 (m, 10H, 2 × Ph), 9.71 (dd, 1H, CHO, J ) 2.4
Hz, 2.0 Hz);13C NMR (CDCl3) δ 46.4 (CH2CHO), 67.0 (C-4),
69.5 (C-5), 72.0 (CH2Ph), 75.1 (CH2Ph), 75.5 (C-1), 77.7 (C-2),
82.7 (C-3), 128.1, 128.2, 128.4, 128.7, 128.9, 137.6, 137.9, 200.3
(CHO); HRFABMS anal. calcd for C21H25O5 [M + H] 357.1702,
found 357.2155.
1-(2, 3-Di-O-ben zyl-r/â-L-a r a bin ofu r a n osyl)-2-p r op a n ol
(38). To a solution of 36 (4.7 g, 11.8 mmol) in ether (100 mL)
was added MeMgBr (3.0 M in ether, 10 mL) at -78 °C, and
the mixture was stirred overnight. Water (50 mL) was added
to the mixture and the aqueous solution was extracted with
EtOAc (100 mL × 2), dried and concentrated. Purification by
chromatagraphy (hexane/EtOAc 1:3) afforded 38 (3.8 g, 87%);
HRFABMS anal. calcd for C22H29O5 [M + H] 373.2015, found
373.1869.
2-(2, 3, 5-Tr i-O-ben zyl-â-L-a r a bin ofu r a n osyl)-eth yl Al-
d eh yd e (32) a n d 2-(2, 3, 5-tr i-O-ben zyl-r-L-a r a bin ofu r a -
n osyl)-eth yl Ald eh yd e (33). Compound 31 (R/â 1:1, 0.8 g,
1.8 mmol) in dichloromethane (30 mL) was ozonalized, and
the ozonide was reduced by Zn/HOAc (see general procedure).
The products were purified by chromatography (hexane/EtOAc
8:1-4:1), and pure â-anomer (32) (0.06 g) was obtained
together with an anomeric mixture (32/33 8:10, 0.6 g). For
32: 1H NMR (CDCl3) δ 2.82 (d, 2H, CH2CHO, J ) 6.0 Hz),
3.51 (dd, 1H, H-5, J ) 10.0, 6.0 Hz), 3.60 (dd, 1H, H-5′, J )10.0,
6.0 Hz), 3.93 (d, 1H, H-3, J ) 2.8 Hz), 3.98 (d, 1H, H-2, J )
3.6 Hz), 4.09 (m, 1H, H-4), 4.32 (d, 1H, CH2Ph, J ) 11.6 Hz),
4.46 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.47 (m, 1H, H-1), 4.51 (d,
1H, CH2Ph, J ) 12.0 Hz), 4.52 (s, 2H, CH2Ph), 4.58 (d, 1H,
CH2Ph, J ) 12.0 Hz), 7.19-7.38 (m, 15H, 3 × Ph), 9.78 (dd,
1H, CHO, J ) 1.6, 1.6 Hz); 13C NMR (CDCl3) δ 43.5 (CH2CHO),
70.5 (C-5), 71.6 (CH2Ph), 71.7 (CH2Ph), 73.5 (CH2Ph), 76.6 (C-
1), 82.9 (C-4), 83.2 (C-2), 83.8 (C-3), 128.0, 128.5, 128.6, 137.6,
137.7, 138.2, 200.6 (CHO); HRFABMS anal. calcd for C28H31O5
[M + H] 447.2171, found 447.2157. For 33: (data extracted
from the spectra of mixture) 1H NMR (CDCl3) δ 2.69 (ddd, 1H,
CHHCHO, J ) 16.4, 5.6, 1.2 Hz), 2.79 (ddd, 1H, CHHCHO, J
) 16.4, 7.2, 2.0 Hz), 3.56 (m, 2H, H-5, 5′), 3.87 (dd, 1H, H-2, J
) 4.0, 2.8 Hz), 4.04 (dd, 1H, H-3, J ) 2.8, 2.4 Hz), 4.25 (m,
1H, H-4), 4.43-4.59 (m, 7H, H-1, 3 × CH2Ph), 7.19-7.37 (m,
15H, 3 × Ph), 9.76 (dd, 1H, CHO, J ) 2.0, 1.6 Hz); 13C NMR
(CDCl3) δ 47.2 (CH2CHO), 70.4 (C-5), 72.0 (CH2Ph), 72.1 (CH2-
Ph), 73.5 (CH2Ph), 77.9 (C-1), 84.4 (C-4), 85.0 (C-3), 87.1 (C-
2), 127.8, 127.9, 128.0, 128.5, 128.6, 137.6, 137.7, 138.2, 200.6
(CHO).
1-(2, 3-Di-O-ben zyl-5-O-tr ityl-r/â-L-a r a bin ofu r a n osyl)-
2-p r op a n ol (39). To a solution of 38 (3.7 g, 9.9 mmol) in
pyridine (50 mL) was added trityl chloride (4.2 g) at room
temperature. The mixture was stirred overnight and diluted
by the addition of ethyl acetate (200 mL), washed with water,
0.1 N HCl, and water, dried, and concentrated. Purification
by chromatography gave 39 (2.4 g) as a mixture of four
diasteromers (45%).
Ep im er iza tion of 32. A solution of 32 (48 mg, 0.108 mmol)
in 4% NaOMe (3 mL) was kept at room temperature overnight,
then neutralized with acetic acid, and concentrated to dryness.
The residue was purified by flash chromatography (hexane/
EtOAc 8:1-4:1) to afford a mixture of 32/33 (ca. 1:1) (40 mg,
83%) as an oil.
1-(2, 3-Di-O-ben zyl-6-O-tr ityl-r/â-L-a r a bin ofu r a n osyl)-
a ceton e (40). To a solution of 39 (2.3 g, 3.7 mmol) in CH2Cl2
(25 mL) were added 4 Å molecular sieves (2.0 g), NaOAc (0.48
g), and PCC (1.04 g), and the mixture was stirred at room
temperature overnight and filtered through Celite. The filtrate
was washed with water, aqueous NaHCO3, and water, dried,
and concentrated. After purification by chromatography 40
was obtained (0.7 g, 31%) as an R/â mixture: 1H NMR
(CDCl3): δ 2.11 (s, 3H, â CH3), 2.16 (s, 3H, R CH3), 2.71(dd,
1H, R CH3COCHH, J ) 16.5, 6.0 Hz), 2.79 (dd, 1H, â CH3-
COCHH, J ) 15.0, 7.5 Hz), 2.80 (dd, 1H, R CH3COCHH, J )
16.5, 9.0 Hz), 2.86 (dd, 1H, â CH3COCHH, J ) 17.5, 7.0 Hz),
3.12 (dd, 1H, H-5â, J ) 9.5, 7.0 Hz), 3.20 (dd, 1H, H-5R, J )
10.0, 6.5 Hz), 3.30 (dd, 1H, H-5′R, J ) 9.5, 5.5 Hz), 3.34 (dd,
1H, H-5′â, J ) 9.0, 4.5 Hz), 3.83 (dd, 1H, H-2R, J ) 3.5, 2.5
Hz), 3.96-3.99 (m, 2H, H-2â, H-3â), 4.06-4.09 (m, 2H, H-3R,
H-4â), 4.21 (m, 1H, H-4R), 4.23 (d, 1H, CH2Ph, J ) 12.0 Hz),
4.38 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.43 (d, 1H, CH2Ph, J )
12.0 Hz), 4.44 (m, 1H, H-1â), 4.47 (m, 1H, H-1R), 4.50 (s, 2H,
CH2Ph), 4.52 (d, 1H, CH2Ph, J ) 12.0 Hz), 4.53 (d, 2H, CH2-
Ph, J ) 11.5 Hz), 7.19-7.43 (m, 50H, 10 × Ph); 13C NMR-
(CDCl3) δ 30.6 (CH3), 43.1 (â CH3COCH2), 47.1 (R CH3COCH2),
64.1 (C-5â), 64.2 (C-5R), 71.3, 71.4, 71.6, 71.8, 76.9 (C-1â), 78.6
(C-1R), 82.4 (C-4R), 82.6 (C-4â), 83.1 (C-3â), 83.5 (C-2â), 85.0
(C-3R), 86.7 (C-2R), 87.1 (Ph3C-O), 126.9, 126.9, 127.5, 127.5,
127.6, 127.6, 127.7, 127.8, 128.3, 128.4, 128.5, 128.6, 128.7,
128.9, 137.7 (2), 143.8, 143.9, 206.7 (CdO).
3-(5-O-Acetyl-2,3-d i-O-ben zyl-r/â-L-a r a bin ofu r a n osyl)-
p r op en e (35). To a solution of 31 (9.5 g, 21.4 mmol) in Ac2O
(25 mL) at 0 °C was added a solution of 0.1% H2SO4/Ac2O (25
mL). Routine work up and purification by chromatography
(hexane/EtOAc 7:1) gave compound 35 (R/â 1:1, 5.93 g, 70%):
1H NMR (CDCl3) δ 2.04 and 2.06 (s and s, 3H each, R and â
COCH3), 2.41-2.45 (m, 2H, R CH2CHdCH2), 2.52-2.55 (m,
2H, â CH2CHdCH2), 3.85-3.87 (m, 2H, H-2â and H-4â), 3.92-
3.90 (m, 1H, H-2R), 3.95-3.97 (m, 1H, H-3R), 3.99-4.28 (m,
8H, H-1R, H-4R, 5R and â, 5′ R and â, H-1â, H-3â), 4.44-4.55
(m, 8H, CH2Ph R and â), 4.58-5.13 (m, 4H, R and â CHdCH2),
5.78-5.87 (m, 2H, R and â CHdCH2), 7.24-7.39 (m, 20H, R
and â 4 × Ph); 13C NMR (CDCl3) δ 21.3 (COCH3), 33.5 (CH2-
CHdCH2 R), 38.0 (CH2CHdCH2 â), 64.6 and 65.2 (C-5R, 5â),
71.9-72.3 (2 × CH2Ph R and â), 76.8 and 78.1 (2 × CHdCH2
R and â), 80.7-82.5 (C-1R, 4R, 3â, 1â), 82.6 and 83.9 (C-2â,
4â), 85.3 (C-3R), 86.62 (C-2R), 117.4 and 117.9 (CHdCH2
R
and â), 171.03 (COCH3); HRFABMS anal. calcd for C24H28O5
[M + H] 397.2015, found 397.2063.
2-(5-O-Acetyl-2, 3-d i-O-ben zyl-r/â-L-a r a bin ofu r a n osyl)-
eth yl Ald eh yd e (36). Ozonolysis of 35 afforded 36 in 76%
yield (R/â 1:1): 1H NMR (CDCl3) δ 2.03 and 2.06 (s and s, 3H
each, R and â AcO), 2.71 and 2.80 (ddd and ddd, 1H each, â
CH2CHO, J ) 16.4, 6.0, 1.6 Hz), 2.85 (dd, 2H, R CH2CHO, J
) 7.2, 1.6 Hz), 3.85 (bd, 1H, H-3R, J ) 2.0 Hz), 3.89 (dd, 1H,
H-2â, J ) 3.5, 2.0 Hz), 3.94 (dd, 1H, H-3â, J ) 3.0, 3.0 Hz),
4.01 (d, 1H, H-2R, J ) 4.0 Hz), 4.10 (m, 1H, H-4R), 4.11-4.21
(m, 4H, H-5R, 5′R and 5â, 5′â), 4.26 (m, 1H, H-4â), 4.38 (d,
1-(2, 3-Di-O-ben zyl-r/â-L-ar abin ofu r an osyl)-aceton e (41).
A mixture of 40 (0.35 g, 0.057 mmol) and ZnBr2 (1.26 g) in
CH2Cl2 (10 mL) was stirred at room temperature overnight.
Routine workup and purification by chromatography gave 41
(0.15 g, 71%) as an anomeric mixture (1:1): 1H NMR (CDCl3)
8104 J . Org. Chem., Vol. 68, No. 21, 2003

Epimerization of 2′-Carbonylalkyl-C-Glycosides
δ 2.15 (s, CH3), 2.71 (dd, 1H, CH3COCHH, J ) 16.5, 6.5 Hz),
2.83 (dd, 1H, CH3COCHH, J ) 16.5, 6.5 Hz), 3.63-3.74 (m,
2H, H-5, 5′), 3.88 (bs, 1H, H-2), 4.02 (bs, 1H, H-3), 4.13 (ddd,
1H, H-4, J ) 8.5, 3.5, 3.5 Hz), 4.55 (m, 1H, H-1), 4.34-4.62
(m, 4H, 2 × CH2Ph), 7.26-7.37 (m, 10H, 2 × Ph); 13C NMR
(CDCl3) δ 30.7, 46.3, 63.0, 71.6, 72.1, 78.8, 83.6, 84.4, 86.1,
137.4, 137.5, 206.7; for â-anomer 30.5, 42.7, 68.9, 71.7, 71.9,
77.1, 82.7, 82.9, 84.3; HRFABMS anal. calcd for C22H27O5 [M
+ H] 371.1858, found 371.1871.
(C-3), 127.9, 128.1, 128.4, 128.6, 137.5, 138.1, 206.7 (COCH3);
HRFABMS anal. calcd for C22H27O5 [M + H] 371.1858, found
371.1905.
Ack n ow led gm en t. This is NRCC publication no.
42479; this work was supported in part by National
Research Council of Canada (W.Z.) and National Science
Council of Taiwan (S.W.). We are grateful to Mr. Ken
Chan and Ms. Lisa Morrison for mass spectroscopic
analysis and Ms. Suzon Laroque for her assistance in
NMR analysis.
1-(2, 3-Di-O-ben zyl-r-L-a r a bin op yr a n osyl)-a ceton e (42).
1
See epimerization Procedure C (Supporting Information). H
NMR (CDCl3) δ 2.12 (s, 3H, CH3), 2.60 (dd, 1H, CH3COCHH,
J ) 11.0, 11.0 Hz), 2.72 (dd, 1H, CH3COCHH, J ) 20., 4.0 Hz),
3.46 (d, 1H, H-5ax, J ) 15.0 Hz), 3.54 (dd, 1H, H-2, J ) 11.5,
11.5 Hz), 3.63 (dd, 1H, H-3, J ) 11.0, 4.0 Hz), 3.68 (dd, 1H,
H-1, J ) 20.0, 4.0 Hz), 3.99 (dd, 1H, H-5eq, J ) 15.8, 3.0 Hz),
4.01 (dd, 1H, H-4, J ) 4.0, 3.0 Hz), 4.61 (d, 1H, CH2Ph, J )
13.5 Hz), 4.68 (d, 1H, CH2Ph, J ) 14.5 Hz), 7.28-7.37 (m, 10H,
2 × Ph); 13C NMR (CDCl3) δ 31.0 (CH3), 45.8 (CH3COCH2),
66.8 (C-4), 69.2 (C-5), 71.7, 75.1, 75.9 (C-1), 77.5 (C-2), 82.6
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and 1H, 13C NMR, COSY, and NOESY spectra of
products (6, 7, 14, 15, 23, 26, 27, 32/33, 36, 37, 41, 42). For
those of compounds 20-22, 24, 25, and 28-30, see Supporting
Information of ref 11. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O034446K
J . Org. Chem, Vol. 68, No. 21, 2003 8105