A high yielding chemical synthesis of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide; examples of regio- and stereodifferentiated glycosylations

Article abstract of DOI:10.1021/jo981203x

Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-2-deoxy-2-tetrachlorophthalimido-β-D- glucopyranoside (8) with the donor phenyl 2,3,4-tri-O-acetyl-6-O-benzyl-1- thio-β-D-galactopyranoside (11) gave the lactosamine derivative 14, which was fucosylated with the donor 15 to give the Le(x) trisaccharide glycoside 2 after deprotection. Regioselective sialylation of the partially protected Le(x) trisaccharide triol 24 with the sialyl donor 25 gave, after deprotection, the SLe(x) tetrasaccharide glycoside 1. The overall yields of 2 and 1 from the monosaccharide starting materials 8, 11, 15, and 25 were 56% and 29%, respectively. In contrast to the virtually complete regio- and stereoselective galactosylation of 8, fucosylation with the benzyl-protected donor 15 gave the corresponding 1→3- and 1→4-linked disaccharides in a ratio of 3.6:1 (highly stereo- but not regioselective glycosylation), whereas fucosylation with acetyl-protected donor 18 gave a 2.2:1 β/α-mixture of 4- O-linked disaccharides (highly regio- but not stereoselective glycosylation).

Full text of DOI:10.1021/jo981203x

9314
J . Org. Chem. 1998, 63, 9314-9322
A High Yield in g Ch em ica l Syn th esis of Sia lyl Lew is x
Tetr a sa cch a r id e a n d Lew is x Tr isa cch a r id e; Exa m p les of Regio-
a n d Ster eod iffer en tia ted Glycosyla tion s
Ulf Ellervik and Go¨ran Magnusson*
Organic Chemistry 2, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124,
SE-221 00 Lund, Sweden
Received J une 22, 1998
Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-
2-deoxy-2-tetrachlorophthalimido-â-D-glucopyranoside (8) with the donor phenyl 2,3,4-tri-O-acetyl-
6-O-benzyl-1-thio-â-D-galactopyranoside (11) gave the lactosamine derivative 14, which was
fucosylated with the donor 15 to give the Lex trisaccharide glycoside 2 after deprotection.
Regioselective sialylation of the partially protected Lex trisaccharide triol 24 with the sialyl donor
25 gave, after deprotection, the SLex tetrasaccharide glycoside 1. The overall yields of 2 and 1
from the monosaccharide starting materials 8, 11, 15, and 25 were 56% and 29%, respectively. In
contrast to the virtually complete regio- and stereoselective galactosylation of 8, fucosylation with
the benzyl-protected donor 15 gave the corresponding 1f3- and 1f4-linked disaccharides in a
ratio of 3.6:1 (highly stereo- but not regioselective glycosylation), whereas fucosylation with acetyl-
protected donor 18 gave a 2.2:1 â/R-mixture of 4-O-linked disaccharides (highly regio- but not
stereoselective glycosylation).
In tr od u ction
The tetrasaccharide R-Neup5NAc-(2f3)-â-D-Galp-(1f4)-
[R-L-Fucp]-(1f3)-â-D-GlcpNAc (Sialyl Lewis x, SLex) has
been identified as a ligand for the recruitment of leuco-
cytes to endothelial cells in connection with inflamma-
tion1 and has also been identified as a tumor-associated
antigen.2 The saccharide itself, as well as its dimer, has
been obtained by chemical synthesis3 and also by a
combination of chemical and enzymatic synthesis.4 We
report an efficient chemical synthesis of the SLex glyco-
(1) (a) Phillips, M. L.; Nudelman, E.; Gaeta, F. C. A.; Perez, M.;
Singhal, A. K.; Hakomori, S.; Paulson, J . C. Science 1990, 250, 1130-
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484.
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ski, Z.; Koprowski, H.; Ginsburg, V. J . Biol. Chem. 1982, 257, 14365-
14369. (b) Fukushima, K.; Hirota, M.; Terasaki, P. I.; Wakisaka, A.;
Togashi, H.; Chia, D.; Suyama, N.; Fukushi, Y.; Nudelman, E.;
Hakomori, S. Cancer Res. 1984, 44, 5279-5285. (c) Månsson, J .-E.;
Fredman, P.; Nilsson, O.; Lindholm, L.; Holmgren, J .; Svennerholm,
L. Biochim. Biophys. Acta, 1985, 834, 110-117.
(3) (a) Nicolaou, K. C.; Hummel, C. W.; Bockovich, N. J .; Wong, C.-
H. J . Chem. Soc., Chem. Commun. 1991, 870-872. (b) Kameyama,
A.; Ishida, H.; Kiso, M.; Hasegawa, A. Carbohydr. Res. 1991, 209, C1-
C4. (c) Kameyama, A.; Ishida, H.; Kiso, M.; Hasegawa, A. J . Carbohydr.
Chem. 1991, 10, 549-560. (d) Hasegawa, A.; Ito, K.; Ishida, H.; Kiso,
M. J . Carbohydr. Chem. 1995, 14, 353-368. (e) Nicolaou, K. C.;
Hummel, C. W.; Iwabuchi, Y. J . Am. Chem. Soc. 1992, 114, 3126-
3128. (f) Danishefsky, S. J .; Gervay, J .; Peterson, J . M.; McDonald, F.
E.; Koseki, K.; Oriyama, T.; Griffith, D. A. J . Am. Chem. Soc. 1992,
114, 8329-8331. (g) Danishefsky, S. J .; Koseki, K.; Griffith, D. A.;
Gervay, J .; Peterson, J . M.; McDonald, F. E.; Oriyama, T. J . Am. Chem.
Soc. 1992, 114, 8331-8333. (h) Hasegawa, A.; Fushimi, K.; Ishida, H.;
Kiso, M. J . Carbohydr. Chem. 1993, 12, 1203-1216. (i) Danishefsky,
S. J .; Gervay, J .; Peterson, J . M.; McDonald, F. E.; Koseki, K.; Griffith,
D. A.; K.; Oriyama, T.; Marsden, S. P. J . Am. Chem. Soc. 1995, 117,
1940-1953. (j) Sprengard, U.; Kretzschmar, G.; Bartnik, E.; Hu¨ls, C.;
Kunz, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 990-993. (k) J ain,
R. K.; Vig, R.; Locke, R. D.; Mohammad, A.; Matta, K. L. Chem.
Commun. 1996, 65-67. (l) Dekany, G.; Wright, K.; Toth, I. J .
Carbohydr. Chem. 1997, 16, 983-999. (m) Kretzschmar, G.; Stahl, W.
Tetrahedron 1998, 54, 6341-6358.
F igu r e 1. Structures of SLex tetrasaccharide and Lex trisac-
charide.
side 1 (Figure 1) in 29% total yield, starting from the
simple monosaccharide building blocks 8, 11, 15, and 25.
A slight deviation from the synthetic scheme yielded the
Lex trisaccharide 2 in 56% total yield. Other synthetic
routes to Lex trisaccharides have been reported.5
(4) (a) Nikrad, P. V.; Kashem, M. A.; Wlasichuk, K. B.; Alton, G.;
Venot, A. P. Carbohydr. Res. 1993, 250, 145-160. (b) Dumas, D. P.;
Ichikawa, Y.; Wong, C. H.; Lowe, J . B.; Nair, R. P. Bioorg. Med. Chem.
Lett. 1991, 1, 425-428. (c) Kondo, H.; Ichikawa, Y.; Wong, C.-H. J .
Am. Chem. Soc. 1992, 114, 8748-8750. (d) Ball, G. E.; O’Neill, R. A.;
Schultz, J . E.; Lowe, J . B.; Weston, B. W.; Nagy, J . O.; Brown, E. G.;
Hobbs, C. J .; Bednarski, M. D. J . Am. Chem. Soc. 1992, 114, 5449-
5451. (e) Ichikawa, Y.; Lin, Y. C.; Dumas, D. P.; Shen, G.-J .; Garcia-
J unceda, E.; Williams, M. A.; Bayer, R.; Ketcham, C.; Walker, L. E.;
Paulson, J . C.; Wong, C.-H. J . Am. Chem. Soc. 1992, 114, 9283-9298.
(f) DeFrees, S.; Gaeta, F.; Lin, Y.-C.; Ishikawa, Y.; Wong, C.-H. J . Am.
Chem. Soc. 1993, 115, 7549-7550. (g) Halcomb, R. L.; Huang, H.;
Wong, C.-H. J . Am. Chem. Soc. 1994, 116, 11315-11322. (h) Seitz,
O.; Wong, C.-H. J . Am. Chem. Soc. 1997, 119, 8766-8776. (i) Blixt,
O.; Norberg, T. J . Org. Chem. 1998, 63, 2705-2710.
10.1021/jo981203x CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/24/1998

Regio- and Stereodifferentiated Glycosylations
J . Org. Chem., Vol. 63, No. 25, 1998 9315
Ta ble 1. Regioselective Ga la ctosyla tion of Glu cosa m in e Der iva tivesa Ha vin g HO-4 a n d HO-3 Un p r otected
acceptor
donor
entry
R1
R2
R3
R4
promoter
O4/O3, yield (%)
1
2
3
4
5
6
7
8
O-TMSEt (12)
O-PMP (8)
O-Lactose deriv.
O-Allyl
S-Et
O-Me
NPhth
NTCP
NHAc
NPhth
NPhth
NPhth
N3
Bn
Bn
Bn
Bn
Bn
Piv
Bn
Ac
SPh (11)
SPh (11)
SMe
SMe
F
MSB, AgOTf
MSB, AgOTf
MSB, AgOTf
MeOTf
SnCl2, AgOTf
SnCl2, AgOTf
BF3Et2O
>87:1 (13, Scheme 2)
>84:1 (14, Scheme 2)
36:4526
61:175d
45:255e
F
48:213k
O-TBS
O-(CH2)8COOMe
OCNHCCl3
OAc
21:6427
N3
TMSOTf
24:424a
a
The acronyms used have the following meaning: TMSEt ) 2-(trimethylsilyl)ethyl; MSB ) methylsulfenyl bromide; PMP )
p-methoxyphenyl; TCP ) tetrachlorophthaloyl; Piv ) pivaloyl; TBS ) tert-butyldimethylsilyl.
Sch em e 1a
Resu lts a n d Discu ssion
The published organochemical procedures for the
synthesis of SLex tetrasaccharides rely on two initial
strategies: (1) galactosylation or fucosylation of a pro-
tected glucosamine derivative, having only HO-4 or HO-3
unprotected, and (2) selective galactosylation or fucosy-
lation of a glycoside acceptor, having HO-3 and HO-4
unprotected. The two methods require either a rather
elaborate protection of the acceptor or good regioselec-
tivity in the glycosylation of HO-4 or HO-3. As shown
in Table 1, the HO-4/HO-3 selectivity was low for most
of the published galactosylations (entries 3-8).
We wished to investigate additional combinations of
protecting groups and activation methods to improve the
HO-4/HO-3 regioselectivity in the first glycosylation step
and thereby raise the overall yield of the SLex synthesis.
The final synthetic protocol will be useful for the syn-
thesis of additional SLex derivatives, such as deoxy
analogues and spacer-arm glycosides for the preparation
of various neoglycoconjugates.6 It should be noted that
the successful use of N-tetrachlorophthaloyl (NTCP)7
protection was of crucial importance for the synthesis of
the SLex-1′′′f2′-lactam, presented in the following pa-
per.28
I. Syn th esis of Glycosyla tion Accep tor 8 a n d
Don or 11. The known8 glucosamine derivative 3 was
treated with tetrachlorophthalic (TCP) anhydride in
pyridine, followed by acetic anhydride, which gave the
TCP-protected compound 4 (91%, Scheme 1). This was
in our hands an improvement over the different pub-
a
Key: (a) Cl4C6(CO)2O, pyridine, ∼22 °C, 10 H, then Ac2O, 0
lished procedures for TCP protection of aminosugars.7
°C, 1 h; (b) p-MeO-C6H4OH, BF3OEt2, CH2Cl2, Ar, 20 °C, 11 h; (c)
0.018 M MeONa-MeOH, ∼22 °C, 12 min; (d) C6H5CH(OMe)2,
TsOH, MeCN, 1 h; (e) NaBH3CN, THF, then HCl-OEt2 (pH 2-3),
3 h; (f) C6H5CH(OMe)2, TsOH, MeCN, 2 h; (g) BH3NMe3, AlCl3,
THF, 60 °C, 1 h.
(5) (a) J acquinet, J .-C.; Sinay¨, P. J . Chem. Soc., Perkin Trans. 1
1979, 314-318. (b) Sato, S.; Ito, Y.; Ogawa, T. Tetrahedron Lett. 1988,
29, 5267-5270. (c) Toepfer, A.; Schmidt, R. R. Tetrahedron Lett. 1992,
33, 5161-5164. (d) Numomura, S.; Iida, M.; Numata, M.; Sugimoto,
M.; Ogawa, T. Carbohydr. Res. 1994, 263, C1-C6. (e) Zhang, Y.-M.;
Brodzky, A.; Sinay¨, P.; Saint-Marcoux, G.; Perly, B. Tetrahedron:
Asymmetry 1995, 6, 1195-1216. (f) Lin, C.-C.; Shimazaki, M.; Heck,
M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritze`n, H.; Takayama, S.; Wu,
S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J . Am. Chem. Soc. 1996, 118,
6826-6840.
p-Methoxyphenol was glycosylated with compound 4,
using boron trifluoride etherate (BF3OEt2) as promoter,9
which gave the glycoside 5 in almost quantitative yield
(98%) as the pure â-anomer. Initial attempts to de-O-
acetylate 5 with methanolic sodium methoxide (MeONa/
MeOH) were unsuccessful, due to the base-sensitive
nature of the NTCP group.10 However, short treatment
(6) Neoglycoconjugates: Preparation and Applications; Lee, Y. C.,
Lee, R. T., Eds.; Academic Press: San Diego, 1994.
(7) (a) Debenham, J . S.; Madsen, R.; Roberts, C.; Fraser-Reid, B. J .
Am. Chem. Soc. 1995, 117, 3302-3303. (b) Debenham, J . S.; Fraser-
Reid, B. J . Org. Chem. 1996, 61, 432-433. (c) Castro-Palomino, J . C.;
Schmidt, R. R. Tetrahedron Lett. 1995, 36, 5343-5346.
(8) Bergmann, M.; Zervas, L. Ber. 1931, 64, 975-980.
(9) Zhang, Z.; Magnusson, G. Carbohydr. Res. 1996, 925, 41-55.

9316 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik and Magnusson
Sch em e 2a
a
Key: (a) AgOTf, MeCN, -70 °C, Ar, 5 min, then MeSBr, ClCH2CH2Cl, -70 °C, 1 h; (b) AgOTf, MeCN, -78 °C, Ar, 5 min, then
MeSBr, ClCH2CH2Cl, -70 °C, 2 h; (c) AgOTf, MeCN, -45 °C, Ar, 5 min, then MeSBr, ClCH2CH2Cl, -70 °C, 1.5 h.
(<15 min) of 5 in a large volume of 0.018 M MeONa/
MeOH solution effected de-O-acetylation (f6, 86%) while
leaving the NTCP group virtually intact. These reaction
conditions are probably close to being optimized. To the
best of our knowledge, this is the first example of de-O-
acetylation under basic conditions in the presence of an
NTCP group. Attempted acid-catalyzed de-O-acetylation,
using HCl in methanol, resulted in the formation of the
methyl glycoside corresponding to 6 as the major product.
The triol 6 was treated with R,R-dimethoxytoluene and
p-toluenesulfonic acid (TsOH) to give the 4,6-O-ben-
zylidene derivative 7 (77%). Reductive opening of the 4,6-
O-benzylidene ring of 7 with sodium cyanoborohydride
(NaCNBH3) in ethereal hydrogen chloride solution11 gave
the diol acceptor 8 (66%).
II. Regioselective Glycosyla tion of Diols. A num-
ber of papers have appeared where regioselective â-ga-
lactosylation of N-protected glucosamine derivatives were
attempted. As shown in Table 1, mixtures of 1f3- and
1f4-linked disaccharides were obtained in all reported
cases (entries 3-8). In contrast, and much to our
surprise, â-galactosylation of the acceptors 8 and 1215
with the donor 11 under activation with methylsulfenyl
bromide (MSB)16 and silver trifluoromethanesulfonate
(AgOTf) gave the 1f4-linked lactosamine derivatives 13
and 14 in 87 and 84% yield, respectively; the correspond-
ing 1f3-linked compounds were not detected by TLC or
NMR. On the other hand, fucosylation of 8 with the
donor 1517 under the same reaction conditions as above
gave a mixture of the 1f3- and 1f4-linked disaccharides
16 and 17 in 84% yield (Scheme 2). Here, the 1f3-linked
compound 16 was formed in excess.
Treatment of the known12 thiophenyl galactoside 9
with R,R-dimethoxytoluene and TsOH gave the 4,6-O-
benzylidene derivative 1013 (92%). Attempted reductive
opening11 of the 4,6-O-benzylidene ring with NaCNBH3
was unsuccessful. Instead, reduction of 10 with tri-
methylaminoborane (BH3NMe3) and aluminum trichlo-
ride (AlCl3),14 followed by O-acetylation of the crude
product with Ac2O in pyridine, gave the glycosyl donor
11 (46%).
The dramatically different regioselectivities in â-D-
galactosylation versus R-L-fucosylation of 8 constitute an
example of regiodifferentiation (matched-mismatched
(13) Lipta´k, A.; J orda´l, I.; Harangi, J .; Na´na´si, P. Acta Chim. Hung.
1983, 113, 415-422.
(14) Ek, M.; Garegg, P. J .; Hultberg, H.; Oscarson, S. J . Carbohydr.
Chem. 1983, 2, 305-311.
(15) Ellervik, U.; Magnusson, G. Carbohydr. Res. 1996, 280, 251-
(10) Debenham, J . S.; Debenham, S. D.; Fraser-Reid, B. Bioorg. Med.
Chem. 1996, 4, 1909-1918.
260.
(16) (a) Dasgupta, F.; Garegg, P. J . Carbohydr. Res. 1988, 177, C13-
C17. (b) Dasgupta, F.; Garegg, P. J . Carbohydr. Res. 1990, 202, 225-
238.
(11) Garegg, P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982,
108, 97-101.
(12) Yde, M.; DeBruyne, C. K. Carbohydr. Res. 1973, 26, 227-229.
(17) Lo¨nn, H. Carbohydr. Res. 1985, 139, 105-113.

Regio- and Stereodifferentiated Glycosylations
J . Org. Chem., Vol. 63, No. 25, 1998 9317
Sch em e 3a
glycosylation). A case of stereodifferentiation, leading to
different R,â-mixtures depending on the structure of the
glycosyl acceptors, was recently reported.18 The observed
regiodifferentiation prompted us to investigate the out-
come of a glycosylation with the acetylated fucosyl donor
1819 (compound 18 is structurally similar to the enanti-
omer of the galactoside 11). Glycosylation of 8 with 18,
under the same reaction conditions as with 11, gave a
mixture of 19 and 20 in 58% yield. As with 11, 18
glycosylated 8 with virtually total regioselectivity, whereas
the â/R stereoselectivity was only 2.2:1.
The varying regioselectivities shown in Table 1 and
Scheme 2 seem to depend on a number of factors, such
as the nature of the different protecting groups, and the
nature and mode of activation of the donor. Additional
glycosylations with other donors and acceptors, as well
as modeling of transition states, are obviously needed in
order to understand and predict the regio- and stereo-
chemical outcome of these glycosylations.
III. Syn th esis of Lex Tr isa cch a r id e 2 a n d SLex
Tetr a sa cch a r id e 1. The NTCP-protected lactosamine
derivative 14 was chosen as starting material for the final
steps toward the Lex and SLex saccharides, since it was
easily obtained in pure form and in good yield (Scheme
2). Furthermore, the NTCP protection gave several
options for manipulations later in the synthetic sequence.
Attempted fucosylation of HO-3 in 14, using different
fucosyl donors under various reaction conditions, was
totally unsuccessful, despite the fact that others have
managed to fucosylate the corresponding NPhth-protect-
ed lactosamine derivatives.3k,5d,e Equally unsuccessful
was our attempted galactosylation of the fucose-contain-
ing disaccharide 23 using the galactosyl donor 11 (Scheme
3), although similar reactions have been performed by
others3b,c,j,m,5f in modest to good yields.
a
Key: (a) H2NCH2CH2NH2, EtOH, 60 °C, 3 h, then Ac2O,
MeOH, H2O, ∼22 °C, 1 h; (b) Br2, CH2Cl2, cyclohexene, then MS
4 Å, Bu4NBr, CH2Cl2, DMF, ∼22 °C, 20 h, then pyridine, 3 h; (c)
H2,Pd-C,AcOH,4 h,then MeONa-MeOH,1 h;(d)H2NCH2CH2NH2,
EtOH, reflux, 3 h, then Ac2O, pyridine, DMAP, ∼22 °C, 16 h.
Sch em e 4a
To diminish the supposed steric hindrance in 14
against fucosylation, the large NTCP group (which had
served its purpose to guide the regioselective galactosy-
lation) was replaced by the much smaller NHAc group.
Thus, treatment of 14 with 1,2-diaminoethane (Scheme
3),7 followed by N-acetylation of the intermediate amine,
gave the N-acetyllactosamine derivative 21 (88%). Simi-
larly, compound 23 was obtained in 89% yield from 16.
Fucosylation of HO-3 in 21 was then successfully
performed by first treating the thiofucoside 1517 with
bromine (Br2, distilled from P2O5) to generate the corre-
sponding fucosyl bromide20 and then add the mixture to
21 in the presence of Bu4NBr,21 thus furnishing the Lex
trisaccharide derivative 22 (83%). Without distillation
of Br2, the yield of 22 dropped to approximately 60%. De-
O-benzylation of 22, followed by O-acetylation, gave the
fully acetylated derivative of 2 for convenient structure
determination. It was interesting to note that the J 1,2
coupling constants (glucosamine residue) of 22 and
O-acetylated 2 were different (4.3 and 6.1 Hz, respec-
tively), indicating the presence of steric strain in 22,
strong enough to perturb the GlcNAc ring. De-O-ben-
zylation and de-O-acetylation of 22 gave the Lex trisac-
charide 2 (91%).
a
Key: (a) MeONa-MeOH, ∼22 °C, 1.5 h; (b) MS 3 Å, CH2Cl2,
MeCN, Ar, -72 °C, 15 min, then AgOTf, MeCN, MeSBr,
ClCH2CH2Cl, -72 °C, 2.5 h, then Ac2O, pyridine, DMAP; (c) H2,
Pd-C, AcOH, 5 h, then MeONa-MeOH, 1 h, then aqueous 1 M
NaOH, 1.5 h.
(18) Spijker, N. M.; van Boeckel, C. A. A. Angew. Chem., Int. Ed.
Engl. 1991, 30, 180-183.
(19) Komba, S.; Ishida, H.; Kiso, M.; Hasegawa, A. Biorg. Med.
Chem. 1996, 4, 1833-1848.
(20) Nilsson, S.; Lo¨nn, H.; Norberg, T. Glycoconj. J . 1989, 6, 21-
Removal of the O-acetyl groups of 22 (Scheme 4), using
MeONa/MeOH, gave the triol acceptor 24 (89%). Sialy-
lation of 24 with the sialyl donor 2522 under promotion
34.
(21) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; J ames, K. J . Am.
Chem. Soc. 1975, 97, 4056.-4062.

9318 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik and Magnusson
of AgOTf and MSB16 was completely regioselective, and
the SLex tetrasaccharide derivative 26 was obtained pure
(after O-acetylation of the unreacted hydroxyl groups in
order to simplify the chromatographic purification) in
65% isolated yield. Such high regioselectivity has been
demonstrated in other sialylations of galactose-based di-
and triols.22,23 The R-sialyl linkage was deduced from the
coupling constant between the carbonyl carbon (C-1′′′)
Hz, H-1′′), 4.93 (d, 1 H, J ) 8.5 Hz, H-1), 4.43 (d, 1 H, J ) 7.8
Hz, H-1′), 4.04 (dd, 1 H, J ) 10.1, 8.6 Hz, H-2), 3.97 (dd, 1 H,
J ) 9.7, 3.2 Hz, H-3′), 3.67 (s, 3 H, OMe), 3.41 (dd, 1 H, J )
9.6, 7.8 Hz, H-2′), 2.65 (dd, 1 H, J ) 12.4, 4.6 Hz, H-3e′′′), 1.91,
1.89 (s, 3H, 2 × NHAc), 1.67 (t, 1 H, J ) 12.2 Hz, H-3a′′′),
1.05 (d, 3 H, J ) 6.6 Hz, H-6′′); 13C NMR (CDCl3) δ 175.4,
174.9, 174.3, 155.2, 151.5, 118.7, 115.4, 102.0, 100.9, 100.0,
99.0, 76.0, 75.8, 75.3, 73.4, 73.3, 72.3, 72.2, 69.6, 68.7, 68.5,
68.1, 67.7, 63.0, 61.9, 59.9, 56.2, 56.1, 52.1, 40.1, 22.5, 22.4,
15.6; HRMS calcd for C38H58O24N2Na (M + Na) 949.3277,
found 949.3276.
and the axial proton in the 3′′′-position24 (J C-1′′′:H-3′′′ax
)
6.4 Hz). As for compound 22 above, 26 was also strained,
which was witnessed by the abnormal coupling constant
J 1,2 ) 3.4 Hz. De-O-benzylation of 26, followed by
O-acetylation, gave a fully O-acetylated derivative of 1,
which had J 1,2 ) 7.7 Hz, as expected for a relaxed
pyranosidic GlcNAc ring.
4-Meth oxyp h en yl (â-D-Ga la ctop yr a n osyl)-(1f4)-[R-L-
fu cop yr a n osyl]-(1f3)-(2-a ceta m id o-2-d eoxy-â-D-glu cop y-
r a n osid e) (2). Compound 22 (105 mg, 0.09 mmol) was
dissolved in AcOH (2.5 mL, distilled from Ac2O), and the
mixture was hydrogenated (H2, 1 atm, Pd-C, 10%, 100 mg)
for 4 h, filtered through Celite, and concentrated. The residue
was dissolved in MeOH (5 mL), 1 M NaOMe-MeOH (0.25 mL)
was added, and the mixture was stirred for 1 h and then
neutralized with Amberlite IR 120 H+. The mixture was
concentrated, and the residue was chromatographed (SiO2, 65:
Hydrogenolysis of the benzyl groups and methanolysis/
hydrolysis of the esters of 26 gave the SLex glycoside 1
in 81% overall yield. The NMR data of 1 are in excellent
agreement with those reported by Wong et al.4e for the
corresponding allyl glycoside.
30:5 CH2Cl2-MeOH-H2O) to give 2 (50.0 mg, 91%): [R]20
D
-57.6 (c 0.6, H2O); 1H NMR (D2O) δ 6.80-6.94 (m, 4 H,
OPMP), 5.00 (d, 1 H, J ) 4.0 Hz, H-1′′), 4.92 (d, 1 H, J ) 8.5
Hz, H-1), 4.60-4.75 (m, HDO, H-5′′), 4.35 (d, 1 H, J ) 7.8 Hz,
H-1′), 4.02 (dd, 1 H, J ) 9.9, 8.7 Hz, H-2), 3.75-3.95 (m, 4 H,
Exp er im en ta l Section
The structures of all new compounds were confirmed by
NMR analysis, including COSY, NOESY, HETCOR, and long-
range HETCOR. NMR spectra were recorded with 400 and
500 MHz instruments. Chemical shifts are given in ppm
downfield from the signal for Me4Si, with reference to internal
CHCl3 or HDO. Melting points are uncorrected. Molecular
sieves were activated for ∼5 min by heating at ∼500 °C under
vacuum (oil pump). CH2Cl2 and MeCN were dried by distil-
lation from CaH2, THF was distilled from Na/benzophenone,
DMF was dried over 4 Å molecular sieves and distilled, 1,2-
diaminoethane was distilled, and bromine was distilled from
P2O5. p-Methoxyphenol was recrystallized before use. Meth-
ylsulfenyl bromide (MSB)16 was prepared in 1,2-dichloroethane
to give a 4 M solution. The solution could be kept in a sealed
glass ampule under Ar at -20 °C for several months.15
Column chromatography was performed on SiO2 (Matrex LC-
H-3,4,4′,3′′), 3.66 (s,
3 H, OMe), 3.50-3.62 (m, 9 H,
H-5,6,3′,5′,6′,2′′,4′′), 3.37 (dd, 1 H, J ) 9.8, 7.9 Hz, H-2′), 1.89
(s, 3 H, NHAc), 1.04 (d, 3 H, J ) 6.6 Hz, H-6′′); 13C NMR
(CDCl3) δ 174.8, 155.2, 151.5, 118.6, 115.4, 102.2, 100.8, 99.0,
75.9, 75.3, 75.1, 73.4, 72.8, 72.2, 71.4, 69.5, 68.7, 68.0, 67.1,
61.9, 59.9, 56.1, 56.1, 22.5, 15.6; HRMS calcd for C27H41O16
-
NNa (M + Na) 658.2323, found 658.2334.
1,3,4,6-Tet r a -O-a cet yl-2-d eoxy-2-(t et r a ch lor op h t h a l-
im id o)-â-D-glu cop yr a n ose (4). 1,3,4,6-Tetra-O-acetyl-2-
amino-2-deoxy-â-D-glucopyranose hydrochloride8 (3, 10.0 g,
26.1 mmol) was dissolved in pyridine, and tetrachloropthalic
anhydride (9.0 g, 31.5 mmol) was added. The mixture was
stirred for 10 h and cooled to 0 °C, and Ac2O was added. The
mixture was stirred for 1 h and co-concentrated with toluene.
The residue was chromatographed (SiO2, 3:1 f 1:1 EtOAc-
heptane), and the crude material was crystallized to give 4
(12.8 g, 80%). The mother liquid was concentrated, and an
gel; 60A, 35-70 MY, Grace) and TLC on Merck SiO2 60 F256
.
Compounds 3,8 9,12 12,15 15,17 18,19 and 2522 were prepared as
described in the literature.
additional crop of crystals was obtained (3.7 g; total yield
1
91%): [R]20 +69.7 (c 0.9, CHCl3); mp 169-171 °C; H NMR
D
4-Meth oxyp h en yl (5-Aceta m id o-3,5-d id eoxy-D-glycer o-
R-D-ga la cto-2-n on u lop yr a n osylon ic a cid )-(2f3)-(â-D-ga -
la ctop yr a n osyl)-(1f4)-[R-L-fu cop yr a n osyl]-(1f3)-(2-a cet-
a m id o-2-d eoxy-â-D-glu cop yr a n osid e) (1). Compound 26
(50 mg, 0.03 mmol) was dissolved in AcOH (1 mL), and Pd-C
(10%, 50 mg) was added. The mixture was hydrogenated (H2,
1 atm) for 5 h, filtered (Celite), and concentrated. The residue
was dissolved in MeOH (3 mL), 1 M MeONa-MeOH (0.1 mL)
was added, and the mixture was stirred for 1 h. Aqueous 1 M
NaOH (0.2 mL) was added, and the mixture was stirred for
1.5 h. A 1:5 mixture of AcOH-H2O (0.125 mL) was added,
the reaction mixture was concentrated, and the residue was
chromatographed (SiO2, 60:35:5:0.1 CH2Cl2-MeOH-H2O-
(CDCl3) δ 6.48 (d, 1 H, J ) 8.8 Hz, H-1), 5.81 (dd, 1 H, J )
10.4, 9.0 Hz, H-3), 5.24 (dd, 1 H, J ) 10.3, 9.1 Hz, H-4), 4.46
(dd, 1 H, J ) 10.4, 8.8 Hz, H-2), 4.37 (dd, 1 H, J ) 12.5, 4.5
Hz, H-6), 4.15 (dd, 1 H, J ) 12.5, 2.1 Hz, H-6), 3.99 (ddd, 1 H,
J ) 10.2, 4.4, 2.1 Hz, H-5), 2.12, 2.06, 2.05, 1.92 (s, 3 H each,
4 × OAc); 13C NMR (CDCl3) δ 171.06, 170.95, 169.8, 169.1,
90.1, 73.1, 71.1, 68.3, 61.8, 54.8, 21.3, 21.2, 21.0, 20.9; HRMS
calcd for C22H19O11NCl4Na (M + Na) 635.9610, found 635.9608.
4-Meth oxyp h en yl 3,4,6-Tr i-O-a cetyl-2-d eoxy-2-(tetr a -
ch lor op h th a lim id o)-â-D-glu cop yr a n osid e (5). To a cold (0
°C) solution of 4 (10.0 g, 16.2 mmol) and 4-methoxyphenol (2.20
g, 18.0 mmol, recrystallized from ligroin) in dry CH2Cl2 (30
mL) was added BF3OEt2 (4.00 mL, 32.8 mmol) under Ar. The
temperature was gradually raised to 20 °C during 2 h, and
the mixture was stirred for 9 h, diluted with CH2Cl2 (100 mL),
and washed with H2O, saturated aqueous NaHCO3, and H2O.
The organic phase was dried (Na2SO4) and concentrated. The
residue was chromatographed (SiO2, 2:1 EtOAc-heptane) to
AcOH) to give 1 (22.9 mg, 81%): [R]20 -25.5 (c 0.9 D2O). 1H
D
NMR (D2O) δ 6.80-6.95 (m, 4 H, OPMP), 5.01 (d, 1 H, J ) 3.9
(22) Marra, A.; Sinay¨, P. Carbohydr. Res. 1990, 195, 303-308.
(23) (a) Hasegawa, A.; Ohki, H.; Nagahama, T.; Ishida, H.; Kiso,
M. Carbohydr. Res. 1991, 212, 277-281. (b) Birberg, W.; Lo¨nn, H.
Tetrahedron Lett. 1991, 32, 7453-7456. (c) Birberg, W.; Lo¨nn, H.
Tetrahedron Lett. 1991, 32, 7457-7458. (d) Lo¨nn, H.; Stenvall, K.
Tetrahedron Lett. 1992, 33, 115-116. (e) Ray, A. K.; Nilsson, U.;
Magnusson, G. J . Am. Chem. Soc. 1992, 114, 2256-2257. (f) Kondo,
H.; Ichikawa, Y.; Wong, C.-H. J . Am. Chem. Soc. 1992, 114, 8748-
8750. (g) Wilstermann, M.; Kononov, L. O.; Nilsson, U.; Ray, A. K.;
Magnusson, G. J . Am. Chem. Soc. 1995, 117, 4742-4754. Wilstermann,
M.; Magnusson, G. J . Org. Chem. 1997, 62, 7961-7971.
(24) (a) Hori, H.; Nakajima, T.; Nishida, Y.; Ohrui, H.; Meguro, H.
Tetrahedron Lett. 1988, 29, 6317-6320. (b) Prytulla, S.; Lauterwein,
J .; Klessinger, M.; Thiem, J . Carbohydr. Res. 1991, 215, 345-349. (c)
Erce´govic, T.; Magnusson, G. J . Chem. Soc., Chem. Commun. 1994,
831-832.
give 5 (10.8 g, 98%): [R]20 +63.3 (c 1.3, CHCl3); 1H NMR
D
(CDCl3) δ 6.75-6.90 (m, 4 H, OPMP), 5.86 (d, 1 H, J ) 8.4
Hz, H-1), 5.78 (dd, 1 H, J ) 10.5, 9.1 Hz, H-3), 5.27 (dd, 1 H,
J ) 10.1, 9.2 Hz, H-4), 4.57 (dd, 1 H, J ) 10.5, 8.5 Hz, H-2),
4.37 (dd, 1 H, J ) 12.2, 5.1 Hz, H-6), 4.17 (dd, 1 H, J ) 12.2,
2.4 Hz, H-6), 3.93 (ddd, 1 H, J ) 10.2, 5.0, 2.6 Hz, H-5), 3.75
(s, 3 H, OMe), 2.12, 2.06, 1.94 (s, 3 H each, 3 × OAc); 13C NMR
(CDCl3) δ 171.05, 171.03, 169.8, 156.2, 150.5, 130.5, 127.3,
119.12, 119.10, 114.9, 97.3, 72.5, 71.3, 69.0, 62.3, 56.0, 55.7,
21.2, 21.0, 20.9; HRMS calcd for C27H23O11NCl4Na (M + Na)
699.9928, found 699.9934.

Regio- and Stereodifferentiated Glycosylations
J . Org. Chem., Vol. 63, No. 25, 1998 9319
4-Meth oxyph en yl 2-Deoxy-2-(tetr ach lor oph th alim ido)-
â-D-glu cop yr a n osid e (6). Compound 5 (10.5 g, 15.5 mmol)
was dissolved in MeOH (1200 mL), and MeONa/MeOH (1 M,
20 mL) was added. The resulting MeONa concentration was
thus 0.018 M, which was found to be crucial. The mixture
was stirred for 12 min, and AcOH (100 mL) was added. The
mixture was stirred for 10 min and co-concentrated twice with
toluene. The residue was filtered through a silica column (1:1
toluene-acetone) to give crude 6 (7.40 g, 86%), which was
immediately used in the next step without further purification.
4-Meth oxyp h en yl 4,6-O-Ben zylid en e-2-d eoxy-2-(tetr a -
ch lor op h th a lim id o)-â-D-glu cop yr a n osid e (7). Crude 6
(7.40 g, 13.4 mmol) was dissolved in MeCN (45 mL). R,R-
Dimethoxytoluene (3.70 mL) and TsOH (20 mg) were added,
and the mixture was stirred for 1 h. Et3N (5 mL) was added,
and the mixture was co-concentrated with toluene. The
residue was chromatographed (SiO2, 3:1 EtOAc-heptane), and
the crude product was crystallized to give 7 (5.25 g, 61%). The
mother liquid was concentrated, and an additional crop of
in dry THF (100 mL) was added BH3NMe3 (11.0 g). The
mixture was cooled to 0 °C, and AlCl3 (22.8 g) was added
during 20 min. The mixture was stirred for 30 min at room
temperature and 60 min at 60 °C, and CH2Cl2 (500 mL) was
added. The mixture was washed with aqueous H2SO4 (0 °C,
1 M), H2O, and saturated aqueous NaHCO3. The water phase
was extracted with EtOAc. The combined organic phase was
dried (Na2SO4) and concentrated. The crude material was
dissolved in pyridine (100 mL), and Ac2O (90 mL) was added.
The mixture was stirred for 20 h and co-concentrated with
toluene. The residue was chromatographed (SiO2, 1:10 f 2:1
EtOAc-heptane) to give 11 (8.5 g, 46%): [R]20 -22.2 (c 1.3,
D
CHCl3); 1H NMR (CDCl3) δ 7.25-7.50 (m, 10 H, ArH), 5.50
(dd, 1 H, J ) 3.3, 0.9 Hz, H-4), 5.25 (t, 1 H, J ) 10.0 Hz, H-2),
5.07 (dd, 1 H, J ) 9.9, 3.3 Hz, H-3), 4.75 (d, 1 H, J ) 10.0 Hz,
H-1), 4.47, 4.56 (ABq, 1 H each, J ) 11.9 Hz, OBn), 3.91 (dt,
1 H, J ) 6.3, 1.0 Hz, H-5), 3.52, 3.62 (dABq, 1 H each, J ) 9.7,
6.3 Hz, H-6), 2.10, 2.05, 1.99 (s, 3 H each, 3 × OAc); 13C NMR
(CDCl3) δ 170.6, 170.5, 170.0, 138.0, 133.4, 132.5, 129.4, 128.9,
128.33, 128.29, 87.2, 76.5, 74.0, 72.6, 68.2, 68.1, 67.9, 21.3,
21.09, 21.06; HRMS calcd for C25H28O8SNa (M + Na) 511.1403,
found 511.1412.
crystals was obtained (1.39 g; total yield 77%): [R]20 +21.1
D
(c 0.9, CHCl3); mp 165-167 °C; 1H NMR (CDCl3) δ 7.35-7.55
(m, 5 H, ArH), 6.75-6.90 (m, 4 H, OPMP), 5.80 (d, 1 H, J )
8.4 Hz, H-1), 5.60 (s, 1 H, ArCH), 4.67 (dd, 1 H, J ) 10.2, 8.8
Hz, H-3), 4.51 (dd, 1 H, J ) 10.6, 8.4 Hz, H-2), 4.42 (dd, 1 H,
J ) 10.3, 4.3 Hz, H-5), 3.85-3.90 (m, 1 H, H-6), 3.75 (s, 3 H,
4-(Tr im eth ylsilyl)eth yl (2,3,4-Tr i-O-a cetyl-6-O-ben zyl-
â-D-galactopyr an osyl)-(1f4)-(6-O-ben zyl-2-deoxy-2-ph th al-
im id o-â-D-glu cop yr a n osid e) (13). To a solution of 11 (763
mg, 1.56 mmol) and 1215 (600 mg, 1.20 mmol) in CH2Cl2 (12.0
mL) at -70 °C under Ar was added a solution of AgOTf (920
mg, 3.58 mmol) in MeCN (5.0 mL). After 5 min, a 4 M solution
of methylsulfenyl bromide16 (MSB) in 1,2-dichloroethane (0.75
mL) was added during 15 min. The mixture was stirred for 1
h, isopropylamine (1.0 mL) was added, and the stirring was
continued at -70 °C for 1.5 h. The mixture was concentrated,
and the residue was chromatographed (SiO2, 3:1 f 1:1
OMe), 3.69-3.74 (m, 2 H, H-4,6), 2.60-2.70 (m, 1 H, OH); 13
C
NMR (CDCl3) δ 156.1, 150.6, 137.2, 129.9, 128.8, 126.6, 118.8,
115.0, 102.4, 97.8, 82.3, 69.0, 68.7, 66.7, 57.4, 56.1; HRMS calcd
for C28H21O8NCl4Na (M + Na) 661.9919, found 661.9909.
4-Meth oxyp h en yl 6-O-Ben zyl-2-d eoxy-2-(tetr a ch lor o-
p h th a lim id o)-â-D-glu cop yr a n osid e (8). Compound 7 (1.74
g, 2.72 mmol) was dissolved in dry THF (30 mL), and molecular
sieves (1.5 g, 3A, activated) and NaBH3CN (1.30 g, 20.8 mmol)
were added. The mixture was stirred for 3 h at room
temperature and cooled to 0 °C. An ice-cold saturated solution
of HCl in Et2O was added slowly until the pH (checked with
a moist pH paper) reached 2-3. The mixture was stirred for
3 h, CH2Cl2 (200 mL) was added, and the mixture was filtered
(Celite). The filtrate was washed successively with saturated
aqueous NaHCO3, H2O, and brine and then concentrated. The
residue was chromatographed (SiO2, 2:1 heptane-EtOAc) to
heptane-EtOAc) to give 13 (964 mg, 87%): [R]20 -5.1 (c 0.8
D
CHCl3); 1H NMR (CDCl3) δ 7.15-7.55 (m, 14 H, ArH), 5.38 (d,
1 H, J ) 2.8 Hz, H-4′), 5.20 (d, 1 H, J ) 8.4 Hz, H-1), 5.19 (dd,
1 H, J ) 10.3, 8.0 Hz, H-2′), 4.94 (dd, 1 H, J ) 10.5, 3.5 Hz,
H-3′), 4.55, 4.75 (ABq, 1 H each, J ) 12.1 Hz, OBn), 4.51, d, 1
H, J ) 8.0 Hz, H-1), 4.45-4.50 (m, 1 H, H-3), 4.32, 4.43 (ABq,
1 H each, J ) 11.8 Hz, OBn), 4.20 (dd, 1 H, J ) 10.8, 8.5 Hz,
H-2), 3.95 (dt, 1 H, J ) 10.0, 5.6 Hz, OCH2CH2SiMe3), 3.85 (t,
1 H, J ) 6.9 Hz, H-5′), 3.65-3.75 (m, 4 H, H-4,5,6), 3.50-3.55
(m, 1 H, OCH2CH2SiMe3), 3.52 (dd, 1 H, J ) 9.5, 7.3 Hz, H-6′),
3.40 (dd, 1 H, J ) 9.5, 5.7 Hz, H-6′), 2.04, 2.00, 1.95 (s, 3 H
each, 3 × OAc), 0.77, 0.86 (ddABq, 1 H each, J ) 14.0, 10.2,
6.8 Hz, OCH2CH2SiMe3), -0.12 (s, 3 H, SiMe3); 13C NMR
(CDCl3) δ 170.5, 170.4, 169.7, 138.6, 137.4, 134.3, 132.3, 128.9,
128.8, 128.3, 128.3, 128.2, 128.2, 101.7, 98.2, 82.3, 74.7, 74.1,
74.0, 72.7, 71.4, 70.3, 69.4, 68.5, 67.8, 67.6, 67.3, 56.5, 21.2,
21.0, 21.0, 18.1, -1.1; HRMS calcd for C45H55O15NSiNa (M +
Na) 900.3239, found 900.3245.
give 8 (1.16 g, 66%): [R]20 +14.0 (c 0.9 CHCl3); 1H NMR
D
(CDCl3) δ 7.30-7.40 (m, 5 H, ArH), 6.70-6.90 (m, 4 H, OPMP),
5.72 (m, virtual coupling similar to entry 19 in ref 25, H-1),
4.64, 4.57 (ABq, 1 H each, J ) 11.9 Hz, OBn), 4.35-4.45 (m,
2 H, H-2,3), 3.74 (s, 3 H, OMe), 3.65-3.90 (m, 4 H, H-4,5,6),
3.23 (bs, 1 H, OH), 2.74 (bs, 1 H, OH); 13C NMR (CDCl3) δ
156.0, 150.8, 140.8, 137.8, 129.0, 128.5, 128.3, 119.0, 114.9,
97.4, 77.7, 74.5, 74.3, 74.0, 71.6, 70.8, 56.9, 56.0; HRMS calcd
for C28H23O8NCl4Na (M + Na) 664.0075, found 664.0070.
P h en yl 4,6-O-Ben zylid en e-1-t h io-â-D-ga la ct op yr a n o-
sid e (10). To a solution of phenylthio-â-D-galactopyranoside12
(9, 7.10 g, 20.7 mmol) in MeCN (60 mL) were added R,R-
dimethoxytoluene (5.10 mL) and TsOH (75 mg). The mixture
was stirred for 2 h, Et3N (2 mL) was added, and the solvent
was removed. The residue was crystallized to give 10 (8.66 g,
A sample of 13 was acetylated; a 1H NMR signal appeared
at δ 5.65 (dd, 1 H, J ) 10.9, 8.9 Hz, H-3).
4-Met h oxyp h en yl (2,3,4-Tr i-O-a cet yl-6-O-b en zyl-â-D-
ga la ct op yr a n osyl)-(1f4)-(6-O-b en zyl-2-d eoxy-2-(t et r a -
ch lor op h th a lim id o)-â-D-glu cop yr a n osid e) (14). To a so-
lution of 11 (266 mg, 0.54 mmol) and 8 (250 mg, 0.39 mmol)
in CH2Cl2 (3.5 mL) at -78 °C under Ar was added a solution
of AgOTf (300 mg, 1.16 mmol) in MeCN (1.75 mL). After 5
min, a 4 M solution of methylsulfenyl bromide16 (MSB) in 1,2-
dichloroethane (0.245 mL) was added during 10 min. The
mixture was stirred for 2 h, isopropylamine (0.3 mL) was
added, and the stirring was continued at -78 °C for 1 h. The
mixture was concentrated, and the residue was chromato-
graphed (SiO2, 3:1 f 2:1 heptane-EtOAc) to give 14 (329 mg,
92%): [R]20 -29.7 (c 1.3, CHCl3); mp 164-165.5 °C; 1H NMR
D
(CDCl3) δ 7.25-7.50 (m, 10 H, ArH), 5.53 (s, 1 H, ArCH), 4.50
(m, 1 H, virtual coupling similar to entry 19 in ref 25, H-1),
4.40 (dd, 1 H, J ) 12.5, 1.6 Hz, H-6), 4.22 (bd (1 H, J ) 1.8
Hz, H-4), 4.04 (dd, 1 H, J ) 12.5, 1.8 Hz, H-6), 3.68-3.75 (m,
2 H, H-2,3), 3.56 (dd, 1 H, J ) 2.8, 1.5 Hz, H-5), 2.57-2.63
(m, 2 H, OH); 13C NMR (CDCl3) δ 137.2, 134.2, 129.8, 128.7,
126.9, 101.9, 87.4, 75.8, 74.2, 70.5, 69.7, 69.2; HRMS calcd for
C
19H20O5SNa (M + Na) 383.0929, found 383.0922.
84%): [R]20 +15.4 (c 0.9 CHCl3); 1H NMR (CDCl3) δ 7.15-
P h en yl 2,3,4-Tr i-O-a cetyl-6-O-ben zyl-1-th io-â-D-ga la c-
D
top yr a n osid e (11). To a solution of 1013 (13.71 g, 38 mmol)
7.40 (m, 10 H, ArH), 6.70-6.90 (m, 4 H, OPMP), 5.63 (d, 1 H,
J ) 8.4 Hz, H-1), 5.39 (d, 1 H, J ) 3.4 Hz, H-4′), 5.20 (dd, 1 H,
J ) 10.5, 7.9 Hz, H-2′), 4.97 (dd, 1 H, J ) 10.4, 3.5 Hz, H-3′),
4.70, 4.53 (ABq, 1 H each, J ) 11.7 Hz, OBn), 4.55 (d, 1 H, J
) 8.3 Hz, H-1′), 4.50-4.55 (m, 1 H, H-3), 4.49, 4.37 (ABq, 1 H
each, J ) 11.9 Hz, OBn), 4.44 (dd, 1 H, J ) 10.8, 8.4 Hz, H-2),
4.36 (d, 1 H, J ) 2.1 Hz, OH), 3.90-3.95 (m, 1 H, H-5′), 3.74
(s, 3 H, OMe), 3.70-3.80 (m, 4 H, H-4,5,6), 3.55 (dd, 1 H, J )
9.6, 7.7 Hz, H-6′), 3.46 (dd, 1 H, J ) 9.6, 5.0 Hz, H-6′), 2.09,
(25) Dahme´n, J .; Frejd, T.; Gro¨nberg, G.; Magnusson, G.; Noori, G.
Carbohydr. Res. 1984, 125, 161-164.
(26) Kameyama, A.; Ishida, H.; Kiso, M.; Hasegawa, A. J . Carbo-
hydr. Chem. 1994, 13, 641-654.
(27) Toepfer, A.; Schmidt, R. R. J . Carbohydr. Chem. 1993, 12, 809-
822.
(28) Ellervik, U.; Grundberg, H.; Magnusson, E. J . Org. Chem. 1998,
63, 9323.

9320 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik and Magnusson
2.01, 1.99 (s, 3 H each, 3 × OAc); 13C NMR (CDCl3) δ 170.6,
170.4, 169.7, 155.9, 150.9, 138.4, 137.4, 128.9, 128.7, 128.3,
128.2, 128.1, 127.8, 119.0, 114.9, 101.7, 97.4, 82.0, 74.9, 74.1,
73.9, 72.8, 71.3, 69.9, 69.4, 68.3, 67.7, 56.8, 56.0, 21.1, 21.04,
20.98; HRMS calcd for C47H45O16NCl4Na (M + Na) 1042.1390,
found 1042.1396.
(SiO2, 3:1 f 2:1 heptane-EtOAc) to give an unseparable
mixture of 19 and 20 (75 mg, 58%, 19:20 2.2:1). The mixture
was conventionally acetylated (pyridine-Ac2O-DMAP), and
the product was purified by chromatography (SiO2, 2:1 hep-
tane-EtOAc) to give a mixture of acetylated 19 and 20.
Selected data for acetylated 19: 1H NMR (CDCl3) δ 5.89 (d, 1
H, J ) 8.4 Hz, H-1), 5.66 (dd, 1 H, J ) 10.5, 8.6 Hz, H-3), 4.64
(d, 1 H, J ) 8.0 Hz, H-1′), 3.73 (s, 3 H, OMe), 2.20, 2.01, 1.97,
1.94 (4 s, OAc), 1.17 (d, 3 H, J ) 6.4 Hz, H-6′); 13C NMR
(CDCl3) δ 171.09, 171.07, 170.7, 169.9, 156.0, 150.7, 138.9,
138.5, 128.7, 128.0, 127.9, 101.7, 96.8, 75.4, 75.1, 74.0, 73.8,
16.3. Selected data for acetylated 20: 1H NMR (CDCl3) δ 5.88
(d, 1 H, J ) 8.5 Hz, H-1), 5.76 (dd, 1 H, J ) 10.4, 8.7 Hz, H-3),
5.21 (d, 1 H, J ) 3.5 Hz, H-1′), 3.74 (s, 3 H, OMe), 2.10, 2.07,
2.06, 1.96 (4 s, OAc), 1.26 (d, 3 H, J ) 6.6 Hz, H-6′); 13C NMR
(CDCl3) δ 171.3, 170.6, 170.4, 169.8, 156.0, 150.8, 140.9, 128.8,
128.1, 127.9, 107.0, 97.0, 75.13, 75.12, 74.0, 73.7, 16.6; HRMS
of the 19/20 mixture calcd for C40H39O15NCl4Na (M + Na)
936.0972, found 936.0961.
A sample of 14 was acetylated; a 1H NMR signal appeared
at δ 5.67 (dd, 1 H, J ) 10.5, 8.7 Hz, H-3).
4-Meth oxyp h en yl (2,3,4-Tr i-O-ben zyl-R-L-fu cop yr a n o-
syl)-(1f3)-(6-O-ben zyl-2-d eoxy-2-(t et r a ch lor op h t h a lim -
id o)-â-D-glu cop yr a n osid e) (16) a n d 4-Met h oxyp h en yl
(2,3,4-Tr i-O-ben zyl-R-L-fu cop yr a n osyl)-(1f4)-(6-O-ben zyl-
2-d eoxy-2-(t et r a ch lor op h t h a lim id o)-â-D-glu cop yr a n o-
sid e) (17). To a mixture of 8 (100 mg, 0.16 mmol), ethyl 2,3,4-
tri-O-benzyl-1-thio-R-L-fucopyranoside17 (15, 147 mg, 0.31
mmol), and AgOTf (100 mg, 0.39 mmol) was added CH2Cl2 (2.0
mL). The solution was cooled to -45 °C under Ar. After 5
min, a 4 M solution of methylsulfenyl bromide16 (MSB) in 1,2-
dichloroethane (0.081 mL) was added during 20 min. The
mixture was stirred for 1.5 h, isopropylamine (0.2 mL) was
added, and the stirring was continued for 1 h at -45 °C. The
4-Met h oxyp h en yl (2,3,4-Tr i-O-a cet yl-6-O-b en zyl-â-D-
galactopyr an osyl)-(1f4)-(2-acetam ido-6-O-ben zyl-2-deoxy-
â-D-glu cop yr a n osid e) (21). Compound 14 (100 mg, 0.10
mmol) was dissolved in dry EtOH (3 mL), and 1,2-diamino-
ethane7 (0.030 mL, 0.5 mmol) was added. The mixture was
heated at 60 °C for 3 h and concentrated. The residue was
dissolved in MeOH-H2O-Ac2O (2.5, 0.5, 0.75 mL), stirred for
1 h, and then concentrated and chromatographed (SiO2, 2:1
mixture was filtered through
a short column (SiO2, 1:1
heptane-EtOAc), concentrated, and chromatographed (SiO2,
8:1 heptane-acetone) to give 16 (107 mg 65%) and 17 (30 mg,
18%). Compound 16: [R]20 +18.6 (c 0.9 CHCl3); 1H NMR
D
(CDCl3) δ 7.15-7.50 (m, 20 H, ArH), 6.70-6.95 (m, 4 H,
OPMP), 5.83 (d, 1 H, J ) 8.5 Hz, H-1), 4.91 (bd, 1 H, J ) 1.9
Hz, H-1′), 4.73, 4.82 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.61,
4.65 (ABq, 1 H, J ) 12.1 Hz, OBn), 4.60, 4.95 (ABq, 1 H each,
J ) 11.4 Hz, OBn), 4.51 (dd, 1 H, J ) 10.8, 8.6 Hz, H-2), 4.47
(d, 1 H, J ) 1.4 Hz, H-4′), 4.18 (dd (1 H, J ) 10.7, 8.0 Hz,
H-3), 4.11, 4.36 (ABq, 1 H each, J ) 13.0 Hz, OBn), 4.16 (q, 1
H, J ) 6.0 Hz, H-5′), 3.90-3.95 (m, 2 H, H-6,2′), 3.74 (s, 3 H,
OMe), 3.55-3.80 (m, 4 H, H-4,5,6,3′), 1.15 (d, 3 H, J ) 6.5 Hz,
H-6′); 13C NMR (CDCl3) δ 164.4, 163.4, 155.9, 150.9, 140.3,
140.3, 138.9, 138.8, 138.6, 138.0, 129.9, 129.6, 128.9, 128.8,
128.7, 128.7, 128.6, 128.3, 128.2, 128.1, 128.0, 127.8, 126.2,
127.2, 119.0, 114.9, 100.4, 97.2, 83.7, 78.9, 78.3, 75.8, 75.4, 74.1,
73.9, 73.5, 71.4, 69.4, 69.1, 56.0, 55.6, 16.9; HRMS calcd for
CH2Cl2-acetone) to give 21 (69 mg, 88%): [R]20 -15.8 (c 1.0
D
CHCl3); 1H NMR (CDCl3) δ 6.48 (d, 1 H, J ) 8.8 Hz, H-1),
7.25-7.50 (m, 10 H, ArH), 6.75-7.00 (m, 4 H, OPMP), 5.97
(d, 1 H, J ) 7.5 Hz, NH), 5.40 (d, 1 H, J ) 8.3 Hz, H-1), 5.24
(d, 1 H, J ) 2.9 Hz, H-4′), 5.16 (dd, 1 H, J ) 10.4, 8.0 Hz,
H-2′), 4.99 (dd, 1 H, J ) 10.4, 3.4 Hz, H-3′), 4.63, 4.50 (ABq, 1
H each, J ) 12.2 Hz, OBn), 4.61 (d, 1 H, J ) 8.4 Hz, H-1′),
4.56, 4.40 (ABq, 1 H each, J ) 11.9 Hz, OBn), 4.34 (d, 1 H, J
) 2.0 Hz, OH), 4.28 (bt, 1 H, J ) 7.7 Hz, H-3), 3.76 (s, 3 H,
OMe), 3.35-3.90 (m, 8 H, H-2,4,5,6,5′,6′), 2.07, 2.02, 2.01, 1.99
(s, 3 H each, 3 × OAc, NHAc); 13C NMR (CDCl3) δ 171.0,
170.54, 170.53, 169.7, 155.8, 151.7, 138.5, 137.6, 128.99,
128.86, 128.5, 128.4, 128.3, 128.2, 128.1, 119.1, 114.9, 101.6,
99.6, 81.8, 74.4, 74.1, 73.9, 72.7, 71.6, 71.3, 69.7, 68.6, 68.0,
67.7, 57.9, 56.1, 24.1, 21.2, 21.1, 21.0; HRMS calcd for
C
55H51O12NCl4Na (M + Na) 1080.2063, found 1080.2050.
A sample of 16 was acetylated; a 1H NMR signal appeared
at δ 5.04 (dd, 1 H, J ) 10.1, 8.4 Hz, H-4).
1
Compound 17: [R]20 -8.8 (c 1.1 CHCl3); H NMR (CDCl3)
C
41H49O15NNa (M + Na) 818.3000, found 818.2996.
4-Met h oxyp h en yl (2,3,4-Tr i-O-a cet yl-6-O-b en zyl-â-D-
D
δ 7.20-7.45 (m, 20 H, ArH), 6.70-6.95 (m, 4 H, OPMP), 5.67
(d, 1 H, J ) 8.3 Hz, H-1), 4.97 (d, 1 H, J ) 3.9 Hz, H-1′), 4.76,
4.86 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.67, 4.82 (ABq, 1 H
each, J ) 11.5 Hz, OBn), 4.63, 4.98 (ABq, 1 H each, J ) 11.4
Hz, OBn), 4.30-4.45 (m, 4 H, H-2,3, OBn), 4.09 (dd, 1 H, J )
10.2, 3.8 Hz, H-2′), 4.03 (q, 1 H, J ) 6.5 Hz, H-5′), 3.99 (d, 1
H, J ) 9.6 Hz, H-6), 3.88 (dd, 1 H, J ) 10.2, 2.7 Hz, H-3′),
3.70-3.80 (m, 2 H, H-5,6), 3.74 (s, 3 H, OMe), 3.67 (bd, 1 H, J
) 1.6 Hz, H-4′), 3.54 (dd, 1 H, J ) 9.5, 8.3 Hz, H-4), 1.10 (d, 3
H, J ) 6.5 Hz, H-6′); 13C NMR (CDCl3) δ 155.8, 151.0, 138.9,
138.7, 138.7, 129.0, 128.90, 128.86, 128.8, 128.74, 128.73,
128.70, 128.67, 128.64, 128.56, 128.33, 128.27, 128.21, 128.1,
128.0, 127.83, 127.81, 119.01, 118.95, 114.9, 100.9, 97.2, 83.1,
79.2, 76.1, 75.5, 75.2, 74.2, 73.6, 73.5, 70.7, 68.7, 56.9, 56.0,
17.1; HRMS calcd for C55H51O12NCl4Na (M + Na) 1080.2063,
found 1080.2050.
ga la ctop yr a n osyl)-(1f4)-[2,3,4-Tr i-O-ben zyl-R-L-fu cop y-
r a n osyl]-(1f3)-(2-a ceta m id o-6-O-ben zyl-2-d eoxy-â-D-glu -
cop yr a n osid e) (22). Ethyl 2,3,4-tri-O-benzyl-1-thio-R-L-fuco-
pyranoside17 (15, 200 mg, 0.42 mmol) was dissolved in dry CH2-
Cl2 (1.5 mL), and freshly distilled Br2 (0.020 mL in 0.250 mL
CH2Cl2) was added. The mixture was stirred for 15 min, and
cyclohexene was added until the color of Br2 disappeared. The
mixture was then added to a mixture of 21 (164 mg, 0.21
mmol), molecular sieves (4A, 750 mg), Bu4NBr (120 mg), and
5:3 CH2Cl2-DMF (1.6 mL). The mixture was stirred for 20
h, pyridine (0.2 mL) was added, and the stirring was continued
for 3 h. The mixture was filtered (Celite) and co-concentrated
with toluene. The residue was chromatographed (SiO2, 2:1
heptane-EtOAc) to give 22 (211 mg, 83%): [R]20D -56.6 (c 1.1
1
CHCl3); H NMR (CDCl3) δ 7.15-7.45 (m, 25 H, ArH), 6.70-
A sample of 17 was acetylated; a 1H NMR signal appeared
at δ 5.72 (dd, 1 H, J ) 10.5, 8.4 Hz, H-3).
6.90 (m, 4 H, OPMP), 6.24 (d, 1 H, J ) 8.4 Hz, NH), 5.46 (d,
1 H, J ) 3.5 Hz, H-4′), 5.32 (d, 1 H, J ) 4.3 Hz, H-1), 5.14 (d,
1 H, J ) 3.7 Hz, H-1′′), 5.10 (dd, 1 H J ) 10.5, 7.9 Hz, H-2′),
4.97, 4.67 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.99 (dd, 1 H,
J ) 10.6, 7.2 Hz, H-3′), 4.81, 4.77 (ABq, 1 H each, J ) 11.8
Hz, OBn), 4.79, 4.68 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.51
(d, 1 H, J ) 7.8 Hz, H-1′), 4.50, 4.34 (ABq, 1 H each, J ) 12.3
Hz, OBn), 4.35, 4.30 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.05-
4.20 (m, 2 H, H-2,2′′), 4.05 (q, 1 H, J ) 6.4 Hz, H-5′′), 3.98 (t,
1 H, J ) 4.8 Hz, H-3′′), 3.93 (dd, 1 H, J ) 10.0, 6.4 Hz, H-6),
3.84 (dd, 1 H, J ) 10.1, 2.7 Hz, H-3), 3.50-3.80 (m, 6 H,
H-4,5,6,5′,6′,4′′), 3.76 (s, 3 H, OMe), 3.43 (dd, 1 H, J ) 9.1, 8.0
Hz, H-6′), 2.04, 1.99, 1.97, 1.92 (s, 3 H each, 3 × OAc, NHAc),
1.06 (d, 3 H, J ) 6.5 Hz, H-6′′); 13C NMR (CDCl3) δ 170.6,
170.5, 170.4, 155.3, 151.6, 139.23, 139.17, 138.4, 137.8, 129.0,
128.88, 128.86, 128.6, 128.4, 128.32, 128.27, 128.1, 128.02,
4-Meth oxyp h en yl (2,3,4-Tr i-O-a cetyl-â-L-fu cop yr a n o-
syl)-(1f4)-(6-O-ben zyl-2-d eoxy-2-(t et r a ch lor op h t h a lim -
id o)-â-D-glu cop yr a n osid e) (19) a n d 4-Met h oxyp h en yl
(2,3,4-Tr i-O-a cetyl-R-L-fu cop yr a n osyl)-(1f4)-(6-O-ben zyl-
2-d eoxy-2-(t et r a ch lor op h t h a lim id o)-â-D-glu cop yr a n o-
sid e) (20). To a solution of 8 (100 mg, 0.16 mmol) and 1819
(83 mg, 0.22 mmol) in CH2Cl2 (1.4 mL) at -78 °C was added
a solution of AgOTf (120 mg, 3.58 mmol) in MeCN (0.7 mL). A
solution of methylsulfenyl bromide16 (MSB) in 1,2-dichloro-
ethane (0.098 mL, 4 M) was added during 10 min. The
mixture was stirred for 1.5 h at -78 °C, isopropylamine (0.1
mL) was added, and the stirring was continued at -78 °C for
1 h. The mixture was filtered through a short column (SiO2,
1:1 heptane-EtOAc), concentrated, and chromatographed

Regio- and Stereodifferentiated Glycosylations
J . Org. Chem., Vol. 63, No. 25, 1998 9321
128.00, 127.99, 127.8, 118.5, 114.8, 100.0, 98.8, 97.5, 79.7, 77.8,
77.3, 75.0, 74.5, 73.9, 73.7, 73.6, 73.4, 73.1, 72.4, 71.0, 69.7,
69.5, 67.7, 67.3, 67.2, 56.1, 23.6, 21.3, 21.1, 21.0, 17.1; HRMS
calcd for C68H77O19NNa (M + Na) 1234.4987, found 1234.4987.
A sample of 22 was de-O-benzylated (H2, Pd-C, AcOH) and
then O-acetylated to give the fully acetylated derivative of 2:
1H NMR (CDCl3) δ 6.75-6.95 (m, 4 H, OPMP), 5.81 (d, 1 H, J
) 8.6 Hz, NH), 5.49 (d, 1 H, J ) 4.0 Hz, H-1′′), 5.44 (d, 1 H, J
) 2.7 Hz, H-4′), 5.39 (d, 1 H, J ) 2.6 Hz, H-4′′), 5.25 (dd, 1 H,
J ) 11.0, 3.4 Hz, H-3′′), 5.14 (dd, 1 H, J ) 10.5, 8.0 Hz, H-2′),
5.12 (d, 1 H, J ) 6.1 Hz, H-1), 5.08 (dd, 1 H, J ) 10.9, 3.9 Hz,
H-2′′), 5.04 (dd, 1 H, J ) 10.4, 3.5 Hz, H-3′), 4.72 (q, 1 H, J )
6.6 Hz, H-5′′), 4.60 (dd, 1 H, J ) 11.7, 3.8 Hz, H-6), 4.49 (d, 1
H, J ) 8.0 Hz, H-1′), 4.46 (dd, 1 H, J ) 11.4, 6.3 Hz, H-6′),
4.30 (dd, 1 H, J ) 11.5, 7.6 Hz, H-6′), 4.25 (dd, 1 H, J ) 11.8,
5.8 Hz, H-6), 4.17 (t, 1 H, J ) 7.4 Hz, H-3), 4.07 (q, 1 H, J )
7.2 Hz, H-2), 3.90-4.00 (m, 2 H, H-4,5′), 3.77 (s, 3 H, OMe),
3.75-3.80 (m, 1 H, H-5), 2.22, 2.17, 2.10, 2.09, 2.08, 2.04, 2.00,
1.99 (s, 27 H, OAc, NHAc), 1.22 (d, 3 H, J ) 6.6 Hz, H-6′′).
4-Meth oxyp h en yl (2,3,4-Tr i-O-ben zyl-R-L-fu cop yr a n o-
syl)-(1f3)-(2-a ceta m id o-6-O-ben zyl-2-d eoxy-â-D-glu cop y-
r a n osid e) (23). Compound 16 (70 mg, 0.066 mmol) was
dissolved in dry EtOH (7 mL), and 1,2-diaminoethane7 (0.200
mL, 3.0 mmol) was added. The mixture was refluxed for 3 h
and concentrated. The residue was filtered through a short
column (SiO2, 20:1 toluene-EtOH), and the eluate was
concentrated. The residue was dissolved in pyridine (5 mL),
and Ac2O (4 mL) and DMAP (∼3 mg) were added. The mixture
was stirred overnight and then co-concentrated with toluene.
The residue was dissolved in MeOH (10 mL), and 1 M MeONa/
MeOH (0.5 mL) was added. The mixture was stirred for 4 h,
filtered on a short column (SiO2, 5:1 CH2Cl2-EtOH), and
chromatographed (SiO2, 20:1 CH2Cl2-EtOH) to give 23 (50 mg,
4.61 (ABq, 1 H each, J ) 12.2 Hz, OBn), 4.47, 4.50 (ABq, 1 H
each, J ) 12.2 Hz, OBn), 4.32 (t, 1 H, J ) 8.8 Hz, H-3), 4.27
(q, 1 H, J ) 6.5 Hz, H-5′′), 4.00-4.15 (m, 2 H, H-4,2′′), 3.85-
3.95 (m, 4 H, H-6,3′′, OH), 3.76 (s, 3 H, OMe), 3.45-3.75 (m,
9 H, H-2,5,2′,3′,5′,6′,4′′), 2.74 (bs, 1 H, OH), 2.65 (bs, 1 H, OH),
1.14 (d, 3 H, J ) 6.5 Hz, H-6′′), 1.67 (s, 3 H, NHAc); 13C NMR
(CDCl3) δ 170.9, 155.7, 151.8, 139.0, 138.9, 138.7, 138.4, 138.2,
129.1, 128.92, 128.90, 128.8, 128.7, 128.6, 128.5, 128.4, 128.2,
128.12, 128.05, 128.0, 127.7, 119.4, 114.8, 101.1, 100.1, 98.2,
80.0, 77.9, 77.7, 77.3, 75.4, 75.2, 75.0, 74.7, 73.8, 73.4, 72.8,
69.4, 69.3, 68.7, 67.7, 56.1, 23.7, 17.3; HRMS calcd for
C
62H71O16NNa (M + Na) 1108.4671, found 1108.4652.
4-Meth oxyp h en yl (Meth yl(5-a ceta m id o-4,7,8,9-tetr a -
O-a cet yl-3,5-d id eoxy-D-glycer o-R-D-ga la ct o-2-n on u lop y-
r a n osyl)on a te)-(2f3)-(4-O-a cetyl-6-O-ben zyl-â-D-ga la cto-
p yr a n osyl)-(1f4)-[2,3,4-tr i-O-ben zyl-R-L-fu cop yr a n osyl]-
(1f3)-(2-acetamido-6-O-benzyl-2-deoxy-â-D-glucopyranoside)
(26). To a mixture of compound 24 (144 mg, 0.132 mmol), the
sialyl donor 2522 (160 mg, 0.264 mmol), and activated molec-
ular sieves (3A, 90 mg) were added CH2Cl2 (1.08 mL) and
MeCN (0.90 mL). The mixture was stirred for 15 min at room
temperature and for 15 min at -72 °C under Ar. A solution
of AgOTf (90 mg) in MeCN (0.90 mL) was added, and the
mixture was left for 5 min. A 4 M solution of methylsulfenyl
bromide16 (MSB) in 1,2-dichloroethane (0.083 mL) was added
during 30 min. The mixture was stirred for 2.5 h, diisopro-
pylamine (0.180 mL) was added, and the mixture was stirred
for another 1.5 h. The reaction mixture was filtered through
a short column (SiO2, 20:1 CH2Cl2-EtOH). The crude product
was acetylated (Ac2O-pyridine) and co-concentrated with
toluene, and the residue was chromatographed (SiO2, 3:1 f
2:1 toluene-acetone) to give 26 (141 mg, 65%): [R]20 -36.0
D
1
(c 1.3 CHCl3); H NMR (CDCl3) δ 7.10-7.43 (m, 25 H, ArH),
6.70-6.92 (m, 4 H, OPMP), 6.46 (d, 1 H, J ) 9.1 Hz, NH),
5.60 (ddd, 1 H, J ) 8.9, 6.0, 2.7 Hz, H-8′′′), 5.37 (dd, 1 H, J )
8.9, 2.7 Hz, H-7′′′), 5.25 (d, 1 H, J ) 3.4 Hz, H-1), 5.19 (d, 1 H,
J ) 3.6 Hz, H-1′′), 5.09 (d, 1 H, J ) 3.8 Hz, H-4′), 5.07 (d, 1 H,
J ) 6.2 Hz, NH), 4.99 (dd 1 H, J ) 10.2, 7.9, H-2′), 4.87-4.95
(m, 1 H, H-4′′′), 4.77, 4.82 (ABq, 1 H each, J ) 11.4 Hz, OBn),
4.72 (d, 1 H, J ) 8.0 Hz, H-1′), 4.67, 4.79 (ABq, 1 H each, J )
11.8 Hz, OBn), 4.66 (dd, 1 H, J ) 10.2, 3.6 Hz, H-3′), 4.63,
4.95 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.37, 4.47 (ABq, 1 H
each, J ) 11.8 Hz, OBn), 4.30-4.40 (m, 2 H, H-2,9′′′), 4.15,
4.32 (ABq, 1 H each, J ) 12.0 Hz, OBn), 3.95-4.12 (m, 7 H,
H-3,4,5,6,2′′,5′′′,9′′′), 3.87, (s, 3 H, OMe), 3.77-3.86 (m, 3 H,
H-5′,3′′,5′′), 3.75 (s, 3 H, OMe), 3.69 (q, 1 H, J ) 4.1 Hz, H-6),
3.65 (dd, 1 H, J ) 10.6, 2.6 Hz, H-6′′′), 3.47 (dd, 1 H, J ) 9.4,
5.5 Hz, H-6′), 3.35-3.45 (m, 2 H, H-6′,4′′), 2.60 (dd, 1 H, J )
12.6, 4.5 Hz, H-3′′′), 2.20, 2.13, 2.09, 2.03, 2.02, 2.00, 1.95, 1.87
(s, 3 H each, 6 × OAc, 2 × NHAc), 1.75 (t, 1 H, J ) 12.6 Hz,
H-3′′′), 0.98 (d, 3 H, J ) 10.5 Hz, H-6′′); 13C NMR (CDCl3) δ
170.9, 170.7, 170.5, 170.4, 170.3, 170.0, 169.7, 167.9 (C-1′′′,
89%): [R]20 -44.3 (c 0.9 CHCl3); 1H NMR (CDCl3) δ 7.25-
D
7.45 (m, 20 H, Ar), 6.75-7.00 (m, 4 H, OPMP), 5.61 (d, 1 H, J
) 7.3 Hz, NH), 5.32 (d, 1 H, J ) 8.4 Hz, H-1), 4.99-5.02 (m,
1 H, H-1′), 4.77, 4.83 (ABq, 1 H each, J ) 11.6 Hz, OBn), 4.67,
4.87 (ABq, 1 H each, J ) 11.7 Hz, OBn), 4.65, 4.98 (ABq, 1 H
each, J ) 11.4 Hz, OBn), 4.58, 4.62 (ABq, 1 H each, J ) 12.1
Hz, OBn), 4.23 (bs, 1 H, OH), 4.12-4.17 (m, 1 H, H-5′), 4.11
(dd, 1 H, J ) 10.1, 3.5 Hz, H-2′), 3.97 (dd, 1 H, J ) 10.0, 2.4
Hz, H-3′), 3.91-3.97 (m, 1 H, H-3), 3.89 (dd, 1 H, J ) 10.9, 2.0
Hz, H6), 3.76 (s, 3 H, OMe), 3.50-3.75 (m, 5 H, H-2,4,5,6,4′),
1.62 (s, 3 H, NHAc), 1.18 (d, 3 H, J ) 6.5 Hz); 13C NMR (CDCl3)
δ 171.4, 155.7, 151.9, 138.9, 138.7, 129.0, 128.9, 128.8, 128.73,
128.72, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 119.2, 114.9,
100.0, 99.8, 84.5, 76.4, 75.53, 75.45, 74.6, 73.9, 73.3, 70.9, 69.9,
68.6, 56.6, 56.1, 23.6, 17.1; HRMS calcd for C49H55O11NNa (M
+ Na) 856.3674, found 856.3672.
A sample of 23 was de-O-benzylated (H2, Pd/C, AcOH) and
then O-acetylated to give the fully acetylated derivative: 1H
NMR (CDCl3) δ 6.79-6.98 (m, 4 H, OPMP), 5.89 (d, 1 H, J )
7.6 Hz, NH), 5.47 (d, 1 H, J ) 7.8 Hz, H-1), 5.35 (dd, 1 H, J )
11.3, 3.5 Hz, H-3′), 5.30 (d, 1 H, J ) 3.4 Hz, H-1′), 5.27 (dd, 1
H, J ) 3.3, 1.3 Hz, H-4′), 5.13 (dd, 1 H, J ) 11.1, 3.5 Hz, H-2′),
5.02 (t, 1 H, J ) 9.0 Hz, H-4), 4.52 (t, 1 H, J ) 9.3 Hz, H-3),
4.23 (dd, 1 H, J ) 12.2, 5.9 Hz, H-6), 4.18 (q, 1 H, J ) 6.8 Hz,
H-5′), 4.10 (dd, 1 H, J ) 11.8, 2.9 Hz, H-6), 3.77 (s, 3 H, OMe),
3.70-3.76 (m, 1 H, H-5), 3.47 (q, 1 H, J ) 9.4 Hz, H-2), 2.17,
2.12, 2.09, 2.07, 2.01, 2.00 (s, 3 H each, 5 × OAc, NHAc), 1.10
(d, 3 H, J ) 6.5 Hz, H-6′).
J
C-1′′′:H-3′′′ax 6.4 Hz),24 154.7, 151.3, 139.0, 138.73, 138.68, 138.4,
137.7, 128.40, 128.37, 128.34, 128.31, 128.19, 128.15, 127.9,
127.71, 127.66, 127.6, 127.44, 127.43, 127.37, 127.3, 127.1,
117.8, 114.4, 99.1, 98.3, 96.9, 96.8, 90.5, 78.9, 74.6, 73.8, 73.4,
73.00 72.8, 72.73, 72.68, 72.1, 71.9, 71.1, 70.2, 70.0, 69.3, 67.9,
67.6, 67.3, 67.0, 62.5, 60.0, 55.6, 53.2, 49.2, 37.6, 23.2, 23.1,
21.4, 20.9, 20.8, 20.6, 16.5; HRMS calcd for C86H102O30N2Na
(M + Na) 1665.6415, found 1665.6438.
A sample of 26 was de-O-benzylated (H2, Pd/C, AcOH) and
then O-acetylated to give the fully acetylated derivative of 1:
1H NMR (CDCl3) δ 6.75-6.95 (m, 4 H, OPMP), 6.67 (d, 1 H, J
) 9.0 Hz, NH), 5.55 (dt, 1 H, J ) 9.5, 3.3 Hz, H-8′′′), 5.47 (d,
1 H, J ) 4.5 Hz, H-1′′), 5.45 (dd, 1 H, J ) 9.5, 2.8 Hz, H-7′′′),
5.35 (d, 1 H, J ) 2.8 Hz, H-4′′), 5.25 (dd, 1 H, J ) 10.9, 3.3 Hz,
H-3′′), 5.09 (d, 1 H, J ) 10.3 Hz, NH′′′), 5.07 (d, 1 H, J ) 7.7
Hz, H-1), 5.04 (dd, 1 H, J ) 10.6, 3.7 Hz, H-2′′), 4.97 (d, 1 H,
J ) 3.7 Hz, H-4′), 4.85-4.95 (m, 3 H, H-2′,5′′,4′′′), 4.74 (d, 1
H, J ) 8.1 Hz, H-1′), 4.70 (dd, 1 H, J ) 11.8, 2.8 Hz, H-6),
4.58 (dd, 1 H, J ) 10.2, 3.5 Hz, H-3′), 4.37 (dd, 1 H, J ) 11.5.
7.0 Hz, H-6′), 4.31 (dd, 1 H, J ) 12.9, 2.7 Hz, H-9′′′), 4.23 (dd,
1 H, J ) 11.6, 6.8 Hz, H-6′), 4.17 (dd, 1 H, J ) 12.0, 5.7 Hz,
H-6), 4.13 (d, 1 H, J ) 9.1 Hz, H-3), 4.10 (dd, 1 H, J ) 12.9,
9.0 Hz, H-9′′′), 4.00-4.09 (m, 2 H, H-2,5′′′), 3.97 (t, 1 H, J )
8.1 Hz, H-4), 3.90 (t, 1 H, J ) 7.0 Hz, H-5′), 3.87 (s, 3 H, OMe),
4-Meth oxyp h en yl (6-O-Ben zyl-â-D-ga la ctop yr a n osyl)-
(1f4)-[2,3,4-tr i-O-ben zyl-R-L-fu copyr an osyl]-(1f3)-(2-acet-
a m id o-6-O-ben zyl-2-d eoxy-â-D-glu cop yr a n osid e) (24). To
a solution of compound 22 (210 mg, 0.17 mmol) in MeOH (10
mL) was added 1 M MeONa-MeOH (0.5 mL). The mixture
was stirred for 1.5 h, quenched by addition of AcOH (0.5 mL),
and co-concentrated with toluene. The residue was chromato-
graphed (SiO2, 20:1 CH2Cl2-EtOH) to give 24 (167 mg, 89%):
1
[R]20 -52.4 (c 1.3 CHCl3); H NMR (CDCl3) δ 7.20-7.40 (m,
D
25 H, ArH), 6.75-6.95 (m, 4 H, OPMP), 6.09 (d, 1 H, J ) 7.2
Hz, NH), 5.26 (d, 1 H, J ) 7.4 Hz, H-1), 5.17 (d, 1 H, J ) 3.5
Hz, H-1′′), 4.72, 4.76 (ABq, 1 H each, J ) 11.5 Hz, OBn), 4.67,
4.93 (ABq, 1 H each, J ) 11.4 Hz, OBn), 4.60, 4.94 (ABq, 1 H
each, J ) 11.5 Hz, OBn), 4.54 (d, 1 H, J ) 7.4 Hz, H-1′), 4.51,

9322 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik and Magnusson
3.77 (s, 3 H, OMe), 3.70-3.75 (m, 1 H, H-5), 3.65 (dd, 1 H, J
) 10.7, 2.8 Hz, H-6′′′), 2.60 (dd, 1 h, J ) 12.8, 4.8 Hz, H-3e′′′),
2.24, 2.17, 2.16, 2.15, 2.12, 2.10, 2.08, 2.06, 2.06, 2.01, 2.00,
1.98, 1.87 (s, 3 H each, 11 × OAc, 2 × NHAc), 1.68 (t, 1 H, J
) 12.4 Hz, H-3a′′′), 1.20 (d, 3 H, J ) 6.5 Hz, H-6′′).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
all title compounds described in the Experimental Section (18
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
Ack n ow led gm en t. This work was supported by the
Swedish Natural Science Research Council.
J O981203X