Pseudosugars, 40: Synthesis of ether- and imino-linked octyl N-acetyl- 5a'-carba-β-lactosaminides and -isolactosaminides: Acceptor substrates for α-(1→3/4)-fucosyltransferase, and enzymatic synthesis of 5a'- carbatrisaccharides

Article abstract of DOI:10.1002/(SICI)1099-0690(199903)1999:3<631::AID-EJOC631>3.0.CO;2-6

Synthesis of ether-linked octyl 5a'-carba-β-lactosaminide 3 and - isolactosaminide 5 was carried out in seven steps, starting from the coupling products of 1,2-anhydro-5a-carba-β-D-mannopyranose derivative 7, and the oxide anions generated from the octyl N-acetyl-β-D-glucosaminide derivatives 13 and 16, respectively, under basic conditions. The 5a-carba-α-D- mannopyranose residues of the coupling products 17 and 26 were transformed into the β-D-gluco configuration through epimerization of the respective 2'- oxo derivatives 19 and 28, and selective reduction, and then into the β-D- galacto configuration by direct nucleophilic substitution of their 4',6'- dimesylates 23 and 31 with an acetate ion. Biological assay has shown that 3 is an acceptor substrate for human-milk α-(1→3/4)-fucosyltransferase and, interestingly, 5 is not. In addition, the imino-linked congeners 4 and 6 have been synthesized by coupling of the 4-amino-4-deoxy- and 3-amino-3-deoxy derivatives 37 and 41 of octyl N-acetyl-β-D-glucosaminide, and the carba- sugar epoxide 8, respectively, and subsequent deprotection. Compound 4 is a substrate while 6 is neither a substrate nor an inhibitor for fucosyltransferase. Small-scale enzymatic synthesis was carried out by treatment of 3 and 4 with GDP-fucose and milk fucosyltransferase, which resulted in conversion into the corresponding trisaccharides 47 and 48, respectively.

Full text of DOI:10.1002/(SICI)1099-0690(199903)1999:3<631::AID-EJOC631>3.0.CO;2-6

FULL PAPER
Pseudosugars, 40[°]
Synthesis of Ether- and Imino-Linked Octyl N-Acetyl-5aЈ-carba-β-
lactosaminides and -isolactosaminides: Acceptor Substrates for α-(1Ǟ3/4)-
Fucosyltransferase, and Enzymatic Synthesis of 5aЈ-Carbatrisaccharides[1]
Seiichiro Ogawa,*[a] Naoki Matsunaga,[a] Hong Li,[b] and Monica M. Palcic[b]
Keywords: Carbohydrates / Cyclitols / Carbohydrate mimetics / Disaccharides, 5aЈ-carba- / N-Acetyl-5aЈ-
carbalactosaminides / Fucosyltransferase
Synthesis of ether-linked octyl 5aЈ-carba-β-lactosaminide 3
and -isolactosaminide 5 was carried out in seven steps,
starting from the coupling products of 1,2-anhydro-5a-carba-
substrate for human-milk α-(1Ǟ3/4)-fucosyltransferase and,
interestingly, is not. In addition, the imino-linked
congeners 4 and 6 have been synthesized by coupling of the
4-amino-4-deoxy- and 3-amino-3-deoxy derivatives 37 and
5
β-
generated from the octyl N-acetyl-β-
derivatives 13 and 16, respectively, under basic conditions. epoxide 8, respectively, and subsequent deprotection.
D-mannopyranose derivative 7, and the oxide anions
D
-glucosaminide
41 of octyl N-acetyl-β-D-glucosaminide, and the carba-sugar
The 5a-carba-α-
products 17 and 26 were transformed into the β-
configuration through epimerization of the respective 2Ј-oxo
D
-mannopyranose residues of the coupling
Compound 4 is a substrate while 6 is neither a substrate nor
an inhibitor for fucosyltransferase. Small-scale enzymatic
synthesis was carried out by treatment of 3 and 4 with GDP-
D-gluco
derivatives 19 and 28, and selective reduction, and then into fucose and milk fucosyltransferase, which resulted in
the β- -galacto configuration by direct nucleophilic conversion into the corresponding trisaccharides 47 and 48,
D
substitution of their 4Ј,6Ј-dimesylates 23 and 31 with an respectively.
acetate ion. Biological assay has shown that 3 is an acceptor
In recent years, some human α-(1Ǟ3/4)-fucosyltransfer- to enzymatic hydrolysis, they should be useful for a trans-
ases have been extensively studied[3] since they are involved ferase assay or in cell-uptake experiments to study oligosac-
in the last steps of the biosynthesis of Lewis oligosaccharide charide biosynthesis, provided they are substrates for fuco-
antigens. These antigens include sialyl Lewis x, which is a syltransferases. These disaccharide mimetics have therefore
tumor-associated structure and a ligand of E-selectin-me- been considered as substrates and inhibitors for the Lewis
diated inflammatory processes.[4] There is interest in de- α-(1Ǟ3/4)-fucosyltransferase available from human milk.
veloping assays for monitoring enzyme activity and specific
fucosyltransferase inhibitors which prevent the synthesis of
these antigens. These inhibitors would represent potential
Results and Discussion
anti-inflammatory or anti-tumor agents.[5]
Previously, we described[6] that the carbatrisaccharide β-
Synthesis of Ether-Linked Octyl
5aЈ-Carbalactosaminide (3) and -isolactosaminide (5)
-GlcpNAc-(1Ǟ2)-5a-carba-α--Manp-(1Ǟ6)-β--GlcpO-
(CH2)7CH3 was shown to act as a structurally minimum
substrate analog for enzyme N-(acetylglucosaminyl)-
Octyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β--gluco-
transferase-V, the kinetic parameters being comparable to pyranoside (9) was prepared[7] in 44% yield from -glucosa-
those of the parent trisaccharide. This paper describes the mine hydrochloride by subsequent per-N,O-acetylation, and
synthesis of pseudo-N-acetyllactosaminides 3 and 4, and - then glycosylation with octanol and ferric chloride in di-
[8]
´
isolactosaminides 5 and 6, where the β--galactopyranose chloromethane. Zemplen de-O-acetylation of 9, followed
moieties of the true substrates 1 and 2 are replaced by ether- by benzylidenation with benzaldehyde in the presence of
and imino-linked 5a-carba-β--galactopyranose residues, zinc chloride, gave the (R)-4,6-O-benzylidene derivative[9]
respectively.[6] Since these carbadisaccharides are resistant 10 in 88% yield. Benzylation of 10 with benzyl bromide and
sodium hydride in DMF gave the 3-O-benzyl derivative[9]
[°]
Part 39: Ref.[2]
11 (82%), which was selectively reduced with sodium cyano-
borohydride in THF to afford the 3,6-di-O-benzyl deriva-
tive 13 (68%). The structure was confirmed by the 1H-NMR
spectrum of the 4-acetate 14 derived from 13 by the conven-
tional acetylation. On the other hand, 10 was first con-
verted into the 3-O-methoxymethyl derivative 12 (90%),
which was subjected to hydrogenolysis with 10% Pd/C cay-
[a]
Department of Applied Chemistry, Faculty of Science and
Technology, Keio University,
Hiyoshi, Kohoku-ku, Yokohama, 223-8522 Japan
Fax: (internat.) ϩ 81(0)45/563-0446
E-mail: ogawa@applc.keio.ac.jp
Department of Chemistry, University of Alberta,
Edmonton, Alberta T6G 2G2, Canada
Fax: (internat.) ϩ 1-403/492-7705
[b]
Eur. J. Org. Chem. 1999, 631Ϫ642
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0303Ϫ0631 $ 17.50ϩ.50/0
631

S. Ogawa, N. Matsunaga, H. Li, M. M. Palcic
FULL PAPER
Scheme 2. Synthesis of the building blocks 13 and 16
1Ј and -2Ј through the 5aЈ-carbahex-2Ј-ulo-1Ј,5Ј-pyranose
derivative 19. Thus, oxidation of 17 with PCC in dichloro-
˚
methane in the presence of molecular sieves (4 A) gave the
crystalline ketone 19 in 75% yield. Treatment of 19 with
DBU in toluene for 2.5 h at 60°C produced the desired
1
anomer 20 in 79% yield. The structure was confirmed H-
NMR-spectroscopically by the appearance of the signal
[δ ϭ 4.27, dd, J1Ј,5aЈ(ax) ϭ 11.7, J1Ј,5aЈ(eq) ϭ 5.9 Hz] due
to 1Ј-H. Selective reduction of the carbonyl function was
successfully carried out by use of boraneϪdimethyl sulfide
in THF to give, after acetylation and separation by silica-
gel column chromatography, the 5aЈ-carbadisaccharide 21
with β--gluco (69%), together with 22 with β--manno con-
figuration (15%). The structures were established on the
1
basis of H-NMR signals due to the C-2Ј protons. In the
spectra of 21 and 22, the signals due to 2Ј-H appear as
doublets of doublets (δ ϭ 4.97, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 9.2 Hz) and
(δ ϭ 5.63, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 2.9 Hz), respectively, supporting
the assigned structures. Attempted inversion[12] of the con-
figuration at C-4Јof 21 to β--galacto configuration was
Scheme 1. The hydroxy groups of N-acetyl-β-lactosaminide and
-isolactosaminide, on which α-(1Ǟ3/4)-fucosyl transferase transfers
an α-Fuc residue: two types of pseudo-N-acetyllactosaminides and
-isolactosaminides, designed as potential acceptor substrates and/or
inhibitors of the transferase
talyst and then totally benzylated to the 4,6-di-O-benzyl de- made through SN2 reaction of the sulfonate ester. Thus, de-
rivative 15 (66%). Removal of the methoxymethyl group O-benzylidenation of 21 with aqueous acetic acid followed
with conc. hydrochloric acid in THF gave the 3-OH unpro- by conventional mesylation gave the 4Ј,6Ј-dimesylate 23
tected derivative 16 (94%).
(72%). Treatment of 23 with excess of sodium acetate in
Coupling of 1,2-anhydro-3-O-benzyl-4,6-O-benzylidene- aqueous DMF for 2 days at 120°C, followed by acetylation,
1
5a-carba-β--mannopyranose[10] 7 and an oxide anion gen- afforded the 4Ј-epimeric diacetate 24 in 85% yield. The H-
erated from the 4-OH-unprotected derivative 13 (1.2 molar NMR spectrum of 24 contained a broad singlet (δ ϭ 5.52)
equiv.) by treatment with sodium hydride in DMF was car- ascribable to equatorial 4Ј-H. Hydrogenolysis of 24 in the
ried out in the presence of 15-crown-5 ether for 26 h at presence of 10% Pd/C in methanol for 2 h at room tempera-
70°C, affording a 66% yield of a single diaxially opened ture, followed by acetylation, gave the hexaacetyl derivative
product 17. Its α--manno configuration was established by 25 (93%) of octyl 2-acetamido-4-O-(5a-carba-β--galactop-
1
1
the H-NMR spectra of 17 and its 2Ј-acetate 18. The H- yranosyl)-2-deoxy-β--glucopyranoside (3). De-O-acety-
NMR spectrum (CDCl3) of the latter revealed a doublet of lation[8] of 25 and purification by silica-gel column chroma-
doublets (δ ϭ 5.59, J1Ј,2Ј ϭ 1.6, J2Ј,3Ј ϭ 2.3 Hz) due to 2Ј- tography with chloroform/methanol (3:1) afforded 3 (91%).
H. Transformation of the α--manno to the β--gluco con-
Similar reaction of the epoxide 7 with an oxide anion
figuration was effected by basic epimerization[11][12] at C- from the 3-unprotected derivative 16 was carried out at
632
Eur. J. Org. Chem. 1999, 631Ϫ642

Pseudosugars, 40
FULL PAPER
sequence of reaction: oxidation with PCC [Ǟ 28 (71%)],
epimerization with DBU [Ǟ 29 (81%)], and selective re-
duction with boraneϪdimethyl sulfide [Ǟ 30 (61%)]. Epi-
merization at C-4Ј was also carried out by SN2 reaction of
the 4Ј,6Ј-dimesylate 31 with an acetate ion, giving the tria-
cetate 32 (82%) having a 5aЈ-carba-β--galactopyranose
residue. Hydrogenolysis of 32 followed by acetylation gave
the hexaacetyl derivative 33 of octyl 2-acetamido-3-O-(5a-
carba-β--galactopyranosyl)-2-deoxy-β--glucopyranoside
(5). De-O-acetylation[8] gave the free carbadisaccharide 5.
Synthesis of Imino-Linked Octyl
5aЈ-Carbalactosaminide (4) and -isolactosaminide (6)
Since 1,2-anhydro-6-O-benzyl-3,4-O-isopropylidene-5a-
carba-α--galactopyranose[13] (8) had been successfully
used to prepare N-alkyl-5a-carba-β--galactopyranosylam-
ines,[13] where the epoxide ring was readily cleaved by alkyl-
amines, giving selectively the diequatorially opening prod-
ucts, the epoxide 8 was therefore expected to be usable and
applicable as the carba-sugar donor for direct incorporation
of an imino-linked 5a-carba-β--galactopyranose residue
into oligosaccharide chain.
Octyl 2-acetamido-4-amino-2,4-dideoxy-β--glucopyr-
anoside (37) was first prepared from 13. Oxidation of 13
with acetic anhydride in DMSO gave the ketone, which
without purification was subsequently reduced with -sel-
ectride in THF at Ϫ15°C gave selectively crystalline epim-
eric alcohol 34 in 58% yield. Mesylation of 34 gave the me-
sylate 35 (87%), treatment of which with excess sodium az-
ide in aqueous DMF at 120°C for 2 days afforded the azide
36 in 96% yield. Hydrogenolysis of both the azido and
benzyl groups in the presence of 10% Pd/C afforded after
purification by ion exchange on Dowex 50W-X2 (Hϩ) resin
with aqueous ammoniacal methanol the free base 37 in 80%
yield. On the other hand, compound 10 was similarly oxid-
ized with acetic anhydride in DMSO followed by selective
reduction of the ketone, giving the epimeric alcohol [Ǟ 38
(76%)]. The alcohol 38 was converted into the mesylate 39
(65%), which was subjected to azidolysis in aqueous DMF
to afford the azide 40 (92%). Hydrogenolysis of 40 with
10% Pd/C afforded after purification by the resin column
octyl 2-acetamido-3-amino-2,3-dideoxy-β--glucopyrano-
side (41) in 90% yield.
Coupling of an equal molar amount of the epoxide 8 and
the amine 37 in 2-propanol in a sealed tube for 3 weeks at
120°C gave, after acetylation and purification by silica-gel
column chromatography, a single carbadisaccharide deriva-
tive 42 as the triacetate in 37% yield. The reactivity of the
Scheme 3. Synthesis of ether-linked octyl N-acetyl-5aЈ-carba-β-lac-
tosaminide (3) and -isolactosaminide (5)
80°C for 4 days to give a single coupling product 26 in bulky amine 37 toward 8 was shown to be very slow,
rather low yield (48%). The reactivity of 16 has been shown thereby producing selectively a desired positional isomer
to be considerably decreased compared to that of 13, seem- which was derived through unfavorable diequatorial attack
ingly due to the steric effects and/or the presence of the at C-1 of the epoxide ring. Large steric hindrance between
acetamido group adjacent to the oxide anion. The α-- the 5-hydroxymethyl group of 37 and the ketal group of 8
1
manno configuration of 26 was firmly confirmed by the 1H- seemed to hamper the nucleophilic attack at C-2. The H-
NMR spectrum of its 2Ј-acetate 27. Transformation of 26 NMR spectrum revealed a doublet of doublets of doublets
into the β--gluco structure was similarly conducted by the (δ ϭ 1.05, J ഠ 11.7 Hz) due to the axial proton of C-5a. De-
Eur. J. Org. Chem. 1999, 631Ϫ642
633

S. Ogawa, N. Matsunaga, H. Li, M. M. Palcic
FULL PAPER
structure. De-O-acetylation[8] and purification on Dowex
50W-X2 (Hϩ) resin gave the free carbadisaccharide 4 in a
quantitative yield.
Similar coupling of 8 and 41 followed by acetylation af-
forded after chromatography on silica gel with acetone/tolu-
ene (1:5) two positional isomers 44 and 45 in 38 and 24%
1
yield, respectively. The H-NMR spectrum of the diequa-
torially opening product 44 revealed two coupled doublets
of doublets (δ ϭ 4.82, J1Ј,2Ј ϭ 8.4, J2Ј,3Ј ϭ 7.3 Hz) and (δ ϭ
3.96, J2Ј,3Ј ϭ 7.3, J3Ј,4Ј ϭ 5.5 Hz) due to 2Ј-H and 3Ј-H,
respectively. Whereas, the spectrum of 45 showed a narrow
doublet of doublets of doublets (δ ϭ 4.89, J ϭ 1.8, 1.8 and
5.9 Hz) due to 1Ј-H, indicating the α--manno configura-
tion of the carba-sugar residue. The nucleophilicity of the
amino group of 41, compared with that of 37, seemed to
be essentially improved by sterically releasing from the in-
fluence of the bulky 5-hydroxymethyl function. The hepta-
N,O-acetyl derivative 46 obtained from 44 showed a doublet
1
of doublet (δ ϭ 5.00, J ഠ 8.2 Hz) due to 2Ј-H in the H-
Scheme 4. Synthesis of the building block 41
NMR spectrum, supporting the assigned structure. De-O-
acetylation of 46 gave the free carbadisaccharide 6.
O-isopropylidenation with aq. acetic acid and subsequent
hydrogenolysis with 10% Pd/C followed by acetylation af-
forded the hepta-N,O-acetyl derivative 43 of octyl 5aЈ-
carba-β-lactosaminide 4 in 83% yield. The H-NMR spec-
trum showed two coupled doublets of doublets (δ ϭ 4.99,
Evaluation of the 5aЈ-Carbadisaccharides 3, 4, 5, and
6 as an Acceptor for α-(1Ǟ3/4)-Fucosyltransferase
1
J1Ј,2Ј ϭ J2Ј,3Ј ϭ 10.3 Hz) and (δ ϭ 4.80, J2Ј,3Ј ϭ 10.3, J3Ј,4Ј
2.9 Hz) ascribed to 2Ј-H and 3Ј-H, supporting the assigned
ϭ
Compounds 3 and 4 were found to be acceptor substrates
for human-milk α-(1Ǟ3/4)-fucosyltransferase[5] with kinetic
parameters comparable to those for standard β--Galp-
(1Ǟ4)-β--GlcpNAcϪO(CH2)8COOCH3. The Km values
are 1.9 ± 0.2 m for 3 and 1.6 ± 0.1 m for 4 both some-
what higher than the Km value of 0.6 m for the standard
acceptor. The Vm(ax) values were 66% (3) and 100% (4)
relative to the standard acceptors. Small-scale reaction of 3
and 4 with GDP-fucose and milk fucosyltransferase re-
sulted in conversion to trisaccharides 47 and 48, respec-
tively. Surprisingly, compounds 5 and 6 were neither ac-
ceptors nor inhibitors for milk fucosyltransferase suggest-
ing that α-(1Ǟ4) transfer is not possible. The milk prep-
aration contains
a
mixture of two different
fucosyltransferase enzymes, a dual specificity α-(1Ǟ3/4)-fu-
cosyltransferase and an α-(1Ǟ3)-fucosyltransferase. These
enzymes were separated by gel-permeation chromatogra-
Scheme 5. Synthesis of imino-linked octyl N-acetyl-5aЈ-carba-β-
lactosaminide (4) and -isolactosaminide (6)
Scheme 6. Enzymatic synthesis of the 5aЈ-carbatrisaccharides 47
and 48
634
Eur. J. Org. Chem. 1999, 631Ϫ642

Pseudosugars, 40
FULL PAPER
phy[14] to see if the panel of substrates could distinguish
between the two enzyme forms. Both forms utilized com-
pounds 3 and 4 as acceptor substrates while 5 and 6 were
neither substrates nor inhibitors for the enzyme. To our
knowledge, this is the first demonstration of a specific sub-
strate for an α-1,3-fucosyltransferase.
(421.5): calcd. C 65.53, H 8.37, N 3.32; found C 65.40, H 8.59,
N 3.32.
Octyl 2-Acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-β--gluc-
opyranoside (11): A solution of 10 (4.64 g, 11 mmol) in DMF (185
mL) was treated with 60% sodium hydride (0.88 g, 22 mmol) for
30 min at room temperature, and, after addition of benzyl bromide
(1.57 mL, 13.2 mmol), it was further stirred for 6 h at room tem-
perature. After the reaction was quenched with methanol, the mix-
ture was diluted with ethyl acetate (1 L) , washed with water, dried,
and concentrated. The crystalline residue was recrystallized from
ethanol to give the benzyl ether[9] 11 (4.62 g, 82%), m.p.
Experimental Section
Melting points: Mel-Temp capillary melting-point apparatus, un-
corrected values. Ϫ Specific rotations: Jasco DIP-370 polarimeter,
28
220Ϫ223°C (from EtOH). Ϫ [α]D ϭ ϩ13 (c ϭ 0.8, CHCl3). Ϫ
1
1-dm cells. Ϫ IR spectra: Jasco IR-810. Ϫ H-NMR spectra: Jeol
C30H41NO6 (511.7): calcd. C 70.42, H 8.08, N 2.74; found C 70.33,
H 8.20, N 3.08.
JNM GSX-270 FT (270 MHz), Jeol Lambda-300 (300 MHz), and
Varian Unity 500 (500 MHz); solvent CDCl3 with internal standard
tetramethylsilane (TMS), CD3OD with external standard acetone,
D2O with external standard acetone. Ϫ Mass spectra: positive-ion
electrospray ionization with a Micromass Zab Hybrid Spec Sector-
TOF. Ϫ TLC: Silica Gel 60 GF (E. Merck, Darmstadt); detection
by charring with concd. H2SO4. Ϫ Column chromatography: Wak-
ogel C-300 (silica gel, 300 Mesh, Wako Chemical, Osaka). Ϫ Or-
ganic solutions, after drying with anhydrous Na2SO4, were concen-
trated at < 50°C at diminished pressure. Ϫ All free carbadisaccha-
rides 3, 4, 5, and 6 were homogeneous on TLC and 1H-NMR-
spectroscopic analyses, and directly used for biological assay and
enzymatic synthesis.
Octyl 2-Acetamido-4,6-O-benzylidene-2-deoxy-3-O-methoxymethyl-
β--glucopyranoside (12): To a solution of 11 (511 mg, 1.21 mmol)
in dichloromethane (15 mL) was added N,N-diisopropylethylamine
(1.27 mL, 7.28 mmol) and it was stirred for 30 min at room tem-
perature. After addition of chloromethyl methyl ether (0.28 mL,
3.64 mmol), it was stirred for 4 h at 40°C. The mixture was diluted
with ethyl acetate (3 L), washed with 0.5  hydrochloric acid, satu-
rated sodium hydrogen carbonate, and water, dried, and concen-
trated. The residue was chromatographed on a silica-gel column
(30 g, acetone/toluene, 1:6) to give 12 (510 mg, 90%) as crystals,
m.p. 208Ϫ210°C (from EtOH), Rf ϭ 0.60 (ethanol/toluene 1:5). Ϫ
28
1
[α]D ϭ ϩ4.5 (c ϭ 1.04, CHCl3). Ϫ H NMR (270 MHz, CDCl3)
(inter alia): δ ϭ 5.79 (d, J2,NH ϭ 8.1 Hz, 1 H, NH), 5.52 (s, 1 H,
PhCH), 4.85 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-H), 4.34 (dd, J5,6a ϭ 4.9,
J6gem ϭ 10.4 Hz, 1 H, 6a-H), 4.23 (dd, J2,3 ϭ 9.9, J3,4 ϭ 8.8 Hz, 1
H, 3-H), 3.77 (dd, J5,6b ϭ 9.9 Hz, 1 H, 6b-H), 3.60 (dd, J4,5 ϭ 9.5
Hz, 1 H, 4-H), 2.01 (s, 3 H, Ac). Ϫ C25H39NO7 (465.6): calcd. C
64.49, H 8.44, N 3.01; found C 64.30, H 8.71, N 3.20.
Octyl 2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β--glucopyranoside
(9): 2-Amino-2-deoxy--glucopyranose hydrochloride (2.0 g, 9.3
mmol) was dissolved in methanolic 1  sodium methoxide (9.3
mL), and the mixture was stirred for 40 min at room temperature.
A white crystalline product was collected by filtration, which was
treated with acetic anhydride (11 mL) in pyridine (23 mL) over-
night at room temperature. After addition of methanol (6 mL), the
mixture was concentrated to dryness. The residue was dissolved in
dichloromethane (25 mL) and the solution was treated with n-oc-
tanol (10 mL, 63 mmol), potassium sulfate (2.5 g, 18 mmol), and
ferric chloride (2.44 g) for 16 h at room temperature. Then the
mixture was diluted with chloroform (300 mL), washed with satd.
aqueous sodium hydrogen carbonate and water thoroughly, dried,
and concentrated. The residue was chromatographed on silica gel
(135 g, ethyl acetate/toluene, 1:1) to give 9 (1.83 g, 44%) as crystals,
m.p. 120Ϫ122°C (from EtOH). Ϫ [α]D28 ϭ ϩ15 (c ϭ 0.96, MeOH).
Octyl
2-Acetamido-3,6-di-O-benzyl-2-deoxy-β--glucopyranoside
(13): To a solution of 11 (1.21 g, 2.64 mmol) in THF (60 mL) were
˚
added molecular sieves (4 A) (1.8 g), a trace of methyl orange,
sodium cyanoborohydride (1.78 g, 28.3 mmol), and it was stirred
for 30 min at room temperature. Satd. hydrochloric acid/diethyl
ether was added to acidify the mixture until it turned pink. After
stirring for 30 min, the mixture was filtered through a Celite bed
and the filtrate was washed with satd. sodium hydrogen carbonate
and water, dried, and concentrated. The residue was chromatog-
raphed on silica gel (120 g, acetone/toluene, 1:6) to give 13 (0.82 g,
Ϫ
1H NMR (270 MHz, CDCl3): δ ϭ 5.56 (d, J2,NH ϭ 8.4 Hz, 1
24
68%) as crystals, m.p. 116Ϫ118°C (from EtOH). Ϫ [α]D ϭ ϩ8
H, NH), 5.32 (dd, J2,3 ϭ 10.6, J3,4 ϭ 9.3 Hz, 1 H, 3-H), 5.06 (dd,
J4,5 ϭ 9.9 Hz, 1 H, 4-H), 4.69 (d, J1,2 ϭ 8.4 Hz, 1 H, 1-H), 4.27
(c ϭ 1.6, MeOH). Ϫ 1H NMR (270 MHz, CDCl3) (inter alia): δ ϭ
5.60 (d, J2,NH ϭ 8.4 Hz, 1 H, NH), 4.87 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-
H), 4.04 (dd, J2,3 9.5, J3,4 ϭ 9.2 Hz, 1 H, 3-H), 3.64 (dd, J4,5 ϭ 8.4
Hz, 1 H, 4-H), 3.53 (dd, J5,6b ϭ 4.8, J6gem ϭ 9.5 Hz, 1 H, 6b-H),
3.23 (ddd, 1 H, 2-H), 1.89 (s, 3 H, Ac) Ϫ C30H43NO6 (513.7): calcd.
C 70.14, H 8.43, N 2.73; found C 69.90, H 8.74, N 2.90.
(dd, J5,6a ϭ 4.8, J6gem ϭ 12.3 Hz, 1 H, 6a-H), 4.13 (dd, J5,6b
ϭ
2.6 Hz, 1 H, 6b-H), 3.86 [ddd, J ϭ 6.0, 6.0, and 9.5 Hz, 1 H,
OCH2(CH2)6Me], 3.79 (ddd, 1 H, 2-H), 3.70 (ddd, 1 H, 5-H), 3.47
[ddd, J ϭ 7.0, 7.0, and 9.5 Hz, 1 H, OCH2(CH2)6Me], 2.08, 2.03,
2.02, and 1.95 (4 s, each 3 H, 4 ϫ Ac), 1.26 [br. s, 12 H,
OCH2(CH2)6Me]. Ϫ C22H37NO9 (459.6): calcd. C 57.50, H 8.12,
N 3.05; found C 57.18, H 8.42, N 3.10.
Octyl 2-Acetamido-4-O-acetyl-3,6-di-O-benzyl-2-deoxy-β--gluco-
pyranoside (14): Compound 13 (20 mg, 0.039 mol) was treated with
acetic anhydride (1 mL) and pyridine (2 mL) overnight at room
temperature. After addition of small methanol, the mixture was
Octyl 2-Acetamido-4,6-O-benzylidene-2-deoxy-β--glucopyranoside
(10): Compound 9 (6.53 g, 14.2 mmol) was dissolved in methanol
(100 mL) and the solution was treated with methanolic 1  sodium concentrated to dryness. The residue was chromatographed on sil-
methoxide (1.5 mL) for 1 h at room temperature. After neutraliz- ica gel (2 g, ethyl acetate/toluene, 1:8) to give 14 (20 mg) as a hygro-
ation with Amberlite IR 120B (Hϩ) resin, the mixture was concen- scopic syrup. Ϫ [α]D20 ϭ ϩ16 (c ϭ 0.26, MeOH). Ϫ 1H NMR (270
trated to dryness. The residue was then treated with benzaldehyde
(220 mL) and zinc chloride (9.14 g, 67 mmol) for 3 h at room
temperature. The reaction mixture was poured into a mixture of
hexane (1 L) and water (500 mL), and precipitates were collected
MHz, CDCl3): δ ϭ 7.34Ϫ7.19 (m, 10 H, 2 ϫ Ph), 5.63 (d, J2,NH ϭ
7.3 Hz, 1 H, NH), 5.02 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.97 (dd,
J3,4 ϭ 9.3, J4,5 ϭ 9.6 Hz, 1 H, 4-H), 4.60Ϫ4.53 (m, 4 H, 2 ϫ
CH2Ph), 4.37 (dd, J2,3 ϭ 9.9 Hz, 1 H, 3-H), 3.86 [ddd, J ϭ 6.6,
by filtration, giving 10[9] (5.27 g, 88%) as crystals, m.p. 115Ϫ118°C 6.6, and 9.7 Hz, 1 H, OCH2(CH2)6Me], 3.66 (ddd, J5,6a ϭ 4.0, J5,6b
28
(from EtOH). Ϫ [α]D ϭ ϩ51 (c ϭ 0.8, CH3Cl).Ϫ C23H35NO6 5.5 Hz, 1 H, 5-H), 3.56Ϫ3.54 (m, 2 H, 6,6-H), 3.46 [ddd, J ϭ 6.6,
Eur. J. Org. Chem. 1999, 631Ϫ642
635

S. Ogawa, N. Matsunaga, H. Li, M. M. Palcic
FULL PAPER
7.0, and 9.7 Hz, 1 H, OCH2(CH2)6Me], 3.16 (ddd, 1 H, 2-H), 1.89
4.86 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.75 and 4.49 (ABq, Jgem ϭ 11.5
and 1.86 (2 s, each
OCH2(CH2)6Me], 0.87 [t, 3 H, J ϭ 7.0 Hz, 1 H, OCH2(CH2)6CH3].
Ϫ C32H45NO7 (555.7): calcd. C 69.16, H 8.16, N 2.52; found C CH2Ph), 4.16Ϫ4.12 (m, 2 H, 1Ј-H, 2Ј-H), 4.11 (dd, J2,3 ϭ 9.2,
3
H,
2
Ac), 1.58Ϫ1.27 [m, 12 H, Hz, each 1 H, CH2Ph), 4.74 and 4.63 (ABq, Jgem ϭ 11.7 Hz, each
1 H), and 4.61 and 4.57 (ABq, Jgem ϭ 12.5 Hz, each 1 H) (2 ϫ
68.97, H 8.45, N 2.67.
J3,4 ϭ 8.8 Hz, 1 H, 3-H), 4.00 (dd, J5Ј,6Јa ϭ 4.4, J6Јgem ϭ 11.0 Hz,
1 H, 6Јa-H), 3.93 (dd, J3Ј,4Ј ϭ J4Ј,5Ј ϭ 9.9 Hz, 1 H, 4Ј-H), 3.83
[ddd, J ϭ 6.6, 6.6, and 9.9 Hz, 1 H, OCH2(CH2)6Me], 3.77Ϫ3.72
(m, 3 H, 6,6-H, 3Ј-H), 3.62 (dd, J3,4 ϭ 8.8, J4,5 ϭ 8.4 Hz, 1 H, 4-
H), 3.57 (dd, J5Ј,6Јb ϭ 11.0 Hz, 1 H, 6Јb-H), 3.51Ϫ3.48 (m, 1 H, 5-
H), 3.44 [ddd, 1 H, OCH2(CH2)6Me], 3.31 (ddd, J2,3 ϭ 9.2, 1 H,
2-H), 2.10Ϫ2.07 (m, 1 H, 5Ј-H), 1.86 (s, 3 H, Ac), 1.57Ϫ1.26 [m,
14 H, 5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.87 [t, J ϭ 6.6 Hz, 3 H,
OCH2(CH2)6CH3]. Ϫ C51H65NO10 (852.1): calcd. C 71.89, H 7.69,
N 1.64; found C 71.81, H 7.66, N 1.81.
Octyl 2-Acetamido-4,6-di-O-benzyl-2-deoxy-3-O-methoxymethyl-β-
-glucopyranoside (15): A solution of 12 (2.54 g, 5.46 mmol) in
ethanol/ethyl acetate (1:1, 30 mL) was hydrogenolyzed in the pres-
ence of 10% Pd/C for 1.5 h at room temperature. The catalyst was
removed by filtration and the filtrate was concentrated. The residue
was dissolved in dry DMF (32 mL) and the solution was treated
with sodium hydride (0.89 g, 22 mmol) for 30 min at room tempera-
ture. To the mixture was added benzyl bromide (1.46 mL,. 12
mmol), and it was stirred for 2 h at room temperature. After ad-
dition of a small amount of methanol, the mixture was diluted with
ethyl acetate (300 mL), washed with water, dried, and concentrated.
The residue was crystallized from ethanol to give 15 (2.0 g, 66%)
Octyl
(2-O-Acetyl-4,6-O-benzylidene-3-O-benzyl-5a-carba-α--
mannopyranosyl)-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (18): Compound 17 (21 mg, 25 µmol) was treated
with acetic anhydride (1 mL) in pyridine (2 mL) overnight at room
temperature. After addition of methanol, the mixture was diluted
with ethyl acetate (30 mL), washed with water, dried, and concen-
trated. The residue was chromatographed on a silica-gel column (2
g, ethyl acetate/toluene, 1:4) to give 18 (17 mg, 77%) as a syrup. Ϫ
25
as crystals, m.p. 124Ϫ125°C (from EtOH). Ϫ [α]D ϭ ϩ35 (c ϭ
1
0.95, CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.35Ϫ7.17 (m,
10 H, 2 ϫ Ph), 5.68 (d, J2,NH ϭ 8.4 Hz, 1 H, NH), 4.82 and 4.64
(ABq, Jgem ϭ 6.6 Hz, each 1 H, CH2OMe), 4.69 and 4.56 (ABq,
Jgem ϭ 11.0 Hz, each 1 H, CH2Ph), 4.61 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-
H), 4.59 and 4.55 (ABq, Jgem ϭ 11.2 Hz, each 1 H, CH2Ph), 3.90
(dd, J5,6a ϭ 5.9, J6gem ϭ 9.9 Hz, 1 H, 6a-H), 3.86 (dd, J5,6b ϭ 3.3,
28
[α]D ϭ Ϫ17 (c ϭ 0.39, MeOH). Ϫ 1H NMR (270 MHz, CDCl3):
δ ϭ 7.63Ϫ7.19 (m, 20 H, Ph), 5.60 (s, 1 H, CHPh), 5.59 (dd, J1Ј,2Ј
ϭ
Hz,
1 H, 6b-H), 3.73Ϫ3.51 [m, 5 H, 2-H, 3-H, 4-H,
1.6, J2Ј,3Ј ϭ 2.3 Hz, 1 H, 2Ј-H), 5.49 (d, J2,NH ϭ 7.8 Hz, 1 H, NH),
4.86 and 4.55 (ABq, Jgem ϭ 11.7 Hz, each 1 H, CH2Ph), 4.86 (d,
OCH2(CH2)6Me], 3.45 [ddd, J ϭ 7.0, 7.0, and 9.9 Hz, 1 H,
OCH2(CH2)6Me], 3.35 (s, 3 H, CH2OCH3), 1.99 (s, 3 H, Ac),
1.56Ϫ1.27 [m, 12 H, OCH2(CH2)6Me], 0.87 [t, J ϭ 7.0 Hz, 3 H,
OCH2(CH2)6CH3]. Ϫ C32H47NO7 (557.7): calcd. C 68.91, H 8.49,
N 2.51; found C 68.68, H 8.68, N 2.79.
J
1,2 ϭ 6.8 Hz, 1 H, 1-H), 4.63 and 4.59, and 4.62 and 4.53 (2 ABq,
Jgem ϭ 12.2 Hz, each 1 H, CH2Ph), 4.12 (dd, J2,3 ϭ 9.3, J3,4 ϭ 8.3
Hz, 1 H, 3-H), 4.08 (m, 1 H, 1Ј-H), 4.00 (dd, J5Ј,6Јa ϭ 4.4, J6Јgem ϭ
11.0 Hz, 1 H, 6Јa-H), 3.87 (dd, J3Ј,4Ј ϭ J4Ј,5Ј ϭ 9.8 Hz, 1 H, 4Ј-H),
3.84 (m, 1 H, 3Ј-H), 3.81 [ddd, J ϭ 6.4, 6.4, and 9.3 Hz, 1 H,
OCH2(CH2)6Me], 3.71 (m, 2 H, 6,6-H), 3.69 (dd, J4,5 ϭ 8.3 Hz, 1
H, 4-H), 3.58 (dd, J5Ј,6Јb ϭ 11.0 Hz, 1 H, 6Јb-H), 3.50Ϫ3.41 [m, 2
H, 5-H, OCH2(CH2)6Me], 3.36 (ddd, J2,3 ϭ 9.3 Hz, 1 H, 2-H), 2.15
(m, 1 H, 5Ј-H), 2.00 (s, 3 H, OAc), 1.79 (s, 3 H, NAc), 1.73Ϫ1.18
[m, 14 H, H-5aЈ,5aЈ, OCH2(CH2)6Me]. Ϫ C53H67NO11 (894.1):
calcd. C 71.20, H 7.55, N 1.57; found C 71.16, H 7.66, N 1.75.
Octyl
2-Acetamido-4,6-di-O-benzyl-2-deoxy-β--glucopyranoside
(16): A mixture of 12 (165 mg, 0.295 mmol), THF (4 mL), and
conc. hydrochloric acid (180 mL) was stirred for 4 h at room tem-
perature. After neutralization with sodium hydrogen carbonate, the
mixture was concentrated. The residue was chromatographed on a
silica-gel column (8 g, acetone/toluene, 1:5) to give 16 (142 mg,
23
94%) as crystals, m.p. 111Ϫ112°C (from EtOH). Ϫ [α]D ϭ Ϫ19
1
(c ϭ 0.9, CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.34Ϫ7.21
Octyl (3-O-Benzyl-4,6-O-benzylidene-5a-carba-α--arabino-hex-2-
ulopyranosyl)-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (19): To a solution of 17 (790 mg, 0.927 mmol) in
dichloromethane (16 mL) were added PCC (1.0 g, 4.64 mmol) and
(m, 10 H, Ph), 5.80 (br. s, 1 H, NH), 4.93 and 4.59 (ABq, Jgem
ϭ
11.4 Hz, each 1 H, CH2Ph), 4.61 and 4.54 (ABq, Jgem ϭ 12.1 Hz,
each 1 H, CH2Ph), 4.43 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-H), 3.93Ϫ3.85
[m, 2 H, 4-H, OCH2(CH2)6Me], 3.75 (dd, J5,6a ϭ 1.1, J6gem 11.1
Hz, 1 H, 6a-H), 3.69 (ddd, J4,5 ϭ 10.6, J5,6b ϭ 3.3 Hz, 1 H, 5-H),
3.54Ϫ3.41 [m, 4 H, H-2, H-3, H-6b, OCH2(CH2)6Me], 2.03 (s, 3
H, Ac), 1.59Ϫ1.27 [m, 12 H, OCH2(CH2)6Me], 0.88 [t, 3 H, J ϭ
7.0 Hz, 1 H, OCH2(CH2)6CH3]. Ϫ C30H43NO6 (513.7): calcd. C
70.15, H 8.44, N 2.73; found C 70.14, H 8.44, N 2.94.
˚
molecular sieves (4 A) (1.0 g), and the suspension was stirred for 1
h at room temperature. After addition of Celite (2.5 g), the reaction
mixture was filtered through a silica-gel column (15 g), which was
washed thoroughly with diethyl ether. The filtrate and washings
were combined and concentrated to give the residue, which was
chromatographed on a silica-gel column (70 g, ethyl acetate/tolu-
Octyl (4,6-O-Benzylidene-3-O-benzyl-5a-carba-α--mannopyranos- ene, 1:5) to give 19 (596 mg, 75%) as crystals, m.p. 138Ϫ140°C
26
yl)-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β--glucopyrano-
side (17): To a solution of 13 (780 mg, 1.47 mmol) in DMF (12
mL) were added sodium hydride (110 mg, 4.4 mmol) and 15-crown-
(from EtOH). Ϫ [α]D ϭ Ϫ44 (c ϭ 0.46, MeOH). Ϫ 1H NMR
(270 MHz, CDCl3): δ ϭ 7.51Ϫ7.23 (m, 20 H, 4 ϫ Ph), 5.54 (s, 1
H, CHPh), 5.52 (d, J2,NH ϭ 7.3 Hz, 1 H, NH), 4.87 (d, J1,2 ϭ 7.7
5 ether (0.88 mL, 4.1 mmol), and the mixture was stirred for 30 Hz, 1 H, 1-H), 4.77 and 4.49 (ABq, Jgem ϭ 11.5 Hz, each 1 H,
min at room temperature. A solution of 1,2-anhydro-3-O-benzyl- CH2Ph), 4.68 (d, J3Ј,4Ј ϭ 9.5 Hz, 1 H, 3Ј-H), 4.67 and 4.40 (ABq,
4,6-O-benzylidene-5a-carba-β--mannopyranose (7, 428 mg, 1.26 Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.65 and 4.55 (ABq, Jgem
ϭ
ϭ
mmol) in DMF (6.5 mL) was added to the mixture, and it was
12.5 Hz, each 1 H, CH2Ph), 4.30 (m, 1 H, 1Ј-H), 4.16 (dd, J2,3
stirred for 26 h at 70°C. After treatment with methanol, the mix-
J3,4 ϭ 8.4 Hz, 1 H, 3-H), 4.10 (dd, J5Ј,6Јa ϭ 4.4, J6Јgem ϭ 11.4 Hz,
ture was diluted with ethyl acetate (200 mL), washed thoroughly 1 H, 6Јa-H), 3.86Ϫ3.39 [m, 8 H, 4-H, 5-H, 6,6-H, 4Ј-H, 6Јb-H,
with water, dried, and concentrated. The residue was chromato- OCH2(CH2)6Me], 3.23 (ddd, J2,3 ϭ 8.4 Hz, 1 H, 2-H), 2.52 (m, 1
graphed on a silica-gel column (110 g, ethyl acetate/toluene, 1:3) to H, 5Ј-H), 2.01Ϫ1.86 [m, 1 H, 5aЈ(eq)-H], 1.83 (s, 3 H, Ac),
20
give 17 (512 mg, 66%) as a colorless syrup. Ϫ [α]D ϭ Ϫ23 (c ϭ
1.56Ϫ1.25 [m, 12 H, OCH2(CH2)6Me], 1.05 [m, 1 H, 5aЈ(ax)-H],
1
0.9, MeOH). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.36Ϫ7.26 (m, 0.87 [t, J ϭ 6.6 Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C51H63NO10 (850.1):
20 H, Ph), 5.62 (d, J2,NH ϭ 7.6 Hz, 1 H, NH), 5.60 (s, 1 H, CHPh),
calcd. C 72.06, H 7.47, N 1.65; found C 72.22, H 7.64, N 1.75.
636
Eur. J. Org. Chem. 1999, 631Ϫ642

Pseudosugars, 40
FULL PAPER
Octyl
(3-O-Benzyl-4,6-O-benzylidene-5a-carba-β--arabino-hex-
the solution was treated with methanesulfonyl chloride (34 mL,
0.45 mmol) for 3 h at room temperature. The mixture was diluted
with ethyl acetate (30 mL), washed with water, dried, and concen-
trated. The residue was chromatographed on silica gel (4 g, ethyl
acetate/toluene, 1:3) to give 23 (52 mg, 72%) as a syrup. Ϫ IR
2-ulopyranosyl)-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (20): To a solution of 19 (84 mg, 98 µmol) in tolu-
ene (3.3 mL) was added DBU (22 mL, 0.15 mmol), and the mixture
was stirred for 2.5 h at 60°C, and then concentrated. The residue
was dissolved in ethyl acetate (30 mL) and the solution was washed (film, cmϪ1): ν˜ ϭ 3280 (NH), 1750 (ester), 1650, 1560 (amide), 1180
24
with water, dried, and concentrated. The product was purified by
a silica-gel column (8 g, ethyl acetate/toluene, 1:3) to give 20 (66
(mesyl). Ϫ [α]D ϭ Ϫ13 (c ϭ 0.32, CHCl3). Ϫ 1H NMR (270
MHz, CDCl3): δ ϭ 7.39Ϫ7.20 (m, 15 H, 3 ϫ Ph), 5.95 (d, J2,NH ϭ
7.7 Hz, 1 H, NH), 5.03 (dd, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 9.5 Hz, 1 H, 2Ј-H),
27
mg, 79%) as crystals, m.p. 215Ϫ218°C (from EtOH). Ϫ [α]D
ϭ
Ϫ22 (c ϭ 0.27, CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ
4.73Ϫ4.42 (m, 7 H, 1-H, 3 ϫ CH2Ph), 4.45 (dd, J3Ј,4Ј ϭ J4Ј,5Ј
7.52Ϫ7.21 (m, 20 H, 4 ϫ Ph), 5.76 (d, J2,NH ϭ 7.7 Hz, 1 H, NH), 9.9 Hz, 1 H, 4Ј-H), 4.16 (m, 2 H, 6Ј,6Ј-H), 3.91Ϫ3.36 (m, 10 H, 2-
5.47 (s, 1 H, CHPh), 4.82 and 4.57 (ABq, Jgem ϭ 12.3 Hz, each 1 H, 3-H, 4-H, 5-H, 6,6-H, 1Ј-H, 3Ј-H, OCH2(CH2)6Me], 3.00 and
H) and 4.76 and 4.61 (ABq, Jgem ϭ 11.7 Hz, each 1 H) (2 ϫ 2.80 (2 s, each 3 H, 2 ϫ Ms), 2.13 (m, 1 H, 5Ј-H), 1.96 and 1.93 (2
CH2Ph), 4.75 (d, J1,2 ϭ 6.9 Hz, 1 H, 1-H), 4.62 and 4.46 (ABq, s, each H, Ac), 1.75Ϫ1.25 [m, 14 H, 5aЈ,5aЈ-H,
Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.27 [dd, J1Ј,5aЈ(ax) ϭ 11.7, OCH2(CH2)6Me], 0.87 [t, J ϭ 6.6 Hz, 3 H, OCH2(CH2)6CH3]. Ϫ
1Ј,5aЈ(eq) ϭ 5.9 Hz, 1 H, 1Ј-H], 4.10 (dd, J5Ј,6Јa ϭ 6.9, J6Јgem ϭ 9.2 C48H67NO15S2 (962.2): calcd. C 59.92, H 7.02, N 1.46; found C
ϭ
3
2 ϫ
J
Hz, 1 H, 6Јa-H), 4.00Ϫ3.38 [m, 11 H, 2-H, 3-H, 4-H, 5-H, 6,6-H, 59.69, H 7.22, N 1.58.
3Ј-H, 4Ј-H, 6Јb-H, OCH2(CH2)6Me], 1.92 (s, 3 H, Ac), 1.86 [m, 1
Octyl (2,4,6-Tri-O-acetyl-3-O-benzyl-5a-carba-β--galactopyrano-
syl)-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β--glucopyrano-
side (24): A mixture of 23 (22 mg, 23 µmol), anhydrous sodium
acetate (38 mg, 0.46 mmol), and aqueous 80% DMF (1.3 mL) was
stirred for 2 d at 120°C, and, after cooling, diluted with ethyl acet-
ate (30 mL). The solution was washed with water, dried, and con-
centrated. The residue was acetylated in the usual manner, and the
H, 5aЈ(eq)-H], 1.69 (m,
1 H, 5Ј-H), 1.58Ϫ1.27 [m, 12 H,
OCH2(CH2)6Me], 1.01 [m, 1 H, 5aЈ(ax)-H], 0.88 [t, J ϭ 7.0 Hz, 3
H, OCH2(CH2)6CH3]. Ϫ C51H63NO10 (850.1): calcd. C 72.06, H
7.47, N 1.65; found C 72.06: H, 7.54, N 1.95.
Octyl
[2-O-Acetyl-4,6-O-benzylidene-3-O-benzyl-5a-carba-β--
gluco- and -mannopyranosyl]-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-
deoxy-β--glucopyranoside (21 and 22): To a solution of 20 (40 mg, product was chromatographed on silica gel (2 g) with acetone/hex-
47 µmol) in THF (2.5 mL) was added 2  boraneϪdimethyl sulfide
(in THF, 70 µL, 0.14 mmol), and it was stirred for 3.5 h at room
temperature. After addition of methanol (0.1 mL), the mixture was
diluted with ethyl acetate (30 mL), washed with water thoroughly,
dried, and concentrated. The residue (ca. 40 mg) was treated with
acetic anhydride (1 mL) in pyridine (2 mL) overnight at room tem-
ane (1:3) to give 24 (17 mg, 85%) as a syrup. Ϫ IR (film, cmϪ1):
23
ν˜ ϭ 3280 (NH), 1750 (ester), 1660 (amide). Ϫ [α]D ϭ Ϫ18 (c ϭ
1
0.89, CHCl3): Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.37Ϫ7.20 (m,
15 H, 3 ϫ Ph), 5.93 (d, J2,NH ϭ 7.3 Hz, 1 H, NH), 5.52 (br. s, 1
H, 4Ј-H), 5.10 (dd, J1Ј,2Ј ϭ 9.5, J2Ј,3Ј ϭ 9.9 Hz, 1 H, 2Ј-H), 4.74
and 4.61 (ABq, Jgem ϭ 11.4 Hz, each 1 H, CH2Ph), 4.68 and 4.38
perature. The mixture was processed in the usual manner to give a (ABq, Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.63 (d, J1,2 ϭ 8.1 Hz,
mixture of the acetates, which was chromatographed on a silica-gel
1 H, 1-H), 4.59 and 4.43 (ABq, Jgem ϭ 12.1 Hz, each 1 H, CH2Ph),
3.87Ϫ3.54 [m, H, 2-H, 3-H, 4-H, 5-H, 6,6-H, 6Ј,6Ј-H,
OCH2(CH2)6Me], 3.42Ϫ3.33 [m, 2 H, 1Ј-H, OCH2(CH2)6Me], 3.20
column (4 g, ethyl acetate/toluene, 1:4) to give 21 (29 mg, 69%) and
9
29
22 (6 mg, 15%) as a syrup. Ϫ 21: [α]D ϭ Ϫ25 (c ϭ 0.91, CHCl3).
Ϫ
1H NMR (270 MHz, CDCl3): δ ϭ 7.49Ϫ7.23 (m, 20 H, 4 ϫ (dd, J3Ј,4Ј ϭ 2.9 Hz, 1 H, 3Ј-H), 2.09, 2.05, 2.01, and 1.93 (4 s, each
Ph), 5.92 (d, J2,NH ϭ 7.7 Hz, 1 H, NH), 5.51 (s, 1 H, CHPh), 4.97
3 H, 4 ϫ Ac), 1.72Ϫ1.24 [m, 15 H, 5Ј-H, 5aЈ,5aЈ-H,
(dd, J1Ј,2Ј ϭ 9.5, J2Ј,3Ј ϭ 9.2 Hz, 1 H, 2Ј-H), 4.88 and 4.58 (ABq, OCH2(CH2)6Me], 0.87 [t, J ϭ 7.0 Hz, 3 H, OCH2(CH2)6CH3]. Ϫ
Jgem ϭ 11.7 Hz, each 1 H, CH2Ph), 4.76Ϫ4.64 (m, 3 H, H-1,
CH2Ph), 4.61 and 4.46 (ABq, Jgem ϭ 12.1 Hz, each 1 H, CH2Ph),
4.02 (dd, J5Ј,6Јa ϭ 4.4, J6Јgem ϭ 11.0 Hz, 1 H, 6Јa-H), 3.84Ϫ3.36
(m, 10 H, 2-H, 3-H, 4-H, 5-H, 6,6-H, 1Ј-H, 4Ј-H, OCH2(CH2)6Me],
3.47 (dd, J3Ј,4Ј ϭ 9.2 Hz, 1 H, 3Ј-H), 3.42 (dd, J5Ј,6Јb ϭ 11.0 Hz, 1
H, 6Јb-H), 1.97 and 1.93 (2 s, each 3 H, 2 ϫ Ac), 1.87Ϫ1.21 [m,
15 H, 5Ј-H, 5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.86 [t, J ϭ 6.8 Hz, 3 H,
OCH2(CH2)6CH3]. Ϫ C53H67NO11 (894.1): calcd. C 71.20, H 7.55,
C50H67NO13 (890.1): calcd. C 67.47, H 7.59, N 1.57; found C 67.40,
H 7.77, N 1.80.
Octyl
(2,3,4,6-Tetra-O-acetyl-5a-carba-β--galactopyranosyl)-
β--glucopyranoside
(1Ǟ4)-2-acetamido-3,6-di-O-acetyl-2-deoxy
(25): A solution of 24 (16.7 mg, 19 mmol) in ethanol (0.5 mL)
was hydrogenolyzed in the presence of 10% Pd/C (5 mg) under
atmospheric pressure of hydrogen for 2 h at room temperature. The
catalyst was removed by filtration and the filtrate was concentrated.
The residue was acetylated in the usual manner and the product
was purified by chromatography on silica gel (1 g, acetone/toluene,
29
N 1.57; found C 71.04, H 7.67, N 1.69. Ϫ 22: [α]D ϭ Ϫ12 (c ϭ
1
0.56, CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.48Ϫ7.15 (m,
20 H, 4 ϫ Ph), 5.63 (dd, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 2.9 Hz, 1 H, 2Ј-H), 5.55
(d, J2,NH ϭ 7.7 Hz, 1 H, NH), 5.51 (s, 1 H, CHPh), 4.79 (dd, J1,2 ϭ
7.7 Hz, 1 H, 1-H), 4.68 (s, 2 H, CH2Ph), 4.65 and 4.47 (ABq,
26
1:3) to give 25 (13 mg, 93%) as a syrup. Ϫ [α]D ϭ Ϫ16 (c ϭ 0.3,
CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 5.64 (d, J2,NH ϭ 9.5
Hz, 1 H, NH), 5.43 (br. s, 1 H, 4Ј-H), 5.22 (dd, J1Ј,2Ј ϭ 9.5, J2Ј,3Ј
10.3 Hz, 1 H, 2Ј-H), 4.92 (dd, J2,3 ϭ 9.2, J3,4 ϭ 7.7 Hz, 1 H, 3-H),
4.78 (dd, J3Ј,4Ј ϭ 2.9 Hz, 1 H, 3Ј-H), 4.52 (dd, J5,6a ϭ 2.8, J6gem
11.5 Hz, 1 H, 6a-H), 4.41 (d, J1,2 ϭ 7.0 Hz, 1 H, 1-H), 4.20 (dd,
5,6b ϭ 4.9 Hz, 1 H, 6b-H), 4.04 (ddd, 1 H, 2-H), 3.98 (dd, J5Ј,6Јa ϭ
ϭ
Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.64 and 4.49 (ABq, Jgem
12.5 Hz, each 1 H, CH2Ph), 3.99Ϫ3.31 [m, 12 H, 2-H, 3-H, 4-H,
5-H, 6,6-H, 1Ј-H, 4Ј-H, 6Ј,6Ј-H, OCH2(CH2)6Me], 3.26 (dd, J3Ј,4Ј
ϭ
ϭ
ϭ
9.5 Hz, 1 H, 3Ј-H), 2.11 and 1.86 (2 s, each 3 H, 2 ϫ Ac), 1.84Ϫ1.25
[m, 15 H, 5Ј-H, 5aЈ,5aЈ-H. OCH2(CH2)6Me], 0.87 [t, J ϭ 6.6 Hz,
3 H, OCH2(CH2)6CH3]. Ϫ C53H67NO11 (894.1): calcd. C 71.20, H
7.55, N 1.57; found C 71.04; H, 7.67, N 1.69.
J
8.4, J6Јgem ϭ 11.0 Hz, 1 H, 6Јa-H), 3.88 (dd, J5Ј,6Јb ϭ 6.2 Hz, 1 H,
6Јb-H), 3.79 [ddd, J ϭ 6.2, 6.2, and 9.5 Hz, 1 H, OCH2(CH2)6Me],
3.57Ϫ3.47 (m, 3 H, 4-H, 5-H, 1Ј-H), 3.41 [ddd, J ϭ 7.0, 7.0, and
Octyl (2-O-Acetyl-3-O-benzyl-4,6-di-O-methanesulfonyl-5a-carba-β- 9.5 Hz, 1 H, OCH2(CH2)6Me], 2.13, 2.10, 2.08, 2.06, 2.05, 1.97,
-glucopyranosyl)-(1Ǟ4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (23): A mixture of 21 (66 mg, 74 µmol) and 60%
and 1.96 (7 s, each 3 H, 7 ϫ Ac), 1.56Ϫ1.25 [m, 15 H, 5Ј-H, 5aЈ,5aЈ-
H, OCH2(CH2)6Me], 0.87 [t, J ϭ 6.8 Hz, 3 H, OCH2(CH2)6CH3].
aqueous acetic acid (4 mL) was stirred for 5 h at 70°C, and then Ϫ C35H55NO16 (745.8): calcd. C 56.36, H 7.43, N 1.88; found C
concentrated. The residue was dissolved in pyridine (1.3 mL) and
56.07, H 7.70, N 1.87.
Eur. J. Org. Chem. 1999, 631Ϫ642
637

S. Ogawa, N. Matsunaga, H. Li, M. M. Palcic
FULL PAPER
Octyl
(5a-Carba-β--galactopyranosyl)-(1Ǟ4)-2-acetamido-2-de-
as described in the preparation of 19. The reaction mixture was
oxy-β--glucopyranoside (3): A solution of 25 (9.0 mg, 12 µmol) in passed through a silica-gel column (15 g) and washed with diethyl
methanol (1 mL) was treated with methanolic 1  sodium methox- ether thoroughly. The filtrate and washings were combined and
ide (0.1 mL) for 3.5 h at room temperature. After neutralization concentrated to give, after recrystallization from ethanol, 28 (384
with Amberlite IR-120B (Hϩ) resin, the mixture was concentrated
and the residue was chromatographed on silica gel (0.6 g) with
chloroform/methanol (3:1) to give 3 (5.8 mg, 91%) as a white pow-
mg, 71%) as crystals, m.p. 176Ϫ178°C. Ϫ IR (film, cmϪ1): ν˜ ϭ
25
3440 (NH), 1740 (CϭO), 1650 (amide). Ϫ [α]D ϭ Ϫ21 (c ϭ 0.9,
CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 7.51Ϫ7.14 (m, 20
der. Ϫ IR (film, cmϪ1): ν˜ ϭ 3440 (NH, OH), 1640 (amide). Ϫ H, 4 ϫ Ph), 5.73 (d, J2,NH ϭ 7.3 Hz, 1 H, NH), 5.56 (s, 1 H,
22
1
[α]D ϭ ϩ11 (c ϭ 0.2, MeOH). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 4.37 (d, J1,2 ϭ 8.4 Hz, 1 H, 1-H), 3.99Ϫ3.22 [m, 14 H, 2-H, 3-
CHPh), 4.70 and 4.52 (ABq, Jgem ϭ 10.4 Hz, each 1 H, CH2Ph),
4.64 (d, J1,2 ϭ 7.0 Hz, 1 H, 1-H), 4.63 (d, J3Ј,4Ј ϭ 10.3 Hz, 1 H,
H, 4-H, 5-H, 6,6-H, 1Ј-H, 2Ј-H, 3Ј-H, 4Ј-H, 6Ј,6Ј-H, 3Ј-H), 4.62 and 4.54 (ABq, Jgem ϭ 11.9 Hz, each 1 H, CH2Ph),
OCH2(CH2)6Me], 1.96 (s, 3 H, Ac), 1.56Ϫ1.29 [m, 15 H, 5Ј-H, 4.57 and 4.39 (ABq, Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.43 [dd,
5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.90 [t,
OCH2(CH2)6CH3].
J
ϭ
7.0 Hz,
3
H,
J1Ј,5aЈ(ax) ϭ J1Ј,5aЈ(eq) ϭ 2.6 Hz, 1 H, 1Ј-H], 4.22 (dd, J5Ј,6Јa ϭ 4.2,
J6Јgem ϭ 11.4 Hz, 1 H, 6Јa-H), 3.91 (dd, J3,4 ϭ 8.4 Hz, 1 H, 3-H),
3.83 [ddd, J ϭ 6.6, 6.6, and 9.9 Hz, 1 H, OCH2(CH2)6Me], 3.75
(m, 2 H, 6,6-H), 3.68Ϫ3.60 (m, 2 H,. 4Ј-H, 6Јb-H), 3.57 (dd, J4,5 ϭ
7.7 Hz, 1 H, 4-H), 3.52Ϫ3.38 [m, 3 H, 2-H, 5-H, OCH2(CH2)6Me],
2.64 (m, 1 H, 5Ј-H), 2.01 (s, 3 H, Ac), 1.56Ϫ1.19 [m, 14 H, 5aЈ,5aЈ-
H, OCH2(CH2)6Me], 0.88 [t, J ϭ 7.0 Hz, 3 H, OCH2(CH2)6CH3].
Ϫ C51H63NO10 (850.1): calcd. C 72.06, H 7.47, N 1.65; found C
71.78, H 7.49, N 1.95.
Octyl (4,6-O-Benzylidene-3-O-benzyl-5a-carba-α--mannopyrano-
syl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--glucopyrano-
side (26): To a solution of 16 (935 mg, 1.82 mmol) in DMF (6 mL)
were added sodium hydride (218 mg, 5.46 mmol) and 15-crown-5
ether (1.1 mL, 5.46 mmol), and the mixture was stirred for 1 h at
room temperature. A solution of 7 (3.08 g, 9.10 mmol) in DMF (8
mL) was then added to it, and the mixture was heated for 4 d at
80°C. After treatment with methanol, the mixture was diluted with
ethyl acetate (350 mL), washed with water, dried, and concentrated.
The residue was chromatographed on silica gel (200 g) with ace-
tone/toluene (1:7) to give 26 (744 mg, 48%) as a colorless syrup. Ϫ
Octyl (3-O-Benzyl-4,6-O-benzylidene-5a-carba-β--arabino-hex-2-
ulopyranosyl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (29): A solution of 28 (329 mg, 0.387 mmol) in
toluene (13 mL) was treated with DBU (87 mL, 0.58 mmol) for 2.5
h at 60°C, and then concentrated. The residue was dissolved in
ethyl acetate (60 mL) and the solution was washed with water,
dried, and concentrated. The product was purified by a silica-gel
column (16 g, ethyl acetate/toluene, 1:3) to give 29 (265 mg, 81%)
as crystals, m.p. 195Ϫ198°C (from EtOH). Ϫ [α]D26 Ϫ39 (c ϭ 0.89,
CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 7.49Ϫ7.17 (m, 20
H, 4 ϫ Ph), 5.49 (s, 1 H, CHPh), 5.49 (br. s, 1 H, NH), 4.84 and
4.65 (ABq, Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.71 and 4.53 (ABq,
28
1
[α]D ϭ Ϫ27 (c ϭ 0.59, CHCl3). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 7.60Ϫ7.19 (m, 20 H, 4 ϫ Ph), 5.79 (d, J2,NH ϭ 7.7 Hz, 1 H,
NH), 5.61 (s, 1 H, CHPh), 4.88 (d, J1,2 ϭ 7.3 Hz, 1 H, 1-H), 4.76
and 4.50 (ABq, Jgem ϭ 11.5 Hz, each 1 H, CH2Ph), 4.65 and 4.54
(ABq, Jgem ϭ 11.9 Hz, each 1 H, CH2Ph), 4.63 and 4.56 (ABq,
Jgem ϭ 10.8 Hz, each 1 H, CH2Ph), 4.19Ϫ4.12 (m, 2 H, 3-H, 1Ј-
H), 4.07 (dd, J5Ј,6Јa ϭ 4.4, J6Јgem ϭ 11.0 Hz, 1 H, 6Јa-H), 3.95 (dd,
J3Ј,4Ј ϭ J4Ј,5Ј ϭ 9.9 Hz, 1 H, H-4Ј), 3.88Ϫ3.54 [m, 8 H, 5-H, 6,6-
H, 2Ј-H, 3Ј-H, 6Јb-H, OCH2(CH2)6Me], 3.44 [ddd, J ϭ 6.6, 6.6,
and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.12 (ddd, J2,3 ϭ 7.0 Hz, 1 H,
2-H), 2.16 (m, 1 H, 5Ј-H), 1.98 (s, 3 H, Ac), 1.64Ϫ1.26 [m, 14 H,
Jgem ϭ 11.4 Hz, each 1 H, CH2Ph), 4.70 and 4.58 (ABq, Jgem
ϭ
12.1 Hz, each 1 H, CH2Ph), 4.68 (d, J1,2 ϭ 7.0 Hz, 1 H, 1-H), 4.45
(m, 1 H, 1Ј-H), 4.04 (dd, J5Ј,6Јa ϭ 4.2, J6Јgem ϭ 10.6 Hz, 1 H, 6Јa-
H), 4.04 (d, J3Ј,4Ј ϭ 10.3 Hz, 1 H, 3Ј-H), 3.89 [ddd, J ϭ 6.6, 6.6,
and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.78 (m, 2 H, 6,6-H), 3.75Ϫ3.67
(m, 2 H, 3-H, 4-H), 3.59 (dd, J4Ј,5Ј ϭ 10.3 Hz, 1 H, 4Ј-H), 3.52
(dd, J5Ј,6Јb ϭ 10.6 Hz, 1 H, 6Јb-H), 3.51Ϫ3.39 [m, 3 H, 2-H, 5-H,
OCH2(CH2)6Me], 2.02 (s, 3 H, Ac), 1.74 (m, 1 H, 5Ј-H), 1.65Ϫ1.28
5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.87 [t,
OCH2(CH2)6CH3]. Ϫ C51H65NO10 (852.1): calcd. C 71.89, H 7.69,
N 1.64; found C 71.63, H 7.67, N 1.81.
J ϭ 7.0 Hz, 3 H,
Octyl
(4-O-Acetyl-4,6-O-benzylidene-3-O-benzyl-5a-carba-α--
mannopyranosyl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (27): Compound 26 (46 mg, 54 mmol) was acetyl-
ated in the usual manner. The product was purified on a silica-gel
column (5 g, ethyl acetate/toluene, 1:4) to give 27 (44 mg, 92%) as
[m, 13 H, 5aЈ(eq)-H, OCH2(CH2)6Me], 1.11 [ddd, J1Ј,5aЈ(ax)
ϭ
J5Ј,5aЈ(eq) ϭ J5aЈgem ϭ 12.8 Hz, 1 H, 5aЈ(ax)-H], 0.88 [t, J ϭ 6.6 Hz,
3 H, OCH2(CH2)6CH3]. Ϫ C51H63NO10 (894.1): calcd. C 72.02, H
7.47, N 1.65; found C 72.26, H 7.60, N 1.85.
20
a syrup. Ϫ [α]D ϭ Ϫ29 (c ϭ 1.04, CHCl3). Ϫ 1H NMR (270
Octyl (2-O-Acetyl-3-O-benzyl-4,6-O-benzylidene-5a-carba-β--glu-
copyranosyl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (30): Compound 29 (233 mg, 0.274 mmol) was re-
duced with 2  boraneϪdimethyl sulfide (THF solution, 0.41 mL,
0.82 mmol) in THF (14 mL) for 13 h at room temperature. The
reaction mixture was processed as described in the preparation of
21 and 22. After conventional acetylation, the product was purified
by a silica-gel column (19 g, ethyl acetate/toluene, 1:5) to give 30
MHz, CDCl3): δ ϭ 7.52Ϫ7.15 (m, 20 H, 4 ϫ Ph), 5.84 (d, J2,NH ϭ
7.7 Hz, 1 H, NH), 5.62 (s, 1 H, CHPh), 5.55 (dd, J1Ј,2Ј ϭ J2Ј,3Ј
ϭ
2.6 Hz, 1 H, 2Ј-H), 4.84 (d, J1,2 ϭ 7.0 Hz, 1 H, 1-H), 4.72 and 4.51
(ABq, Jgem ϭ 11.4 Hz, each 1 H, CH2Ph), 4.63Ϫ4.53 (m, 4 H, 2 ϫ
CH2Ph), 4.17 (dd, J2,3 ϭ 7.3, J3,4 ϭ 9.2 Hz, 1 H, 3-H), 4.13 (m, 1
H, 1Ј-H), 4.08 (dd, J5Ј,6Јa ϭ 4.0, J6Јgem ϭ 11.0 Hz, 1 H, 6Јa-H),
3.89 (dd, J3Ј,4Ј ϭ J4Ј,5Ј ϭ 9.9 Hz, 1 H, 4Ј-H), 3.86 (dd, 1 H, 3Ј-H),
3.83 [ddd, J ϭ 6.6, 6.6, and 9.9 Hz, 1 H, OCH2(CH2)6Me],
3.73Ϫ3.55 (m, 5 H, 4-H, 5-H, 6,6-H, 6Јb-H), 3.42 (ddd, 1 H, 2-H),
2.17 (m, 1 H, 5Ј-H), 2.02 and 1.96 (2 s, each 3 H, 2 ϫ Ac),
1.87Ϫ1.26 [m, 14 H, 5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.87 [t, J ϭ 7.0
Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C53H67NO11 (894.1): calcd. C 71.20,
H 7.55, N 1.57; found C 71.12, H 7.93, N 1.76.
20
(149 mg, 61%) as a syrup. Ϫ [α]D ϭ Ϫ5.5 (c ϭ 0.45, CHCl3). Ϫ
1H NMR (270 MHz, CDCl3): δ ϭ 7.47Ϫ7.16 (m, 20 H, 4 ϫ Ph),
5.67 (d, J2,NH ϭ 7.3 Hz, 1 H, NH), 5.48 (s, 1 H, CHPh), 5.00 (dd,
J1Ј,2Ј ϭ J2Ј,3Ј ϭ 9.2 Hz, 1 H, 2Ј-H), 4.88 and 4.53 (ABq, Jgem
ϭ
12.1 Hz, each 1 H, CH2Ph), 4.87 (d, J1,2 ϭ 7.3 Hz, 1 H, 1-H),
4.66Ϫ4.58 (m, 4 H, 2 ϫ CH2Ph), 4.04 (dd, J2,3 ϭ J3,4 ϭ 8.4 Hz, 1
H, 3-H), 3.95 (dd, J5Ј,6Јa ϭ 4.0, J6Јgem ϭ 11.0 Hz, 1 H, 6Јa-H), 3.83
[ddd, J ϭ 6.6, 6.6, and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.75Ϫ3.40
Octyl (3-O-Benzyl-4,6-O-benzylidene-5a-carba-α--arabino-hex-2-
ulopyranosyl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (28): Compound 26 (541 mg, 0.634 mmol) was oxi-
[m,
8
H, 4-H, 5-H, 6,6-H, 1Ј-H, 2Ј-H, 3Ј-H, 4Ј-H,
dized with PCC (684 mg, 3.17 mmol) in dichloromethane (11 mL) OCH2(CH2)6Me], 3.31 (dd, J5Ј,6Јb ϭ 10.6, J6Јgem ϭ 11.0 Hz, 1 H,
638 Eur. J. Org. Chem. 1999, 631Ϫ642

Pseudosugars, 40
6Јb-H), 3.13 (ddd, 1 H, 2-H), 2.01 and 1.93 (2 s, each 3 H, 2 ϫ OCH2(CH2)6CH3]. Ϫ C35H55NO16 (745.8): calcd. C 56.36, H 7.43,
FULL PAPER
Ac), 1.91Ϫ1.26 [m, 14 H, 5Ј-H, 5aЈeq-H, OCH2(CH2)6Me], 0.88 [t,
J ϭ 6.6 Hz, 3 H, OCH2(CH2)6CH3], 0.76 [m, 1 H, 5aЈ(ax)-H]. Ϫ
C53H67NO11 (894.1): calcd. C 71.20, H 7.55, N 1.57; found C 71.05,
H 7.70, N 1.82.
N 1.88; found C 56.26, H 7.69, N 2.11.
Octyl (5a-Carba-β--galactopyranosyl)-(1Ǟ3)-2-acetamido-2-de-
oxy-β--glucopyranoside (5): Compound 33 (12 mg, 15 µmol) was
treated with methanolic sodium methoxide as described in the
preparation of 3, and the product was purified by a silica-gel col-
umn (0.7 g) with methanol/chloroform (1:3) as an eluent to give 5
Octyl (2-O-Acetyl-3-O-benzyl-4,6-di-O-methanesulfonyl-5a-carba-β-
-glucopyranosyl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--
glucopyranoside (31): Compound 30 (131 mg, 0.146 mmol) was
treated with 60% aqueous acetic acid (8 mL) for 1 h at 70°C, and
the resulting diol was mesylated as described in the preparation of
23 to give, after silica-gel chromatography (15 g, ethyl acetate/tolu-
20
(7.3 mg, 96%) as a white powder. Ϫ [α]D ϭ Ϫ42 (c ϭ 0.37,
MeOH). Ϫ 1H NMR (270 MHz, CD3OD): δ ϭ 4.35 (d, J1,2 ϭ 8.1
Hz, 1 H, 1-H), 3.94Ϫ3.17 [m, 14 H, 2-H, 3-H, 4-H, 5-H, 6,6-H, 1Ј-
H, 2Ј-H, 3Ј-H, 4Ј-H, 6Ј,6Ј-H, OCH2(CH2)6Me], 1.97 (s, 3 H, Ac),
1.86Ϫ1.30 [m, 15 H, 5Ј-H, 5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.90 [t, J ϭ
7.0 Hz, 3 H, OCH2(CH2)6CH3].
21
ene, 1:2), 31 (114 mg, 81%) as a colorless syrup. Ϫ [α]D ϭ Ϫ12
(c ϭ 1.0, CHCl3). Ϫ IR (film, cmϪ1): ν˜ ϭ 3300 (NH), 1740 (ester),
1
1660 (amide), 1180 (mesyl). Ϫ H NMR (270 MHz, CDCl3): δ ϭ
Octyl 2-Acetamido-3,6-di-O-benzyl-2-deoxy-β--galactopyranoside
(34): To a solution of 13 (256 mg, 0.498 mmol) in dry DMSO (7.7
mL) was added acetic anhydride (1.4 mL), and it was stirred over-
night at room temperature. The reaction mixture was diluted with
ethyl acetate (50 mL) and washed with water thoroughly, dried,
and concentrated. The residue (ca. 290 mg) was dissolved in THF
(5.8 mL) and the solution was treated with -Selectride (2.5 mL,
2.5 mmol) for 7 h at Ϫ15°C. The mixture was diluted with diethyl
ether (50 mL), washed with aqueous satd. ammonium chloride and
water, dried, and concentrated. The residue was chromatographed
7.39Ϫ7.22 (m, 15 H, 3 ϫ Ph), 5.68 (d, J2,NH ϭ 8.1 Hz, 1 H, NH),
5.05 (dd, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 9.7 Hz, 1 H, 2Ј-H), 4.76Ϫ4.55 (m, 7 H,
1-H, 3 ϫ CH2Ph), 4.48 (dd, J3Ј,4Ј ϭ J4Ј,5Ј ϭ 10.1 Hz, 1 H, 4Ј-H),
4.21 (dd, J5Ј,6Јa ϭ 3.7, J6Јgem ϭ 10.3 Hz, 1 H, 6Јa-H), 4.12 (dd,
J5Ј,6Јb ϭ 4.4 Hz, 1 H, 6Јb-H), 3.85Ϫ3.48 [m, 9 H, 2-H, 3-H, 4-H,
5-H, 6,6-H, 1Ј-H, 3Ј-H, OCH2(CH2)6Me], 3.41 [ddd, J ϭ 6.6, 7.0,
and 9.5 Hz, 1 H, OCH2(CH2)6Me], 2.97 and 2.80 (2 s, each 3 H, 2
ϫ Ms), 2.19 (m, 1 H, 5Ј-H), 2.03 and 1.97 (2 s, each 3 H, 2 ϫ Ac),
1.70Ϫ1.26 [m, 14 H, 5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.88 [t, J ϭ 7.0
Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C48H67NO15S2 (962.2): calcd. C
59.92, H 7.02, N 1.46; found C 59.98, H 7.19, N 1.58.
on silica gel (25 g) with ethyl acetate/toluene (1:3) to give 34 (149
mg, 58%) as crystals, m.p. 114Ϫ116°C (from EtOH). Ϫ [α]D
28
ϭ
ϩ17 (c ϭ 1.0, MeOH). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ
7.38Ϫ7.24 (m, 10 H, 2 ϫ Ph), 5.63 (d, J2,NH ϭ 7.3 Hz, 1 H, NH),
4.93 (d, J1,2 ϭ 8.4 Hz, 1 H, 1-H), 4.70Ϫ4.49 (m, 4 H, 2 ϫ CH2Ph),
4.25 (dd, J2,3 ϭ 10.6, J3,4 ϭ 3.3 Hz, 1 H, 3-H), 4.07 (dd, J4,5 ϭ 3.3
Hz, 1 H, 4-H), 3.84 [ddd, J ϭ 6.6, 6.6, and 9.9 Hz, 1 H,
OCH2(CH2)6Me], 3.81 (m, 1 H, 5-H), 3.76 (dd, J5,6a ϭ 5.9, J6gem ϭ
13.2 Hz, 1 H, 6a-H), 3.66 (m, 1 H, 6b-H), 3.47 [ddd, J ϭ 7.0, 7.0,
and 9.9 Hz, 1 H, OCH2(CH2)6Me], 3.47 (ddd, 1 H, 2-H), 1.91 (s,
3 H, Ac), 1.57Ϫ1.25 [m, 12 H, OCH2(CH2)6Me], 0.87 [t, J ϭ 7.0
Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C30H43NO6 (513.7): calcd. C 70.15,
H 8.44, N 2.73; found C 69.89, H 8.74, N 3.03.
Octyl (2,4,6-Tri-O-acetyl-3-O-benzyl-5a-carba-β--galactopyrano-
syl)-(1Ǟ3)-2-acetamido-4,6-di-O-benzyl-2-deoxy-β--glucopyrano-
side (32): A mixture of 31 (105 mg, 0.109 mmol), anhydrous sodium
acetate (178 mg, 2.17 mmol), and 80% aqueous DMF (6.3 mL)
was stirred for 2 d at 120°C. The reaction mixture was processed as
described in the preparation of 24, and the product was acetylated
conventionally. Silica-gel chromatography (8 g, acetone/hexane,
21
1:3) gave 32 (79 mg, 82%) as a colorless syrup. Ϫ [α]D ϭ ϩ18
1
(c ϭ 0.9, CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.35Ϫ7.16
(m, 15 H, 3 ϫ Ph), 5.65 (d, J2,NH ϭ 7.0 Hz, 1 H, NH), 5.53 (br. s,
1 H, 4Ј-H), 5.16 (dd, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 10.1 Hz, 1 H, 2Ј-H), 4.88 (d,
J
1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.69 and 4.34 (ABq, Jgem ϭ 12.1 Hz, each
Octyl 2-Acetamido-3,6-di-O-benzyl-2-deoxy-4-O-methanesulfonyl-β-
-galactopyranoside (35): To a solution of 34 (131 mg, 0.255 mmol)
in pyridine (2.6 mL) was added methanesulfonyl chloride (59 mL,
0.77 mmol), and it was stirred for 2.5 h at room temperature. The
mixture was diluted with ethyl acetate (30 mL), washed with water
thoroughly, dried, and concentrated. Silica-gel chromatography (15
g, ethyl acetate/toluene, 1:4) gave 35 (131 mg, 87%) as a syrup. Ϫ
[α]D ϭ ϩ31 (c ϭ 0.3, CHCl3). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 7.40Ϫ7.24 (m, 10 H, 2 ϫ Ph), 5.56 (d, J2,NH ϭ 7.0 Hz, 1 H,
NH), 5.36 (dd, J3,4 ϭ 2.8 Hz, 1 H, 4-H), 4.95 (d, J1,2 ϭ 8.4 Hz, 1
H, 1-H), 4.82 and 4.42 (ABq, Jgem ϭ 11.0 Hz, each 1 H, CH2Ph),
4.66 and 4.50 (ABq, Jgem ϭ 11.4 Hz, each 1 H, CH2Ph), 4.37 (dd,
1 H, CH2Ph), 4.62Ϫ4.51 (m, 4 H, 2 ϫ CH2Ph), 4.04 (dd, J2,3
ϭ
8.1, J3,4 ϭ 8.4 Hz, 1 H, 3-H), 3.89Ϫ3.40 [m, 9 H, 4-H, 5-H, 6,6-H,
1Ј-H, 6Ј,6Ј-H, OCH2(CH2)6Me], 3.24 (dd, J3Ј,4Ј ϭ 2.9 Hz, 1 H, 3Ј-
H), 3.13 (ddd, 1 H, 2-H), 2.09, 2.05, 2.01, and 1.88 (4 s, each 3 H,
4 ϫ Ac), 1.77Ϫ1.27 [m, 15 H, 5Ј-H, 5aЈ,5aЈ-H, OCH2(CH2)6Me],
0.88 [t, J ϭ 6.6 Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C50H67NO13 (890.1):
calcd. C 67.47, H 7.59, N 1.57; found C 67.26, H 7.87, N 1.82.
27
1
Octyl
(2,3,4,6-Tetra-O-acetyl-5a-carba-β--galactopyranosyl)-
(1Ǟ3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-β--glucopyranoside
(33): A solution of 32 (35 mg, 39 mmol) in ethanol (1 mL) was
hydrogenolyzed in the presence of 10% Pd/C catalyst as described
in the preparation of 25, and the product was acetylated conven-
tionally. Silica-gel chromatography (3 g, acetone/hexane, 1:3) gave
J2,3
ϭ 11.0 Hz, 1 H, 3-H), 3.86Ϫ3.78 [m, 2 H, 5-H,
OCH2(CH2)6Me], 3.71 (m, 2 H, 6,6-H), 3.45 [ddd, J ϭ 7.0, 7.0,
and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.31 (ddd, 1 H, 2-H), 3.04 (s,
3 H, Ms), 1.92 (s, 3 H, Ac), 1.54Ϫ1.25 [m, 12 H, OCH2(CH2)6Me],
0.87 [t, J ϭ 7.0 Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C31H45NO8S
(591.8): calcd. C 62.92, H 7.67, N 2.37; found C 62.69, H 7.87,
N 2.46.
24
33 (20 mg, 70%) as a colorless syrup. Ϫ [α]D ϭ Ϫ24 (c ϭ 0.65,
MeOH). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 5.70 (d, J2,NH ϭ 7.0
Hz, 1 H, NH), 5.41 (br. s, 1 H, 4Ј-H), 5.20 (dd, J1Ј,2Ј ϭ J2Ј,3Ј
10.1 Hz, 1 H, 2Ј-H), 5.05 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-H), 4.87 (dd,
J3,4 ϭ 8.8, J4,5 ϭ 9.5 Hz, 1 H, 4-H), 4.74 (dd, J3Ј,4Ј ϭ 2.9 Hz, 1 H,
ϭ
3Ј-H), 4.33 (dd, J2,3 ϭ 9.2 Hz, 1 H, 3-H), 4.14 (dd, J5,6a ϭ 5.1, Octyl 2-Acetamido-4-azido-3,6-di-O-benzyl-2,4-dideoxy-β--gluco-
J6gem ϭ 12.3 Hz, 1 H, 6a-H), 4.07 (dd, J5,6b ϭ 2.9 Hz, 1 H, 6b-H), pyranoside (36): A mixture of 35 (125 mg, 0.211 mmol), sodium
3.97 (dd, J5Ј,6Јa ϭ 8.6, J6Јgem ϭ 11.2 Hz, 1 H, 6Јa-H), 3.88Ϫ3.80 azide (548 mg, 8.44 mmol), and aqueous 80% DMF (2.5 mL) was
[m, 2 H, 6Јb-H, OCH2(CH2)6Me], 3.67Ϫ3.43 [m, 3 H, 5-H, 1Ј-H, stirred for 2 d at 120°C, and, after cooling, the mixture was diluted
OCH2(CH2)6Me], 2.97 (ddd, 1 H, 2-H), 2.13, 2.08, 2.07, 2.06, 2.05, with ethyl acetate (30 mL) and washed with water, dried, and con-
2.01, and 1.96 (7 s, each 3 H, 7 ϫ Ac), 1.72Ϫ1.27 [m, 15 H, 5Ј-H,
centrated. The residue was chromatographed on silica gel (10 g,
5aЈ,5aЈ-H, OCH2(CH2)6Me], 0.88 [t,
Eur. J. Org. Chem. 1999, 631Ϫ642
J
ϭ
7.0 Hz,
3
H, acetone/toluene, 1:19) to give 36 (101 mg, 96%) as crystals, m.p.
639

S. Ogawa, N. Matsunaga, H. Li, M. M. Palcic
FULL PAPER
27
117Ϫ119°C (from EtOH). Ϫ [α]D ϭ ϩ83 (c ϭ 0.44, CHCl3). Ϫ
Octyl 2-Acetamido-3-azido-4,6-O-benzylidene-2,3-dideoxy-β--glu-
1H NMR (270 MHz, CDCl3): δ ϭ 7.36Ϫ7.24 (m, 10 H, 2 ϫ Ph), copyranoside (40): A mixture of 39 (91 mg, 0.183 mmol), sodium
5.64 (d, J2,NH ϭ 7.3 Hz, 1 H, NH), 4.91 (d, J1,2 ϭ 8.4 Hz, 1 H, 1-
H), 4.86 and 4.63 (ABq, Jgem ϭ 11.4 Hz, each 1 H, CH2Ph), 4.65 stirred for 24 h at 120°C. After cooling, the reaction mixture was
and 4.55 (ABq, Jgem ϭ 12.1 Hz, each 1 H, CH2Ph), 4.21 (dd, J2,3 ϭ diluted with ethyl acetate (30 mL), washed with water, dried, and
J3,4 ϭ 9.9 Hz, 1 H, 3-H), 3.83 (ddd, J ϭ 6.6, 6.6, and 9.9 Hz, 1 H, concentrated. The residue was chromatographed on silica gel (8 g)
azide (300 mg, 4.58 mmol), and aqueous 80% DMF (2 mL) was
OCH2(CH2)6Me], 3.75 (dd, J5,6a ϭ 2.6, J6gem ϭ 11.2 Hz, 1 H, 6a-
H), 3.70 (dd, J5,6b ϭ 4.0 Hz, 1 H, 6b-H), 3.60 (dd, J3,4 ϭ 9.9,
J4,5 ϭ 9.5 Hz, 1 H, 4-H), 3.44 [ddd, J ϭ 7.0, 7.0, and 9.9 Hz, 1 H,
with acetone/toluene (1:13) to give 40 (75 mg, 92%) as white crys-
26
tals, m.p. 235Ϫ237°C (from EtOH). Ϫ [α]D ϭ Ϫ9 (c ϭ 0.13,
1
CHCl3). Ϫ H NMR (270 MHz, CDCl3): δ ϭ 7.48Ϫ7.27 (m, 5 H,
OCH2(CH2)6Me], 3.38 (ddd, 1 H, 5-H), 3.10 (ddd, 1 H, 2-H), 1.87 Ph), 5.86 (d, J2,NH ϭ 7.7 Hz, 1 H, NH), 5.56 (s, 1 H, CHPh), 5.02
(s, 3 H, Ac), 1.54Ϫ1.26 [m, 12 H, OCH2(CH2)6Me], 0.87 [t, J ϭ (d, J1,2 ϭ 8.4 Hz, 1 H, 1-H), 4.49 (dd, J2,3 ϭ 8.8, J3,4 ϭ 9.2 Hz, 1
7.0 Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C30H42N4O5 (538.7): calcd. C H, 3-H), 4.35 (dd, J5,6a ϭ 4.4, J6gem ϭ 10.3 Hz, 1 H, 6a-H), 3.84
66.89, H 7.86, N 10.40; found C 66.42, H 7.83, N 10.47.
[ddd, J ϭ 6.6, 6.6, and 9.9 Hz, 1 H, OCH2(CH2)6Me], 3.77 (dd,
J5,6b ϭ 9.5 Hz, 1 H, 6b-H), 3.58 (ddd, J4,5 ϭ 8.8, J5,6b ϭ 10.3 Hz,
1 H, 5-H), 3.51 (dd, 1 H, 4-H), 3.49 [ddd, J ϭ 6.6, 6.6, and 9.9 Hz,
1 H, OCH2(CH2)6Me], 3.08 (ddd, 1 H, 2-H), 2.03 (s, 3 H, Ac),
1.56Ϫ1.27 [m, 12 H, OCH2(CH2)6Me], 0.88 [t, J ϭ 7.0 Hz, 3 H,
OCH2(CH2)6CH3]. Ϫ C23H34N4O5 (446.6): calcd. C 61.86, H 7.68,
N 12.55; found C 61.59, H 7.68, N 12.34.
Octyl 2-Acetamido-4-amino-2,4-dideoxy-β--glucopyranoside (37):
A solution of 36 (99 mg, 0.200 mmol) in ethanol/ethyl acetate (1:1)
(4 mL) containing 1  hydrochloric acid (0.4 mL) was hydro-
genolyzed in the presence of 10% Pd/C (10 mg) for overnight at
room temperature. The solution was filtered and the filtrate was
27
concentrated to give 37 (53 mg, 80%) as a white powder. Ϫ [α]D
ϭ
Ϫ37 (c ϭ 0.13, MeOH). Ϫ 1H NMR (270 MHz, CD3OD): δ ϭ
4.55 (d, J1,2 ϭ 8.4 Hz, 1 H, 1-H), 3.87Ϫ3.09 [m, 8 H, 2-H, 3-H, 4-
H, 5-H, 6,6-H, OCH2(CH2)6Me], 2.02 (s, 3 H, Ac), 1.54Ϫ1.20 [m,
Octyl 2-Acetamido-3-amino-2,3-dideoxy-β--glucopyranoside (41):
A solution of 40 (69 mg, 0.154 mmol) in ethanol/ethyl acetate (1:1.)
(4.1 mL) was hydrogenolyzed in the presence of 10% Pd/C catalyst
(10 mg) and 1  hydrochloric acid (0.3 mL) overnight at room
temperature. The mixture was filtered and the filtrate was concen-
trated and the residue was chromatographed on a column of
Dowex 50W-X2 (Hϩ) resin (10 mL) with aqueous conc. ammonia/
methanol (1:8) to give 41 (46 mg, 90%) as a white powder. Ϫ
[α]D27 ϭ Ϫ12 (c ϭ 0.2, MeOH). Ϫ 1H NMR (270 MHz, CD3OD):
δ ϭ 4.57 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-H), 3.90Ϫ3.21 [m, 8 H, 2-H, 3-
H, 4-H, 5-H, 6,6-H, OCH2(CH2)6Me], 2.03 (m, 3 H, Ac),
12 H, OCH2(CH2)6Me], 0.90 [t,
J
ϭ
7.0 Hz,
3
H,
OCH2(CH2)6CH3]. Ϫ This compound was without further purifi-
cation used in the next reaction.
Octyl 2-Acetamido-4,6-O-benzylidene-2-deoxy-β--allopyranoside
(38): To a solution of 10 (482 mg, 1.14 mmol) in DMSO (14 mL)
was added acetic anhydride (3.2 mL), and it was stirred overnight
at room temperature. The mixture was diluted with ethyl acetate
(100 mL), washed with water, dried, and concentrated. The residue
(ca. 507 mg) was treated with -Selectride (11.4 mL, 11.4 mmol) in
THF (30 mL) for 2 h at Ϫ10°C. The reaction mixture was pro-
cessed as described for the preparation of 34 to give after chroma-
tography on silica gel (50 g, acetone/toluene, 1:5) compound 38
(365 mg, 76%) as white crystals, m.p. 220Ϫ222°C (from EtOH). Ϫ
1.56Ϫ1.18 [m, 12 H, OCH2(CH2)6Me], 0.90 [br. s,
OCH2(CH2)6CH3].
3 H,
Octyl 3,6-Di-O-acetyl-2-acetamido-4-(2-O-acetyl-6-O-benzyl-1-de-
oxy-3,4-O-isopropylidene-5a-carba-β--glucopyranos-1-yl)amino-
2,4-dideoxy-β--glucopyranoside (42): A mixture of 8 (183 mg,
0.632 mmol) and 37 (21 mg, 63 µmol) in 2-propanol (1.5 mL) was
heated in a sealed tube for 3 weeks at 120°C, and then concen-
trated. The residue was acetylated conventionally, and the products
were chromatographed on a silica-gel column (5 g) with acetone/
toluene (1:5) to give 42 (18 mg, 38%) as a white powder. Ϫ [α]D27 ϭ
ϩ18 (c ϭ 0.8, CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ
7.39Ϫ7.27 (m, 5 H, Ph), 5.55 (d, J2,NH ϭ 7.3 Hz, 1 H, NH),
4.80Ϫ4.73 (m, 2 H, 3-H, 2Ј-H), 4.58Ϫ4.48 (m, 3 H, 6a-H, CH2Ph),
4.39 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-H), 4.26 (dd, J3Ј,4Ј ϭ 4.8, J4Ј,5Ј ϭ 3.7
Hz, 1 H, 4Ј-H), 4.17 (dd, J5,6b ϭ 5.5, J6gem ϭ 11.4 Hz, 1 H, 6b-H),
3.95 (dd, J2Ј,3Ј ϭ 7.7 Hz, 1 H, 3Ј-H), 3.92 (m, 1 H, 2-H), 3.80 [ddd,
26
1
[α]D ϭ Ϫ58 (c ϭ 0.78, CHCl3). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 7.90Ϫ7.23 (m, 5 H, Ph), 5.99 (d, J2,NH ϭ 9.2 Hz, 1 H, NH),
5.59 (s, 1 H, CHPh), 4.66 (d, J1,2 ϭ 8.8 Hz, 1 H, 1-H), 4.38 (dd,
J5,6a ϭ 4.8, J6gem ϭ 10.3 Hz, 1 H, 6a-H), 4.27 (dd, J2,3 ϭ 2.8, J3,4 ϭ
2.6 Hz, 1 H, 3-H), 4.15 (ddd, 1 H, 2-H), 3.97 (ddd, J4,5 ϭ 9.2,
J5,6b ϭ 10.3 Hz, 1 H, 5-H), 3.86 [ddd, J ϭ 6.2, 6.2, and 9.5 Hz, 1
H, OCH2(CH2)6Me], 3.79 (dd, 1 H, 6b-H), 3.65 (dd, 1 H, 4-H),
3.44 [ddd, J ϭ 7.0, 7.0, and 9.5 Hz, 1 H, OCH2(CH2)6Me], 2.02 (s,
3 H, Ac), 1.55Ϫ1.27 [m, 12 H, OCH2(CH2)6Me], 0.88 [t, J ϭ 7.0
Hz, 3 H, OCH2(CH2)6CH3]. Ϫ C23H35NO6 (421.5): calcd. C 65.53,
H 8.37, N 3.32; found C 65.25, H 8.61, N 3.40.
Octyl
2-Acetamido-4,6-O-benzylidene-2-deoxy-3-O-methanesul-
J ϭ 6.2, 6.2, and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.61 (dd, J5Ј,6Јa
ϭ
fonyl-β--altropyranoside (39): Compound 38 (151 mg, 0.359 mmol)
was treated with methanesulfonyl chloride (83 mL, 1.08 mmol) in
pyridine (3 mL) as described for preparation of 35 to give 39 (117
mg, 65%) as white crystals, m.p. 181Ϫ183°C (from EtOH). Ϫ
6.6, J6Јgem ϭ 9.2 Hz, 1 H, 6Јa-H), 3.44 (dd, J5Ј,6Јb ϭ 8.8 Hz, 1 H,
6Јb-H), 3.41 [ddd, J ϭ 6.6, 6.6, and 9.5 Hz, 1 H, OCH2(CH2)6Me],
3.33 (m, 1 H, 5-H), 2.67 (dd, J3,4 ϭ 9.5, J4,5 ϭ 9.9 Hz, 1 H, 4-H),
2.28 (m, 1 H, H-1Ј), 2.09, 2.07, 2.04, and 1.93 (4 s, each 3 H, 4 ϫ
Ac), 2.00Ϫ1.97 [m, 2 H, 5Ј-H, 5aЈ(eq)-H], 1.72Ϫ1.26 [m, 12 H,
OCH2(CH2)6Me], 1.49 and 1.32 (2 s, each 3 H, CMe2), 1.05 [ddd,
26
1
[α]D ϭ Ϫ70 (c ϭ 0.4, CHCl3). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 7.44Ϫ7.23 (m, 5 H, Ph), 5.74 (d, J2,NH ϭ 8.4 Hz, 1 H, NH),
5.57 (s, 1 H, CHPh), 5.27 (dd, J2,3 ϭ J3,4 ϭ 2.6 Hz, 1 H, 3-H), 4.66
(d, J1,2 ϭ 8.8 Hz, 1 H, 1-H), 4.41 (dd, J5,6a ϭ 4.4, J6gem ϭ 9.9
Hz, 1 H, 6a-H), 4.27 (ddd, 1 H, 2-H), 3.93Ϫ3.84 [m, 2 H, 5-H,
OCH2(CH2)6Me], 3.81 (dd, J4,5 ϭ 9.5 Hz, 1 H, 4-H), 3.79 (dd,
J
1Ј,5aЈ(ax) ϭ J5Ј,5aЈ(ax) ϭ J5aЈgem ϭ 11.7 Hz, 1 H, 5aЈ(ax)-H], 0.87 [t.
3 H, J ϭ 7.0 Hz, 1 H, OCH2(CH2)6CH3]. Ϫ C39H60N2O12 (748.9):
calcd. C 62.55, H 8.08, N 3.74; found C 62.55, H 8.31, N 3.78.
J5,6b ϭ 9.9 Hz, 1 H, 6b-H), 3.46 [ddd, J ϭ 7.0, 7.0, and 9.5 Hz, 1 Octyl 3,6-Di-O-acetyl-2-acetamido-2,4-dideoxy-4-(2,3,4,6-tetra-O-
H, OCH2(CH2)6Me], 2.96 (s, 3 H, Ms), 2.03 (s, 3 H, Ac), 1.66Ϫ1.28 acetyl-1-deoxy-5a-carba-β--glucopyranos-1-yl)amino-β--gluco-
[m, 12 H, OCH2(CH2)6Me], 3.97 (ddd, J4,5 ϭ 9.2, J5,6b ϭ 10.3 Hz, pyranoside (43): A mixture of 42 (29 mg, 38 µmol) and 80% aque-
1 H, 5-H), 0.88 [t, 3 H, J ϭ 7.0 Hz, 1 H, OCH2(CH2)6CH3]. Ϫ
ous acetic acid (0.6 mL) was stirred for 2 h at 60°C, and then
C24H37NO8S (499.6): calcd. C 57.70, H 7.46, N 2.80; found C concentrated. The residue (ca. 26 mg) was dissolved in ethanol (2
57.43, H 7.68, N 2.96.
640
mL), and the solution was acidified with aqueous 1  hydrochloric
Eur. J. Org. Chem. 1999, 631Ϫ642

Pseudosugars, 40
FULL PAPER
acid and hydrogenolyzed in the presence of 10% Pd/C under atmos-
pheric pressure of hydrogen for 2 h. The solution was filtered and
concentrated. The residue was acetylated conventionally and the
product was purified by a silica-gel chromatography (2.5 g, acetone/
J2,NH ϭ 7.3 Hz, 1 H, NH), 4.89 [dd, J1Ј,2Ј ϭ J1Ј,5aЈ(eq) ϭ 1.8,
J1Ј,5aЈ(ax) 5.9 Hz, 1 H, 1Ј-H], 4.79 (dd, J3,4 ϭ J4,5 ϭ 9.2 Hz, 1 H, 4-
H), 4.53 (m, 2 H, CH2Ph), 4.31 (m, 1 H, 4Ј-H), 4.30 (dd, J5,6a
ϭ
4.4, J6gem ϭ 12.1 Hz, 1 H, 6a-H), 4.21 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-
toluene, 1:5) to give 43 (24 mg, 83%) as a colorless syrup. Ϫ H), 4.07 (dd, J5,6b ϭ 2.2 Hz, 1 H, 6b-H), 4.04Ϫ3.97 (m, 2 H, 3-H,
27
1
[α]D ϭ Ϫ21 (c ϭ 0.2, CHCl3). Ϫ H NMR (270 MHz, CDCl3):
δ ϭ 5.60 (d, J2,NH ϭ 8.4 Hz, 1 H, NH), 5.45 (br. s, 1 H, 4Ј-H), 3.66 (m, 1 H, 5-H), 3.59 (dd, J5Ј,6Јa ϭ 7.7, J6Јgem ϭ 9.0 Hz, 1 H,
4.99 (dd, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 10.3 Hz, 1 H, 2Ј-H), 4.81 (dd, J2,3 ϭ 11.0, 6Јa-H), 3.46 [ddd, J ϭ 7.0, 7.0, and 9.5 Hz, 1 H, OCH2(CH2)6Me],
3,4 ϭ 9.9 Hz, 1 H, 3-H), 4.80 (dd, J3Ј,4Ј ϭ 2.9 Hz, 1 H, 3Ј-H), 4.55 3.41 (dd, J5Ј,6Јb ϭ 6.6 Hz, 1 H, 6Јb-H), 2.87 (m, 1 H, 2Ј-H), 2.59
3Ј-H), 3.86 [ddd, J ϭ 6.6, 6.6, and 9.5 Hz, 1 H, OCH2(CH2)6Me],
J
(dd, J5,6a ϭ 1.8, J6gem ϭ 11.7 Hz, 1 H, 6a-H), 4.43 (d, J1,2 ϭ 8.1 (m, 1 H, 2-H), 2.13, 2.07, 2.03, and 1.96 (4 s, each 3 H, 4 ϫ Ac),
Hz, 1 H, 1-H), 4.15 (dd, J5,6b ϭ 5.9 Hz, 1 H, 6b-H), 4.18Ϫ3.86 (m, 1.67Ϫ1.26 [m, 15 H, 5Ј-H, 5aЈ,5aЈ-H, OCH2(CH2)6Me], 1.49 and
3 H, 2-H, 6Ј,6Ј-H), 3.80 (ddd, J 6.6, 6.6, and 9.9 Hz, 1 H) and 3.42
1.31 (2 s, each 3 H, CMe2), 0.88 [t, 3 H, J ϭ 7.0 Hz, 1 H,
(ddd, J 7.0, 7.0, and 9.9 Hz, 1 H) [OCH2(CH2)6Me], 3.34 (m, 1 H, OCH2(CH2)6CH3]. Ϫ C39H60N2O12 (748.9): calcd. C 62.55, H 8.08,
H-5), 2.69 (dd, J3,4 9.9, J4,5 9.5 Hz, 1 H, H-4), 2.52 (m, 1 H, H-
1Ј), 2.18Ϫ1.98 [m, 2 H, H-5Ј, H-5aЈ(eq)], 2.10, 2.09, 2.08, 2.06,
2.05, 1.95, and 1.94 (7 s, each 3 H, 7 ϫ Ac), 1.59Ϫ1.26 [m, 12 H,
N 3.74; found C 62.31, H 8.33, N 3.63.
Octyl 2-Acetamido-4,6-di-O-acetyl-2,3-dideoxy-3-(2,3,4,6-tetra-O-
acetyl-1-deoxy-5a-carba-β--glucopyranos-1-yl)amino-β--gluco-
pyranoside (46): Compound 44 (57 mg, 76 µmol) was treated with
80% aqueous acetic acid (1 mL) and then hydrogenolyzed as in the
preparation of 43. After conventional acetylation, the product was
purified by a silica-gel chromatography (5 g, acetone/toluene, 1:8)
OCH2(CH2)6Me], 1.17 [m,
1 H, H-5aЈ(ax)], 0.87 [t, 3 H,
OCH2(CH2)6CH3]. Ϫ C35H56N2O15 (744.9): calcd. C 56.44, H 7.58,
N 3.76; found C 56.18, H 7.86, N 3.65.
Octyl 2-Acetamido-4-(1-deoxy-5a-carba-β--glucopyranos-1-yl)am-
ino-2,4-dideoxy-β--glucopyranoside (4): Compound 43 (4.4 mg, 5.9
µmol) was treated with methanolic sodium methoxide conven-
tionally. The product was purified by a column of Dowex 50W-X2
(Hϩ) resin (1 mL) with satd. aqueous ammonia/methanol (1:8) as
an eluent to give 4 (2.9 mg, ca. 100%) as a white powder. Ϫ
[α]D19 ϭ Ϫ36 (c ϭ 0.5, MeOH). Ϫ 1H NMR (270 MHz, CD3OD):
δ ϭ 4.36 (d, J1,2 8.4 Hz, 1 H, H-1), 3.97 (br. s, 1 H, H-4Ј),
3.88Ϫ3.83 (m, 2 H, H-6,6), 3.62 (dd, J2,3 9.9 Hz, 1 H, H-2),
3.62Ϫ3.34 [m, 7 H, H-3, H-2Ј, H-3Ј, H-6Ј,6Ј, OCH2(CH2)6Me],
3.19 (m, 1 H, H-5), 2.67 (dd, J3,4 9.9, J4,5 9.5 Hz, 1 H, H-4), 2.60
(m, 1 H, H-1Ј), 1.96 (s, 3 H, Ac), 1.82 [m, 1 H, H-5aЈ(eq)],
1.64Ϫ1.30 [m, 13 H, H-5Ј, OCH2(CH2)6Me], 1.26 [m, 1 H, H-
5aЈ(ax)], 0.90 [t, 3 H, OCH2(CH2)6CH3].
24
to give 46 (35 mg, 62%) as a colorless syrup. Ϫ [α]D ϭ Ϫ16 (c ϭ
1.1, CHCl3). Ϫ 1H NMR (270 MHz, CDCl3): δ ϭ 5.58 (br. s, 1 H,
NH), 5.43 (br. s, 1 H, 4Ј-H), 5.00 (dd, J1Ј,2Ј ϭ J2Ј,3Ј ϭ 8.2 Hz, 1 H,
2Ј-H), 4.80Ϫ4.70 (m, 3 H, 1-H, 4-H, 3Ј-H), 4.26 (dd, J5,6a ϭ 5.1,
J6gem ϭ 11.9 Hz, 1 H, 6a-H), 4.10 (dd, J5,6b ϭ 1.1 Hz, 1 H, 6b-H),
3.93Ϫ3.85 (m, 2 H, 6Ј,6Ј-H), 3.82 [ddd, J ϭ 6.6, 6.6, and 9.9 Hz,
1 H, OCH2(CH2)6Me], 3.67 (m, 1 H, 5-H), 3.45 [ddd, J ϭ 6.6, 6.6,
and 9.9 Hz, 1 H, OCH2(CH2)6Me], 3.25Ϫ3.19 (m, 2 H, 2-H, 3-H),
2.79Ϫ2.65 (m, 1 H, 1Ј-H), 2.12, 2.09, 2.08, 2.07, 2.04, 2.02, and
1.96 (7 s, each 3 H, 7 ϫ Ac), 1.87Ϫ1.27 [m, 15 H, 5Ј-H, 5aЈ,5aЈ-H,
OCH2(CH2)6Me], 0.88 [t, 3 H, OCH2(CH2)6CH3]. Ϫ C35H56N2O15
(744.9): calcd. C 56.44, H 7.58, N 3.76; found C 56.24, H 7.85,
N 3.79.
Octyl 2-Acetamido-4,6-di-O-acetyl-3-(2-O-acetyl-6-O-benzyl-1-de-
oxy-3,4-O-isopropylidene-5a-carba-β--glucopyranos-1-yl)amino-
2,3-dideoxy-β--glucopyranoside (44) and 1-O-Acetyl-6-O-benzyl-
Octyl
2-Acetamido-3-(1-deoxy-5a-carba-β--glucopyranos-1-yl)-
amino-2,3-dideoxy-β--glucopyranoside (6): Compound 46 (29 mg,
39 µmol) was treated in methanol with methanolic sodium methox-
ide and the product was purified similarly in the preparation of 4
3,4-O-isopropylidene-2-(octyl
4,6-O-acetyl-2-acetamido-2,3-dide-
oxy-β--glucopyranosid-3-yl)amino-5a-carba-α--talopyranoside
(45): A mixture of 8 (129 mg, 0.443 mmol) and 41 (74 mg, 0.22
mmol) in 2-propanol (1.5 mL) was heated in a sealed tube for 3
weeks at 120°C, and then concentrated. The residue was acetylated
conventionally, and the products were chromatographed on a silica-
gel column (15 g) with acetone/toluene (1:5) to give 44 (63 mg,
38%) and 45 (39 mg, 24%) as a white powder. Ϫ 44: Rf ϭ 0.60
24
to give 6 (17 mg, 91%) as a white powder. Ϫ [α]D ϭ Ϫ45 (c ϭ
0.9, MeOH). Ϫ 1H NMR (270 MHz, CD3OD): δ ϭ 4.36 (d, J1,2 ϭ
8.1 Hz, 1 H, 1-H), 3.97 (br. s, 1 H, 4Ј-H), 3.89Ϫ3.24 [m, 11 H, 2-
H, 4-H, 5-H, 6,6-H, 2Ј-H, 3Ј-H, 6Ј,6Ј-H, OCH2(CH2)6Me], 2.66
(dd, J2,3 ϭ J3,4 ϭ 9.5 Hz, 1 H, 3-H), 2.53 [ddd, J1Ј,2Ј ϭ 8.4,
J1Ј,5aЈ(ax) ϭ 11.4, J1,5aЈ(eq) ϭ 3.3 Hz, 1 H, 1Ј-H], 1.97 (s, 3 H, NAc),
1.75 [m, H, 5aЈ(eq)-H], 1.53Ϫ1.30 [m, 13 H, 5Ј-H,
OCH2(CH2)6Me], 1.22 [m, 1 H, 5aЈ(ax)-H], 0.90 [t, J ϭ 6.6 Hz, 3
H, OCH2(CH2)6CH3].
1
27
(ethanol/toluene 1:5). Ϫ [α]D ϭ ϩ10 (c ϭ 0.7, CHCl3). Ϫ 1H
NMR (270 MHz, CDCl3): δ ϭ 7.38Ϫ7.23 (m, 5 H, Ph), 5.69 (br.
s, 1 H, NH), 4.82 (dd, J1Ј,2Ј ϭ 8.4, J2Ј,3Ј ϭ 7.3 Hz, 1 H, 2Ј-H), 4.79
(d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.73 (dd, J3,4 ϭ J4,5 ϭ 9.2 Hz, 1 H,
Evaluation of the 5aЈ-Carbadisaccharides 3, 4, 5, and 6 as Acceptor
Substrates for α-(1Ǟ3/4)-Fucosyltransferase, and Enzymatic Syn-
4-H), 4.52 (m, 2 H, CH2Ph), 4.27 (m, 1 H, 4Ј-H), 4.23 (dd, J5,6a
ϭ
5.1, J6gem ϭ 12.1 Hz, 1 H, 6a-H), 4.09 (dd, J5,6b ϭ 2.6 Hz, 1 H, thesis of 5aЈ-Carbatrisaccharides 47 and 48: Human-milk α-(1Ǟ3/
6b-H), 3.96 (dd, J3Ј,4Ј ϭ 5.5 Hz, 1 H, 3Ј-H), 3.82 [ddd, J ϭ 6.2,
6.2, and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.65 (m, 1 H, 5-H), 3.60
4)-fucosyltransferase was isolated by ion-exchange chromatography
on SP-Sephadex C-50 and affinity chromatography on a GDP-
(dd, J5Ј,6Јa ϭ 7.0, J6Јgem ϭ 8.8 Hz, 1 H, 6Јa-H), 3.45 [ddd, J ϭ 7.0, hexanolamine Sepharose column.[14] Standard assays with 0.5 m
7.0, and 9.5 Hz, 1 H, OCH2(CH2)6Me], 3.42 (dd, J5Ј,6Јb ϭ 7.3 Hz, of the test compounds were utilized to screen for potential sub-
1 H, 6Јb-H), 3.30 (m, 1 H, 2-H), 3.18 (m, 1 H, 3-H), 2.50 (m, 1 H,
1Ј-H), 2.13, 2.07, 2.03, and 1.99 (4 s, each 3 H, 4 ϫ Ac), 1.96Ϫ1.89 terizations, radiochemical assays were carried out at 37°C em-
strates and inhibitions of fucosyltransferase.[14] For kinetic charac-
[m, 2 H, H-5Ј, H-5aЈ(eq)], 1.58Ϫ1.27 [m, 12 H, OCH2(CH2)6Me],
1.50 and 1.31 (2 s, each 3 H, CMe2), 1.13 [ddd, J1Ј,5aЈ(ax)
5Ј,5aЈ(ax) ϭ J5aЈgem ϭ 11.7 Hz, 1 H, 5aЈ(ax)-H], 0.88 [t, J ϭ 7.0 Hz,
ploying six concentrations of acceptors 3 or 4, 50 µ GDP-Fuc
donor (including 100000 dpm GDP-[3H]Fuc), 20 m Hepes buffer,
pH ϭ 7.0, 20 m MnCl2, 0.2% bovine serum albumin and enzyme
ϭ
J
3 H, OCH2(CH2)6CH3]. Ϫ C39H60N2O12 (748.9): calcd. C 62.55, H in 20 mL final volume. To confirm that substrates were converted
8.08, N 3.74; found C 62.25, H 8.35, N 4.04. Ϫ 45: Rf ϭ 0.56
to products small-scale enzymatic synthesis was carried out. Fucos-
yltransferase (14 milliunits in 350 mL of 20 m Hepes buffer, pH ϭ
7.0, 20 m MnCl2, 0.2% bovine serum albumin) was added to 0.25
27
(ethanol/toluene, 1:5). Ϫ [α]D ϭ Ϫ13 (c ϭ 0.6, CHCl3). Ϫ 1H
NMR (270 MHz, CDCl3): δ ϭ 7.36Ϫ7.25 (m, 5 H, Ph), 5.54 (d,
Eur. J. Org. Chem. 1999, 631Ϫ642
641

S. Ogawa, N. Matsunaga, H. Li, M. M. Palcic
FULL PAPER
[1]
[2]
[3]
A part of this work has previously been reported: S. Ogawa, N.
Matsunaga, M. M. Palcic, Carbohydr. Lett. 1997, 2, 299Ϫ306.
S. Ogawa, K. Hirai, T. Odagiri, N. Matsunaga, T. Yamazaki,
and A. Nakajima, Eur. J. Org. Chem. 1998, 1099Ϫ1109.
J. P. Prieels, D. Monnom, M. Dolmans, T. A. Beyer, R. L. Hill,
J. Biol. Chem. 1981, 256, 10456Ϫ10463; B. A. Macher, E. H.
Holmes, S. J. Swiedler, C. L. M. Stults, C. A. Srnka, Glycobio-
logy 1991, 1, 577Ϫ584.
S. I. Hakomori, Adv. Cancer Res., 1989, 52, 257Ϫ331; H.
Schachter, in Molecular Glycobiology (Eds.: M. Fukuda, O.
Hindsgaul), IRL Press, Oxford, New York, Tokyo, 1994, pp.
88Ϫ162.
M. M. Palcic, A. P. Venot, R. M. Ratcliffe, O. Hindsgaul, Car-
bohydr. Res. 1989, 190, 1Ϫ11; Y. Ichikawa, Y.-C. Lin, D. P.
Dumas, G.-J. Shen, E. Garcia-Junceda, M. A. Williams, R.
Bayer, C. Ketcham, L. E. Walker, J. C. Paulson, C.-H. Wong, J.
Am. Chem. Soc. 1992, 114, 9283Ϫ9298; M. Du, O. Hindsgaul,
Carbohydr. Res. 1995, 286, 87Ϫ105.
mg of 3, 4, or 6. Reaction was initiated by the addition of 0.5 mg
of GDP-Fuc. After incubation at ambient temperature for three
weeks with addition of 20 µg of GDP-Fuc every 2 d, reaction prod-
ucts were isolated by loading the reaction mixtures onto Waters
C18 reverse-phase cartridges. The cartridges were washed with 40
mL of water, then the products eluted with 20 mL of 60% MeOH/
H2O. The MeOH/H2O eluate was concentrated under diminished
pressure, the residue was dissolved in water (10 mL), passed
through a Millex-GV filter (0.22 µ) and the filtrate was lyophil-
ized. Under these conditions, no reaction was observed for com-
[4]
[5]
pound 6 while 3 and 4 were converted to 47 and 48, respectively.
1
Ϫ 47: H NMR (500 MHz, D2O) (inter alia): δ ϭ 5.19 (d, J1”,2”
ϭ
4.0 Hz, 1 H, 1ЈЈ-H), 4.51 (d, J1,2 ϭ 8.2 Hz, 1 H, 1-H), 4.43 (br. q,
J ϭ 6.8 Hz, 1 H, 5ЈЈ-H), 2.02 (s, 3 H, Ac), 1.21 (d, 3 H, J ϭ
6.8 Hz, 1 H, 6ЈЈ-H). Ϫ HRMS: C29H53NO14Na (662.3364): found
[6]
[7]
[8]
S. Ogawa, T. Furuya, H. Tsunoda, O. Hindsgaul, K. Stangier,
M. M. Palcic, Carbohydr. Res. 1995, 271, 197Ϫ205.
I. Takai, Y. Ishido, S. Adachi, Jpn. Pat. Appl. JP 72491, 1991
(Chem. Abstr. 1991, 115, 72149).
1
662.3366. Ϫ 48: H NMR (500 MHz, D2O) (inter alia): δ ϭ 5.15
(d, J1ЈЈ,2ЈЈ ϭ 4.0 Hz, 1 H, 1ЈЈ-H), 4.48 (br. q, J ϭ 6.7 Hz, 1 H, 5ЈЈ-
H), 4.47 (d, J1,2 ϭ 8.4 Hz, 1 H, 1-H), 2.90 (t, J3,4 ϭ J4,5 ϭ 9.7 Hz,
1 H, 4-H), 2.02 (s, 3 H, Ac), 1.21 (d, 3 H, J ϭ 6.7 Hz, 1 H, 6ЈЈ-H).
Ϫ HRMS: C29H54N2O13Na (661.3524): found 661.3521.
´
G. Zemplen, E. Pacus, Ber. Dtsch. Chem. Ges. 1929, 62,
1613Ϫ1614.
[9]
C. Malet, O. Hindsgaul, Carbohydr. Res. 1997, 303, 51Ϫ65.
S. Ogawa, T. Tonegawa, K. Nishi, Carbohydr. Res. 1992, 229,
173Ϫ182.
[10]
[11]
[12]
Acknowledgments
S. Ogawa, K. Hirai, M. Ohno, T. Furuya, S. Sasaki, H. Tsu-
noda, Liebigs Ann. 1996, 673Ϫ677.
S. Ogawa, K. Hirai, T. Yamazaki, A. Nakajima, N. Matsunaga,
Carbohydr. Lett. 1996, 2, 183Ϫ188.
The authors thank K. Hokazono for performing elementary analy-
ses, and O. Hindsgaul (University of Alberta, Canada) for helpful
discussions for designing 5aЈ-carbadisaccharides. This work was
partly supported by a Grant-in-Aid Scientific Research (B) from
the Ministry of Education and Culture (Japan), and the Medical
Research Council of Canada.
[13]
[14]
H. Tsunoda, S. Ogawa, Liebigs Ann. Chem. 1994, 103Ϫ107.
S. Gosselin, M. M. Palcic, Bioorg. Med. Chem. 1996, 4,
2023Ϫ2028.
Received September 10, 1998
[O98410]
642
Eur. J. Org. Chem. 1999, 631Ϫ642