Synthesis of anomerically pure, furanose-free α-benzyl-2-amino-2- deoxy-D-altro- and D-manno-pyranosides and some of their derivatives

Article abstract of DOI:10.1080/00397910701410871

The anomerically pure benzyl α-d-glycoside of 2-amino-2-deoxy- mannopyranoside was synthesized from d-glucopyranose via 2-amino-2-deoxy-d- altrose intermediates. Unlike the direct synthesis from mannosamine in the literature, our method provides furanose-

Full text of DOI:10.1080/00397910701410871

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Synthesis of Anomerically
Pure, Furanose‐Free
α‐Benzyl‐2‐amino‐2‐deoxy‐d‐altro‐ and
d‐manno‐pyranosides and Some of Their
Derivatives
Tony M. K. Chiu a , Katina Sigillo a , Paul H. Gross a & Andreas H. Franz a
a Department of Chemistry, University of the Pacific, Stockton, California,
USA
Version of record first published: 11 Jul 2007.
To cite this article: Tony M. K. Chiu , Katina Sigillo , Paul H. Gross & Andreas H. Franz (2007): Synthesis of
Anomerically Pure, Furanose‐Free α‐Benzyl‐2‐amino‐2‐deoxy‐d‐altro‐ and d‐manno‐pyranosides and Some of
Their Derivatives, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 37:14, 2355-2381
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Synthetic Communicationsw, 37: 2355–2381, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701410871
Synthesis of Anomerically Pure,
Furanose-Free a-Benzyl-2-amino-2-deoxy-
D-altro- and D-manno-pyranosides and
Some of Their Derivatives
Tony M. K. Chiu, Katina Sigillo, Paul H. Gross, and
Andreas H. Franz
Department of Chemistry, University of the Pacific, Stockton,
California, USA
Abstract: The anomerically pure benzyl a-D-glycoside of 2-amino-2-deoxy-
mannopyranoside was synthesized from D-glucopyranose via 2-amino-2-deoxy-D-
altrose intermediates. Unlike the direct synthesis from mannosamine in the literature,
our method provides furanose-free products. A new method for the preparation of cis-
2,3-oxazolidinones of 2-amino-2-deoxy-sugars was developed. A selective removal of
the glycosidic benzyl group in the presence of 4,6-O-benzylidene protection was
developed, which may provide new routes for the synthesis of oligosaccharides.
Furanose-free derivatives of a-benzyl-2-amino-2-deoxy-mannopyranuronic acids syn-
thesized here offered possibilities for direct comparisons to prior literature
preparations.
Keywords: altrosamine, mannosamine, mannosaminuronic acid, oxazolidinone
1
INTRODUCTION
Aminosugars constitute abundant building blocks of naturally occurring
polysaccharides or antibiotics and are frequently found in the cell walls of
bacteria.[1–12] The most frequently found aminosugars are members of the
class of 2-amino-2-deoxy-D-hexoses. N-Acetyl-D-glucosamine, for example,
Received in the USA December 8, 2006
Address correspondence to Andreas H. Franz, Department of Chemistry, University
of the Pacific, Stockton, CA 95211, USA. E-mail: afranz@pacific.edu
2355

2356
T. M. K. Chiu et al.
is a major constituent of biologically important polysaccharides such as
hyaluronic acid,[13] heparin/heparan,[14,15] and keratan sulfate[16,17] and is the
anchor for N-linked glycans in many glycoproteins. N-Acetyl-D-galactosamine
can be found in the chondroitin sulfate family,[17,18] in dermatan sulfate,[18,19]
and as the O-glycosidically linked unit in many glycosylated proteins. It
has been shown that metabolic pathways of N-acetyl-D-glucosamine and N-
acetyl-D-mannosamine can be exploited for cell surface engineering.[20–23]
Altered cell surface oligosaccharides thus offer a way for the study of cell–
cell interactions. For such studies to be meaningful, it is important to have
well-characterized simple carbohydrate building blocks and synthetic
strategies in hand. The syntheses of 2-amino-2-deoxy-mannopyranosides can
be accomplished from 2-acetamido-2-deoxy-mannopyranoside directly;[24,25]
however, these syntheses suffer from the labor-intensive preparation of the
starting material,[26] anomeric mixtures, and furanosidic by-products.[24]
Syntheses of altropyranosides pose special problems because of the propensity
of this configuration to form 1,6-anhydro sugars.[27]
In this article, we report the synthesis of anomerically pure, furanose-free
2-amino-2-deoxy-pyranose derivatives of D-altrose and D-mannose starting
from inexpensive D-glucose. The protected mannosamines were subsequently
converted into 2,3-oxazolidinones and 2-amino-2-deoxy-mannopyranuronic
1
1
1
acids. All structures were confirmed by H, 13C, H-1H COSY, and H-13C
correlation spectroscopy (COSY) (HETCOR) nuclear magnetic resonance
(NMR) spectroscopy. Observed coupling constants were correlated with the
molecule’s average solution conformation by the Karplus equation.
2
RESULTS AND DISCUSSION
To synthesize benzyl-a-D-glycosides of 2-amino-2-deoxy-mannopyranose
(mannosamine) and 2-amino-2-deoxy-mannopyranosido-6-uronic acid (man-
nosamine uronic acid), we prepared a series of precursors from D-glucose
(1, Table 1, Scheme 1).
The benzyl glycoside of a-D-glucopyranose (2) was prepared by conden-
sation of 1 with benzyl alcohol in the presence of toluenesulfonic acid and was
convertedinsituintothe4,6-O-benzylidene derivative 3byastandardmethod.[28]
Because 3 was isolated as a hydrate, we found that the subsequent trans-
formation of 3 into 4, which was similar to the methyl glucoside analog,[29]
significantly improved yields upon recrystallization and azeotropic drying
of the starting material prior to treatment with methanesulfonyl chloride
in pyridine. We subsequently converted the dimesylate into epoxide 5 with
allo-configuration analogously to a published method for the methyl
glucoside[28] with slight modifications. We found that CH2Cl2 and
dioxane not only have equally good solvent properties compared to the
reported 1,2-dichloroethane but also show no reactivity toward strong bases
under the conditions employed.

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2357
Table 1. 1H NMR chemical shifts and coupling constants for compounds 4–6 and 8
Ring proton
H-1
4
5
6
8
5.20
3J1,2 3.9
4.62
3J2,1 3.9
3J2,3 9.6
5.03
3J1,2 2.7
3.46
3J2,1 3.0
3J2,3 4.2
4.61
3J1,2 , 1
3.35
3J2,1 , 1
3J2,3 , 1.8
4.76
3J1,2 , 1
4.47
3J2,1 , 1
3J2,3 3.3
3J2,NH 8.7
4.13
3J3,2 3.0
3J3,4 3.0
3J3,OH 7.2
3.71
3J4,3 3.0
3J4,5 9.6
4.34 (subm)
H-2
H-3
5.12
3J3,2 9.6
3J3,4 9.6
3.52
3J3,2 4.5
3J3,4 , 1
4.02
3J3,2 , 1
3J3,4 , 1
H-4
H-5
3.72
3J4,3 9.3
3J4,5 9.3
3.97
ꢀ4.10 (subm)
3.95
3J4,3 3.0
3J4,5 9.6
4.23
3J4,3
—
—
3J4,5
3.94
3J5,4 9.9
3J5,6a 9.9
3J5,6b 5.1
3.74
3J5,4 8.7
3J5,6a 3.0
3J5,6b 1.8
3.63
3J5,4 9.9
3J5,6a 9.9
3J5,6b 5.1
3.84
3J5,4
3J5,6a
3J5,6b
—
—
—
H-6a
3.80
3J6a,5 3.3
2J6a,6b 11.7
3J6a,5 10.2
2J6a,6b 10.2
3J6a,5 3.3
2J6a,6b 12.0
4J6a,4? , 1
ꢀ4.10 (subm)
3J6a,5 10.2
2J6a,6b 10.2
H-6b
NH
4.23
3J6b,5 5.1
2J6b,6a 10.5
—
4.35
3J6b,5 5.4
2J6b,6a 10.2
—
4.29
3J6b,5 4.8
2J6b,6a 12.9
5.68
3J6b,5
—
2J6b,6a
—
—
3JNH,2 8.4
Note. d in ppm, J in Hz; solvent was CDCl3 unless stated otherwise.
The locked conformation of 5 resulted in good diastereoselectivity
(6:7 . 20:1) caused by trans-diaxial opening of the epoxide by NH3.[30–32]
Separation of 6 and 7[33] was accomplished by repeated crystallizations
from EtOH followed by a final recrystallization from THF-i-Pr2O.
Compound 6 was selectively N-acetylated and 3-O-methanesulfonylated
to yield compound 9 via 8. The methyl glycoside analogs of 8 and 9 had been
reported previously in the synthesis of mannomuramic acid.[34] In the
synthesis of compound 10 from 9, we considered that NaOAc in aq. methoxy-
ethanol had been shown to cause displacement of one or two mesyl groups
with configurational inversion.[35] The reaction is generally limited to a
mesyl group with a neighboring amido group situated trans. Compound 8,
which tends to form a hydrate, was dried overnight in a vacuum pistol over
P2O5 at 608C prior to mesylation in pyridine. Compound 9 was found to be
unstable when stored or heated. It had previously been noted that the
analogous methyl-glycosides of 8 and 9 degraded upon recrystallization

2358
T. M. K. Chiu et al.
Scheme 1. Synthesis of compounds 10, 11, and 21–24.
because of the eliminated methanesulfonic acid.[36] The diaxial arrangement
of the mesyl and acetamido group favored substitution with inversion of con-
figuration during subsequent treatment of 9 with KOAc in methoxyethanol
and ethoxyethanol at elevated temperature for 2 days. Compound 10 with
manno-configuration was isolated in good overall yield. The basicity of the
medium is crucial in determining the extent and the mode of neighboring
group participation of different acylamido groups.[37] Strongly basic media
promote formation of aziridines.[37] Weak bases such as the acetate ion give
rise to carbonyl oxygen participation and intermediate formation of
oxazoline, which hydrolyzes spontaneously into the amido alcohol.

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2359
N-Deacetylation of 10 by KOH in boiling EtOH[38] yielded the free base
11 as a convenient starting material for subsequent synthetic steps (Scheme 2).
1
The H NMR spectrum of 11 is shown in Fig. 1. The interpretation of
NMR data in this article was based on the Karplus equation, which
3
expresses the angular dependence between J and the three-bond dihedral
angle f empirically.[39–41] In six-membered-ring systems, the approximate
3
coupling constant is J ¼ 3–5 Hz for e-e or e-a protons (fꢀ608, gauche)
and 9–11 Hz for a-a trans-diaxial protons (fꢀ1808). The structure of 11
was confirmed based upon 1H NMR and 1H-1H COSY data (Fig. 1,
Table 2). All observed coupling values were in agreement with the a-D-
manno-pyrano-configuration (4C1-conformation).
The broad singlet at 4.85 ppm, which showed as an unresolved doublet
pattern, was assigned to H-1. Proton 2 gave rise to a double doublet at
3
3.34 ppm with a constant of J2,1 ¼ 1.5 Hz. The other splitting of
3J2,3 ¼ 4.8 Hz was consistent with a 608 gauche angle and an equatorial-
axial relationship between H-2 and H-3. Proton 3 caused a double doublet
3
at 4.11 ppm with a small gauche coupling value of J3,2 ¼ 4.5 Hz and a
Scheme 2. Synthesis of compounds 14, 17, 18, and 25–27.

2360
T. M. K. Chiu et al.
Figure 1. a) 1HNMR spectrum of compound 11;b)1H-1HCOSY spectrumof compound 11.
3
large trans-diaxial coupling value of J3,4 ¼ 9.6 Hz. Proton 4 produced a
3
triplet at 3.72 ppm. The two coupling constants of J4,3 ¼ 9.3 Hz and
3J4,5 ¼ 9.3 Hz agreed with trans-diaxial 1808 angles toward both H-3 and
H-5. Proton 5 gave rise to a double triplet at 3.94 ppm. The two large

Table 2. 1H NMR chemical shifts and coupling constants for compounds 10–14
Ring proton
H-1
10
11
12
13
13 (acetone)
14 (pyridine)
4.96
3J1,2 1.2
4.85
3J1,2 , 1
3.34
3J2,1 1.5
3J2,3 4.8
5.00
3J1,2 , 1
ꢀ4.27 (subm)
3J2,1 , 1
3J2,3 4.8
3J2,NH 4.8
4.33
3J3,2 5.4
3J3,4 9.9
3J3,OH 2.7
3.63
3J4,3 9.6
3J4,5 9.6
3.90
3J5,4 9.9
3J5,6a 9.9
3J5,6b 4.8
3.74
4.76
3J1,2 , 1
4.90
3J1,2 1.2
4.09
3J2,1 1.2
3J2,3 4.5
3J2,NH 8.4
4.01
5.70
3J1,2 2.1
H-2
ꢀ4.52 (subm)
ꢀ4.14 (subm)
ꢀ5.05 (subm)
3J2,1 0.9
3J2,1
—
—
3J2,1
—
—
3J2,3
3J2,NH
—
3J2,3
3J2,3
—
3J2,NH
—
3J2,NH
—
H-3
4.37
3J3,2 4.8
3J3,4 9.9
3J3,OH 2.1
3.68
3J4,3 9.6
3J4,5 9.6
3.94
3J5,4 10.2
3J5,6a 10.2
3J5,6b 4.8
3.79
3J6a,5 9.9
2J6a,6b 9.9
4.24
4.11
3J3,2 4.5
3J3,4 9.6
3J3,OH
3.49
3J3,2 ,1
3J3,4 8.7
3J3,OH
—
4.89
3J3,2 6.9
3J3,4 4.8
3J3,2 4.2
3J3,4 9.0
3J3,OH 4.2
ꢀ3.70 (subm)
—
H-4
H-5
3.72
3J4,3 9.3
3J4,5 9.3
3.91
3J5,4 9.9
3J5,6a 9.9
3J5,6b 4.5
3.80
3J6a,5 9.6
2J6a,6b 9.6
4.24
3J6b,5 4.2
2J6b,6a 9.6
—
ꢀ3.73 (subm)
ꢀ5.05 (subm)
3J4,3
3J4,5
—
—
3J4,3
3J4,5
—
—
3J4,3
3J4,5
—
—
ꢀ4.05 (subm)
3J5,4
3J5,6a
3J5,6b
ꢀ3.70 (subm)
3J5,4
3J5,6a
3J5,6b
ꢀ5.05 (subm)
3J5,4
3J5,6a
—
—
—
—
—
—
—
—
3J5,6b 5.1
—
H-6a
H-6b
NH
3.61
3J6a,5 , 1
2J6a,6b 11.1
ꢀ3.84 (subm)
3J6b,5 , 1
2J6b,6a 9.6
6.34
ꢀ3.70 (subm)
3J6a,5
2J6a,6b
3J6a,5 10.2
2J6a,6b 10.2
4.21
—
—
ꢀ4.15 (subm)
—
3J6b,5 4.8
2J6b,6a 9.9
5.82
3J6b,5 4.5
2J6b,6a 9.9
5.00
3J6b,5 3.0
2J6b,6a
6.17
—
8.56
3JNH,2 7.8
3JNH,2 7.5
3JNH,2
—
3JNH,2
—
3JNH,2 7.2
Note. d in ppm, J in Hz; solvent was CDCl3 unless stated otherwise.

2362
T. M. K. Chiu et al.
constants of 3J5,4 ¼ 9.9 Hz and 3J5,6a ¼ 9.9 Hz are due to a trans-diaxial 1808
angle between H-5 and H-4 as well as H-5 and H-6a. The other constant of
3J5,6b ¼ 4.5 Hz was due to a 608 gauche angle and an axial-equatorial relation-
ship between H-5 and H-6b. A 1808 trans-diaxial angle to H-5
(3J6a,5 ¼ 9.6 Hz) and a geminal coupling with H-6b (2J6a,6b ¼ 9.6 Hz)
produced a triplet at 3.79 ppm for H-6a. Proton 6b caused a double doublet
3
at 4.24 ppm. The smaller coupling of J6b,5 ¼ 4.2 Hz was due to a gauche
angle and an equatorial-axial relationship between H-6b and H-5, whereas
3
the larger coupling of J6a,6b ¼ 9.6 Hz was due to a geminal coupling with
H-6a. The benzylidene hydrogen without neighboring protons caused a
singlet at 5.57 ppm. The two hydrogens of the benzyl group created two
doublets at 4.52 ppm and 4.73 ppm, respectively.
Compound 11 was quantitatively converted to 12 (Scheme 2), which was
de-O-benzylidenated by aq. acetic acid to give 13, which was difficult to crys-
tallize. The final compound was assumed to be a hydrate, consequently with a
broad melting-point range. However, the observed optical rotation of þ59.08
was significantly higher than the one previously reported.[25] NMR analysis
clearly supported the a-pyranose configuration of 13 synthesized by us,
which implies that the previously reported compound was possibly contami-
nated by the b-anomer or the furanoside form or both.
To accomplish oxidation to the carboxylic acid, compound 13 was
dissolved in dioxane and was treated with oxygen in the presence of
platinum catalyst for 10 h at 808C. However, the desired product 14 was
isolated in only low yield (21%) accompanied by the oxazolidinone 15.
Evidently, the cis-configuration of 2-benzyloxycarbonylamido and 3-OH-
groups in 13 favored the cyclization with concurrent elimination of benzyl
alcohol. An analogous reaction has been reported in the literature,[42,43]
albeit with formation of a six-membered tetrahydro-1,3-oxazine-2-one ring.
Apparently, the same kind of reaction can result in the formation of a five-
membered oxazolidinone ring involving a single equatorial OH-group.
Compound 15 was unreactive toward Pt-catalyzed oxidation (vide infra).
Better results were obtained after de-O-benzylidenation of 10 and oxidation of
the intermediate 16 to give benzyl-2-acetamido-2-deoxy-mannopyranosiduro-
1
nic acid 17 in 73% yield. Figure 2 shows the H NMR spectrum of 17 with
1
3
assignments based on H-1H COSY correlations. The J values of the ring
protons were all in agreement with the a-D-mannopyrano-configuration
(4C1) (Table 3).
Trimethylsilylation of the amino alcohol 11 in the presence of hexam-
ethyldisilazane followed by treatment with phosgene was used to prepare
oxazolidinone-protected derivative 20 in excellent yield (90%) with
virtually no side products. This new method for the preparation of cis-
fused gluco-oxazolidinones appears to be particularly useful because it had
previoulsy been shown that trans-fused gluco-oxazolidinone systems can
be obtained in the same way.[44] Alternatively, compound 20 was obtained
from 11 with diphenylcarbonate and NaOPh in DMF in only 72% yield. It

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2363
Figure 2. a) 1H NMR spectrum of compound 17; b) 1H-1H COSY spectrum of
compound 17.
could also be obtained from the mesylate derivative 22 (Scheme 1) in boiling
ethoxyethanol; however, it was accompanied by several unidentified side
products. Analogously, mesylate derivative 24 gave 20 with inversion of
configuration as one of the components in a complicated product mixture.

Table 3. 1H NMR chemical shifts and coupling constants for compounds 15, 17, 18, 20, and 21
Ring proton
H-1
15
15 (acetone)
17 (pyridine)
18 (pyridine)
20
21
5.01
3J1,2 , 1
4.01
4.99
3J1,2 , 1
4.09
3J2,1 0.6
3J2,3 7.5
5.74
3J1,2 2.4
5.28
6.18
3J1,2 , 1
4.95
3J1,2 , 1
4.16
3J2,1 , 1
3J2,3 7.5
4.82
3J1,2 , 1
H-2
ꢀ4.31 (subm)
ꢀ4.23 (subm)
3J2,1 , 1
3J2,3 7.5
3J2,NH , 1
4.55
3J2,1 2.4
3J2,3 7.2
3J2,NH 4.2
ꢀ4.90 (subm)
3J2,1 , 1
3J2,1
—
3J2,3 5.1
3J2,3 3.3
3J2,NH
4.16
3J2,NH , 1
ꢀ4.50 (subm)
3J2,1 , 1
3J2,3 ꢀ 7
3J2,NH ꢀ 7
ꢀ3.70 (subm)
—
H-3
H-4
H-5
H-6a
H-6b
NH
4.81
3J3,2 4.5
3J3,4 9.6
4.77
3J3,2 7.5
3J3,4 7.5
3J3,2 7.5
3J3,4 , 1
3J3,2
3J3,4
—
—
3J3,2 3.3
3J3,4 , 1
3J3,OH 6.9
3.74 (subm)
3J4,3 5.4
ꢀ3.92 (subm)
4.98
3J4,3 8.7
3J4,5 8.7
4.69
3J4,3 9.6
3J4,5 9.6
3.92
3J4,3 9.6
3J4,5 9.6
3J4,3
3J4,5
—
—
3J4,3
3J4,5
—
—
3J4,5
—
3J4,OH 3.9
ꢀ4.90 (subm)
ꢀ3.90 (subm)
3J5,4
3J5,6a
3J5,6b
ꢀ3.80 (subm)
3J5,4 , 1
3J5,6a 10.5
3J5,6b 5.1
ꢀ4.40 (subm)
3.86
ꢀ4.25 (subm)
3J5,4
3J5,6a
—
3J5,4
—
3J5,4
—
—
3J5,4 9.9
3J5,6a 9.9
3J5,6b 4.5
3.76
—
—
—
3J5,6a
3J5,6b
—
—
—
3J5,6a
—
3J5,6b 5.1
3J5,6b 5.1
3.76
3J6a,5 11.4
2J6a,6b 11.4
3.62
ꢀ3.74 (subm)
ꢀ4.32 (subm)
3J6a,5 , 1
2J6a,6b 9.9
3J6a,OH , 1
3.71
3J6a,5 4.8
3J6a,5
—
3J6a,5 9.6
2J6a,6b 9.6
2J6a,6b
—
2J6a,6b
—
3.89
3J6b,5 4.8
2J6b,6a 10.2
—
4.49
3J6b,5 , 1
2J6b,6a 11.4
4.26
3J6b,5 4.5
2J6b,6a 10.2
ꢀ4.30 (subm)
3J6b,5 5.4
2J6b,6a 10.8
3J6b,5 , 1
2J6b,6a 11.7
3J6b,OH , 1
6.8
6.67
3JNH,2
8.85
3JNH,2 7.5
—
5.68
3JNH,2
5.01
3JNH,2 8.7
3JNH,2
—
—
—
Note. d in ppm, J in Hz; solvent was CDCl3 unless stated otherwise.

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2365
The stability of oxazolidinone protection groups toward acid is greater
than toward base and allowed us to remove the benzylidene group in 20 to
give 15 with retention of the 2,3-oxazolidinone group. We also observed
that the oxazolidinone 15 was stable toward palladium-catalyzed hydrogeno-
lysis and Pt-catalyzed oxidation. We attribute this to reduced adsorption of
hydrophilic 15 on the catalyst surface. Although the benzylidene and the
benzyl group in 20 were cleaved at comparable rates under hydrogenation
conditions, compound (Scheme 2, Table 4) 25 was still isolated in satisfactory
yield, because de-O-benzylidenated by-products were water soluble and easily
removed during workup.
Peptide chemistry has seen the use of the p-nitrobenzyloxycarbonyl
moiety as protective groups.[45] Such groups with electron-withdrawing
nitro-substituents could be removed very quickly by hydrogenation. In
analogy, an electron-donating substituent such as p-methoxy can be
expected to slow down the hydrogenolytic rate of the benzylidene group.
Table 4. 1H NMR chemical shifts and coupling constants for compounds 22, 23, and
25–27
Ring proton
H-1
22
23
25 (acetone)
ꢀ4.0 (subm)
26
27
4.78
3J1,2 ,1
4.92
3J1,2 ,1
4.94
3J1,2 , 1
4.15
3J2,1 , 1
3J2,3 7.8
3J2,NH
5.56
3J1,2 , 1
4.6
3J2,1 , 1
3J2,3 8.1
3J2,NH 9.3
5.09
3J3,2 7.5
3J3,4 7.5
4.53
3J4,3 9.6
3J4,5 , 1
3.78
3J5,4 9.9
3J5,6a 9.9
3J5,6b 4.8
3.94
3J6a,5 9.9
2J6a,6b 9.9
H-2
ꢀ5.13 (subm) ꢀ4.30 (subm)
4.73
3J2,1 7.2
3J2,3 7.2
3J2,1 , 1
3J2,3 , 1
3J2,1
3J2,3
—
—
—
H-3
H-4
H-5
5.06
3J3,2 , 1
3J3,4 , 1
3.09
3J3,2 6.6
3J3,4 , 1
ꢀ 4.2 (subm)
4.76
3J3,2
3J3,4
—
—
3J3,2 7.8
3J3,4 7.8
3.9
ꢀ3.73 (subm) ꢀ4.30 (subm) ꢀ3.80 (subm)
3J4,3 1.5
3J4,5 4.5
3J4,3
3J4,5
—
—
3J4,3 9.6
3J4,5 9.6
3J4,3 9.6
3J4,5 9.6
ꢀ4.33 (subm) ꢀ3.80 (subm) ꢀ3.78 (subm) ꢀ3.85 (subm)
3J5,4
3J5,6a
3J5,6b
—
3J5,4
3J5,6a
3J5,6b
—
3J5,4 9.6
3J5,6a 9.6
3J5,6b , 1
3J5,4 9.9
3J5,6a 9.9
3J5,6b 4.5
3.74
3J6a,5 9.6
2J6a,6b 9.6
—
—
—
—
H-6a
ꢀ3.69 (subm) ꢀ3.80 (subm) ꢀ4.2 (subm)
3J6a,5 3.3 3J6a,5 3J6a,5
2J6a,6b 2J6a,6b
4J6a,4?
—
—
2J6a,6b
4J6a,4?
—
—
—
—
—
H-6b
NH
4.24
3J6b,5 5.1
ꢀ4.30 (subm) ꢀ4.0 (subm)
3J6b,5 3J6b,5
2J6b,6a 2J6b,6a
ꢀ7.4 (subm)
3JNH,2
4.24
3J6b,5 4.5
4.48
3J6b,5 4.5
—
—
2J6b,6a 10.2
ꢀ5.13 (subm)
—
—
2J6b,6a 10.2 J6b,6a 10.2
2
5.26
3JNH,2 9.0
5.78
3JNH,2
9.81
3JNH,2
—
3JNH,2
—
—
—
Note. d in ppm, J in Hz; solvent was CDCl3 unless stated otherwise.

2366
T. M. K. Chiu et al.
This approach proved fruitful with compound 26 (Scheme 2), in which the ani-
sylidene group was somewhat more stable toward hydrogenation, resulting in
27 with improved yield. The anisylidene group could be removed with dilute
acid in a subsequent step.
3
CONCLUSION
Benzyl-a-D-glycosides of 2-amino-2-deoxy-altropyranose, 2-amino-2-deoxy-
mannopyranose, and 2-amino-2-deoxy-mannopyranosido-6-uronic acid were
synthesized in good overall yields from a-D-glucose. Readily available
starting material, high diastereoselectivities, good yields, and easy workup
procedures allowed bulk production of pyranosidic furanose- and 1,6-
anhydro-free derivatives of altrosamine and (Chart 1) mannosamine.
Compounds were unequivocally identified by their NMR spectra and consti-
tute well-characterized building blocks for further synthetic investigations of
1
1
1
Chart 1. Compounds analyzed by H, 13C, H-1H COSY and H-13C COSY-NMR
spectroscopy.

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2367
amino sugars. In view of their central roles in the biosynthesis of sialic acids
and considering recent advances in cell surface engineering, a variety of
derivatives of these sugars may provide an experimental basis for modification
and more detailed understanding of cell surface properties.
4
EXPERIMENTAL
Melting points were determined in a Thomas Hoover melting-point apparatus
model No. 6404H and are uncorrected. Infrared spectra were taken with a
Perkin-Elmer 337 spectrophotometer (KBr pellets). Optical rotations were
measured with a O. C. Rudolph & Sons, Inc., model No. 956 polarimeter.
The homogeneity of the compounds synthesized was determined by silica-
gel thin-layer chromatography (TLC). The compounds were visualized by
extinction of UV fluorescence and by spraying with 10–15% H2SO4–
MeOH followed by heating for about 15 min at 1208C.
Deuterated solvents (CDCl3, D2O, pyridine-d5, acetone-d6, Me2SO-d6)
were purchased from Aldrich (Milwaukee, WI) and dried over molecular
˚
sieves (5 A). Traces of acid were removed by storing CDCl3 over K2CO3.
Standard 5 mm (OD) NMR tubes (Kimble & Kontes) were used.
Approximately 10 mg of substance were added to the tube followed by
0.8 mL of deuterated solvent. NMR spectra were recorded at room tempera-
ture (rt) on a Varian Mercury 300-MHz instrument. The number of 1H
NMR transients was 128 and that of 13C NMR was 2048. Two-dimensional
1H-1H COSY spectra were recorded with eight transients. All spectra were
recorded spinning (y ¼ 20 Hz). Chemical shift values are given in parts per
million (ppm) relative to tetramethylsilane (Me4Si) or one of the standard
solvent peaks. Coupling constants J are given in Hertz.
All mass spectra were recorded on a Varian 1200 LC triple-quad mass
spectrometer in electrospray ionization (ESI) mode (positive). Solutions of
cꢀ1025 M were used in MeOH/H2O (1:1). The analyte solution was sprayed
by continuous infusion from the tip of a capillary with pneumatic assist (N2
sheath gas) at a flow rate of 10 mL/min. Desolvation of the spray was accom-
plished at elevated temperature (q ¼ 508C API chamber, q ¼ 120–1508C
capillary). The instrument was operated at ꢀ5 ꢀ 1026 Torr with a mass
window of m/z 0–1500. The detector was set to 1.2–1.5 kV. A full mass
spectrum was acquired from which a single ion of interest was subsequently
isolated in quadrupole 1 with a mass tolerance of +3 u. Collision-induced dis-
sociation (CID) of the isolated ion was carried out at an argon background
pressure of 1.0–1.4 mTorr with an excitation amplitude of 20–30 V (p-p).
Benzyl-4,6-O-benzylidene-a-D-glucopyranoside (3)
Anhydrous D-glucopyranose (270 g, 1.5 mol) was added to a solution of p-
.
TsOH H2O (32 g) in BnOH (2.2 L) in a two-necked, round-bottomed

2368
T. M. K. Chiu et al.
flask fitted with a reflux condenser and a capillary tube, which was fed
with dry N2. The condenser was connected to a vacuum pump by way
of a trap cooled to 2788C. The mixture was magnetically stirred at
958C/3 mm Hg for 3–4 h, after which time a total of 57 mL of water
had been collected in the trap. The reaction mixture was neutralized
with NaOMe, and the benzyl alcohol was distilled off in vacuo. The
residual syrup was digested three times with i-Pr2O (1 L total), which
was decanted. The residue was shaken with a solution of freshly
prepared anhydrous ZnCl2 (150 g) and benzaldehyde (1.5 L) at rt for
30 h, and i-Pr2O was added (1 L). The mixture was poured slowly with
rapid stirring into ice water (3 L) and petroleum ether (2 L). The precipi-
tate was filtered off and was washed three times, alternating cold water
and petroleum ether. Compound 3 was recrystallized from EtOH and
was azeotropically dried (EtOH/PhCH3) to give 138 g (25% from
D-glucose), mp 160–1628C, lit.[46] 161–1628C; [a]2D0 þ1088 (c, 1.0 in
CHCl3), lit.[46] [a]2D0 þ1078.
Benzyl-4,6-O-benzylidene-2,3-di-O-methanesulfonyl-a-D-
glucopyranoside (4)
A solution of compound 3 (11.0 g, 21.4 mmol) in absolute pyridine (30 mL)
was cooled to 258C, and methanesulfonyl chloride (6 mL) was added
dropwise with magnetic stirring. The reaction mixture was stirred for 2 h
and then kept at 258C for 18 h and at rt for 5 h. The mixture was
poured on ice with stirring. The solid was filtered off, air dried, and recrys-
tallized from i-Pr-OH. Yield: 12.5 g (82.3%); mp 136–1388C; [a]2D5 þ82.58
(c 1.00, pyridine); IR (n in cm21): 1340 (sulfonate SO2), 770, 705 (C6H5);
1H NMR (CDCl3, d in ppm): d 2.96 (s, 3H, SO2CH3), d 3.11 (s, 3H,
3
3
3
SO2CH3), d 3.72 (t, 1H, J4,3 9.3, J4,5 9.3, H-4), d 3.74 (t, 1H, J6a,5
2
10.2, J6a,6b 10.2, H-6a), d 3.97 (dt, 1H, J5,4 9.9, J5,6a 9.9, J5,6b 5.1,
3
3
3
3
2
3
H-5), d 4.23 (dd, 1H, J6b,5 5.1, J6b,6a 10.5, H-6b), d 4.62 (dd, 1H, J2,1
3
3.9, J2,3 9.6, H-2), d 4.66 (d, 1H, JCH2Ph,CH2Ph 11.7, CH2Ph), d 4.76
2
2
(d, 1H, JCH2Ph,CH2Ph 11.7, CH2Ph), d 5.12 (t, 1H, J3,2 9.6, J3,4 9.6,
3
3
3
H-3), d 5.20 (d, 1H, J1,2 3.9, H-1), d 5.52 (s, 1H, CHPh), d 7.30–7.45
(m, 10H, Harom); 13C NMR (CDCl3, d in ppm): d 36.17, 38.82, 38.94,
62.44, 68.54, 70.84, 75.75, 77.12, 79.04, 97.06, 101.89, 125.82, 127.97,
128.11, 128.25, 128.39, 129.32, 135.88, 136.03. Anal. calcd. for
C22H26O10S2 (514.56): C, 51.35%; H, 5.10%; O, 31.10%; S, 12.47%.
Found: C, 51.13%; H, 5.38%; O, 31.15%; S, 12.30%.
Benzyl-2,3-anhydro-4,6-O-benzylidene-a-D-allopyranoside (5)
The compound was prepared in analogy to a previously published procedure for
methyl-glucoside.[28] Compound 5: mp 1898C; [a]2D5 þ1058 (c 1.00, pyridine);

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2369
1
IR (n in cm21): 3475 (NH), 1675 (amide C55O), 770, 765 (C6H5); H NMR
3
3
(CDCl3, d in ppm): d 3.46 (dd, 1H, J2,1 3.0, J2,3 4.2, H-2), d 3.52 (dd ꢀ d,
3
3
4
3
1H, J3,4 , 1, J3,2 4.5, H-3), d 3.63 (ddd ꢀ dt, 1H, J6a,4 n. res., J6a,5 3.3,
2J6a,6b 12.0, H-6a), d 3.94 (ddd, 1H, J5,4 8.7, J5,6a 3.0, J5,6b 1.8, H-5), d
4.05–4.18 (m, 2H, H-4, H-6b), d 4.65 (d, 1H, 2JCH2Ph,CH2Ph 12.3, CH2Ph), d
4.78 (d, 1H, 2JCH2Ph,CH2Ph 12.6, CH2Ph), d 5.03 (d, 1H, 3J1,2 2.7, H-1), d 5.54
(s, 1H, CHPh), d 7.27–7.50 (m, 10H, Harom); 13C NMR (CDCl3, d in ppm): d
50.97, 53.68, 60.45, 69.12 70.03, 78.21, 93.28, 103.00, 126.49, 128.03,
128.19, 128.50, 128.64, 129.41. Anal. calcd. for C20H20O5 (340.40): C,
70.58%; H, 5.92%; O, 23.51%. Found: C, 70.82%; H, 5.89%; O, 23.66%.
3
3
3
Benzyl-2-amino-4,6-O-benzylidene-2-deoxy-a-
D-altropyranoside (6)
Compound 5 (23.0 g, 67.6 mmol), satwated NH3 in MeOH (920 mL), and con-
centrated NH4OH (230 mL) were heated at 1108C in a 2-L stainless steel
autoclave for 2 d. The solvent was removed in vacuo, and the crystalline
residue was dissolved in THF and re-precipitated with i-Pr2O. The product was
recrystallized from absolute EtOH. Yield: 24.3 g (87%); mp 159–1608C; [a]D25
þ73.78 (c 0.68, pyridine); IR (n in cm21): 3500, 3400 (NH2), 750, 700 (C6H5);
3
1H NMR (CDCl3, d in ppm): d 3.35 (d, 1H, J2,3 1.8, H-2), d 3.45 (s, 2H,
CH2Ph), d 3.84 (t, 1H, 2J6a,6b 10.2, 3J6a,5 10.2, H-6a), d 3.95 (dd, 1H, 3J4,3 3.0,
3
3
3
3J4,5 9.6, H-4), d 4.02 (s, 1H, H-3), d 4.23 (td, 1H, J5,4 9.9, J5,6a 9.9, J5,6b
5.1, H-5), d 4.35 (dd, 1H, 3J6b,5 5.4, 2J6b,6a 10.2, H-6b), d 4.61 (s, 1H, H-1), d
5.64 (s, 1H, CHPh), d 7.32–7.51 (m, 10H, Harom); 13C NMR (CDCl3, d in
ppm): d 54.73, 56.00, 58.90, 69.59, 71.15, 76.71, 102.62, 103.65, 126.45,
128.45, 129.30, 137.45; ESI-MS m/z 358.1 [M þ H]þ. Anal. calcd. for
C20H23NO5 (357.40): C, 67.20%; H, 6.49%; N, 3.92%; O, 22.39%. Found: C,
67.48%; H, 6.76%; N, 3.47%; O, 22.62%.
A
small amount of benzyl-3-amino-4,6-O-benzylidene-3-deoxy-a-
D-glucopyranose (7) was isolated from the mother liquors[33] of the
crystallizations.
Benzyl-2-acetamido-4,6-O-benzylidene-2-deoxy-a-
D-altropyranoside (8)
To a solution of 6 (15 g, 37.5 mmol) in dioxane (40 mL) and MeOH (300 mL),
Ac2O (5.4 mL) was added. The reaction mixture was stirred at rt for 1 h.
Pyridine (5.4 mL) and another portion of Ac2O (5.4 mL) were added, and
stirring continued for 1 h at rt followed by a third portion of pyridine
(10.8 mL) and Ac2O (5.4 mL). The resulting mixture was evaporated in
vacuo, and Et2O (200 mL) was added. The product was filtered and washed
with Et2O. Recrystallization from dioxane-chloroform gave 8. Yield: 15.0 g
(89%); mp 205–2078C; [a]2D5 þ51.28 (c 1.84, pyridine); IR (n in cm21):

2370
T. M. K. Chiu et al.
1
3475 (NH), 1675 (amide C55O), 765, 700 (C6H5); H NMR (CDCl3, d in
3
ppm): d 2.03 (s, 1H, CH3Ac), d 3.07 (d, 1H, JOH,3 7.5, OH), d 3.71 (dd, 1H,
3
2
3J4,3 3.0, J4,5 9.6, H-4), d 3.80 (ddd, 1H, J6a,6b 11.7, J6a,5 3.3, H-6a), d
3
3
3
4.13 (dt, 1H, J3,2 3.0, J3,OH 7.2, J3,4 3.0, H-3), d 4.29 (dd, 1H, J6b,5 4.8,
3
2J6b,6a 12.9, H-6b), d 4.34 (subm., 1H, H-5), d 4.47 (ddd, 1H, J2,NH 8.7,
3
3
2
3J2,3 3.3, J2,1 , 1, H-2), d 4.59 (d, 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d 4.76
2
(s, 1H, H-1), d 4.77 (d, 1H, JCH2Ph,CH2Ph 12.3, CH2Ph), d 5.63 (s, 1H,
CHPh), d 5.68 (d, 2H, JNH,2 8.4, NH), d 7.33–7.50 (m, 10H, Harom); 13C
3
NMR (CDCl3, d in ppm): d 23.27, 52.01, 58.61, 67.55, 68.93, 69.95, 76.97,
77.09, 98.66, 102.22, 125.99, 127.95, 128.06, 128.09, 128.44, 128.97,
135.82, 136.75, 168.71. Anal. calcd. for C22H25NO6 (399.4): C, 66.14%; H,
6.31%; N, 3.51. Found: C, 66.75%; H, 6.47%; N, 3.46%.
Benzyl-2-acetamido-4,6-O-benzylidene-2-deoxy-3-
O-methanesulfonyl-a-D-altropyranoside (9)
To a solution of 8 (5.5 g, 15.3 mmol) in absolute pyridine (20 mL), methane-
sulfonyl chloride (2 mL) was added dropwise with stirring at 08C. After 24 h
at 08C, the reaction mixture was poured on ice with stirring. The precipitate
was filtered off and recrystallized once from CH2Cl2-Et2O and once from
i-PrOH. It is important to preheat the solvents and cool them immediately
for satisfactory crystallization. Yield: 5.8 g (92%); mp 96–1008C; [a]D25
þ31.08 (c 1.00, pyridine). Anal. calcd. for C23H27NSO8 (447.52): C,
57.85%; H, 5.70%; N, 2.93%; S, 6.71%. Found: C, 57.09%; H, 5.87%; N,
2.41%; S, 6.04%. The compound was found to be unstable over time and
was used immediately in the synthesis of 10.
Benzyl-2-acetamido-4,6-O-benzylidene-2-deoxy-a-
D-mannopyranoside (10)
A mixture of compound 9 (5.5 g, 11 mmol), potassium acetate (8 g), water
(20 mL), distilled methoxyethanol (80 mL), and ethoxyethanol (100 mL)
was refluxed for 30 h, decolorized twice with charcoal, and then evaporated.
The residue was shaken with water, filtered off, and recrystallized from
i-PrOH. Yield: 3.70 g (79%); mp 220–2228C; [a]2D5 þ29.08 (c 1.62,
pyridine); IR (n in cm21): 3350 (NH), 1625 (amide C55O), 750, 700
1
(C6H5); H NMR (CDCl3, d in ppm): d 2.08 (s, 3H, CH3), d 2.95 (d, 1H,
3
3
3
3JOH,3 2.1, OH), d 3.68 (t, 1H, J4,3 9.6, J4,5 9.6, H-4), d 3.79 (t, 1H, J6a,5
2
9.9, J6a,6b 9.9, H-6a), d 3.94 (td, 1H, J5,4 10.2, J5,6a 10.2, J5,6b 4.8, H-5),
3
3
3
3
d 4.24 (dd, 1H, J6b,5 4.8, J6b,6a 9.9, H-6b), d 4.37 (ddd, 1H, J3,2 4.8,
2
3
3J3,OH 2.1, J3,4 9.9, H-3), d 4.52 (ddd, subm., 1H, J2,1 0.9, H-2), d 4.54
3
3
2
(d, 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d 4.71 (d, 1H, JCH2Ph,CH2Ph 11.7,
2
3
CH2Ph), d 4.96 (d, 1H, J1,2 1.2, H-1), d 5.58 (s, 1H, CHPh), d 5.82 (d, 1H,
3JNH,2 7.5), d 7.31–7.50 (m, 10H, Harom); 13C NMR (CDCl3, d in ppm): d

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2371
23.73, 36.57, 53.98, 63.39, 67.54, 69.04, 70.06, 79.96, 99.14, 102.58, 126.43,
128.14, 128.30, 128.50, 128.74, 129.44, 136.78, 137.15, 171.70. Anal. calcd.
.
for C22H25NO6 0.5 H2O (418.4): C, 64.70%; H, 6.42%; N, 3.43%. Found: C,
65.08%; H, 6.42%; N, 3.57%.
Benzyl-2-amino-4,6-O-benzylidene-2-deoxy-a-
D-mannopyranoside (11)
A mixture of compound 10 (2.8 g, 6.7 mmol), KOH (12 g), and 95% EtOH
(40 mL) was refluxed under N2 for 10 h and then poured into hot water
(150 mL). The resulting lumps of crude product were broken up. The suspension
was stirred at 258C overnight. The product was filtered and was recrystallized
from EtOH–water with charcoal decolorization followed by recrystallization
from THF-i-Pr2O. Yield: 2.3 g (95%); mp 129–1318C; [a]2D5 þ57.58 (c 2.2,
DMF); IR (n in cm21): 3450, 3400 (NH), 750, 700 (C6H5); 1H NMR (CDCl3,
3
3
d in ppm): d 1.64 (s, broad, NH2/OH), d 3.34 (dd, 1H, J2,1 1.5, J2,3 4.8,
3
3
3
2
H-2), d 3.72 (t, 1H, J4,3 9.3, J4,5 9.3, H-4), d 3.80 (t, 1H, J6a,5 9.6, J6a,6b
9.6, H-6a), d 3.91 (td, 1H, 3J5,4 9.9, 3J5,6a 9.9, 3J5,6b 4.5, H-5), d 4.11 (dd, 1H,
3J3,2 4.5, J3,4 9.6, H-3), d 4.24 (dd, 1H, J6b,5 4.2, J6b,6a 9.6, H-6b), d 4.52
3
3
2
2
2
(d, 1H, JCH2Ph,CH2Ph 11.7, CH2Ph), d 4.73 (d, 1H, JCH2Ph,CH2Ph 12.0,
CH2Ph), d 4.85 (s, 1H, H-1), d 5.57 (s, 1H, CHPh), d 7.30–7.51 (m, 10H,
Harom); 13C-NMR (CDCl3, d in ppm): d 36.56, 54.89, 63.63, 67.88, 69.18,
69.59, 79.95, 100.34, 101.69, 102.51, 126.47, 128.15, 128.18, 128.45, 128.70,
129.32, 137.14, 137.43. ESI-MS m/z 358.2 [M þ H]þ, m/z 380.3 [M þ Na]þ,
m/z 396.2 [M þ K]þ. Anal. calcd. for C20H23NO5 (357.4): C, 67.20%; H,
6.49%; N, 3.92%. Found: C, 67.95%; H, 6.44%; N, 3.82%.
Benzyl-4,6-O-benzylidene-2-benzyloxycarbonylamido-2-deoxy-a-D-
mannopyranoside (12)
Alcohol-free CHCl3 (40 mL), KHCO3 (4 g), and water (40 mL) were shaken
for 1 h at rt. Compound 11 (0.8 g, 2.2 mmol) and benzylchloroformate (0.4 g)
were added, and the mixture was shaken for 10 h at rt. The CHCl3 layer was
separated and was evaporated in vacuo at rt. Hexane (50 mL) and i-Pr2O
(10 mL) were added to the residue, and the precipitate was filtered. Recrystal-
lization from i-Pr2O afforded 12. Yield: 1.05 g (95%); mp 117–1188C; [a]D25
þ8.58 (c 1.04, pyridine); IR (n in cm21): 3355 (NH), 1710 (C55O), 745, 695
(C6H5); 1H NMR (CDCl3, d in ppm): d 2.54 (s, 1H, OH), d 3.63 (t, 1H, 3J4,3
9.6, 3J4,5 9.6, H-4), d 3.74 (t, 1H, 3J6a,5 10.2, 2J6a,6b 10.2, H-6a), d 3.90 (dt, 1H,
3
3
3
2
3J5,4 9.9, J5,6a 9.9, J5,6b 4.8, H-5), d 4.21 (dd, 1H, J6b,5 4.5, J6b,6a 9.9,
3
3
H-6b), d 4.27 (t, subm., 1H, J2,NH 4.8, J2,3 4.8, H-2), d 4.33 (ddd, subm.,
3
1H, J3,2 5.4, J3,OH 2.7, J3,4 9.9, H-3), d 4.52 (d, 1H, JCH2Ph,CH2Ph 11.7,
3
3
2
2
CH2Ph), d 4.68 (d, 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d 5.00 (s, 1H, NH), d
5.10 (s, 1H, H-1), d 5.06–5.15 [m, mixing, 2H, C(O)OCH2Ph], d 6.53

2372
T. M. K. Chiu et al.
(s, 1H, CHPh), d 7.30–7.47 (m, 15H, Harom); 13C NMR (CDCl3, d in ppm): d
36.18, 54.77, 63.02, 67.05, 67.26, 68.67, 69.69, 77.08, 79.44, 99.06, 102.20,
126.03, 127.72, 127.88, 128.11, 128.34, 128.38, 129.05, 136.44, 136.75.
Anal. calcd. for C28H29NO7 (491.51): C, 68.42%; H, 5.94%; N, 2.85%.
Found: C, 68.07%; H, 6.12%; N, 2.35%.
Benzyl-2-benzyloxycarbonylamido-2-deoxy-a-
D-mannopyranoside (13)
A solution of compound 12 (1.0 g, 2.0 mmol) in glacial acetic acid (9 mL) was
heated to 808C, and water (9 mL) was added dropwise over 0.5 h. The mixture
was stirred and heated for 3 h. The solvents were evaporated in vacuo followed
by repeated co-evaporation with water and finally with toluene for azeotropic
drying. The remaining syrup was dissolved in a small volume of CHCl3
followed by a small volume of i-Pr2O saturated with water. The solvents were
evaporated under a stream of nitrogen. The residue was washed with methyl
cyclohexane and petroleum ether, and the crystalline precipitate was filtered
and dried in a desiccator (CaCl2) overnight. Yield: 0.7 g (85%); mp
(decomp.) 51–608C; [a]2D5 þ59.08 (c 1.0, dioxane); previously reported as
mixture with þ38.7 (c 0.64, dioxane)[25]; 1H NMR (CDCl3, d in ppm): d 3.49
(d, 1H, 3J3,4 8.7, H-3), d 3.61 (d, 1H, 2J6a,6b 11.1, H-6a), d 3.73 (s, broad, 1H,
2
H-4), d 3.84 (d, broad, 1H, J6b,6a 9.6, H-6b), d 4.05 (s, broad, 1H, H-5), d
2
4.14 (s, broad, 1H, H-2), d 4.35 (d, 1H, JCH2Ph,CH2Ph 11.4, CH2Ph), d 4.54
2
(d, 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d 4.76 (s, 1H, H-1), d 4.92 (d, 1H,
2
2JCH2Bz,CH2Bz 12.0, CH2Bz), d 5.03 (d, 1H, JCH2Bz,CH2Bz 11.7, CH2Bz), d
6.34 (s, 1H, NH), d 7.14–7.31 (m, 10H, Harom); 13C NMR (CDCl3, d in
ppm): d 54.52, 61.16, 67.07, 69.28, 69.85, 71.95, 77.08, 98.84, 127.66,
1
127.71, 127.93, 128.04, 128.24, 128.27, 135, 86, 136.64, 157.03; H NMR
(acetone-d6, d in ppm): d 3.60–3.85 (m, 4H, H-4, H-5, H-6a, OH), d 4.01 (dt,
1H, 3J3,2 4.2, 3J3,OH 4.2, 3J3,4 9.0, H-3), d 4.09 (ddd, 1H, 3J2,1 1.2, 3J2,NH 8.4,
3
3J2,3 4.5, H-2), d 4.15 (dd, 1H, subm., J6b,5 3.0, H-6b), d 4.52 (d, 1H,
2
2JCH2Ph,CH2Ph 11.4, CH2Ph), d 4.75 (d, 1H, JCH2Ph,CH2Ph 11.7, CH2Ph), d
3
4.90 (d, 1H, J1.2 1.2, H-1), d 5.05 [m, mixing, 2H, C(O)OCH2Ph], d 6.17
3
(d, 1H, JNH,2 7.2, NH), d 7.26–7.42 (m, 10H, Harom); 13C NMR (acetone, d
in ppm): d 16.46, 31.38, 62.12, 66.18, 68.10, 68.80, 69.98, 73.66, 99.06,
127.72, 127.94, 128.01, 128.45, 128.48. Anal. calcd. for C21H25NO7 (411.42):
C, 59.85%; H, 6.46%; N, 3.33%. Found: C, 60.12%; H, 6.22%; N, 3.37%.
Benzyl-2-benzyloxycarbonylamido-2-deoxy-a-D-
mannopyranuronic Acid (14)
To a solution of compound 13 (1.0 g, 2.43 mmol) in dioxane (10 mL) and water
(100 mL), freshly reduced Pt (0.5 g from Adam’s catalyst PtO2) was added. The
mixture was stirred vigorously at 708C, and oxygen was introduced at a rate of

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2373
approximately 12 bubbles per second. The pH of the solution was kept between
7.0 and 7.5 with satwated KHCO3. After 8 h, the suspension was filtered; the
filtrate was concentrated, cooled, and acidified to pH 3 (3 M HCl). The
yellow precipitate was filtered and recrystallized from aq. EtOH. Yield:
0.22 g (21%); mp 171–1728C; [a]D25 þ35.08 (c 1.0, dioxane) reported as
mixture with þ45.65 (c 0.34, dioxane)[25]; 1H NMR (pyridine-d5, d in ppm):
d 4.71 (d, 1H, 2JCH2Ph,CH2Ph 11.7, CH2Bz), d 4.89 (dd, 1H, 3J3,2 6.9, 3J3,4 4.8,
H-3), d 5.00–5.07 (m, 3H, H-2, H-4, H-5), d 5.08 (d, 1H, 2JCH2Ph,CH2Ph 12.3,
2
CH2Bz), d 5.24 (d, 1H, JCH2Ph,CH2Ph 12.6, CH2Ph), d 5.30 (d, 1H,
3
2JCH2Ph,CH2Ph 12.0, CH2Ph), d 5.70 (d, 1H, J1,2 2.1, H-1), d 7.23–7.50
(m, 10H, Harom), d 8.56 (d, 1H, 3JNH,2 7.8, NH); 13C NMR (pyridine-d5, d in
ppm): d 55.92, 66.78, 69.94, 70.81, 70.86, 74.84, 100.29, 128.06, 128.22,
128.33, 128.40, 128.86, 130.32, 132.95, 138.35, 158.01, 173.75.
Benzyl-a-D-mannopyranosido-[2,3:40,50]-20-oxazolidinone (15)
Compound 20 (0.9 g, 3.2 mmol) was dissolved in glacial acetic acid (20 mL).
The solution was heated to 908C, water (10 mL) was added dropwise over
10 min, and stirring was continued for 1 h. The solution was cooled to rt,
and the solvents were evaporated in vacuo. Repeated co-evaporation with
water was followed by ethanol and finally toluene was performed. The
residue was recrystallized from 1,2-dichloroethane. Yield: 0.6 g (85%); mp
125–1268C; [a]2D5 þ33.68 (c 1.0, pyridine); IR (n in cm21): 3350 (NH),
1775 (C55O), 740, 690 (C6H5); 1H NMR (acetone, d in ppm): d 3.70
3
(s, subm., 1H, H-4), d 3.74 (dd, subm., 1H, J6a,5 4.8, H-6a), d 3.80 (dd,
3
subm., 1H, J5,6a 10.5, J5,6b 5.1, H-5), d 3.89 (d, 1H, J6b,5 4.8, J6b,6a 10.2,
3
3
2
3
H-6b), d 4.09 (dd, 1H, J2,3 7.5, J2,1 0.6, J2,NH , 1, H-2), d 4.50
3
3
3
2
(t, subm., 1H, J3,2 ꢀ7, H-3), d 4.53 (d, subm., 1H, JCH2Ph,CH2Ph 11.7,
2
d 4.77 (d, subm., 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d
CH2Ph),
4.78 (subm., 1H, OH), d 4.99 (s, 1H, H-1), d 6.67 (s, broad, 1H, NH),
d 7.25–7.40 (m, 5H, Harom.); 13C NMR (acetone, d in ppm): d 31.40, 56.30,
61.76, 61.88, 68.61, 68.68, 70.42, 79.29, 95.84, 127.86, 128.33, 128.47,
1
137.70; H NMR (CDCl3, d in ppm): d 2.24 (s, broad, 2H, OH), d 3.62
3
3
3
(dtꢀd, 1H, J6a,5 , 1, J6a,6b 9.9, J6a,OH , 1, H-6a), d 3.71 (ddꢀd, 1H,
3
3
3J6b,5 , 1, J6b,6a 11.7, J6b,OH , 1, H-6b), d 3.85–3.95 (m, 2H, H-4, H-5),
3
d 4.01 (d, 1H, J2,1 , 1, J2,3 7.5, H-2), d 4.44 (d, 1H, JCH2Ph,CH2Ph 11.7,
3
2
3
CH2Ph), d 4.55 (d, 1H, J3,2 7.5, J3,4 , 1, H-3), d 4.61 (d, 1H,
3
2JCH2Ph,CH2Ph 12.0, CH2Ph), d 5.01 (s, 1H, J1,2 , 1, H-1), d 6.80 (s, broad,
3
1H, NH), d 7.20–7.35 (m, 5H, Harom.); 13C NMR (CDCl3, d in ppm): d
36.18, 56.23, 60.85, 66.75, 69.22, 69.36, 77.09, 79.52, 95.36, 127.93,
128.36, 136.41, 159.55. Anal. calcd. for C14H17NO6 (295.28): C, 56.94%;
H, 5.80%; N, 4.75%. Found: C, 57.12%; H, 5.89%; N, 4.88%.
An attempt to oxidize the product to the uronic acid derivative was
unsuccessful.

2374
T. M. K. Chiu et al.
Benzyl-2-acetamido-2-deoxy-a-D-mannopyranosiduronic Acid (17)
A solution of compound 10 (1.5 g, 3.6 mmol) in glacial acetic acid (9 mL)
was heated to 808C with stirring. Water (9 mL) was added dropwise over
20 min, and heating was continued for 20 min. After removal of the
solvents in vacuo, water was added and evaporated in vacuo three times.
We could not crystallize the de-O-benzylidenation product, benzyl-2-
acetamido-2-deoxy-mannose (16), or its tri-O-acetyl derivative (19). The
remainder, presumably 16, was oxidized at 808C in a suspension of freshly
reduced Pt (0.5 g from Adam’s catalyst PtO2) in water (100 mL) with
vigorous stirring and oxygenation. The pH was kept constant between 7.0
and 7.5 with KHCO3. After 3 h, the mixture was filtered; the filtrate was con-
centrated in vacuo and acidified to pH 3 with 3 M HCl. The precipitation was
complete after storage at 08C overnight, and the product was filtered off.
Recrystallization from EtOH-i-PrOH gave compound 17. Yield: 0.85 g
(73%); mp 208–2098C; [a]D25 þ59.08 (c 1.0, pyridine); IR (n in cm21):
1
3340 (NH), 1700 (C55O), 760, 700 (C6H5); H NMR (pyridine-d5, d in
2
ppm): d 2.07 (s, 3H, CHa3c), d 4.70 (d, 1H, JCH2Ph,CH2Ph 11.4, CH2Ph), d
3
3
3
4.85–4.95 (m, 2H, H-5, H-3), d 4.98 (dt, 1H, J4,3 8.7, J4,5 8.7, J4,OH
2
3.9, H-4), d 5.06 (d, 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d 5.28 (ddd, 1H,
3J2,1 2.4, J2,NH 4.2, J2,3 7.2, H-2), d 5.74 (d, 1H, J1,2 2.4, H-1), d 6.60
3
3
3
(s, broad, 2H, OH), d 7.22–7.45 (m, 5H, Harom), d 8.85 (d, 1H, JNH,2 7.5,
3
NH); 13C NMR (pyridine-d5, d in ppm): d 23.36, 54.06, 69.90, 70.52,
70.67, 74.83, 100.13, 128.03, 128.30, 128.83, 138.27, 171.34, 173.55.
Anal. calcd. for C15H19NO7 (325.3): C, 55.38%; H, 5.89%; N, 4.31%.
Found: C, 55.25%; H, 5.56%; N, 4.48%.
Benzyl-2-amino-2-deoxy-a-D-mannopyranoside ꢁ HCl (18)
A solution of compound 11 (0.2 g, 0.56 mmol) in EtOH (4 mL) was refluxed
with conc. HCl (4 equiv.) for 2 min and was evaporated in vacuo. EtOAc was
added to the residue, and the mixture was kept at 258C overnight. The crude
product was filtered off and recrystallized from EtOH-i-PrOH-Et2O. Yield:
0.18 g (84%); mp 200–2018C; [a]2D5 þ65.38 (c 1.0, water); 1H NMR
3
3
(pyridine-d5, d in ppm): d 4.31 (ddꢀd, subm., 1H, J2,1 ,1, J2,3 5.1, H-2),
3
d 4.32 (subm., 1H, H-6a), d 4.40 (subm., 1H, J5,6b 5.4, H-5), d 4.49 (ddꢀd,
3
1H, J6b,5 , 1, J6b,6a 11.4, H-6b), d 4.62 (d, 1H, JCH2Ph,CH2Ph 11.7,
2
2
3
CH2Ph), d 4.69 (t, 1H, J4,3 9.6, J4,5 9.6, H-4), d 4.81 (dd, 1H, J3,2 4.5,
3
3
2
3J3,4 9.6, H-3), d 4.97 (d, 1H, JCH2Ph,CH2Ph 11.4, CH2Ph), d 6.18 (s, 1H,
H-1), d 5.7–6.6 (s, broad, OH), d 7.20–7.40 (m, 5H, Harom); 13C NMR
(pyridine-d5, d in ppm): d 36.72, 55.87, 62.29, 68.48, 69.65, 70.31, 75.29,
98.65, 122.98, 124.36, 128.15, 128.53, 128.85, 136.10, 138.07, 149.14,
.
150.69. Anal. calcd. for C13H20ClNO5 0.5 H2O (314.8): C, 49.44%; H,
6.90%; N, 4.51%. Found: C, 49.65%; H, 6.73%; N, 4.45%.

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2375
Benzyl-4,6-O-benzylidene-a-D-mannopyranosido-[2,3:40,50]-20-
oxazolidinone (20)
Method A
Compound 11 (1.43 g, 4.0 mmol) was heated in DMF (28 mL) with diphenyl-
carbonate (1.2 g, 5.6 mmol) and sodium phenoxide (0.12 g, 1.0 mmol) for
20 h at 1108C. Ice-cold water was added, and the precipitate was filtered
and recrystallized from absolute EtOH. Yield: 1.2 g (72%); mp 136–1388C;
[a]2D5 –30.08 (c 1.03, pyridine); IR (n in cm21): 3325 (NH), 1760 (C55O),
1
3
735, 692 (C6H5); H NMR (CDCl3, d in ppm): d 3.76 (t, 1H, J6a,5 9.6,
3
2J6a,6b 9.6, H-6a), d 3.86 (td, 1H, J5,4 9.9, J5,6a 9.9, J5,6b 4.5, H-5), d 3.92
3
3
3
3
3
(ddꢀt, 1H, J4,3 9.6, J4,5 9.6, H-4), d 4.16 (d, 1H, J2,3 7.5, H-2), d 4.26
3
(dd, 1H, J6b,5 4.5, J6b,6a 10.2, H-6b), d 4.51 (d, 1H, JCH2Ph,CH2Ph 11.7,
2
2
2
3
CH2Ph), d 4.68 (d, 1H, JCH2Ph,CH2Ph 11.7, CH2Ph), d 4.77 (t, 1H, J3,2 7.5,
3J3,4 7.5, H-3), d 4.95 (s, 1H, H-1), d 5.57 (s, 1H, CHPh), d 5.68 (s, 1H,
NH), d 7.31–7.51 (m, 10H, Harom); 13C NMR (CDCl3, d in ppm): d 36.17,
56.33, 59.78, 68.60, 69.64, 74.78, 77.08, 78.57, 95.99, 101.71, 125.92,
128.05, 128.07, 128.16, 128.46, 129.00, 136.04, 136.52, 158.29. Anal.
calcd. for C21H21NO6 (383.4): C, 65.78%; H, 5.52%; N, 3.66%. Found: C,
65.83%; H, 5.77%; N, 3.70%.
Method B
Compound 11 (0.3 g, 0.8 mmol), hexamethyldisilazane (1.5 mL), and dried
xylene (20 mL) were refluxed for 12 h. The solution was concentrated in
vacuo, and the residual solution was added dropwise to CHCl3 (4 mL) contain-
ing phosgene (0.4 g, 4 mmol). The mixture was stirred at rt for 3 h and was
evaporated in vacuo. The solid residue was dissolved in a minimal amount
of dioxane, water (10 mL) was added, and the mixture was kept at 08C for
2 h. The crude precipitate was filtered and recrystallized from absolute
EtOH. Yield: 0.29 g (90%) with identical physical properties.
Benzyl-4,6-O-benzylidene-2-benzyloxycarbonylamido-2-deoxy-a-D-
altropyranoside (21)
Alcohol-free CHCl3 (40 mL), KHCO3 (4 g), and water (40 mL) were shaken
at rt for 1 h. Compound 6 (0.8 g, 2.2 mmol) and benzylchloroformate (0.4 g,
2.6 mmol) were added, and the mixture was shaken for 10 h at rt. The CHCl3
layer was separated and evaporated under reduced pressure at rt. Hexane
(50 mL) and i-Pr2O (10 mL) were added to the residue; the precipitate was
filtered off and recrystallized from i-PrOH. Yield: 1.0 g (92%); mp 161.5–
162.58C; [a]2D5 þ24.88 (c 1.8, pyridine); IR (n in cm21): 3350 (NH), 1700
1
(C55O), 745, 690 (C6H5); H NMR (CDCl3, d in ppm): d 3.09 (d, 1H,

2376
T. M. K. Chiu et al.
3
3
3JOH,3 7.2, OH), d 3.74 (dd, subm., 1H, J4,3 5.4, H-4), d 3.76 (t, 1H, J6a,5
2
11.4, J6a,6b 11.4, H-6a), d 4.16 (dt, 1H, J3,2 3.3, J3,OH 6.9, H-3), d 4.19–
3
3
3
3
4.26 (m, subm., 1H, J2,3 3.3, H-2), d 4.23–4.29 (m, subm., 1H, J5,6b 5.1,
3
H-5), d 4.30 (dd, subm., 1H, J6b,5 5.4, J6b,6a 10.8, H-6b), d 4.58 (d, 1H,
2
2JCH2Ph,CH2Ph 12.0, CH2Ph), d 4.77 (d, 1H, JCH2Ph,CH2Ph 12.3, CH2Ph), d
2
3
4.82 (s, 1H, H-1), d 5.01 (d, 1H, JNH,2 8.7, NH), d 5.11 (s, 2H, CH2Bz),
d 5.60 (s, 1H, CHPh), d 7.32–7.50 (m, 10H, Harom); 13C NMR (CDCl3, d
in ppm): d 53.83, 59.04, 67.70, 68.36, 69.34, 70.37, 77.11, 99.17, 102.65,
126.40, 128.37, 128.46, 128.51, 128.63, 128.83, 128.85, 129.36, 135.99,
136.20, 137.17, 155.15. Anal. calcd. for C28H29NO7 (491.51): C, 68.42%;
H, 5.94%; N, 2.85%. Found: C, 68.39%; H, 5.83%; N, 2.80%.
Benzyl-4,6-O-benzylidene-2-benzyloxycarbonylamido-2-deoxy-3-O-
methanesulfonyl-a-D-altropyranoside (22)
A solution of compound 21 (1.32 g, 3.2 mmol) in absolute pyridine (3 mL) was
cooled to 258C, and methanesulfonyl chloride (0.47 g, 4.1 mmol) was added
dropwise with stirring. The reaction mixture was stirred for 2 h, kept in a
freezer for 18 h, kept at rt for 3 h, and then poured on ice with stirring. The
precipitate was filtered off, dried (desiccator, CaCl2), and recrystallized from
i-PrOH. Yield: 1.5 g (88%); mp 149–1518C; [a]2D5 þ12.28 (c 1.0, pyridine);
1H NMR (CDCl3, d in ppm): d 1.56 (s, 3H, SO2CH3), d 2.99 (s, broad, 4H,
3
OCH2Ph), d 3.69 (dd, subm., 1H, J6a,5 3.3, H-6a), d 3.73 (dd, subm., 1H,
3J4,3 1.5, 3J4,5 4.5, H-4), d 4.24 (dd, 1H, 3J6b,5 5.1, 2J6b,6a 10.2, H-6b), d 4.33
2
(subm., 1H, H-5), d 4.55 (d, 1H, JCH2Ph,CH2Ph 12.6, CH2Ph), d 4.78
2
(d, subm., 1H, JCH2Ph,CH2Ph 12.0, CH2Ph), d 4.78 (dꢀs, subm., 1H,
3J1,2 , 1, H-1), d 5.06 (tꢀs, 1H, 3J3,2 , 1, 3J3,4 , 1, H-3), d 5.13 (tꢀd, 1H,
3
3J2,1 , 1, J2,3 , 1, H-2), d 5.58 (s, 1H, CHPh), d 7.29–7.46 (m, 15H,
Harom); 13C NMR (CDCl3, d in ppm): d 36.57, 39.03, 59.20, 69.23, 69.82,
74.33, 98.44, 102.48, 126.22, 127.73, 128.09, 128.50, 128.70, 128.83,
129.43, 136.93. Anal. calcd. for C29H31NO9S (569.60): C, 61.60%; H,
5.49%; N, 2.46%; S, 5.63%. Found: C, 60.62%; H, 5.64%; N, 2.18%; S, 5.04%.
Benzyl-4,6-O-benzylidene-2-deoxy-2-phenoxycarbonylamido a-D-
altropyranoside (23)
A solution of compound 6 (1.78 g, 5 mmol) in CHCl3 was agitated for 15 min
with a solution of 5% KHCO3 in water (250 mL). Phenylchloroformate (0.8 g,
5.1 mmol) was added, and the mixture was stirred overnight. The CHCl3 layer
was separated and evaporated in vacuo. The residue was triturated with
i-Pr2O, filtered off, and recrystallized from EtOH–petroleum ether. Yield:
2.15 g (90%); mp 144–1458C; [a]2D5 þ40.08 (c 1.0, pyridine); 1H NMR
3
3
(CDCl3, d in ppm): d 3.09 (ddꢀd, 1H, J3,2 6.6, J3,4 , 1, H-3), d 3.78–

a-Benzyl-2-amino-2-deoxy-D-altro- and D-manno-pyranosides
2377
3.88 (m, 2H, H-5, H-6a), d 4.22–4.38 (m, 3H, H-2, H-4, H-6b), d 4.62 (d, 1H,
2JCH2Ph,CH2Ph 11.7, CH2Ph), d 4.81 (d, 1H, 2JCH2Ph,CH2Ph 11.4, CH2Ph), d 4.92
3
3
(dꢀs, 1H, J1,2 , 1, H-1), d 5.26 (d, 1H, JNH,2 9.0, NH), d 5.67 (s, 1H,
CHPh), d 7.1–7.5 (m, 15H, Harom.); 13C NMR (CDCl3, d in ppm): d 53.56,
58.68, 67.88, 68.95, 70.03, 77.08, 98.66, 102.29, 121.21, 125.47, 126.02,
128.00, 128.09, 128.48, 129.00, 129.18. Anal. calcd. for C27H27NO7
(477.49): C, 67.91%; H, 5.70%; N, 2.94%. Found: C, 68.41%; H, 6.01%; N,
3.04%.
4,6-O-Benzylidene-a-D-mannopyranosido-[2,3:40,50]-20-
oxazolidinone (25)
Compound 20 (0.2 g, 0.5 mmol) and 10% Pd/C (0.2 g) were stirred in dioxane
(25 mL) in a hydrogenation apparatus (pH2 ¼ 1 atm) for 24 h. The catalyst
was filtered off, the solvent was evaporated in vacuo, and water was added
to the residue. The crude precipitate was filtered off and recrystallized from
dichloroethane and EtOAc-i-Pr2O. Yield: 84.3 mg (60%); mp 155–1608C
1
3
dec.; H NMR (b-anomer, acetone, d in ppm): d 3.78 (t, subm., 1H, J5,6b
2
9.6, J5,4 9.6, H-5), d 3.80 (t, subm., 1H, J4,5 9.6, J4,3 9.6, H-4), d 3.9–4.1
(m, 2H, H-1, H-6b), d 4.1–4.3 (m, 2H, H-6a, H-3), d 4.73 (t, 1H, J2,1 7.2,
3
3
3
3J2,3 7.2, H-2), d 5.34 (s, 1H, NH), d 5.74 (s, 1H, CHPh), d 7.3–7.6 (m, 6H,
Harom., NH); 13C NMR (b-anomer, acetone-d6, d in ppm): d 57.43, 59.83,
68.70, 68.87, 69.40, 74.69, 79.02, 79.34, 92.08, 92.29, 101.52, 101.67,
126.50, 128.12, 128.94. Anal. calcd. for C14H15NO6 (293.27): C, 57.34%;
H, 5.16%; N, 4.78%. Found: C, 57.05%; H, 5.26%; N, 4.66%.
Benzyl-4,6-O-(p-methoxy)-benzylidene-a-D-mannopyranosido-
[2,3:40,50]-20-oxazolidinone (26)
Compound 15 (1.0 g, 3.4 mmol), anisaldehyde (10 mL), and fused ZnCl2
(1.0 g) were shaken at rt for 2 d. Et2O (20 mL) was added, and undissolved
ZnCl2 was filtered off. The solution was shaken with water (8 mL) and
i-Pr2O (12 mL) and stored at 08C for 3 h. The crude precipitate was
filtered and recrystallized from absolute EtOH. Yield: 0.9 g (75%); mp
187.5–188.58C; [a]2D5 –47.08 (c 1.0, pyridine); IR (n in cm21): 1750
(C55O, oxazolidinone), 745, 700 (C6H5); 1H NMR (CDCl3, d in ppm):
3
2
d 3.74 (t, 1H, J6a,5 9.6, J6a,6b 9.6, H-6a), d 3.79 (s, 3H, OCH3), d
3
3.85 (td, subm., 1H, J5,4 9.9, J5,6a 9.9, J5,6b 4.5, H-5), d 3.90 (t, 1H,
3
3
3
3
3J4,3 9.6, J4,5 9.6, H-4), d 4.15 (d, 1H, J2,3 7.8, H-2), d 4.24 (dd, 1H,
3J6b,5 4.5, J6b,6a 10.2, H-6b), d 4.51 (d, 1H, JCH2Ph,CH2Ph 11.4,
2
2
2
CH2Ph), d 4.68 (d, 1H, JCH2Ph,CH2Ph 11.7, CH2Ph), d 4.76 (t, 1H, J3,2
3
3
7.8, J3,4 7.8, H-3), d 4.94 (s, 1H, H-1), d 5.52 (s, 1H, CHPh), d 5.78
(s, 1H, NH), d 6.85–7.40 (m, 9H, Harom); 13C NMR (CDCl3, d in

2378
T. M. K. Chiu et al.
ppm): d 36.17, 55.21, 56.33, 59.76, 68.56, 69.63, 74.81, 78.50, 96.00,
101.68, 113.48, 127.24, 128.04, 128.14, 128.45, 129.03, 136.05, 158.44,
159.96. Anal. calcd. for C22H23NO7 (413.50): C, 63.90%; H, 5.61%;
N, 3.39%. Found: C, 63.82%; H, 5.54%; N, 3.34%.
4,6-O-(p-Methoxy)-benzylidene-a-D-mannopyranosido-[2,3:40,50]-
20-oxazolidinone (27)
Compound 26 (0.21 g, 0.5 mmol) and 10% Pd/C (27 mg) were stirred in
dioxane (25 mL) in a hydrogenation apparatus (pH2 ¼ 1 atm) for 24 h. The
catalyst was filtered off, the solvent was evaporated in vacuo, and water
was added to the residue. The crude precipitate was filtered off and was
recrystallized from absolute EtOH. Yield: 112 mg (70%); [a]2D5 –1708 (c
1.0, pyridine); IR (n in cm21): 1730 (C55O, oxazolidinone), 830 (p-MeO-
1
C6H5); H NMR (CDCl3, d in ppm): d 3.67 (s, 3H, OCH3), d 3.78 (dt,
3
3
3
3
2
1H, J5,4 9.9, J5,6a 9.9, J5,6b 4.8, H-5), d 3.94 (t, 1H, J6a,5 9.9, J6a,6b
3
2
9.9, H-6a), d 4.48 (dd, 1H, J6b,5 4.5, J6b,6a 10.2, H-6b), d 4.53 (ddꢀd,
3
3
3
3
subm., 1H, J4,3 ꢀ9.6, J4,5 , 1, H-4), d 4.60 (ddꢀt, 1H, J2,1 , 1, J2,3
3
8.1, J2,NH 9.3, H-2), d 5.02 (s, broad, 1H, OH-1), d 5.09 (t, 1H, J3,2 7.5,
3
3J3,4 7.5, H-3), d 5.56 (dꢀs, broad, 1H, J1,2 , 1, H-1), d 5.72 (s, 1H,
3
CHPh), d 7.04 (d, 1H, J 8.1, Harom, AB-splitting), d 7.66 (d, 1H, J 8.7,
Harom, AB-splitting), d 9.81 (s, broad, 1H, NH); 13C NMR (CDCl3, d in
ppm, a/b-mixture): d 36.59, 55.34, 57.06, 58.48, 60.45, 64.94, 69.60,
69.79, 75.55, 76.48, 79.88, 80.11, 92.84, 93.38, 102.05, 102.20, 113.95,
128.34, 128.39, 130.79, 159.65, 160.15, 160.58. Anal. calcd. for
C15H17NO7 (323.29): C, 55.73%; H, 5.31%; N, 4.33%. Found: C, 55.63%;
H, 5.44%; N, 4.36%.
3
3
ACKNOWLEDGMENTS
We express gratitude for the financial support of K. S. (undergraduate research
participant) through a Dreyfus Senior Scientist Mentor Grant to P. H. G. and
through a College of the Pacific Dean’s Research Award.
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