Formation of β-lactams fused to the pyranoid ring via the Mitsunobu reaction

Article abstract of DOI:10.1016/S0008-6215(98)00017-2

N-Tosyl-2-C-carbamoyl glycosides having the α-L-arabino- and β-D- xylo- configuration form under Mitsunobu conditions 2-C:3-N-carbonyl-2,3- dideoxy-3-N-tosylamino-α-L-lyxo- and β-Darabinopyranosides, respectively, having the β-lactam ring fused to the pyranoid one; neither the formation of the γ-lactam ring nor that of the 3,4-epoxide were observed. The γ-lactam 2-C:4-N-carbonyl-2,4-dideoxy-4-N-tosylamino-β-D-xylopyranoside can be obtained after protection of the 3-hydroxy group in the starting glycoside of α-L-arabino-configuration. The structure and configuration of methyl 2-C:3- N-carbonyl-2,3-dideoxy-3-N-tosylamino-β-D-ribopyranoside and methyl 2-C:3- N-carbonyl-2,3-dideoxy-3-N-tosylamino-β-D-erythro-pyranosid-4-ulose were proved by X-ray crystallography.

Full text of DOI:10.1016/S0008-6215(98)00017-2

Carbohydrate Research 307 (1998) 33±43
Formation of ꢀ-lactams fused to the pyranoid
ring via the Mitsunobu reaction
O. Zegrocka, W. Abramski, Z. Urbanczyk-Lipkowska, M. Chmielewski*
Institute of Organic Chemistry of the Polish Academy of the Sciences, PL - 01-224 Warsaw, Poland
Received 4 August 1997; accepted 10 December 1997
Abstract
N-Tosyl-2-C-carbamoyl glycosides having the ꢁ-l-arabino- and ꢀ-d-xylo- con®guration form
under Mitsunobu conditions 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosylamino-ꢁ-l-lyxo- and ꢀ-d-
arabinopyranosides, respectively, having the ꢀ-lactam ring fused to the pyranoid one; neither the
formation of the ꢂ-lactam ring nor that of the 3,4-epoxide were observed. The ꢂ-lactam 2-C:4-N-
carbonyl-2,4-dideoxy-4-N-tosylamino-ꢀ-d-xylopyranoside can be obtained after protection of the
3-hydroxy group in the starting glycoside of ꢁ-l-arabino-con®guration. The structure and con®g-
uration of methyl 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosylamino-ꢀ-d-ribopyranoside and methyl
2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosylamino-ꢀ-d-erythro-pyranosid-4-ulose were proved by
X-ray crystallography. # 1998 Elsevier Science Ltd. All rights reserved
Keywords: N-Tosyl-2-C-carbamoyl glycosides; 2-C:3-N-Carbonyl-2,3-dideoxy-3-N-tosylamino-ꢁ-l-lyxo- and
ꢀ-D-ribopyranosides; Intramolecular Mitsunobu reaction; ꢀ-Lactams
1. Introduction
application of a direct Mitsunobu [diethyl azodi-
carboxylate (DEAD)±triphenylphosphine (TPP)]
procedure for that purpose has failed due to the
low activity of the N-unsubstituted carba-
moyl group [2]. Syntheses carried out in our
laboratory [3±5] have employed the direct forma-
tion of sugar ꢀ-lactams by a [2+2]cycloaddition of
isocyanates to glycals [6,7]. An attempt to perform
[2+2]cycloaddition of chlorosulfonyl isocyanate to
2,3-unsaturated glycosides has failed due to the low
stability of the sugar substrate in the presence of
the acid-contaminated isocyanate [8].
Cycloadducts of trichloroacetyl isocyanate or
tosyl isocyanate with glycals in the presence of
alcohol undergo a rapid opening of a four-mem-
bered ring to a€ord 2-C-carbamoyl glycosides hav-
ing a trans-located aglycone with respect to the
Compounds having a four-membered ꢀ-lactam
ring fused to the sugar ring have been reported to
be intermediates in the synthesis of aminodeoxy
sugars [1], carbapenems [2], clavams [3], 1-oxace-
phems [4], and uracyl derivatives [5]. While in case
of aminodeoxy sugars bicyclic skeletons were
formed from non-carbohydrate precursors [1], the
other syntheses [2±5] involved the transformation
of readily available carbohydrate substrates. The
synthesis of 6-epithienamycin led to the introduc-
tion of the ꢀ-lactam ring by an intramolecular N-
alkylation of the 4-C-carbamoyl glycoside by the
neighbor C-3 atom bearing a leaving group;
* Corresponding author.
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00017-2

34
O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
carbamoyl function [9,10]. Owing to the high ste-
reoselectivity of the [2+2]cycloaddition, the con-
®guration of glycosides obtained by alcoholysis of
the cycloadduct is de®ned and the carbamoyl group
is always anti to the C-3 substituent. Deprotection
at O-3 forms the ꢀ-hydroxy amide fragment sui-
table for the ꢀ-lactam ring construction via the
Appel (carbon tetrachloride-TPP) or Mitsunobu
procedure.
For the present studies we selected readily avail-
able l-arabinal and d-xylal which should provide,
after the cycloaddition-alcoholysis procedure, ꢁ-
l-arabino- and ꢀ-d-xylo-carbamoyl glycosides,
respectively. Both glycosides di€er only by the
con®guration at C-4. Our choice of glycals resulted
from the expectation that cyclization of ꢁ-l-ara-
bino- and ꢀ-d-xylo-carbamoyl glycosides to form a
ꢀ-lactam ring fused to the pyranoid one, should
provide in both cases the (S) con®guration at C-3
(C-4 of the azetidin-2-one ring). This would allow
to use bicyclic ꢀ-lactams as precursors in the
synthesis of carbapenem antibiotics (Scheme 1).
Preliminary experiments using the Appel proce-
dure allowed to obtain ꢀ-lactam 6 from glycoside 5
in 54% yield. We failed, however, to remove the O-
silyl and N-tosyl groups from 6. All experiments
using standard procedures gave decomposition
products.
We noticed that the HO-4 group in l-arabinal 1
could be selectively benzylated to give 7 in 48%
yield. Subsequent standard silylation of the HO-
3 group with trimethylsilylchloride followed by a
[2+2]cycloaddition of tosyl isocyanate and sub-
sequent methanolysis of the resulting cycloadduct
provided glycoside 10.
The Mitsunobu procedure allowed to trans-
form glycoside 10 into 11 in 46% yield. Reduction
of the tosyl substituent in 11 with sodium naph-
thalene deprotected the nitrogen atom to a€ord 12.
Subsequent hydrogenolysis of the benzyl group at
O±4 over 10% Pd-C gave ꢀ-lactam 13 (Scheme 3).
Cyclization of the glycosides 4, 14, 15, and 16 in
boiling tetrahydrofuran in the presence of DEAD
and TPP a€orded the respective ꢀ-lactams 17, 18,
20, and 21 in 42±52% yield (Scheme 4). We did not
notice epoxide or ꢂ-lactam formation. The last
observation is particularly interesting in the case of
the ꢁ-l-arabino glycosides 4 and 14 because from
the former we expected the formation of at least
some amount of the less strained ꢂ-lactam ring. It
should be noted that compound 26 (Scheme 5)
obtained from the known glycoside 24 [9] by a
standard reaction sequence involving introduction
of a tert-butoxycarbonyl function to the amide
nitrogen atom and subsequent de-O-benzylation,
unexpectedly did not undergo cyclization either
under Appel or Mitsunobu conditions.
2. Results and discussion
For the ®rst cyclizations we used 4-O-protected
ꢁ-l-arabino glycoside 5. The 4-O-protected arabi-
no glycoside 5 was prepared from l-arabinal 1 by a
four-step reaction sequence, which involved silyla-
tion, followed by [2+2]cycloaddition of tosyl iso-
cyanate to the glycal double bond, methanolysis of
the cycloadduct 3, and regioselective protection of
the HO-4 group in 4 by the tert-butyldiphenylsilyl
function (Scheme 2).
Scheme 1.
Scheme 2.

O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
35
Scheme 3.
Scheme 4.
hydroxy group at C-3. The suitably protected 2-
carbamoyl glycoside 28 was obtained from glycal 9
(Scheme 6) using standard transformations con-
sisting of the [2+2]cycloaddition of tosyl iso-
cyanate, methanolysis of the cycloadduct, and
hydrogenolytic removal of the benzyl group at O-4.
Compound 28 was subjected to a Mitsunobu reac-
tion at 55ꢀC to a€ord 29 in 45% yield.
Oxidation of the HO-4 group in the methyl gly-
cosides 13, 17, 20, and 22 with the ruthenium
tetroxide-sodium periodate reagent [14] gave the
same N-unsubstituted compound 30 (Scheme 7)
from both 13 and 22, and the same N-tosyl com-
pound 31 from both 17 and 20. The benzyl glyco-
sides 18, 19, 21, and 23 under the same conditions
underwent decomposition. The tosyl-free benzyl -
glycosides 19 and 23 can be oxidized by the methyl
sulfoxide±acetic anhydride reagent to a€ord the
same ketone 32 from both compounds.
Scheme 5.
The Mitsunobu reaction involving vic-diols have
been investigated in the past [11±13]. In the case of
acyclic vic-diols, the AcylOH-DEAD-TPP-reagent
provided respective monoesters, whereas in the
case of cyclic trans-diols, the respective epoxides
were formed [12,13]. We did not ®nd any informa-
tion on cyclization to the vic-diol fragment using a
Mitsunobu procedure.
Formation of the bicyclic compound having a ꢂ-
lactam ring required the selective protection of the
Structures and con®gurations of all ꢀ-lactam
compounds were easily proved by their spectral
Scheme 6.

36
O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
Scheme 7.
and analytical data. The additional proof of the
geometry of the bicyclic ꢀ-lactams came from a X-
ray crystallographic analysis of the glycosides 20
and 31 (Tables 1 and 2, Figs. 1 and 2).
Fig. 2). This new molecular skeleton has a
slightly di€erent geometry compared to the mole-
cules having the 2-C-1-N-carbonyl-2-deoxy-glyco-
pyranosylamine
skeletons
33
investigated
Our X-ray investigations performed for the
representative group of 2-C:1-N-carbonyl-2-deoxy-
glycosylamines 33 have shown that the conforma-
tion of the pyranoid ring in such a fused bicyclic
system strongly depends on substitution and con-
®guration [15±17]; the boat-like conformation O,3B
dominates, however. In the case of compound 20 a
similar geometry 1,4B of the pyranoid ring was
observed (Tables 1 and 2, Fig. 1). Introduction of a
carbonyl function at C-4 (31) caused a ¯attening
towards a twist-boat conformation (Tables 1 and 2,
previously [15±17]. In particular, the new topol-
ogy of the ꢀ-lactam and sugar rings introduces
less strain in the latter. That might be seen by the
valence angles close to the tetrahedral values for
hydrogen atoms located at the rings fusion
(Tables 1 and 2). Due to the electron withdrawing
e€ect of the tosyl group located at the ꢀ-lactam
nitrogen atom, the C=O bond length in both
compounds is very short [1.186(4) and 1.190(4)A].
Electrophilic properties of the ꢀ-lactam carbo-
nyl group versus the ketone one in such a strained
Table 1
Crystal data and structure re®nement for compounds 20 and 31
Identi®cation code
Empirical formula
Formula weight
Temperature (K)
Wavelength (A)
Crystal system
Space Group
Unit cell dimensions (A):
a
20
31
C14H17NO6S
327.35
293(2)
1.54178
Orthorhombic
P212121
C14H17NO6S
325.34
293(2)
1.54178
Orthorhombic
P212121
7.3070(10).
8.7200(10).
25.223(4)
1607.1(4)
4
8.6150(10)
12.342(2)
13.902(2)
1478.1(4)
4
b
c
Volume (A3)
Z
3
1
Density (calculated) (Mg m
Absorption coecient (mm
F(000)
Crystal size (mm)
ꢃ-range for data collection (ꢀ)
Index ranges
Re¯ections collected
Independent re¯ections
Re®nement method
Data / restraints / parameters
Goodness-of-®t on F2
Final R indices [I>2ꢄ (I)]
R indices (all data)
Absolute structure parameter
Extinction coecient
)
)
1.353
2.050
1.466
2.229
688
0.17Â0.20Â0.30
680
0.20Â0.20Â0.35
3.50 to 74.69
0ꢁhꢁ9, 0ꢁkꢁ10, 0ꢁlꢁ31
1831
4.79 to 74.69
0ꢁhꢁ10, 0ꢁkꢁ15, 0ꢁlꢁ17
1564
1564 [R(int) = 0.0000]
1831 [R(int) = 0.0000]
Full-matrix least-squares on F2
1830/0/204
1564/0/200
0.931
R1=0.0361, wR2=0.1032
R1=0.0363, wR2=0.1039
0.13(3)
1.045
R1=0.0456, wR2=0.1317
R1=0.0460, wR2=0.1346
0.02(3)
0.0008(4)
0.0066(7)
Largest di€. peak and hole
3
Áꢅ(eA
)
0.190 and 0.249
0.175 and 0.213

O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
37
Table 2
Selected bond lengths [A], angles [ꢀ] and torsion angles [ꢀ] for
compounds 20 and 31
bicyclic system are noteworthy. Compound 31
treated with ethyl (triphenylphosphoranylidene)
acetate (34) underwent an unexpected reaction at
the ꢀ-lactam carbonyl group leaving the ketone
function untouched. The addition of the reagent
was followed by the opening of the four-membered
ꢀ-lactam ring to a€ord the stable ylide 35. Reac-
tion of ꢀ-lactams having an electron with-
drawing group at the nitrogen atom with Wittig
reagents are known [18] but they lead to a C=C
double bond formation without opening of the
four-membered ring. The nucleophilic ring opening
of activated monocyclic ꢀ-lactams by trimethylsul-
phoxonium ylide, lithiated sulphones and cuprates,
however, has been reported [19]. Removal of the
tosyl substituent from the nitrogen atom in 31
decreased the reactivity of the ꢀ-lactam carbo-
nyl group. Ylide 34 reacted with ketone 30 to give
the expected mixture of ole®ns 36.
20
31
O(1)-C(1)
O(1)-C(5)
C(1)-O(2)
C(1)-C(2)
C(2)-C(7)
C(2)-C(3)
C(3)-N(8)
C(3)-C(4)
C(4)-C(5)
C(6)-O(2)
O(3)-C(7)
C(7)-N(8)
1.406(4)
1.442(4)
1.411(4)
1.502(4)
1.532(4)
1.541(4)
1.502(4)
1.511(4)
1.530(4)
1.428(5)
1.186(4)
1.403(4)
1.419(3)
1.416(4)
1.388(4)
1.510(5)
1.525(5)
1.554(4)
1.488(4)
1.202(3)
1.497(4)
1.441(4)
1.190(4)
1.409(4)
C(1)-O(1)-C(5)
O(1)-C(1)-O(2)
O(1)-C(1)-C(2)
O(2)-C(1)-C(2)
C(1)-C(2)-C(7)
C(1)-C(2)-C(3)
C(7)-C(2)-C(3)
N(8)-C(3)-C(4)
N(8)-C(3)-C(2)
C(4)-C(3)-C(2)
O(4)-C(4)-C(3)
O(4)-C(4)-C(5)
C(3)-C(4)-C(5)
O(1)-C(5)-C(4)
C(1)-O(2)-C(6)
O(3)-C(7)-N(8)
O(3)-C(7)-C(2)
N(8)-C(7)-C(2)
C(7)-N(8)-C(3)
C(7)-N(8)-S(1)
C(3)-N(8)-S(1)
C(5)-O(1)-C(1)-O(2)
C(5)-O(1)-C(1)-C(2)
O(1)-C(1)-C(2)-C(7)
O(2)-C(1)-C(2)-C(7)
O(1)-C(1)-C(2)-C(3)
O(2)-C(1)-C(2)-C(3)
C(1)-C(2)-C(3)-N(8)
C(7)-C(2)-C(3)-N(8)
C(1)-C(2)-C(3)-C(4)
C(7)-C(2)-C(3)-C(4)
N(8)-C(3)-C(4)-O(4)
C(2)-C(3)-C(4)-O(4)
N(8)-C(3)-C(4)-C(5)
C(2)-C(3)-C(4)-C(5)
C(1)-O(1)-C(5)-C(4)
O(4)-C(4)-C(5)-O(1)
C(3)-C(4)-C(5)-O(1)
O(1)-C(1)-O(2)-C(6)
C(2)-C(1)-O(2)-C(6)
C(1)-C(2)-C(7)-O(3)
C(3)-C(2)-C(7)-O(3)
C(1)-C(2)-C(7)-N(8)
C(3)-C(2)-C(7)-N(8)
O(3)-C(7)-N(8)-C(3)
C(2)-C(7)-N(8)-C(3)
117.5(2)
117.5(2)
112.9(3)
112.3(2)
105.6(2)
115.1(2)
113.8(3)
87.6(2)
114.4(2)
87.2(2)
113.8(3)
108.3(3)
109.0(3)
111.1(3)
115.6(2)
114.8(3)
132.2(3)
136.6(3)
91.2(2)
94.1(2)
132.3(2)
131.6(2)
69.1(3)
50.1(4)
50.7(4)
174.1(2)
48.2(3)
75.1(3)
116.5(3)
0.0(2)
112.6(2)
109.8(2)
105.8(2)
113.0(3)
113.0(2)
87.2(2)
113.3(3)
87.2(2)
115.2(2)
120.9(3)
121.5(3)
117.7(2)
115.1(2)
113.0(3)
131.3(3)
137.4(3)
91.3(2)
94.3(2)
134.4(2)
129.6(2)
48.0(3)
69.6(3)
51.9(3)
173.7(2)
45.2(3)
76.6(3)
114.3(3)
0.4(2)
In summary, we demonstrated that intramole-
cular amide formation between functional groups
located within the pyranoid ring can be performed
by the Mitsunobu procedure, even in the presence of
a trans-vic-diol fragment. The preference of ꢀ-lac-
tam formation over ꢂ-lactam should be noted.
3. Experimental
General.ÐAll melting points were uncorrected.
Optical rotations were measured using a Jasco
1.0(3)
0.2(4)
115.5(2)
64.2(3)
162.4(3)
55.4(4)
42.7(4)
3.4(4)
162.9(3)
43.6(4)
59.0(4)
178.0(3)
63.1(4)
178.3(3)
115.2(3)
0.0(2)
114.1(3)
107.7(4)
154.0(3)
71.9(3)
26.3(4)
42.1(4)
173.8(3)
6.5(4)
64.3(4)
175.7(3)
64.8(5)
178.6(5)
114.3(3)
0.5(2)
178.5(3)
0.0(2)
178.7(4)
0.5(2)
Fig. 1. ORTEP drawing of compound 20. Thermal ellipsoids
shown at 50% probability level.

38
O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
(CDCl3): ꢇ 4.18 (d, 1 H, J1,2 8.2 Hz, H-1), 3.73±3.86
(m, 2 H, H-3,4), 3.64 (dd, 1 H, J4,5a 2.2, J5a,5b
13.0 Hz, H- 5), 3.39 (s, 3 H, OCH3), 3.09 (bd, 1 H,
H-5b), 2.73 (dd, 1 H, J2,3 9.8 Hz, H-2), 2.44 (s, 3 H,
Ts), 1.08 (s, 9 H, t-Bu); MS (LSIMS): m/z
584 [M+H]+. Anal. Calcd for C30H37NO7S: C,
61.72; H, 6.39; N, 2.40. Found: C, 61.7; H, 6.8; N,
2.4.
Methyl 4-O-tert-butyldiphenylsilyl-2-C:3-N-carb-
onyl-2,3-dideoxy-3-N-tosylamino-a-l-lyxopyranoside
(6).ÐCompound 5 (0.4 g, 0.68 mmol) in MeCN
(3 mL) was treated with TPP (0.38 g, 1.37 mmol)
and cooled to 0ꢀC. Subsequently, CCl4 (0.13 mL,
1.37 mmol) and Et3N (0.19 mL, 1.37 mmol) were
added. The solution was kept at room temperature
for 2.5 h, then concentrated, and puri®ed by chro-
matography using 5:1 hexane±EtOAc as eluent
to give 6 as a syrup (0.21 g, 54%); [ꢁ]d 46.0ꢀ (c
0.6, CH2Cl2); IR (®lm): ꢆ 1820 cm (C=O); H
NMR (CDCl3): ꢇ 4.85 (d, 1 H, J1,2 1.3 Hz, H-1),
4.24 (m, 2 H, H-3,4), 3.52 (dd, 1 H, J4,5a 6.4, J5a,5b
12.1 Hz, H-5a), 3.39 (dd, 1 H, J2,3 6.6 Hz, H-2),
3.35 (dd, 1 H, J4,5b 5.8 Hz, H-5b), 3.33 (s, 3 H,
OCH3), 2.43 (s, 3 H, Ts), 1.09 (s, 9 H, t-BuPh2Si).
Anal. Calcd for C32H39NO6SSi: C, 63.69; H, 6.23;
N, 2.47. Found: C, 63.8; H, 6.3; N, 2.4.
Fig. 2. ORTEP drawing of compound 31. Thermal ellipsoids
shown at 50% probability level.
DIP-360 digital polarimeter. IR spectra were
obtained on a FT-IR-1600 Perkin-Elmer spectro-
1
1
1
photometer. The H NMR spectra were recorded
with a Bruker AM-500 spectrometer. Mass spectra
were obtained with an AMD-604 spectrometer.
Column chromatography was performed on Merck
Kieselgel 60 (230-400 mesh).
Methyl 2-deoxy-2-C-(N-tosylcarbamoyl)-a-l-arab-
inopyranoside (4).Ð3,4-Di-O-trimethylsilyl-l-arab-
inal 2 (4.0 g, 16.0 mmol) in MeCN (30 mL) was
treated with p-toluenesulfonyl isocyanate (3.6 mL,
24.0 mmol) and left for 4 h. Subsequently, the mix-
ture was cooled to 0ꢀC, treated with MeOH (8 mL)
and conc HCl (0.01 mL), and left for 15 min. The
solution was concentrated and puri®ed by chroma-
tography using 1:2:0.1 hexane±EtOAc±MeOH as
eluent to a€ord 4 (3.4 g, 61%); [ꢁ]d +35ꢀ (c 0.8,
CH2Cl2); IR (®lm): ꢆ 3385 (OH), 3224 (NH), 1717
1,5-Anhydro-4-O-benzyl-2-deoxy-l-erythro-pent-1-
enitol (7).ÐCrude l-arabinal 1 (2.0 g, 17.2 mmol)
in DMF (16 mL) was cooled to 0ꢀC and treated
with NaH (0.48 g, 20.6 mmol), then upon stirring
benzyl bromide (2.4 mL, 20.6 mmol) was slowly
added. The mixture was cooled and stirred for an
additional 4 h. Subsequently, the solution was
diluted with EtOAc, ®ltered through Celite and
concentrated. Chromatographic puri®cation using
4:1 hexane±EtOAc as eluent gave 7 (1.7 g, 48%),
mp 56±57ꢀC; [ꢁ]d 102.3ꢀ (c 0.4, CH2Cl2); IR
1 1
(C=O) cm ; H NMR (CDCl3): ꢇ 4.25 (d, 1 H, J1,2
8.4 Hz, H-1), 4.13 (d, 1 H, J5a,5b 12.8 Hz, H-5a), 3.95
(m, 2 H, H-3,4), 3.51 (d, 1 H, H-5b), 3.30 (s, 3 H,
OCH3), 2.89 (dd, 1 H, J2,3 10.1 Hz, H-2), 2.41 (s, 3
H, Ts); HRMS (LSIMS): m/z 346.09554 [M+H]+;
Calcd for C14H20NO7S: 346.09605.
1
1
(®lm): ꢆ 3218 (OH), 1640 (C=C) cm ; H NMR
(CDCl3): ꢇ 6.43 (dd, 1 H, J1,2 6.0, J1,3 0.8 Hz, H-1),
4.90 (dd, 1 H, J2,3 4.9 Hz, H-2), 4.66 and 4.69 (2 d,
each 1 H, J 11.8 Hz, Bn), 4.23 (t, 1 H, J3,4 4.1 Hz,
H-3), 3.95 (d, 2 H, H-5a,5b), 3.75 (dt, 1 H, J4,5a 6.3,
J4,5b 6.8 Hz, H-4). Anal. Calcd for C12H14O3: C,
69.80; H, 6.84. Found: C, 70.0; H, 7.1.
Methyl 4-O-tert-butyldiphenylsilyl-2-deoxy-2-C-
(N-tosylcarbamoyl)-a-l-arabinopyranoside (5).Ð
Compound 4 (0.25 g, 0.72 mmol) in DMF (10 mL)
was treated with 4-dimethylaminopyridine (0.3 g)
and tert-butyldiphenylsilyl chloride (0.3 g) for
6 days. Subsequently, the mixture was poured into
water, and extracted with CH2Cl2. The extract was
washed, dried, and concentrated. The crude pro-
duct was puri®ed on a silica gel column to a€ord 5
(0.27 g, 62%); [ꢁ]d +45.0ꢀ (c 0.8, CH2Cl2); IR
1,5-Anhydro-4-O-benzyl-2-deoxy-3-O-trimethyl-
silyl-l-erythro-pent-1-enitol (8).ÐCompound
7
(1.0 g, 4.84 mmol) in pyridine was cooled to 0ꢀC
and treated with Me3SiCl (1.4 mL, 11.6 mmol). The
mixture was kept for 2 h at room temperature,
subsequently the solution was poured into ice-
water and extracted with hexane. The extract was
washed, dried, concentrated, and distilled from an
1
1
(®lm): ꢆ 3460 (OH), 1715 (C=O) cm ; H NMR

O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
39
air bath to give 8 (1.1 g, 81%), bp 70±73ꢀC / 0.1
Torr; [ꢁ]d 296ꢀ (c 1, CH2Cl2); IR (®lm): ꢆ 1640
4.67 and 4.80 (2 d, each 1 H, J 11.8 Hz, Bn), 4.26
(dd, 1 H, J2,3 6.9, J3,4 2.4 Hz, H-3), 3.99 (ddd, 1 H,
J4,5a 6.6, J4,5b 8.9 Hz, H-4), 3.67 (dd, 1 H, J5a,5b
11.9 Hz, H-5a), 3.53 (dd, 1 H, H-5b), 3.40 (dd, 1 H,
H-2), 3.32 (s, 3 H, OCH3), 2.45 (s, 3 H, Ts); HRMS
(LSIMS): m/z 440.11416 [M+Na]+; Calcd for
C12H23NO6SNa: 440.11437. Anal. Calcd for
C21H23NO6S: C, 60.41; H, 5.55; N, 3.35. Found: C,
61.0; H, 5.8; N, 3.3.
1
1
(C=C) cm ; H NMR (CDCl3): ꢇ 6.34 (d, 1 H,
J1,2 6.0 Hz, H-1), 4.78 (dd, 1 H, J2,3 5.3 Hz, H-2),
4.59 and 4.69 (2 d, each 1 H, J 12.1 Hz, Bn), 4.31
(m, 1 H, H-3), 3.95 (t, 1 H, J4,5a 10.0, J5a,5b
10.2 Hz, H-5a), 3.90 (dq, 1 H, J3,5b 1.2, J4,5b 3.7 Hz,
H-5b), 3.65 (dt, 1 H, J3,4 3.7 Hz, H-4); HRMS
(LSIMS): m/z 301.1237 [M+Na]+; Calcd for
C15H22NaO3Si: 301.1236.
Methyl 3-amino-4-O-benzyl-2-C:3-N-carbonyl-2,3-
dideoxy-a-l-lyxopyranoside (12).ÐA solution of
naphthalene (0.55 g, 4.32 mmol) in dry 1,2-dime-
thoxyethane (DME, 5 mL) was stirred with sodium
(0.1 g, 4.32 mmol) under N2 for 30 min. Subse-
quently, a solution of compound 11 (0.30 g,
0.72 mmol) in DME (0.5 mL) was added slowly.
Stirring and cooling were continued for 10 min,
then a saturated solution of NH4Cl was added
dropwise until the blue color disappeared. The
mixture was diluted with water and extracted with
EtOAc (3Â5 mL). The combined extracts were
dried and concentrated, and the residue was pur-
i®ed by chromatography using 3:1 hexane±EtOAc
as eluent to give 12 as a syrup (0.13 g, 68.6%); [ꢁ]d
45.1ꢀ (c 0.3, CH2Cl2); IR (®lm): ꢆ 3298 (NH),
1,5-Anhydro-4-O-benzyl-3-O-tert-butyldimethyl-
(9).ÐCom-
silyl-2-deoxy-l-erythro-pent-1-enitol
pound 7 (1.40 g, 6.78 mmol) in DMF (10 mL) was
treated with tert-butyldimethylsilyl chloride (1.38 g,
8.48 mmol). The mixture was kept for 8 h at room
temperature, then poured into ice-water, and the
solution was extracted with toluene. The extract
was washed, dried, concentrated, and puri®ed by
chromatography to a€ord 9 as a syrup (1.88 g,
86.5%); [ꢁ]d 185ꢀ (c 0.9, CH2Cl2); IR (®lm): ꢆ
1
1
1640 (C=C) cm ; H NMR (CDCl3): ꢇ 6.32 (d,
1 h, J1,2 6.0 Hz, H-1), 4.76 (dd, 1 H, J2,3 5.3 Hz, H-
2), 4.72 and 4.57 (2 d, each 1 H, J 12.0 Hz, Bn),
3.32 (m, 1 H, H-3), 3.97 (t, 1 H, J4,5a 10.0, J5a,5b
10.2 Hz, H-5a), 3.90 (m, 1 H, J3,5b 1.4, J4,5b 3.6 Hz,
H-5b), 3.63 (dt, 1 H, J3,4 3.6 Hz, H-4), 0.09, 0.10,
and 0.91 (3 s, 3,3,9 H, t-BuMe2Si); HRMS
(LSIMS): m/z 343.17056 [M+Na]+; Calcd for
C12H28NaO3Si: 343.17054.
1
1
1759 (C=O) cm ; H NMR (CDCl3): ꢇ 4.93 (s, 1
H, H-1), 3.53 and 4.69 (2 d, each 1 H, J 12.1 Hz,
Bn), 3.58±3.82 (m, 3 H, H-3,4,5a), 3.51 (t, 1 H,
J4,5b 8.9, J5a,5b 9.3 Hz, H-5b), 3.42 (dd, 1 H, J1,2
0.7, J2,3 5.7 Hz, H-2); HRMS (LSIMS): m/z
286.13436 [M+H]+; Calcd for C14H17NNaO4:
286.13437.
Methyl 4-O-benzyl-2-deoxy-2-C-(N-tosylcarbam-
oyl)-a-l-arabinopyranoside (10).ÐCompound 10
was obtained from 8 according to the procedure
described for 4; yield 64% as a syrup; [ꢁ]d +53.7ꢀ
(c 1.3, CH2Cl2); IR (®lm): ꢆ 3516 (OH), 3226 (NH),
Methyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-
a-d-lyxopyranoside (13).ÐCompound 12 (0.10 g,
0.30 mmol) was hydrogenated in MeOH (1.5 mL)
over 10% Pd-C (wet, Degussa type) for 3 h. Sub-
sequently, the mixture was ®ltered through Celite
and the solution was concentrated. The crude pro-
duct was puri®ed by chromatography using
1:1.5:0.1 hexane±EtOAc±MeOH as eluent to a€ord
13 (0.046 g, 89%); mp 117±118ꢀC; [ꢁ]d 86.8ꢀ (c
0.3, CH2Cl2); IR (®lm): ꢆ 3450 (OH), 3204 (NH),
1
1
1715 (C=O) cm ; H NMR (CDCl3): ꢇ 4.25 (d, 1
H, J1,2 8.3 Hz, H-1), 4.10 (m, 1 H, H-5a), 3.90
(bdd, 1 H, J2,3 10.4, J3,4 3.6 Hz, H-3), 3.58 (m, 1 H,
H-4), 3.40 (s, 3 H, OCH3), 3.29 (dd, 1 H, J3,5b 1.1,
J5a,5b 13.3 Hz, H-5b), 2.66 (dd, 1 H, H-2), 2.42 (s, 3
H, Ts); HRMS (LSIMS): m/z 436.14244 [M+H]+;
Calcd for C12H25NO7S: 436.14300.
Methyl 4-O-benzyl-2-C:3-N-carbonyl-2,3-dideoxy
a
1
1
-3-N-tosylamino-a-l-lyxopyranoside (11).ÐTo
1760 (C=O) cm ; H NMR (CDCl3): ꢇ 5.01 (d, 1
H, J1,2 1.6 Hz, H-1), 4.29 (m, 1 H, H-3), 3.89±3.97
(m, 3 H, H-4,5a,5b), 3.50 (s, 3 H, OCH3), 3.49 (dd,
1 H, J2,3 5.5 Hz, H-2); HRMS (LSIMS): m/z
174.0766 [M+H]+; Calcd for C7H12NO4:
174.0766.
solution of compound 10 (0.80 g, 1.83 mmol) in
THF (8 mL) was added TPP (0.76 g, 2.75 mmol)
and DEAD (0.36 mL, 2.75 mmol). The mixture
was boiled under re¯ux for 4 h, then cooled and
concentrated. The crude product was puri®ed by
chromatography (4:1 hexane±EtOAc) to a€ord 11
Benzyl 2-deoxy-2-C-(N-tosylcarbamoyl)-a-l-arab-
inopyranoside (14).ÐCompound 14 was obtained
from 3,4-di-O-trimethylsilyl-l-arabinal 2 according
to the procedure described for 4 using benzyl alcohol
as syrup (0.35 g, 45.8%); [ꢁ]d
58.6ꢀ (c 2,
1
CH2Cl2); IR (®lm): ꢆ 1798 (C=O) cm ; 1H
NMR (CDCl3): ꢇ 4.89 (d, 1 H, J1,2 1.0 Hz, H-1),

40
O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
instead of MeOH; yield 65%; [ꢁ]d +7.0ꢀ (c 0.2,
CH2Cl2); IR (®lm): ꢆ 3276 (OH), 1704 (C=O) cm ;
1797 (C=O) cm ; H NMR (CDCl3): ꢇ 5.18 (d, 1
H, J1,2 1.3 Hz, H-1), 4.56 and 4.78 (2 d, each 1 H, J
11.5 Hz, Bn), 4.16±4.36 (m, 2 H, H-3,4), 4.04 (dd, 1
H, J4,5a 4.3, J5a,5b 12.9 Hz, H-5a), 3.90 (bd, 1 H, H-
5b), 3.46 (dd, 1 H, J2,3 6.3 Hz, H-2), 2.45 (s, 3 H,
Ts); HRMS (LSIMS): m/z 404.11664 [M+H]+;
Calcd for C20H22NO6S: 404.11678.
1
1
1
1H NMR (CDCl3): ꢇ 4.36 (d, 1 H, J1,2 8.3 Hz, H-1),
4.04 (dd, 1 H, J4,5a 1.8, J5a,5b 12.3 Hz, H-5a), 3.84 (dd,
1 H, J2,3 10.5, J3,4 3.2 Hz, H-3), 3.78 (bs, 1 H, H-4),
3.25 (d, 1 H, H-5b), 2.85 (dd, 1 H, H-2), 2.35 (s, 3 H,
Ts). Anal. Calcd for C20H23NO7S: C, 56.99; H, 5.50;
N, 3.32. Found: C, 57.3; H, 5.6; N, 3.3.
Benzyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-
a-d-lyxopyranoside (19).ÐCompound 19 was
obtained from 18 according to the procedure
described for 12; yield 58.0% isolated as a syrup; [ꢁ]d
12.2ꢀ (c 1.1, CH2Cl2); IR (®lm): ꢆ 3410 (OH, NH),
Methyl 2-deoxy-2-C-(N-tosylcarbamoyl)-b-d-xylo-
pyranoside (15).ÐCompound 15 was obtained
from 3,4-di-O-trimethylsilyl-d-xylal according to
the procedure described for 4; yield 58%; mp 180±
182ꢀC; [ꢁ]d +15.3ꢀ (c 0.4, MeOH); IR (KBr): ꢆ 1720
1
1
1772 (C=O) cm ; H NMR (CDCl3): ꢇ 5.20 (d, 1
H, J1,2 1.5 Hz, H-1), 4.61 and 4.84 (2 d, each 1 H, J
11.5 Hz, Bn), 4.34 (dd, 1 H, J4,5a 4.0, J5a,5b 12.1 Hz,
H-5a), 3.90±4.06 (m, 3 H, H-3,4,5), 3.51 (bm, 1 H,
H-2). Anal. Calcd for C13H15NO4: C, 62.63; H, 6.06;
N, 5.62. Found: C, 62.8; H, 6.2; N, 5.5.
1 1
(C=O) cm ; H NMR (CDCl3): ꢇ 4.30 (d, 1 H, J1,2
8.3 Hz, H-1), 4.03 (dd, 1 H, J4,5a 5.3, J5a,5b 11.5 Hz,
H-5a), 3.82 (dd, 1 H, J2,3 10.1, J3,4 8.7 Hz, H-3), 3.67
(m, 1 H, H-4), 3.45 (s, 3 H, OCH3), 3.25 (dd, 1 H,
J4,5b 9.9 Hz, H-5b), 2.46 (dd, 1 H, H-2), 2.35 (s, 3 H,
Ts). Anal. Calcd for C14H19NO7S: C, 48.69; H, 5.54;
N, 4.05. Found: C, 48.3; H, 5.6; N, 4.0.
Methyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-
a-l-lyxopyranoside (13).ÐCompound 13 was
obtained from 17 according to the procedure
described for 12 (60.0%). Spectral and analytical
data of 13 are described above.
Benzyl 2-deoxy-2-C-(N-tosylcarbamoyl)-b-d-xylo-
pyranoside (16).ÐCompound 16 was obtained
from 3,4-di-O-trimethylsilyl-d-xylal according to
the procedure described for 4 using benzyl alcohol
instead of MeOH; yield 59% isolated as a syrup,
[ꢁ]d 10.0ꢀ (c 0.95, CH2Cl2); IR (®lm): ꢆ 3270
Methyl 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosyl-
amino-b-d-ribopyranoside (20).ÐCompound 20
was obtained from 15 according to the procedure
described for 11 (47.0%); mp 152±154ꢀC; [ꢁ]d
+7.7ꢀ (c 0.5, CH2Cl2); IR (®lm): ꢆ 3280 (OH),
1
1
(OH), 1714 (C=O) cm ; H NMR (CDCl3): ꢇ
4.44 (d, 1 H, J1,2 8.3 Hz, H-1), 4.32 and 4.69 (2 d,
each 1 H, J 11.8 Hz, Bn), 3.98 (dd, 1 H, J4,5a 5.2,
J5a,5b 11.3 Hz, H-5a), 3.80 (dd, 1 H, J2,3 10.3, J3,4
9.0 Hz, H-3), 3.66 (m, 1 H, H-4), 3.38 (bt, 1 H, J4,5b
10.5 Hz, H-5b), 2.64 (dd, 1 H, H-2), 2.37 (s, 3 H,
Ts). Anal. Calcd for C14H19NO7S: C, 56.99; H,
5.50; N, 3.32. Found: C, 56.7; H, 5.5; N, 3.3.
1
1
1795 (C=O) cm ; H NMR (CDCl3): ꢇ 4.87 (d, 1
H, J1,2 1.4 Hz, H-1), 4.50 (ddd, 1 H, J3,4 2.9, J4,5a
6.7, J4,5b 9.9 Hz, H-4), 4.36 (ddd, 1 H, J3,5a 1.0, J2,3
6.7 Hz, H-3), 3.98 (ddd, 1 H, J5a,5b 10.7 Hz, H-5a),
3.73 (t, 1 H, H-5b), 3.38 (dd, 1 H, H-2), 3.40 (s, 3
H, OCH3), 2.47 (s, 3 H, Ts); HRMS (EI): m/z
327.0775 (M+ꢂ); Calcd for C14H17NO6S: 327.0776.
Anal. Calcd for C14H17NO6S: C, 51.36; H, 5.23; N,
4.28. Found: C, 51.4; H, 5.2; N, 4.3
Methyl 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosyl-
amino-a-l-lyxopyranoside (17).ÐCompound 17
was obtained from 4 according to the procedure
described for 11; yield 52% isolated as a syrup; [ꢁ]d
24.3ꢀ (c 0.9, CH2Cl2); IR (®lm): ꢆ 3453 (OH),
Benzyl 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosyl-
amino-b-d-ribopyranoside (21).ÐCompound 21
was obtained from 16 according to the procedure
described for 11 (42.0%); mp 101±103ꢀC; [ꢁ]d
25.2ꢀ (c 1, CH2Cl2); IR (®lm): ꢆ 3383 (OH), 1796
(C=O) cm ; H NMR (CDCl3): ꢇ 5.08 (d, 1 H,
J1,2 1.5 Hz, H-1), 4.58 (m, 1 H, H-4), 4.50 and 4.73
(2 d, each 1 H, J 11.6 Hz, Bn), 4.38 (ddd, 1 H, J2,3
6.6, J3,5a 1.1, J3,4 2.7 Hz, H-3), 3.98 (bdd, 1 H, J4,5a
6.6, J5a,5b 10.5 Hz, H-5a), 3.74 (t, 1 H, J4,5b
10.1 Hz, H-5b), 3.49 (dd, 1 H, H-2), 2.46 (s, 3 H,
Ts); HRMS (EI): m/z 403.1085 (M+ꢂ); Calcd for
C20H21NO6S: 403.10895. Anal. Calcd for
C20H21NO6S: C, 59.53; H, 5.25; N, 3.47. Found: C,
59.0; H, 5.3; N, 3.3.
1
1
1798 (C=O) cm ; H NMR (CDCl3): ꢇ 4.96 (d, 1
H, J1,2 1.3 Hz, H-1), 4.26 (bm, 1 H, H-4), 4.22
(ddd, 1 H, J2,3 6.3, J3,4 3.1, J3,5b 1.4 Hz, H-3), 4.02
(dd, 1 H, J4,5a 4.7, J5a,5b 12.5 Hz, H-5a), 3.86 (m, 1
H, J4,5b 2.2 Hz, H-5b), 3.45 (s, 1 H, OCH3), 3.44
(dd, 1 H, H-2), 2.46 (s, 3 H, Ts); HRMS (LSIMS):
1
1
m/z
C14H17NNaO6S: 350.06742.
350.06698
[M+Na]+;
Calcd
for
Benzyl 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosyl-
amino-a-l-lyxopyranoside (18).ÐCompound 18
was obtained from 14 according to the procedure
described for 11 (46.2%); mp 122±123ꢀC [ꢁ]d
64.6ꢀ (c 1.1, CH2Cl2); IR (®lm): ꢆ 3455 (OH),

O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
41
Methyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-b-d-
ribopyranoside (22).ÐCompound 22 was obtained
from 20 according to the procedure described for
12; yield 63.2% isolated as a syrup; [ꢁ]d 43.2ꢀ (c
0.4, CH2Cl2); IR (®lm): ꢆ 3319 (NH, OH), 1745
(C=O) cm ; H NMR (CDCl3): ꢇ 4.85 (d, 1 H,
J1,2 1.5 Hz, H-1), 4.33 (bm, 1 H, H-4), 3.97 (t, 1 H,
J2,3 5.7, J3,4 4.1 Hz, H-3), 3.82 (dd, 1 H, J4,5a 5.9,
J5a,5b 10.8 Hz, H-5a), 3.67 (dd, 1 H, J4,5b 8.5 Hz, H-
5b), 3.37 (dt, 1 H, J2,NH 1.6 Hz, H-2), 3.32 (s, 3 H,
OCH3); HRMS (LSIMS): m/z 174.0766 [M+H]+;
Calcd for C7H12NO4: 174.0766.
(10 mL) in the presence of 10% Pd-C under stan-
dard conditions to a€ord 26 as a syrup (0.51 g,
99%); [ꢁ]d +15.4ꢀ (c 1, H2O); 1H NMR (D2O) (5:4
mixture of amide isomers): ꢇ 4.50 (d, 0.6 H, J1,2
8.6 Hz, H-1 major), 4.47 (d, 0.4 H, J1,2 8.6 Hz, H-1
minor), 4.07 (dd, 0.6 H, J3,4 3.3, J2,3 11.0 Hz, H-3
major), 4.00 (dd, 1 H, J4,5a 2.1, J5a,5b 13.2 Hz, H-5a
major and minor), 3.99 (dd, 0.4 H, J2,3 11.0, J3,4
3.3 Hz, H-3 minor), 3.89 (m, 1 H, H-4), 3.69 (dd,
0.6 H, J4,5b 3.3 Hz, H-5b major), 3.68 (dd, 0.4 H,
J4,5b 3.3 Hz, H-5b minor), 3.49 and 3.50 (2 s, 3 H,
OCH3 major and minor), 2.72 (bs, 0.6 H, H-2a
major), 2.66 (dd, 0.4 H, J2,3 11.0 Hz, H-2a minor),
1.25 and 1.50 (2 s, 9 H, t-Bu major and minor);
HRMS (EI): m/z 259.1062 [M-CH3OH]+; Calcd
for C11H17NO6: 259.1056.
1
1
Benzyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-
b-d-ribopyranoside (23).ÐCompound 23 was
obtained from 21 according to the procedure
described for 12; yield 67% isolated as a syrup; [ꢁ]d
77.9ꢀ (c 0.7, CH2Cl2); IR (®lm): ꢆ 3298 (NH,
Methyl 4-O-benzyl-3-O-tert-butyldimethylsilyl-2-
deoxy-2-C-(N-tosylcarbamoyl)-a-l-arabinopyrano-
side (27).ÐCompound 27 was obtained from 9
according to the procedure described for 4; yield
48% isolated as a syrup; [ꢁ]d +65.6ꢀ (c 1, CH2Cl2);
1
OH), 1746 (C=O) cm ; 1H NMR (CDCl3): ꢇ 5.13
(d, 1 H, J1,2 1.5 Hz, H-1), 4.45 (m, 1 H, H-4), 4.04
(m, 1 H, H-3), 3.90 (dd, 1 H, J4,5a 5.9, J5a,5b
10.7 Hz, H-5a), 3.76 (dd, 1 H, J4,5b 8.7 Hz, H-5b),
3.49 (m, 1 H, J2,NH 1.1, J2,3 5.6 Hz, H-2); Anal.
Calcd for C13H15NO4: C, 62.63; H, 6.06; N, 5.62.
Found: C, 62.6; H, 6.3; N, 5.5.
1
IR (®lm): ꢆ 1717 (C=O) cm ; 1H NMR (CDCl3):
ꢇ 4.25 (d, 1 H, J1,2 8.3 Hz, H-1), 4.16 (dd, 1 H, J4,5a
2.3, J5a,5b 12.9 Hz, H-5a), 4.07 (dd, 1 H, J3,4 3.1 Hz,
H-3), 3.54 (bt, 1 H, H-4), 3.36 (dd, 1 H, J4,5b
1.1 Hz, H-5b), 3.35 (s, 3 H, OCH3), 2.83 (dd, 1 H,
J2,3 10.4 Hz, H-2), 2.51 (s, 3 H, Ts), 0.90, 0.10, and
0.09 (3 s, 3,3,9 H, t-BuMe2Si); HRMS (LSIMS): m/z
518.20312 [M-OCH3]+; Calcd for C26H36NO6SSi:
518.20326.
Methyl 3,4-di-O-benzyl-2-C-(N-tert-butoxycarb-
onyl)carbamoyl-2-deoxy-a-l-arabinopyranoside
(25).ÐTo a solution of 24 (0.18 g, 0.5 mmol) in
THF (5 mL) was added KH (0.15 g, 20% disper-
sion in mineral oil), and the resulting suspension
was stirred for 10 min. Subsequently, 2-(tert-butoxy-
carbonyloxyi mino)-2-phenylacetonitrile (BOC-ON;
0.15 g, 0.6 mmol) was added and the stirring was
continued for an additional 5 min. The mixture was
then treated with t-BuOH (2 mL) and diluted with
toluene (25 mL). The resulting solution was washed
with water, dried, and concentrated. The crude
product was puri®ed by chromatography using
6:1:3:2 CHCl3±EtOAc±toluene±hexane as eluent to
a€ord 25 (0.22 g, 94%); mp 95±96ꢀC; [ꢁ]d +54.6ꢀ
(c 1, CH2Cl2); IR (®lm): ꢆ 3320 (NH), 1775 (C=O)
Methyl 3-O-tert-butyldimethylsilyl-2-deoxy-2-C-
(N-tosylcarbamoyl)-a-l-arabinopyranoside (28).Ð
Catalytic hydrogenolysis of 27 in MeOH in the
presence of 10% Pd-C under conditions described
for 26 a€orded 28; yield 92.6% isolated as a syrup;
[ꢁ]d +48.7ꢀ (c 1.2, CH2Cl2); IR (®lm): ꢆ 3657
1
1
(OH), 3211 (NH), 1717 (C=O) cm ; H NMR
(CDCl3): ꢇ 4.13 (dd, 1 H, J4,5a 1.9, J5a,5b 13.0 Hz,
H-5a), 4.11 (d, 1 H, J1,2 8.3 Hz, H-1), 4.05 (dd, 1 H,
J2,3 10.3, J3,4 3.4 Hz, H-3), 3.67 (bs, 1 H, H-4), 3.43
(d, 1 H, J4,5b 1.2 Hz, H-5b), 3.30 (s, 3 H, OCH3),
2.62 (dd, 1 H, H-2), 2.42 (s, 3 H, Ts), 0.08, 0.05,
and 0.80 (3 s, 3,3,9 H, t-BuMe2Si); HRMS
(LSIMS): m/z 460.18211 [M+H]+; Calcd for
C20H34NO7SSi: 460.18253.
1 1
cm ; H NMR (CDCl3): ꢇ 7.56 (bs, 1 H, NH), 4.61
and 4.75 (2 d, each 1 H, J 12.4 Hz, Bn), 4.47 (dd,1
H, J1,2 8.3 Hz, H-1), 4.43 and 4.48 (2 d, each 1 H, J
11.3 Hz, Bn), 4.14 (dd, 1 H, J4,5a 2.2, J5a,5b 13.0 Hz,
H-5a), 3.87 (dd, 1 H, J2,3 11.0, J3,4 3.1 Hz, H-3),
3.63 (bt, 1 H, H-4), 3.49 (s, 3 H, OCH3), 3.31 (dd, 1
H, J4,5b 0.9 Hz, H-5b), 2.90 (bs, 1 H, H-2), 1.49 (s, 9
H, t-Bu). Anal. Calcd for C26H33NO7: C, 66.22; H,
7.05; N, 2.96. Found: C, 66.3; H, 7.1; N, 3.1.
Methyl 3-O-tert-butyldimethylsilyl-2-C:4-N-carb-
onyl-2,4-dideoxy-4-N-tosylamino-b-d-xylopyrano-
side (29).ÐCompound 29 was obtained according
to the procedure described for 11; yield 45.3%
isolated as a syrup; [ꢁ]d 7.4ꢀ (c 1, CH2Cl2); IR
Methyl 2-C-(N-tert-butoxycarbonyl-carbamoyl)-
2-deoxy-a-l-arabinopyranoside (26).ÐCompound
25 (0.83 g, 1.8 mmol) was hydrogenated in MeOH
1
1
(®lm): ꢆ 1801 (C=O) cm ; H NMR (CDCl3): ꢇ
4.88 (d, 1 H, J1,2 1.0 Hz, H-1), 4.26 (ddd, 1 H, J3,4

42
O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
2.3, J4,5a 6.2, J4,5b 8.6 Hz, H-4), 4.07 (dd, 1 H, J2,3
6.7 Hz, H-3), 3.64 (dd, 1 H, J5a,5b 11.8 Hz, H-5a),
3.44 (m, 1 H, H-5), 3.35 (dd, 1 H, H-2), 3.33 (s, 3
H, OCH3), 2.45 (s, 3 H, Ts), 0.10, 0.20, and 0.90 (3
s, 3,3,9 H, t-BuMe2Si). Anal. Calcd for C20H31
NO6SSi: C, 54.39; H, 6.60; N, 2.96. Found: C,
54.3; H, 6.7; N, 2.8.
Methyl 2-C-[carbethoxymethylene (triphenylphos-
phorane)]carbonyl-2,3-dideoxy-3-N-tosylamino-4-ulo-
b-d-erythro-pyranoside
(35).ÐCompound
31
(0.3 g, 0.092 mmol) in toluene (2 mL) was treated
with ethyl (triphenylphosphoranylidene)acetate
(34; 0.038 g, 0.11 mmol) and kept at room tem-
perature for 8 h. Subsequently, the solvent was
evaporated and the residue was puri®ed by chro-
matography to give 35 as a foam (0.032 g, 58%);
[ꢁ]d +51.7ꢀ (c 1, CH2Cl2); IR (®lm): ꢆ 3366 (NH),
Methyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-
b-d-erythro-pyranosid-4-ulose (30).ÐCompound
30 was obtained from 13 or 22 according to the
procedure described for 31; yield 93% isolated as a
syrup; [ꢁ]d +36.4ꢀ (c 0.25, CH2Cl2); IR (®lm): ꢆ
3313 (NH), 1769 (C=O, ꢀ-lactam), 1731 (C=O)
1
1
1734 (C=O) cm ; H NMR (CDCl3): ꢇ 5.47 (d, 1
H, J1,2 2.1 Hz, H-1), 5.03 (d, 1 H, J3,NH 7.8 Hz, NH),
4.68 (dd, 1 H, J2,3 4.9 Hz, H-2), 4.27 (m, 1 H, H-3),
3.85 and 3.93 (2 d, each 1H, J5a,5b 16.2 Hz, H-5a,5b),
3.65 and 3.81 (2 dq, each 1 H, Et), 3.51 (s, 3 H,
OCH3), 2.36 (s, 3 H, Ts), 0.69 (t, 3 H, Et); MS (EI):
m/z 673 (M+ꢂ). Anal. Calcd for C36H36NO8PS: C,
64.17; H, 5.38; N, 2.07. Found: C, 64.6; H, 6.0; N,
1.8.
1
1
cm ; H NMR (CDCl3): ꢇ 6.20 (bm, 1 H, NH),
5.10 (d, 1 H, J1,2 1.1 Hz, H-1), 4.17 and 4.44 (2 d,
each 1 H, J5a,5b 18.2 Hz, H-5a,5b), 4.01 (bd, 1 H,
J2,3 5.2 Hz, H-3), 3.77 (m, 1 H, J2,NH 1.8 Hz, H-2),
3.45 (s, 3 H, OCH3); HRMS (EI): m/z 171.05388
(M+ꢂ); Calcd for C7H9NO4: 171.05316.
Methyl 2-C:3-N-carbonyl-2,3-dideoxy-3-N-tosyl-
amino-b-d-erythro-pyranosid-4-ulose (31).ÐCom-
pound 17 or 20 (0.30 g, 0.91 mmol) dissolved in a
mixture of CCl4 (1.8 mL), MeCN (0.6 mL), and
water (0.5 mL), was oxidized with RuO2±NaIO4 in
the presence of benzyltriethylammonium chloride
according to [14] to a€ord 31 (0.27 g, 91%); mp
Methyl 3-amino-2-C:3-N-carbonyl-4-C-ethoxy-
carbonylmethylene-2,3,4-trideoxy-b-d-erythro pyr-
anoside (36).ÐCompound 30 (0.021 g, 0.12 mmol)
in toluene (0.8 mL) was treated with ethyl (triph-enyl-
phosphoranylidene)acetate (34; 0.063 g, 0.18 mmol)
and kept for 18 h at room temperature. Subsequently,
the mixture was concentrated and puri®ed by chro-
matography to give 36 as a syrup (0.014 g, 48%);
[ꢁ]d 7.4ꢀ (c 0.9, CH2Cl2); IR (®lm): ꢆ 3316 (NH),
1768 (C=O, ꢀ-lactam), 1711 (C=O), 1650 (C=O)
ꢀ
131±132 C; [ꢁ]d 13.1ꢀ (c 1, CH2Cl2); IR (®lm): ꢆ
1
1810 (C=O, ꢀ-lactam), 1740 (C=O) cm ; 1H
NMR (CDCl3): ꢇ 5.06 (d, 1 H, J1,2 1.2 Hz, H-1),
4.25 (bd, 1 H, J2,3 5.8 Hz, H-3), 3.99 and 4.05 (2 d,
each 1 H, J 18.2 Hz, H-5a,5b), 3.75 (dd, 1 H, H-2),
3.40 (s, 3 H, OCH3), 2.47 (s, 3 H, Ts); HRMS
(LSIMS): m/z 325.0615 (M+ꢂ); Calcd for
C14H15NO6S: 325.0620.
1 1
cm ; H NMR (CDCl3): ꢇ 6.86 (m, 1 H, CH), 6.33
(bd, 1 H, NH), 5.09 (d, 1 H, J1,2 1.3 Hz, H-1), 4.90
(m, 1 H, J3,4 4.7 Hz, H-3), 4.44 (m, 1 H, H-5a), 4.18
(dq, 2 H, Et), 4.13 (dt, 1 H, J3,5 1.0, J4,5b 1.0, J5a,5b
15.3 Hz, H-5b), 3.40 (s, 3 H, OCH3), 3.38±3.41 (m,
1 H, H-2), 1.29 (t, 3 H, Et); HRMS (LSIMS): m/z
Benzyl 3-amino-2-C:3-N-carbonyl-2,3-dideoxy-b-
d-erythro-pyranosid-4-ulose (32).ÐCompound 19
or 23 (0.11 g, 0.44 mmol) was dissolved in Me2SO
(0.9 mL) and Ac2O (0.26 mL) and kept at 0ꢀC for
48 h. Subsequently, EtOH (0.5 mL) and H2O
(1 mL) were added and the temperature was
allowed to rise to room temperature. After 30 min,
30% NH4OH (1.5 mL) was added and the mixture
was extracted with CH2Cl2. The extract was
washed, dried, and concentrated. The product was
puri®ed by chromatography to give 32 as a syrup
(0.035 g, 35%); [ꢁ]d 16.2ꢀ (c 0.45, CH2Cl2); IR
(®lm): ꢆ 3396 (NH), 1780 (C=O, ꢀ-lactam), 1743
242.10272
242.10283.
[M+H]+;
Calcd
C11H16NO5:
X-ray structure determination of compounds 20
and 31.ÐThe crystals suitable for X-ray structure
analysis were obtained by slow evaporation of a
hexane±Et2O solution. Data were collected on an
Enraf±Nonius Mach3 di€ractometer with graphite
monochromatized CuKꢁ radiation in the ꢃ-range
3.73 to 74.93ꢀ. Lorentz and polarization correc-
tions were applied to the independent re¯ections.
The structures were solved by direct methods [20]
1 1
(C=O) cm ; H NMR (CDCl3): ꢇ 5.32 (d, 1 H, J1,2
1
Tables of atomic coordinates, bond lengths, and bond
1.2 Hz, H-1), 4.23 and 4.46 (2 d, each 1 H, J5a,5b
18.2 Hz, H-5a,5b), 4.02 (d, H, J2,3 5.3 Hz, H-3), 3.79
(m, 1 H, H-2). Anal. Calcd for C13H13NO4: C,
63.15; H, 5.39; N, 5.66. Found: 63.1; H, 5.5; N, 5.4.
angles have been deposited with the Cambridge Crystal-
lographic Data Centre. These tables may be obtained, on
request, from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 IEZ, UK.

O. Zegrocka et al./Carbohydrate Research 307 (1998) 33±43
43
and re®ned against F2 using SHELXL93 [21].1 All
but hydroxy H-atoms were placed in ideal posi-
tions and re®ned with the riding model and ®xed
isotropic displacement parameters. Crystal-
lographic parameters, data collection and structure
re®nement details are shown in Tables 1 and 2.2
[11] A.M. Pantard and S.A. Evans, J. Org. Chem., 53
(1988) 2300±2303.
[12] O. Mitsunobu, J. Kimura, K. Izumi, and N.
Yamagida, Bull. Chem. Soc. Jpn., 49 (1976) 510±
513.
[13] H.H. Brandstetter and E. Zbiral, Helv. Chim. Acta,
63 (1980) 327±343; R.D. Guthrie, I.D. Jenkins, R.
Yamasaki, B.W. Skeleton, and A.H. White, J.
Chem. Soc., Perkin Trans. 1, (1981) 2328±2334;
R.J. Ferrier, P. Schmidt, and P.C. Tyler, J. Chem.
Soc., Perkin Trans. 1, (1985) 301±303.
[14] N. Nakata, Tetrahedron, 19 (1963) 1959±1963; P.E.
Morris Jr., D.E. Kiely, G.S. Vigee, and P. Kovac,
J. Carbohydr. Chem., 9 (1990) 661±673.
[15] M. Chmielewski, Z. Ka•uza, H. Dodziuk, K.
Suwinska, D. Rosenbaum, H. Duddeck, P.
Magnus, and J.C. Hu€man, Carbohydr. Res., 203
(1990) 183±194.
References
[1] D.J. Hart and D.-Ch. Ha, Tetrahedron Lett., 26
(1985) 5493±5496; J. Gallucci, D.-Ch. Ha, and D.J.
Hart, Tetrahedron, 45 (1989) 1283±1292.
[2] A. Knierzinger and A. Vasella, J. Chem. Soc.,
Chem. Commun., (1984) 9±11.
[3] M. Chmielewski and J. Grodner, J. Carbohydr.
Chem., 11 (1992) 691±698.
[4] C. Be•zecki and M. Chmielewski, J. Carbohydr.
Chem., 13 (1994) 1103±1114; J. Grodner and M.
Chmielewski, Tetrahedron, 51 (1995) 829±836.
[5] D. Mostowicz and M. Chmielewski, Carbohydr.
Lett., 1 (1994) 95±98.
[16] Z. Urbanczyk-Lipkowska, K. Suwinska, R.
Luboradzki, D. Mostowicz, Z. Ka•uza, J. Grodner,
and M. Chmielewski, Carbohydr. Res., 256 (1994)
1±11.
[17] Z. Urbanczyk-Lipkowska, K. Suwinska, D. Mos-
towicz, and M. Chmielewski, J. Chem. Cryst., 25
(1995) 693±699.
[18] J.E. Baldwin, A.J. Edwards, Ch.N. Farthing, and
A.T. Russell, Synlett, (1993) 49±50 and references
cited therein.
[19] J.E. Baldwin, R.M. Adlington, Ch.R.A. Godfrey,
D.W. Gollins, M.L. Smith, and A.T. Russell, Syn-
lett, (1993) 51±53.
[20] G.M. Sheldrick, Acta Cryst., A 46 (1990) 467.
[21] G.M. Sheldrick, Shelxl 93. Program for Re®nement
of Crystal Structure. University of Gottingen,
1993.
[6] M. Chmielewski, Z. Ka•uza, J. Grodner, and R.
Urbanski, in R.M. Guliano (Ed.), Cycloaddition
Reactions in Carbohydrate Chemistry, ACS Sym-
posium Series, 494 (1992) 50±65.
[7] M. Chmielewski, Z. Ka•uza, and B. Furman, J.
Chem. Soc., Chem. Commun., (1996) 2689±2696.
[8] R.H. Hall, A. Jordaan, and G.J. Laurens, J. Chem.
Soc., (1973) 38±44; R.H. Hall, A. Jordaan, and
O.G. de Villiers, J. Chem. Soc., (1975) 626±629.
[9] D. Mostowicz, C. Be•zecki, and M. Chmielewski,
J. Carbohydr. Chem., 7 (1988) 805±810.
[10] D. Mostowicz, O. Zegrocka, and M. Chmielewski,
Carbohydr. Res., 212 (1991) 283±288.