Synthesis of some O-, S- and N-glycosides of hept-2-ulopyranosonamides

Article abstract of DOI:10.1016/j.carres.2009.02.011

(O-Peracylated α-d-gluco- and -galacto-hept-2-ulopyranosylbromide)onamides gave the corresponding (alkyl β-d-glyco-hept-2-ulopyranoside)onamides under Koenigs-Knorr conditions, and similar aryl glycosides were obtained with sodium phenolates; (aryl and he

Full text of DOI:10.1016/j.carres.2009.02.011

Carbohydrate Research 344 (2009) 921–927
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Carbohydrate Research
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Note
Synthesis of some O-, S- and N-glycosides of hept-2-ulopyranosonamides
Veronika Nagy a,1, Katalin Czifrák a, Attila Bényei b, László Somsák a,
*
a Department of Organic Chemistry (POB 20), University of Debrecen, H-4010 Debrecen, Hungary
b Department of Physical Chemistry (POB 7), University of Debrecen, H-4010 Debrecen, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
(O-Peracylated
(alkyl b- -glyco-hept-2-ulopyranoside)onamides under Koenigs–Knorr conditions, and similar aryl glyco-
sides were obtained with sodium phenolates; (aryl and hetaryl 2-thio-b- -gluco-hept-2-ulopyrano-
side)onamides were formed with thiophenols in the presence of K2CO3 in acetone, and reactions with
aniline in CH2Cl2 furnished (N-phenyl b- -glyco-hept-2-ulopyranosylamine)onamides. Some deprotected
derivatives of -gluco configuration obtained by the Zemplén protocol showed no significant inhibition
against rabbit muscle glycogen phosphorylase b.
a-D-gluco- and -galacto-hept-2-ulopyranosylbromide)onamides gave the corresponding
Received 30 December 2008
Received in revised form 6 February 2009
Accepted 7 February 2009
D
D
Available online 14 February 2009
D
D
Keywords:
Hept-2-ulopyranosonamides
O-glycoside
Ó 2009 Elsevier Ltd. All rights reserved.
S-glycoside
N-glycoside
C-(2,3,4,6-Tetra-O-acyl-1-bromo-1-deoxy-b-D-glycopyranosyl)for-
(entries 8 and 9), and similarly, those of 2 with EtOH or n-BuOH
mamides (3,4,5,7-tetra-O-acyl-
a
-
D
-glyco-hept-2-ulopyranosylbro-
(entries 12 and 13) gave significant amounts of the corresponding
mide)onamides)1–5 (e.g., 11,2 and 25) proved versatile starting
materials for the syntheses of diverse monosaccharide derivatives.
Thus, their reactions with nucleophiles such as H2O,6 azide ion,7,8
nitriles,9 acetone and DMSO,10 cyanate and thiocyanate ions,2,3,6
the latter two resulting in cyclisations to give glycopyranosylid-
ene-spiro-(thio)hydantoins efficient glucose analogue glycogen
phosphorylase inhibitors (GPIs),11–15 as well as eliminations to
O-peracylated a-D
-glyco-hept-2-ulopyranosonamides 152 and 164,5
besides the expected glycosides 7 and 8 as well as 12 and 14,
respectively. The reaction of 2-nitrophenol with 1 in the presence
of AgOTf and Et3N or DBU gave 9 in 32% and 24% yields, respec-
tively. Under phase transfer conditions (2-nitrophenol in CH2Cl2,
ꢀ1 M NaOH in water, Bu4NBr) 9 could not be observed in the reac-
tion mixture. Therefore, we turned to the sodium salt of 2-nitro-
phenol (entry 10), however, this reaction again gave 9 in a low
yield accompanied by 15. On the contrary, sodium 4-nitropheno-
late (entry 11) gave the expected 10 in good yield. The steric acces-
sibility of the nucleophilic part of the reagents may be responsible
for the large differences in the outcomes of these reactions. Depro-
tection of glycosides 4 and 12 was effected by the Zemplén proto-
col, while 10 was deacetylated by KCN/MeOH to give 5, 13 and 11,
respectively.
substituted glycals1 were reported. Several derivatives of
with a CONH2 moiety in the -anomeric position were shown to
D-glucose
a
be GPIs,16–18 although a clearcut conclusion for the role of this group
could not yet be drawn.8 In order to produce new compounds of this
type, and to study the reactivity of (hept-2-ulopyranosylbromide)
onamides towards further nucleophiles, we have investigated
the preparation of some O-, S- and N-glycosides derivatives from 1
and 2.
Treatment of 1 with MeOH or EtOH as the solvent in the pres-
ence of Ag2CO319 gave methyl and ethyl glycosides 3 and 4, respec-
tively (Table 1, entries 1 and 2). Decreasing the amount of EtOH in
CH2Cl2 as co-solvent was investigated (entries 3–6) to show that as
few as 2 equiv of the alcohol gave satisfactory results. Changing the
promoter to the more efficient AgOTf significantly reduced the
reaction time and increased the yield (entry 6). A large excess of
n-BuOH gave the corresponding glycoside 7 in satisfactory yield
(entry 7). On the other hand, reactions of 1 with t-BuOH or BnOH
For the formation of N-phenyl-glycosylamines,20,21 1 and 2
were reacted with aniline to give 17 and 18, respectively (Scheme
1). The latter was deprotected by the Zemplén method to yield 19.
To obtain S-glycosides,22 2 was reacted with thiols in acetone in
the presence of K2CO3 to give the expected products 20, 22 and 24
in good yields (Scheme 1). For deprotection of these compounds
the Zemplén method was applied to give 21, 23 and 25, respec-
tively, without difficulties.
Structure elucidation of the new compounds was straightfor-
ward by NMR methods. The 4C1 conformation of the pyranose rings
followed from the vicinal proton–proton coupling constants. For
most representative compounds, the configuration of the anomeric
carbon was established on the basis of three-bond heteronuclear
couplings between H-2 (parent sugar numbering) and the
* Corresponding author. Tel.: +36 52 512 900/22348; fax: +36 52 453 836.
E-mail address: somsak@tigris.unideb.hu (L. Somsák).
1
Present address: Department of Biochemistry and Medical Chemistry, Medical
School, University of Pécs, H-7601 Pécs, POB 99, Hungary.
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.02.011

922
V. Nagy et al. / Carbohydrate Research 344 (2009) 921–927
Table 1
Preparation of (alkyl or aryl b-D-glyco-hept-2-ulopyranosid)onamides
R1
R1
R
R
R1
R
R'OH or
R2
R2
R2
O
O
O
R'ONa
OR'
CONH2
OH
CONH2
R
R
R
+
promoter,
solvent,
rt
R
R
R
CONH2
Br
1 R = R1 = OAc, R2 = H
2 R = R2 = OBz, R1 = H
3, 4, 6-10 R = R1 = OAc, R2 = H
12, 14
R = R2 = OBz, R1 = H
15 R = R1 = OAc, R2 = H
16 R = R2 = OBz, R1 = H
i
4
10
12
5 R = R1 = OH, R2 = H, R' = Et (98%)
11 R = R1 = OH, R2 = H, R' = 4-NO2-C6H4 (99%)
13 R = R2 = OH, R1 = H, R' = Et (98%)
ii
i
i
NaOMe, MeOH, rt
ii KCN, MeOH, rt
Entry
Starting compound
R0OH or R0ONa (equiv)
Promoter
Solvent
Reaction time
Product(s) (Yield [%])
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
MeOH (as solvent)
EtOH (as solvent)
EtOH (70)
EtOH (10)
EtOH (2)
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgOTf
Ag2CO3
Ag2CO3
Ag2CO3
MeOH
EtOH
2 h
2 h
2 h
1 d
2 d
5 min
2 d
7 d
7 d
3 (89)
—
—
—
—
—
—
—
4 (85)
4 (84)
4 (93)
4 (50)
4 (80)
6 (90)
7 (21)
8 (31)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
EtOH (2)
n-BuOH (70)
t-BuOH (10)
C6H5CH2OH (10)
15 (29)
15 (9)
ONa
10
11
1
1
—
—
CH2Cl2
CH3CN
36 d
1 d
9 (24)
15 (25)
NO2
(5)
ONa
10 (82)
—
O2N
(5)
12
13
2
2
EtOH (50)
n-BuOH (43)
Ag2CO3
Ag2CO3
CH2Cl2
CH2Cl2
2 d
6 d
12 (87)
14 (56)
16 (10)
16 (31)
exocyclic carbonyl of the amide group measured as earlier.8 The
values larger than 4 Hz suggested trans arrangement of the rele-
vant atoms in the 4C1 conformation.8 In case of 4, a single crystal
X-ray structure determination unequivocally confirmed the ano-
meric configuration (Fig. 1).
The investigated substitution reactions were clean, that is, dis-
regarding by-products 15 and 16 no other compounds than the iso-
lated products were observed by TLC. This reveals exclusive
stereoselectivity for each transformation. An explanation for this
can be an SN2 type replacement of bromine in the cases of pheno-
lates, aniline and thiolates. In the reactions with alcohols promoted
by silver salts neighbouring group participation of the 2-acyloxy
substituent in the possible intermediate glycosylium ion may ac-
count for the inversion. However, given the electron-withdrawing
character of the carboxamido group, formation of the glycosylium
ion may be unfavourable. Therefore, an electrophilically assisted
R1
R
OR
R2
R
O
R'SH, K2CO3, acetone, rt
from2
O
RO
RO
CONH2
SR'
R
RO
Br
CONH
2
1 R = R1 = OAc, R2 = H
2 R = R2 = OBz, R1 = H
R'
R = Bz
R = H
i
i
20 (79%)
21 (86%)
PhNH2, CH2Cl2, rt
22 (73%)
24 (76%)
23 (62%)
25 (47%)
N
R1
R
R2
N
S
O
i
NHPh
R
R
CONH2
17 R = R1 = OAc, R2 = H (75%)
18 R = R2 = OBz, R1 = H (55%)
i
19 R = R2 = OH, R1 = H (54%)
i NaOMe, MeOH, rt
Scheme 1.

V. Nagy et al. / Carbohydrate Research 344 (2009) 921–927
923
The crude product was crystallised from EtOAc–hexane or purified
by column chromatography.
1.3. General procedure II for the preparation of C-(2,3,4,6-tetra-
O-acyl-1-deoxy-1-phenylamino-a-D-glycopyranosyl)formamides
((N-phenyl 3,4,5,7-tetra-O-acyl-b-
D-glyco-hept-2-ulopyranosyl-
amin)onamides)
To a soln of C-(2,3,4,6-tetra-O-acyl-1-bromo-1-deoxy-b-
D-gly-
copyranosyl)formamide, ((3,4,5,7-tetra-O-acyl- -glyco-hept-2-
a
-D
ulopyranosylbromide)onamide) (11,2 or 2,5 0.3 mmol) in dry
CH2Cl2 (2 mL) containing molecular sieves (0.1 g, 3 Å), aniline
(50 equiv to 1 and 5 equiv to 2) was added. The reaction mixture
was stirred at rt until TLC (1:1 EtOAc–hexane) showed the com-
plete transformation of the starting sugar (1–2 d). The mixture
was then filtered on a Celite pad and the solvent was evaporated.
The residue was dissolved in EtOAc, the soln was washed with
water, diluted hydrochloric acid, and satd aq NaHCO3 soln. After
drying and solvent removal the crude product was crystallised
from EtOAc–hexane or purified by column chromatography.
Figure 1. Ortep view at 40% probability level and partial crystallographic number-
ing scheme of compound 4. Selected torsion angles (°) for the two molecules in the
asymmetric unit: O5–C1–O1–C8: 58 and 46; O1–C1–C7–N1: ꢂ3 and ꢂ12.
1.4. General procedure III for the preparation of C-(2,3,4,6-
tetra-O-benzoyl-1-deoxy-1-aryl- or heteroarylsulfanyl-
glucopyranosyl)formamides ((aryl or heteroaryl 3,4,5,7-tetra-O-
benzoyl-2-thio-b- -gluco-hept-2-ulopyranosid)onamides)
a-D-
D
substitution of bimolecular character can also be taken into
consideration.
To a soln of C-(1-bromo-1-deoxy-2,3,4,6-tetra-O-benzoyl-b-
D-
glucopyranosyl)-formamide,5 ((3,4,5,7-tetra-O-benzoyl-
a
-D
-gluco-
The deprotected compounds were assayed against rabbit mus-
cle glycogen phosphorylase b as described earlier,3,6 and showed
hept-2-ulopyranosylbromide)onamide) (2, 0.20 g, 0.28 mmol) in
dry acetone (3 mL) containing molecular sieves (0.1 g, 3 Å), a thiol
(1.40 mmol) and K2CO3 (0.20 g, 1.40 mmol) were added. The reac-
tion was stirred at rt until TLC (1:2 EtOAc–hexane) showed complete
transformation of the starting material. The mixture was then fil-
tered, diluted with CH2Cl2 (5 mL), washed with satd aq NaHCO3 soln
(2 ꢁ 5 mL), and water (1 ꢁ 5 mL). After drying and solvent removal,
the crude product was purified by column chromatography.
no significant inhibition (13 21% at 625 lM; 19 IC50 > 60 mM; 21,
23, 25 no inhibition at 625 lM).
1. Experimental
1.1. General methods
Melting points were measured in open capillary tubes or on a
Kofler hot-stage and are uncorrected. Optical rotations were deter-
mined with a Perkin–Elmer 241 polarimeter at rt. NMR spectra
were recorded with Bruker 200 (200/50 MHz for 1H/13C), Bruker
360 (360/90 MHz for 1H/13C) or Avance DRX 500 (500/125 MHz
for 1H/13C) spectrometers. Chemical shifts are referenced to Me4Si
(1H) or to the residual solvent signals (13C). TLC was performed on
DC-Alurolle Kieselgel 60 F254 (Merck), and the plates were visual-
ised under UV light and by gentle heating. For column chromatog-
raphy, Kieselgel 60 (Merck, particle size 0.063–0.200 mm) was
used. Dichloromethane was distilled from P4O10 and acetone from
CaSO4 and stored over 4 Å molecular sieves. Organic soln were
dried over anhydrous MgSO4 and were concentrated under dimin-
ished pressure at 40–50 °C (water bath).
1.5. General procedure IV for the Zemplén-deacylation
To a soln of an O-acyl protected compound in dry MeOH 1–2
drops of a ꢀ1 M methanolic NaOMe soln were added, and the reac-
tion mixture was maintained at rt until completion of the transfor-
mation TLC (1:1 CHCl3–MeOH). Amberlyst 15 (H+ form) was then
added to remove sodium ions, the resin was filtered off, and the
solvent was removed under diminished pressure. If the residue
was chromatographically not uniform it was purified by column
chromatography or crystallisation.
1.6. C-(2,3,4,6-Tetra-O-acetyl-1-methoxy-
a-
D-galactopyranosyl)
formamide ((methyl 3,4,5,7-tetra-O-acetyl-b-
D
-galacto-hept-2-
ulopyranosid)onamide) (3)
This compound was prepared from
1 (0.30 g 0.66 mmol)
1.2. General procedure I for the preparation of C-(2,3,4,6-tetra-
according to General procedure I. The crude product was crystal-
lised to give 3 (0.22 g, 85%) as a yellowish crystalline product.
O-acetyl-1-alkoxy-a-D-glycopyranosyl)formamides ((alkyl 3,4,5,7-
tetra-O-acetyl-b- -galacto-hept-2-ulopyranosid)onamides)
D
Mp: 120–122 °C;
[a
]
D
+69 (c 1.03, CHCl3); 1H NMR (CDCl3,
360 MHz): d (ppm) 6.65 (s,1H, NH), 5.93 (s, 1H, NH), 5.86 (dd,
1H, J2,3 10.5 Hz, J3,4 3.1 Hz, H-3), 5.53 (d, 1H, J2,3 10.5 Hz, H-2),
5.50 (dd, 1H, J3,4 3.1 Hz, J4,5 1.5 Hz, H-4), 4.85 (ddd, 1H, J5,6
To a soln of a C-(2,3,4,6-tetra-O-acyl-1-bromo-1-deoxy-b-
D
-gly-
copyranosyl)formamide, ((3,4,5,7-tetra-O-acyl-a-D-glyco-hept-2-
ulopyranosylbromide)onamide) (11,2 or 2,5 0.3 mmol) in dry
CH2Cl2 (2 mL) containing molecular sieves (0.1 g, 3 Å) an alcohol
(Table 1) and Ag2CO3 (1 equiv, 0.3 mmol, 0.08 g) or silver triflate
0
0
6.3 Hz, J5,6 5.3 Hz, H-5), 4.12 (dd, 1H, J6,6 11.0 Hz, H-6), 4.05 (dd,
1H, J6,6 11.0 Hz, H-60), 3.48 (s, 3H, CH3), 2.14, 2.04, 2.01, 1.95
0
(4 ꢁ s, 12H, OCOCH3); 13C NMR (CDCl3, 90 MHz): d (ppm): 170.4
(1 equiv, 0.3 mmol, 0.07 g) and Et3N (1 equiv, 0.3 mmol, 39 lL)
3
(CONH2, JH-2,CO = ꢀ4.7 Hz), 169.7 (2), 169.6 (2) (CO), 97.5 (C-1),
were added. The reaction mixture was stirred in the dark at rt until
TLC (1:1 EtOAc–hexane) showed the complete transformation of
the starting material. The mixture was then filtered on a Celite
pad, and the solvent was removed under diminished pressure.
71.1, 70.0, 67.4, 64.7 (C-2 to C-5), 61.5 (C-6), 49.8 (OCH3), 20.7,
20.6, 20.5 (COCH3). Anal. Calcd for C16H23NO11 (405.36): C, 47.41;
H, 5.72; N, 3.46. Found: C, 47.00; H, 5.52; N, 3.23.

924
V. Nagy et al. / Carbohydrate Research 344 (2009) 921–927
1.7. C-(2,3,4,6-Tetra-O-acetyl-1-ethoxy-
formamide ((ethyl 3,4,5,7-tetra-O-acetyl-b-
ulopyranosid)onamide) (4)
a
-
D
-galactopyranosyl)-
H-6, H-60), 2.10, 2.02, 2.00, 1.93 (4 ꢁ s, 12H, OCOCH3), 1.42 (s,
D
-galacto-hept-2-
9H, C(CH3)3); 13C NMR (CDCl3, 90 MHz): d (ppm) 171.4 (CONH2,
3JH-2,CO = ꢀ5.8 Hz), 170.3, 169.8, 169.7 (2) (CO), 98.7 (C(CH3)3),
80.1 (C-1), 71.3, 70.0, 96.9, 67.5 (C-2 to C-5), 61.4 (C-6), 30.1
(C(CH3)3), 20.8, 20.6 (3) (COCH3). Anal. Calcd for C19H29NO11
(447.44): C, 51.00; H, 6.53; N, 3.13. Found: C, 51.17; H, 6.52; N,
3.30.
This compound was prepared from
1
(0.20 g 0.44 mmol)
according to General procedure I. The crude product was crystal-
lised from hexane to give 4 (0.16 g, 85%) as a white crystalline
product. Mp 135–137 °C; [a]
D +57 (c 1.04, CHCl3); 1H NMR (CDCl3,
360 MHz): d (ppm) 6.69 (s, 1H, NH), 6.26 (s, 1H, NH), 5.85 (dd, 1H,
1.11. C-(2,3,4,6-Tetra-O-acetyl-1-benzyloxy-a-D-galactopyran-
J2,3 10.3 Hz, J3,4 3.6 Hz, H-3), 5.51 (d, 1H, J2,3 10.3 Hz, H-2), 5.46 (dd,
osyl)formamide ((benzyl 3,4,5,7-tetra-O-acetyl-b-D-galacto-
0
1H, J3,4 3.6 Hz, J4,5 1.2 Hz, H-4), 4.81 (pseudo t, 1H, J5,6 6.8 Hz, J5,6
hept-2-ulopyranosid)onamide) (8)
6.7 Hz, H-5), 4.10–3.99 (m, 2H, H-6, H-60), 3.88–3.70 (m, 2H,
CH2), 2.12, 2.05, 1.99, 1.91 (4 ꢁ s, 12H, OCOCH3), 1.19 (t, 3H,
This compound was prepared from 1 (0.20 g 0.44 mmol)
CH3), 13C NMR (CDCl3, 90 MHz):
d
(ppm) 170.3 (CONH2
according to General procedure I, and was purified by column
chromatography (1:1 EtOAc–hexane) to give 8 (0.07 g, 31%) as a
white crystalline product (the second fraction was compound
3JH-2,CO = ꢀ6.1 Hz), 169.9 (2), 169.7 (2) (CO), 97.4 (C-1), 70.9, 70.0,
67.4, 65.4 (C-2 to C-5), 61.4 (C-6). 58.3 (CH2), 20.7, 20.6, 20.5 (2)
(COCH3), 15.3 (CH3). Anal. Calcd for C17H25NO11 (419.10): C,
48.69; H, 6.01; N, 3.34. Found: C, 48.54; H, 6.04; N, 3.49.
15,2 9%). Mp 163–164 °C; [ D +16 (c 1.03, CHCl3); 1H NMR (CDCl3,
a]
360 MHz): d (ppm) 7.42–7.33 (m, 5H, ArH), 6.63 (s, 1H, NH), 5.93
(dd, 1H, J2,3 10.3 Hz, J3,4 3.1 Hz, H-3), 5.68 (d, 1H, J2,3 10.3 Hz, H-
0
1.8. C-(1-Ethoxy-
a-
D-galactopyranosyl)formamide ((ethyl b-
D
-
2), 5.58–5.54 (m, 2H, H-4, NH), 4.93 (pseudo t, 1H, J5,6 6.8 Hz, J5,6
galacto-hept-2-ulopyranosid)onamide) (5)
6.6 Hz, H-5) 4.90, 4.74 (2 ꢁ d, 2H, J 10.5 Hz, CH2), 4.18–4.12 (m,
2H, H-6, H-60), 2.17, 2.08, 2.03, 1.98 (4 ꢁ s, 12H, OCOCH3), 13C
3
This compound was prepared from
according to General procedure IV to give 5 (0.12 g, 98%) as a yel-
lowish oil. Rf = 0.32 (7:3 CHCl3–MeOH); [
+61 (c 1.26, H2O); 1H
4
(0.20 g 0.47 mmol)
NMR (CDCl3, 90 MHz): d (ppm) 170.3 (CONH2, JH-2,CO = ꢀ6.1 Hz),
169.9, 169.8 (2), 169.7 (CO), 136.7, 128.5, 128.4, 128.0 (ArC), 97.5
(C-1), 71.2, 69.9, 67.3, 65.7 (C-2 to C-5), 64.7 (CH2),61.3 (C-6),
20.7, 20.5, 20.5 (3) (COCH3). Anal. Calcd for C22H27NO11 (481.46):
C, 54.88; H, 5.65; N, 2.91. Found: C, 54.09; H, 5.62; N, 2.92.
a]
D
NMR (D2O, 360 MHz): d (ppm) 4.28–3.55 (m, 8H, H-2, H-3, H-4, H-
5, H-6, H-60, CH2), 1.18 (t, 3H, J 7.3 Hz, CH3), 13C NMR (D2O,
3
90 MHz): d (ppm) 173.7 (CONH2, JH-2,CO = ꢀ4.8 Hz), 100.6 (C-1),
76.4, 72.8, 71.0, 70.1 (C-2 to C-5), 62.7 (C-6), 59.4 (CH2), 15.9
(CH3). Anal. Calcd for C9H17NO7 (251.24): C, 43.03; H, 6.82; N,
5.58. Found: C, 43.54; H, 6.63; N, 5.12.
1.12. C-[2,3,4,6-Tetra-O-acetyl-1-(2-nitrophenoxy)-
a-D-galacto-
pyranosyl]formamide ((2-nitrophenyl 3,4,5,7-tetra-O-acetyl-b-
D-galacto-hept-2-ulopyranosid)onamide) (9)
1.9. C-(2,3,4,6-Tetra-O-acetyl-1-n-buthoxy-
a-
D-galactopyran-
To a soln of 1 (0.20 g, 0.44 mmol) in dry CH2Cl2 (2 mL) contain-
osyl)formamide ((n-buthyl 3,4,5,7-tetra-O-acetyl-b-
hept-2-ulopyranosid)onamide) (6)
D
-galacto-
ing molecular sieves (3 Å), sodium 2-nitrophenolate (0.35 g,
2.20 mmol) was added. The reaction mixture was stirred at rt until
TLC (1:1 EtOAc–hexane) showed complete transformation of the
starting sugar (36 d). Then the mixture was filtered on a Celite
pad, and the solvent was removed. The oily residue was purified
by column chromatography (1:1 EtOAc–hexane) to give 9 (0.04 g,
24%) as a yellow oil (the second fraction was compound 15,2
0.04 g, 25%). Characterisation of 9: Rf = 0.72 (1:3 EtOAc–hexane);
This compound was prepared from
1 (0.20 g 0.44 mmol)
according to General procedure I. The crude product was crystal-
lised from hexane to give 6 (0.18 g, 90%) as a white crystalline
product. Mp: 97–99 °C; [a]
+48 (c 1.24, CHCl3); 1H NMR (CDCl3,
D
360 MHz): d (ppm) 6.65 (s, 1H, NH), 6.42 (s, 1H, NH), 5.84 (dd,
1H, J2,3 10.5 Hz, J3,4 3.1 Hz, H-3), 5.50 (d, 1H, J2,3 10.5 Hz, H-2),
[a]
+52 (c 0.49, CHCl3); 1H NMR (CDCl3, 360 MHz): d (ppm)
D
5.47 (dd, 1H, J3,4 3.1 Hz, J4,5 1.2 Hz, H-4), 4.81 (pseudo t, 1H, J5,6
7.97–7.85 (m, 2H, ArH), 7.56 (m, 1H, ArH) 7.28 (s, 1H, NH), 7.26–
7.23 (m, 1H, ArH), 6.23 (s, 1H, NH), 5.79 (dd, 1H, J2,3 10.2 Hz, J3,4
3.1 Hz, H-3), 5.62 (d, 1H, J2,3 10.2 Hz, H-2), 5.54 (dd, 1H, J3,4
0
0
5.8 Hz, J5,6 .8 Hz, H-5), 4.15–3.99 (m, 2H, H-6, H-6 ), 3.80–3.64 (m,
2H, CH2), 2.11, 2.01, 1.98, 1.91 (4 ꢁ s, 12H, OCOCH3), 1.60–1.55
(m, 2H, CH2), 1.38–1.32 (m, 2H, CH2), 0.91 (t, 3H, J 6.8 Hz, CH3);
13C NMR (CDCl3, 90 MHz): d (ppm) 170.3, 169.9, 169.7, 169.6
0
3.1 Hz, J4,5 1.1 Hz, H-4), 5.19 (pseudo t, 1H, J5,6 6.1 Hz, J5,6 6.1 Hz,
H-5), 4.11–4.06 (m, 2H, H-6, H-60), 2.09, 2.03, 2.01, 1.89 (4 ꢁ s,
12H, OCOCH3); 13C NMR (CDCl3, 90 MHz): d (ppm): 170.3, 169.5,
169.3, 168.6 (2) (CO), 146.1, 134.0, 126.1, 124.3, 121.5 (ArC),
100.7 (C-1), 72.6, 69.9, 67.3, 65.3 (C-2 to C-5), 61.4 (C-6), 20.5,
20.4, 20.3 (2) (COCH3). Anal. Calcd for C21H24N2O13 (512.43): C,
49.22; H, 4.72; N, 5.47. Found: C, 50.05; H, 4.53; N, 5.29.
3
(CO), 170.0 (CONH2, JH-2,CO = ꢀ6.1 Hz), 97.3 (C-1), 70.9, 70.0,
67.3, 65.4 (C-2 to C-5), 62.1 (C-6), 61.3, 31.5 (CH2), 20.6, 20.5,
20.5 (COCH3) 19.0 (CH2), 13.6 (CH3). Anal. Calcd for C19H29NO11
(447.44): C, 51.00; H, 6.53; N, 3.13. Found: C, 51.15; H, 6.57; N,
3.29.
1.10. C-(2,3,4,6-Tetra-O-acetyl-1-t-buthoxy-
a-
D-galactopyran-
1.13. C-[2,3,4,6-Tetra-O-acetyl-1-(4-nitrophenoxy)-
a-D-galacto-
osyl)formamide ((t-buthyl 3,4,5,7-tetra-O-acetyl-b-D-galacto-
pyranosyl]formamide ((4-nitrophenyl 3,4,5,7-tetra-O-acetyl-b-
hept-2-ulopyranosid)onamide) (7)
D-galacto-hept-2-ulopyranosid)onamide) (10)
This compound was prepared from
1
(0.20 g 0.44 mmol)
To a soln of 1 (1.0 g, 2.20 mmol) in dry CH3CN (10 mL) contain-
according to General procedure I, and was purified by column
chromatography (1:1 EtOAc–hexane) to give 7 (0.04 g, 21%) as a
colourless oil (the second fraction was compound 15,2 29%). Char-
ing molecular sieves (3 Å), sodium 4-nitrophenolate (1.77 g,
11 mmol) was added. The reaction mixture was stirred at rt until
TLC (1:1 EtOAc–hexane) showed the complete transformation of
the starting sugar (1 d). Then the mixture was filtered on a Celite
pad and the solvent was removed. The oily residue was purified
by column chromatography (1:1 EtOAc–hexane) to give 10
acterisation of 7: Rf = 0.42 (3:1 EtOAc–hexane); [a] +19 (c 1.02,
D
CHCl3); 1H NMR (CDCl3, 360 MHz): d (ppm) 6.81 (s, 1H, NH), 6.19
(s, 1H, NH), 5.84 (dd, 1H, J2,3 10.5 Hz, J3,4 3.1 Hz, H-3), 5.60 (d,
1H, J2,3 10.5 Hz, H-2), 5.50 (dd, 1H, J3,4 3.1 Hz, J4,5 1.5 Hz, H-4),
(0.93 g, 82%) as white crystals from EtOH. Mp: 233–235 °C; [
a]
D
4.91 (pseudo t, 1H, J5,6 6.3 Hz, J5,6 6.3 Hz, H-5), 4.13–4.10 (m, 2H,
+27 (c 1.10, CHCl3); 1H NMR (CDCl3, 360 MHz): d (ppm) 8.13 (d,
0

V. Nagy et al. / Carbohydrate Research 344 (2009) 921–927
925
2H, J 9.2 Hz, ArH), 7.37 (d, 2H, J 9.2 Hz, ArH), 6.87 (s, 1H, NH), 6.67
1.17. C-(2,3,4,6-Tetra-O-benzoyl-1-n-buthoxy-a-D-glucopyran-
(s, 1H, NH), 5.77 (dd, 1H, J2,3 9.8 Hz, J3,4 2.6 Hz, H-3), 5.54 (d, 1H, J2,3
osyl)formamide ((n-buthyl 3,4,5,7-tetra-O-benzoyl-b-D-gluco-
9.8 Hz, H-2), 5.50 (dd, 1H, J3,4 2.6 Hz, J4,5 1.3 Hz, H-4), 5.00 (pseudo
hept-2-ulopyranosid)onamide) (14)
t, 1H, J5,6 6.5 Hz, J5,6 6.5 Hz, H-5), 4.13 (m, 2H, H-6, H-60), 2.11, 1.99
0
(2), 1.96 (3 ꢁ s, 12H, OCOCH3), 13C NMR (CDCl3, 90 MHz): d (ppm)
This compound was prepared from 2 (0.50 g, 0.71 mmol)
according to General procedure I, and was purified by column
chromatography (1:2 EtOAc–hexane) to give 14 (0.27 g, 56%) as a
white crystalline product (the second fraction was compound
3
170.1 (CONH2, JH-2,CO = ꢀ5.8 Hz), 169.5, 169.4, 168.8 168.3 (CO),
157.2, 143.9, 124.8, 120.9, (ArC), 99.8 (C-1), 72.4, 69.8, 67.0, 66.1
(C-2 to C-5), 61.2 (C-6), 20.4, 20.3 (3) (COCH3). Anal. Calcd for
C21H24N2O13 (512.43): C, 49.22; H, 4.72; N, 5.47. Found: C, 49.05;
H, 4.66; N, 5.32.
16,4,5 0.14 g, 31%). Characterisation of 14: mp 171–173 °C; [
a]
D
+64 (c 1.10, CHCl3); 1H NMR (CDCl3, 360 MHz): d (ppm) 8.10–
7.24 (m, 20H, ArH), 6.79 (s, 1H, NH), 6.63 (t, 1H, J 9.2 Hz, J 9.2 Hz,
H-3 or H-4), 6.39 (s, 1H, NH), 5.88–5.82 (m, 2H, H-2, H-3 or H-4),
1.14. C-[1-(4-nitrophenoxy)-a-D-galactopyranosyl]formamide
0
((4-nitrophenyl b- -galacto-hept-2-ulopyranosid)onamide) (11)
D
5.09 (ddd, 1H, J4,5 9.2 Hz, J5,6 3.5, J5,6 3.0 Hz, H-5), 4.75 (dd, 1H,
0
0
0
J6,6 12.1 Hz, J5,6 3.5 Hz, H-6), 4.40 (dd, 1H, J6,6 12.1 Hz, J5,6
To a soln of 10 (0.20 g, 0.39 mmol) in dry MeOH (5 mL) some
crystals of KCN (ꢀ5 mg) were added. The reaction mixture was
stirred at rt until TLC (7:3 CHCl3–MeOH) showed the complete
transformation of the starting material (1 d). The reaction mixture
was neutralised with a cation exchange resin Amberlyst 15 (H+
form). After filtration, the solvent was removed to give 11
3.0 Hz, H-60), 3.85–3.80 (m, 2H, CH2), 1.57–1.50 (m, 2H, CH2),
1.32–1.22 (m, 2H, CH2), 0.83 (t, 3H, J 7.1 Hz, J 6.8 Hz, CH3). 13C
3
NMR (CDCl3, 90 MHz): d (ppm) 169.9 (CONH2, JH-2,CO = ꢀ4.7 Hz),
165.3 (2), 164.9 (2) (CO), 133.4–128.1 (ArC), 97.5 (C-1), 72.2,
72.1, 69.3, 68.9 (C-2 to C-5), 62.6 (C-6), 62.5, 31.6, 19.0 (CH2),
13.6 (CH3); Anal. Calcd for C39H37NO11 (695.74): C, 67.33; H,
5.36; N, 2.01. Found: C, 66.95; H, 5.47; N, 2.32.
(0.15 g, 99%) as a yellowish oil. Rf = 0.65 (7: 3 CHCl3–MeOH); [a]
D
+3 (c 0.17, H2O); 1H NMR (D2O, 360 MHz): d (ppm) 8.21 (d, 2H, J
8.6 Hz, ArH), 7.45 (d, 2H, J 8.6 Hz, ArH), 4.51 (pseudo t, 1H, J5,6
6.8 Hz, J5,6’ 5.1 Hz, H-5), 4.15–4.10 (m, 3H, H-2, H-3, H-4), 3.86–
3.78 (m, 2H, H-6, H-60); 13C NMR (D2O, 90 MHz): d (ppm) 170.9
1.18. C-(2,3,4,6-Tetra-O-acetyl-1-deoxy-1-phenylamino-
a-D-
galactopyranosyl)formamide ((N-phenyl 3,4,5,7-tetra-O-acetyl-
b-D
-galacto-hept-2-ulopyranosylamin)onamide) (17)
3
(CONH2, JH-2,CO = ꢀ4.6 Hz), 158.5, 143.5, 125.6 (2), 120.8 (2) (Ar),
101.8 (C-1), 76.9, 70.5, 69.5, 68.2 (C-2 to C-5), 61.4 (C-6). Anal.
Calcd for C13H16N2O9 (344.28): C, 45.35; H, 4.68; N, 8.14. Found:
C, 45.33; H, 4.67; N, 8.10.
This compound was prepared from 1 (0.20 g, 0.44 mmol)
according to General procedure II. The oily residue was crystallised
from Et2O to give 17 (0.16 g, 75%) as a white crystalline product.
Mp: 200–201 °C, [
a
]
ꢂ30 (c 1.02, CHCl3); 1H NMR (CDCl3,
D
1.15. C-(2,3,4,6-Tetra-O-benzoyl-1-ethoxy-
a-D
-glucopyranosyl)
360 MHz): d (ppm) 7.25–7.10 (m, 2H, ArH), 6.88–6.75 (m, 3H,
ArH), 6.47 (s, 1H, NH), 6.02 (s, 1H, NH), 5.56 (dd, 1H, J3,4 2.9 Hz,
H-3), 5.52 (dd, 1H, J4,5 0.9 Hz, H-4), 5.42 (pseudo t, 1H, J5,6 7.2 Hz,
H-5), 5.38 (d,1H, J2,3 9.8 Hz, H-2), 5.05 (s, 1H, NH), 4.08 (dd, 1H,
formamide ((ethyl 3,4,5,7-tetra-O-benzoyl-b-
D-gluco-hept-2-
ulopyranosid)onamide) (12)
J6,6 11.1 Hz, Hz, H-6), 4.02 (dd, 1H, J5,6 6.8 Hz, H-60), 2.11 (2),
1.99, 1.96 (3 ꢁ s, 12H, OCOCH3); 13C NMR (CDCl3, 90 MHz) d
(ppm) 171.3, 170.9, 170.3, 170.1, 169.5 (CO), 141.8, 128.9 (2),
120.7, 117.2 (2) (ArC), 86.82 (C-1), 71.4, 70.2, 68.7, 67.8 (C-2 to
C-5), 61.9 (C-6), 20.8, 20.5 (3) (COCH3). Anal. Calcd for
C21H26N2O10 (466.45): C, 54.08; H, 5.62; N, 6.01. Found: C, 54.88;
H, 5.50; N, 5.84.
0
0
This compound was prepared from 2 (0.20 g, 0.28 mmol)
according to General procedure I, and was purified by column
chromatography (1:1 EtOAc–hexane) to give 12 (0.16 g, 87%) as
a white crystalline product (the second fraction was compound
16,4,5 0.02 g, 10%). Characterisation of 12: mp 88–91 °C; [
a]
D
+65 (c 1.08, CHCl3); 1H NMR (CDCl3, 360 MHz): d (ppm) 8.01–
7.24 (m, 20H, ArH), 6.82 (s, 1H, NH), 6.62 (t, 1H, J 8.8 Hz, J
8.8 Hz, H-3 or H-4), 6.18 (s, 1H, NH), 5.88–5.80 (m, 2H, H-2,
0
H-3 or H-4), 5.09 (ddd, 1H, J4,5 8.8 Hz, J5,6 6.7 Hz, J5,6 3.2 Hz,
1.19. C-(2,3,4,6-Tetra-O-benzoyl-1-deoxy-1-phenylamino-
glucopyranosyl)formamide ((N-phenyl 3,4,5,7-tetra-O-benzoyl-
a-D-
0
H-5), 4.73 (dd, 1H, J6,6 12.1 Hz, J5,6 6.7 Hz, H-6), 4.41 (dd, 1H,
J6,6 12.1 Hz, J5,6 3.2 Hz, H-60), 3.89 (q, 2H, J 6.8 Hz, CH2), 1.18
b-D
-gluco-hept-2-ulopyranosylamin)onamide) (18)
0
0
(t, 3H,
J
6.8 Hz, CH3); 13C NMR (CDCl3, 90 MHz):
d
(ppm):
3
169.8 (CONH2, JH-2,CO = ꢀ4.1 Hz), 166.0, 165.3, 164.9 (2) (CO),
133.4–127.5 (ArC), 97.5 (C-1), 72.1, 72.0, 69.2, 68.8 (C-2 to C-
5), 62.5 (C-6), 58.7 (CH2), 15.2 (CH3). Anal. Calcd for
C37H33NO11 (667.68): C, 66.56; H, 4.98; N, 2.10. Found: C,
65.75; H, 4.87; N, 2.22.
This compound was prepared from 2 (0.50 g, 0.71 mmol)
according to General procedure II and was purified by column
chromatography (1:2 EtOAc–hexane) to give 18 (0.26 g, 55%) from
EtOH as yellowish crystals. Mp 96–97 °C [a]D +108 (c 1.33, CHCl3);
1H NMR (CDCl3, 360 MHz): d (ppm) 8.11–6.80 (m, 25H, ArH), 6.56
(s, 1H, NH), 6.36 (t, 1H, J 9.1 Hz, J 9.1 Hz, H-3 or H-4), 5.90–5.68 (m,
3H, H-2, H-3 or H-4, NH), 5.27 (s, 1H, NH), 5.11–4.55 (m, 2H, H-5,
1.16. C-(1-Ethoxy-
gluco-hept-2-ulopyranosid)onamide) (13)
a-D-glucopyranosyl)formamide ((ethyl b-D-
H-6), 4.45 (dd,1H, J6,6 12,1 Hz, J5,6’ 3.2, Hz, H-60); 13C NMR (CDCl3,
0
3
90 MHz): d (ppm) 171.2 (CONH2, JH-2-CO = ꢀ4.7 Hz), 166.2 (2),
This compound was prepared from 12 (0.06 g, 0.13 mmol)
according to General procedure IV, and was purified by column
chromatography (7:2:1 CHCl3–MeOH–EtOAc) to give 13 (0.02 g,
98%) as a colourless oil. Rf = 0.25 (7:2:1 CHCl3–MeOH–EtOAc);
165.5, 165.4 (CO), 142.0, 128.6 (2), 121.0, 117.5 (2) (ArC), 134.1–
128.3 (benzoyl ArC), 87.0 (C-1), 73.7, 72.8, 70.9, 69.7 (C-2 to C-5),
64.0 (C-6). Anal. Calcd for C41H34N2O10 (714.74): C, 68.90; H,
4.72; N, 3.92. Found: C, 68.65; H, 4.80; N, 3.26.
[
a]
+18 (c 0.37, H2O); 1H NMR (D2O, 200 MHz):
d (ppm)
D
3.90–3.54 (m, 8H, H-2, H-3, H-4, H-5, H-6, H-60, CH2), 1.22 (t,
3H, J 7.0 Hz, CH3); 13C NMR (D2O, 50 MHz): d (ppm) 172.6
(CONH2), 99.7 (C-1), 76.4, 75.0, 73.1, 69.5 (C-2 to C-5), 61.4
(C-6), 59.7 (CH2), 15.0 (CH3). Anal. Calcd for C9H17NO7
(251.24): C, 43.03; H, 6.82; N, 5.58. Found: C, 43.12; H, 6.75;
N, 5.47.
1.20. C-(1-Deoxy-1-phenylamino-
a-D-glucopyranosyl)formamide
((N-phenyl b- -gluco-hept-2-ulopyranosylamin)onamide) (19)
D
This compound was prepared from 18 (0.15 g, 0.21 mmol)
according to General procedure IV, and was purified by column
chromatography (7:2:1 CHCl3–MeOH–EtOAc) to give 19 (0.039 g,

926
V. Nagy et al. / Carbohydrate Research 344 (2009) 921–927
54%) as a yellowish crystalline product. Mp 140–143 °C; [
a
]
D +115
1.24. C-[1-Deoxy-1-(2-pyridylsulfanyl)-
formamide ((2-pyridyl 2-thio-b-D-gluco-hept-2-
ulopyranosid)onamide) (23)
a
-
D
-glucopyranosyl]-
(c 0.212, H2O); 1H NMR (D2O, 360 MHz): d (ppm) 7.24–6.82 (m, 5H,
ArH), 3.84–3.77 (m, 3H, H-5, H-6, H-60), 3.61 (d, 1H, J2,3 9.2 Hz, H-
2), 3.60–3.51 (m, 2H, H-3, H-4); 13C NMR (D2O, 90 MHz): d (ppm)
3
175.4 (CONH2, JH-2,CO = ꢀ4.0 Hz), 144.5, 129.9 (2), 120.1, 115.6
This compound was prepared from 22 (0.20 g, 0.27 mmol)
according to General procedure IV, and was purified by column
chromatography (7:3 CHCl3–MeOH) to give 23 (0.05 g, 62%) as a
(2) (ArC), 88.7 (C-1), 74.5, 74.4, 73.1, 69.7 (C-2 to C-5), 60.9 (C-6).
Anal. Calcd for C13H18N2O6 (298.30): C, 52.35; H, 6.08; N, 9.39.
Found: C, 52.44; H, 6.23; N, 9.16.
colourless oil. Rf = 0.64 (7:3 CHCl3–MeOH); [
a
]
D
+53 (c 0.28,
H2O); 1H NMR (D2O, 360 MHz): d (ppm) 8.59–7.55 (m, 4H, pyri-
0
dine), 3.93 (dd, 1H, J6,6 11.9 Hz, J5,6 1.0 Hz, H-6), 3.84 (dd, 1H,
1.21. C-(2,3,4,6-Tetra-O-benzoyl-1-deoxy-1-phenylsulfanyl-
glucopyranosyl)formamide ((phenyl 3,4,5,7-tetra-O-benzoyl-2-
thio-b- -gluco-hept-2-ulopyranosid)onamide) (20)
a-D-
J6,6 11.9 Hz, J5,6 2.6 Hz, H-60), 3.72 (t, 1H, J 9.2 Hz, J 9.2 Hz, H-3
0
0
or H-4), 3.66–3.58 (m, 3H, H-2, H-3 or H-4, H-5); 13C NMR
D
3
(D2O, 90 MHz): d (ppm) 171.8 (CONH2, JH-2,CO = ꢀ5.8 Hz), 150.6,
150.4, 139.2, 133.1, 125.5 (pyridine), 89.3 (C-1), 78.2, 74.8 (2),
69.2 (C-2 to C-5), 60.8 (C-6); Anal. Calcd for C12H16NO6S
(316.24): C, 45.56; H, 5.10; N, 8.86. Found: C, 45.59; H, 5.13; N,
8.89.
This compound was prepared from 2 (0.50 g, 0.70 mmol)
according to General procedure III, and was purified by column
chromatography (1:2 EtOAc–hexane) to give 20 (0.41 g, 79%) as a
white crystalline product. Mp: 89–92 °C; [a] +33 (c 0.25, CHCl3);
D
1H NMR (CDCl3, 360 MHz): d (ppm) 8.06–7.14 (m, 25H, ArH),
6.59 (s, 1H, NH2), 6.51 (s, 1H, NH2), 6.11, 5.78, (2 ꢁ pseudo t, 2H,
J ꢀ9.2 Hz in each, H-3, H-4), 5.72 (d, 1H, J2,3 9.2 Hz, H-2), 4.81–
4.76 (m, 2H, H-5, H-6), 4.46 (dd, 1H, J = 11.9, 4.0 Hz, H-60); 13C
1.25. C-[2,3,4,6-Tetra-O-benzoyl-1-deoxy-1-(2-benzothiazolyl-
sulfanyl)-a-D-glucopyranosyl]formamide ((2-Benzothiazolyl
3,4,5,7-tetra-O-benzoyl-2-thio-b-D-gluco-hept-2-ulopyranosid)-
3
onamide) (24)
NMR (CDCl3, 90 MHz) d (ppm): 168.1 (CONH2, JH-2,CO = ꢀ4.6 Hz),
166.0, 165.4, 164.9, 164.4 (CO), 136.6, 133.2 (2), 129.7 (3) (thio-
phenyl), 133.1–127.2 (ArC benzoyl), 88.8 (C-1), 73.4, 71.9, 71.2,
This compound was prepared from 2 (0.60 g, 0.84 mmol)
according to General procedure III, and was purified by column
chromatography (1:1 EtOAc–hexane) to give 24 (0.51 g, 76%) as a
68.8 (C-2 to C-5), 62.6 (C-6); Anal. Calcd for C41H33NO10
S
(731.28): C, 67.30; H, 4.55; N, 1.91. Found: C, 67.35; H, 4.59; N,
1.96.
yellow crystalline product. Mp: 105–108 °C; [
a]
ꢂ9 (c 0.17,
D
CHCl3); 1H NMR (CDCl3, 360 MHz): d (ppm) 8.08–7.10 (m, 24H,
ArH, benzothiazole), 7.24 (s, 1H, NH2), 6.37 (s, 1H, NH2), 6.18 (t,
1H, J 9.2 Hz, J 9.2 Hz, H-3 or H-4), 6.07 (d, 1H, J2,3 9.2 Hz, H-2),
5.98 (t, 1H, J 9.2 Hz, J 9.2 Hz, H-3 or H-4), 5.06 (ddd, 1H, J4,5
1.22. C-(1-Deoxy-1-phenylsulfanyl-a-D-glucopyranosyl)formamide
((phenyl 2-thio-b- -gluco-hept-2-ulopyranosid)onamide) (21)
D
0
0
9.2 Hz, J5,6 4.0 Hz, J5,6 1.0 Hz, H-5), 4.84 (dd, 1H, J6,6 13.2 Hz, J5,6
This compound was prepared from 20 (0.20 g, 0.27 mmol)
according to General procedure IV, and was purified by column
chromatography (7:3 CHCl3–MeOH) to give 21 (0.07 g, 86%) as a
4.0 Hz, H-6), 4.57 (dd, 1H, J6,6 13.2 Hz, J5,6 1.0 Hz, H-60); 13C NMR
0
0
3
(CDCl3, 90 MHz):
d
(ppm) 167.4 (CONH2, JH-2,CO = ꢀ4.9 Hz),
165.9, 165.3, 164.9, 164.3 (CO), 157.1, 152.2, 137.3, 126.2, 125.2,
123.0, 120.9 (benzothiazole), 133.7–128.2 (ArC benzoyl), 88.7 (C-
1), 74.3, 71.5 (2), 68.6 (C-2 to C-5), 62.8 (C-6); Anal. Calcd for
C42H32N2O10S2 (788.86): C, 63.95; H, 4.09; N, 3.55. Found: C,
63.99; H, 4.11; N, 3.50.
colourless oil. Rf = 0.74 (1:1 CHCl3–MeOH); [
a]
+64 (c 0.19,
D
H2O); 1H NMR (D2O 360 MHz): d (ppm) 7.72–7.46 (m, 5H, ArH),
0
0
0
3.92 (dd, 1H, J6,6 13.2 Hz, J5,6 1.0 Hz, H-6), 3.80 (dd, 1H, J6,6
13.2 Hz, J5,6 4.0 Hz, H-60), 3.64 (t, 1H, J 9.2 Hz, J 9.2 Hz, H-3 or H-
0
4), 3.60–3.51 (m, 3H, H-2, H-3 or H-4, H-5); 13C NMR (D2O
3
90 MHz): d (ppm) 172.2 (CONH2, JH-2,CO = ꢀ5.8 Hz), 137.3 (2),
1.26. C-[1-Deoxy-1-(2-benzothiazolylsulfanyl)-
a
-D
-glucopyran-
130.9, 129.7 (2), 128.0 (tiophenyl), 89.1 (C-1), 78.2, 74.8, 74.6,
69.4 (C-2 to C-5), 61.0 (C-6), Anal. Calcd for C13H17NO6S
(315.35): C, 49.52; H, 5.43; N, 4.44. Found: C, 49.57; H, 5.38; N,
4.48.
osyl]formamide ((2-benzothiazolyl 2-thio-b-
D-gluco-hept-2-
ulopyranosid)onamide) (25)
This compound was prepared from 24 (0.20 g, 0.25 mmol)
according to General procedure IV, and was purified by column
chromatography (7:3 CHCl3–MeOH) to give 25 (0.04 g, 47%) as a
1.23. C-[2,3,4,6-Tetra-O-benzoyl-1-deoxy-1-(2-pyridylsulfanyl)-
a-
D
-glucopyranosyl]formamide ((2-pyridyl 3,4,5,7-tetra-O-
yellow crystalline product. Mp: 183–185 °C; [
a
]
+95 (c 0.27,
D
DMSO); 1H NMR (DMSO-d6, 360 MHz): d (ppm) 8.07–7.41 (m,
4H, benzothiazole), 7.78 (s, 1H, NH2), 7.54 (s, 1H, NH2), 6.26 (d,
1H, J 5.3 Hz, OH), 5.32 (d, 1H, J 4.0 Hz, OH), 5.11 (d, 1H, J 5.3 Hz,
benzoyl-2-thio-b- -gluco-hept-2-ulopyranosid)onamide) (22)
D
This compound was prepared from 2 (0.70 g, 0.98 mmol)
according to General procedure III, and was purified by column
chromatography (1:1 EtOAc–hexane) to give 22 (0.56 g, 73%) as a
0
OH), 4.56 (pseudo t, 1H, J 5.3 Hz, J 4.0 Hz, OH), 3.78 (dd, 1H, J6,6
11.9 Hz, J5,6 6.6 Hz, H-6), 3.68–3.56 (m, 5H, H-2, H-3, H-4, H-5,
H-60); 13C NMR (DMSO-d6, 90 MHz): d (ppm) 169.6 (CONH2,
3JH-2,CO = ꢀ5.9 Hz), 159.9, 151.7, 136.9, 126.1, 125.2, 122.1, 121.4
(benzothiazole), 87.8 (C-1), 79.1, 74.7, 74.5, 69.1 (C-2 to C-5),
60.9 (C-6), Anal. Calcd for C14H16NO6S2 (372.42): C, 45.15; H,
4.33; N, 7.52. Found: C, 45.05; H, 4.35; N, 7.54.
yellow crystalline product. Mp: 78–80 °C; [a]D +62 (c 0.17, CHCl3);
1H NMR (CDCl3, 360 MHz): d (ppm) 8.33 (d, 1H, J 2.6 Hz, pyridine),
8.06–7.23 (m, 23H, ArH, pyridine), 7.04 (s, 1H, NH2), 6.60 (s, 1H,
NH2), 6.21 (pseudo t, 1H, J 9.2 Hz, J 9.2 Hz, H-3 or H-4), 6.05 (d,
1H, J2,3 9.2 Hz, H-2), 5.89 (pseudo t, 1H, J 10.6 Hz, J 9.2 Hz, H-3 or
H-4), 4.99 (ddd, 1H, J 10.6 Hz, J 4.0 Hz, J 2.6 Hz, H-5), 4.73 (dd, H,
0
J 11.9 Hz, J 2.6 Hz, H-6), 4.49 (dd, 1H, J6,6 11.9 Hz, J5,6 4.0 Hz, H-
1.27. X-ray data collection and reduction
3
60); 13C NMR (CDCl3, 90 MHz):
d
(ppm) 168.6 (CONH2, JH-
2,CO = ꢀ5.9 Hz), 165.8, 165.3, 164.9, 164.4 (CO), 152.5, 149.4,
136.8, 133.1, 122.7 (pyridine), 133.4–128.1 (ArC benzoyl), 88.1
(C-1), 73.7, 71.9, 71.6, 68.9 (C-2 to C-5), 62.8 (C-6); Anal. Calcd
for C40H32N2O10S (732.77): C, 65.57; H, 4.40; N, 3.82. Found: C,
65.58; H, 4.36; N, 3.86.
Crystals of 4 were grown from EtOAc by slow evaporation of the
soln. A colourless block crystal (0.67 ꢁ 0.56 ꢁ 0.4 mm) was fixed
on a glass capillary using epoxy glue. Data were collected at
293(1) K, Bruker-Nonius MACH3 diffractometer, Mo K
a radiation
k = 0.71073 Å, motion, hmax = 25.4°. The structure was solved
x

V. Nagy et al. / Carbohydrate Research 344 (2009) 921–927
927
using the SIR-92 software23 and was refined on F2 using SHELX-97
References
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-
suite.25 Crystal data: formula C17H25NO11, M = 419.38, monoclinic,
space group P21, a = 8.569(2) Å, b = 18.397(6) Å, c = 13.688(8),
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This work was supported by the Hungarian Scientific Re-
search Fund (Grants: OTKA 46081 and 61336). The authors
thank P. Gergely and T. Docsa for the glycogen phosphorylase
assays.