Novobiocin-related compounds: Synthesis of 3-benzoylamino-2-oxo-2H-1-benzopyran-7-yl D-glycopyranosides by the trichloroacetimidate methodology

Article abstract of DOI:10.1016/S0008-6215(00)00142-7

A general stereoselective method for the synthesis of 4-deoxynovobiocin-related glycosides is described. 3-Benzoylamino-2H-1-benzopyran-7-yl 2,3,4,6-tetra-O-acetyl-D-glycopyranosides of glucose, galactose and mannose were synthesised from appropriate O-glycosyltrichloroacetimidates and N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-yl)benzamides in boiling methylene chloride in the presence of boron trifluoride etherate. Heating of these products in a mixture of triethylamine and methanol gave the corresponding deprotected 3-benzoylamino-2-oxo-2H-1-benzopyran-7-yl β-D-glycopyranosides. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(00)00142-7

www.elsevier.nl/locate/carres
Carbohydrate Research 328 (2000) 591–597
Note
Novobiocin-related compounds: synthesis of
3-benzoylamino-2-oxo-2H-1-benzopyran-7-yl
D-glycopyranosides by the trichloroacetimidate
methodology
Marjan Jesˇelnik a, Janez Plavec b, Slovenko Polanc a, Marijan Kocˇevar a,*
a Faculty of Chemistry and Chemical Technology, Uni6ersity of Ljubljana, Asˇkercˇe6a 5, SI-1000 Ljubljana, Slo6enia
b National Institute of Chemistry, Hajdriho6a 19, SI-1115 Ljubljana, Slo6enia
Received 16 February 2000; accepted 5 May 2000
Abstract
A general stereoselective method for the synthesis of 4-deoxynovobiocin-related glycosides is described. 3-Benzoy-
lamino-2H-1-benzopyran-7-yl 2,3,4,6-tetra-O-acetyl-D-glycopyranosides of glucose, galactose and mannose were
synthesised from appropriate O-glycosyltrichloroacetimidates and N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-
yl)benzamides in boiling methylene chloride in the presence of boron trifluoride etherate. Heating of these products
in a mixture of triethylamine and methanol gave the corresponding deprotected 3-benzoylamino-2-oxo-2H-1-ben-
zopyran-7-yl b-
D-glycopyranosides. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Stereoselective synthesis; Coumarins; Mannosides; Galactosides; Glucosides
DNA girase or topoisomerase [3]. These re-
Glycosides containing the 2H-1-benzopy-
ran-2-one moiety are important biologically
active compounds [1]. Some decades ago,
novobiocin, an antibiotic substance produced
by the cultures Streptomices spheroides and
ni6eus, and other 2H-1-benzopyran antibiotics
were used clinically [2–4]. Due to the develop-
ment of resistance and their toxicity they are
now very rarely employed [2]. Recently, some
drug-receptor binding models were introduced
and enabled a systematic and rational design
of novel inhibitors of various enzymes, such as
sults, obtained from investigations involving
novobiocin, launched further studies of this
compound [5a,b] and related derivatives [5c].
It has also been shown that the 4-hydroxy
group in novobiocin is not indispensable for
the molecule to be bound in the enzyme [3b,c];
similar results were also observed with some
related derivatives [5c].
Since noviosyl derivatives are neither easily
available nor cheap substrates, we became in-
terested in the preparation of model com-
pounds possessing the 4-deoxynovobiocin-like
pattern, i.e., compounds containing a benzoyl-
amino moiety at C-3 of the 2H-1-benzopyran-
2-one system and a sugar moiety at C-7,
bound by the O-glycosidic linkage. We wanted
* Corresponding author. Tel.: +386-1-4760547; fax: +
386-1-4258243.
E-mail address: marijan.kocevar@uni-lj.si (M. Kocˇevar).
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00142-7

592
M. Jesˇelnik et al. / Carbohydrate Research 328 (2000) 591–597
to prepare them in both forms, a and b. A
critical point in the synthesis of such com-
pounds is the formation of the glycosidic
bond. In the past it was formed with variable
success by glycosylation of 7-hydroxy-2H-1-
benzopyran-2-one (umbelliferone) derivatives
with glycosyl halides [4,6,7], under Mit-
sunobu’s conditions [5c], by trichloroacetimi-
date methodology [8], etc. For the formation
of the glycosidic linkage we have chosen
trichloroacetimidate methodology, which was
known to be a powerful tool for the formation
of the glycosides with less reactive compounds
like phenols [9]. The a/b selectivity in glycosy-
lation can be to some extent controlled by an
appropriate selection of protecting group, a
catalyst and a solvent.
in the formation of the corresponding thermo-
dynamically more stable a-mannosides 8a,b,
which we obtained in good yields (73 and
81%).
The acetylated products 6a,b–8a,b can be
deprotected as shown by the preparation of
products 6c, 7c and 8c,d. Deprotection was
carried out by heating mixtures of acetylated
derivatives in a 0.5 M solution of triethyl-
amine in methanol. The corresponding prod-
ucts were obtained in 73–98% yields.
The structural integrity and the configura-
tion at the anomeric centre in 6a–c, 7a–c and
8a–d was determined with the use of NMR
spectroscopy. Products 6a,b and 7a,b exhibit
typical doublet signals for anomeric protons
between d 5.55 and 5.73 ppm with the cou-
pling constants J1,2 of 7.7–7.9 Hz. Similarly,
the deacetylated compounds 6c and 7c show
doublets at 4.96 and 4.91 ppm with the cou-
pling constants J1,2 of 7.2 and 7.5 Hz. The
trans-diaxial orientation of 1%-H and 2%-H pro-
tons, and therefore the b configuration at C-1%
in 6a–c and 7a–c, was further established
with the observation of strong NOE interac-
tions between 1%-H and the axial protons 3%-H
Here we report a highly efficient and
stereoselective preparation of a series of 3-
benzoylamino-2H-1-benzopyran-7-yl
D-gly-
copyranosides 6–8 starting from various
O-glycosyltrichloroacetimidates 1–3 [9c,10]
and N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-
yl)benzamides 4 and 5 [11] in methylene chlo-
ride and in the presence of boron trifluoride
etherate as an acidic catalyst. Starting from
anomerically-pure a- and b-2,3,4,6-tetra-O-
acetyl- -glucopyranosyl trichloroacetimidates
D
(1-a [10a] and 1-b [9c]) we prepared the corre-
sponding b-glycosides 6a,b. Due to the low
solubility of the benzopyran derivatives 4 and
5 in methylene chloride, the reactions were
carried out in boiling methylene chloride in
the presence of BF3·Et2O. Although the tri-
chloroacetimidates slowly decompose under
the applied conditions, they can still be de-
tected in the reaction mixture after 4 h of
heating (as examined in separate experiments
for 1-b and 2). They were used in quantities of
1.46–2.1 mmol (in the case of 1-a 5 mmol) per
mmol of the benzopyran derivatives 4 and 5;
they were added in two portions to the reac-
tion mixtures. No formation of a-products
was detected in these particular cases (Scheme
1, Table 1). Glycosidation of compounds 4
and 5 with related a-galactopyranosyl tri-
chloroacetimidate (2), which was obtained by
the separation of the mixture of anomers [10a]
by column chromatography, gave products
7a,b in 89 and 77% yields. Finally, the reac-
tions between a-mannopyranosyl trichloroimi-
date (3) [10b] and compounds 4 or 5 resulted
Scheme 1.

M. Jesˇelnik et al. / Carbohydrate Research 328 (2000) 591–597
593
Table 1
Reaction conditions and yields of the products 6a,b–8a,b
Starting
benzopyran
(mmol)
Trichloroacetimidate
(basic+additional amount)
(mmol)
Reaction time and additional
reaction time (h)
mL of solvent; mmol of Product
catalyst
(yield, %) a
4 (0.57)
4 (0.19)
5 (0.76)
5 (0.48)
4 (0.57)
5 (0.92)
4 (0.57)
5 (0.71)
1-b (0.69+0.34)
1-a (0.23+0.72)
1-b (0.98+ 0.39)
1-a (0.62+0.40)
2 (0.69+0.23)
2 (1.11+0.23)
3 (0.69+0.46)
3 (1.06+0.35)
1.5; 1.0
3; 0.5
4; 2
1; 0.5
1; 0.5
1; 0.5
1.5; 0.5
4; 1
5; 0.24
6a (65)
6a (57)
6b (62)
6b (51)
7a (89)
7b (77)
8a (73)
8b (81)
3 b; 0.16
4; 0.24
4 b; 0.24
4; 0.24
8; 0.16
4 b; 0.24
4 b; 0.24
a Yields of TLC-pure products.
b Starting volume of CH2Cl2 was 1 mL smaller; an additional amount of trichloroimidate was added in 1 mL of CH2Cl2.
and 5%-H. The anomeric configuration of man-
nosides 8a–d was elucidated on the basis of
diagnostic [12] heteronuclear one-bond 13C–
1H coupling constants of anomeric carbon
atoms. In the case of compounds 8a and 8c,
the JC-1%,H-1% coupling constants were 174.6 and
170.9 Hz, which are typical for an equatorial
hydrogen and thus a-anomeric glycosidic link-
age. The absence of NOESY cross-peaks be-
tween the anomeric proton and the axial
protons at C-3 and C-5 in 8c is consistent with
the equatorial position of the anomeric proton
and therefore the a-anomeric linkage. An in-
spection of the proton–proton coupling con-
stants along the pyranose seven-spin system
indicates that sugar moieties in 6a–c, 7a–c
and 8a–d adopt conformations that are close
with Varian VXR-300, Unity+ 300 and
Bruker Advance DPX 300 spectrometers, us-
ing TMS as an internal standard. The cou-
pling constants (J) are given in Hz. IR spectra
were obtained with a Perkin–Elmer Spectrum
1000 spectrophotometer. Mass spectra were
recorded with a VG-Analytical AutoSpec Q
instrument. Elemental analyses (C, H, N) were
performed with a Perkin–Elmer 2400 CHN
Analyzer. Optical rotations were measured in
a 1 dm path-length cell on a Perkin–Elmer
241 MC Polarimeter and the concentrations
are given in g/100 mL. Column chromatogra-
phy was performed with Silica Gel 60 (E.
Merck, 60–63 mm). Thin-layer chromatogra-
phy was carried out on Fluka silica gel TLC
cards. The starting compounds 1–5 [9c,10,11]
were prepared as described in the literature.
Compound 2 was obtained as an anomeri-
cally-pure a product from the mixture of
anomers [10a] by a column chromatography,
using a mixture of EtOAc and light petroleum
(1:5) as an eluant. Methylene chloride was
dried over P4O10 and distilled before use. All
other reagents were used as received from
commercial suppliers.
4
to C1 chair canonical forms.
In conclusion, we prepared some com-
pounds related to novobiocin, which might be
of interest for further investigations towards
biologically active compounds. Our results
have shown that trichloroacetimidates can
also be successfully used at temperatures
above room temperature. This seems to be
especially useful when applying substrates,
which are poorly soluble in the solvent used.
General procedure for the synthesis of gly-
cosides 6a,b–8a,b.—To a suspension of a ben-
zopyran derivative (4 or 5) in dry CH2Cl2
under an atmosphere of dry nitrogen (dried
over a drierite column) a basic amount of an
appropriate trichloroimidate (1, 2 or 3) was
added. After stirring for 10 min at ambient
temperature BF3·OEt2 was added, and the
1. Experimental
Melting points were determined on a Kofler
1
micro hot stage, and are uncorrected. H and
13C NMR (75 MHz) spectra were recorded

594
M. Jesˇelnik et al. / Carbohydrate Research 328 (2000) 591–597
12.5, 6%-Ha), 4.23 (1 H, dd, J1 5.0, J2 12.5,
6%-Hb), 4.32 (1 H, m, 5%-H), 5.04 (1 H, dd,
J1=J2 9.4, 4%-H), 5.17 (1 H, dd, J1 7.9, J2 9.4,
2%-H), 5.45 (1 H, dd, J1 =J2 9.4, 3%-H), 5.63 (1
H, d, J 7.9, 1%-H), 7.13 (1 H, d, J 9, 6-H), 7.61
(4 H, m, 5-H, 3 H of Ph), 7.96 (2 H, m, Ph),
8.57 (1 H, s, 4-H), 9.63 (1 H, br s, NH); 13C
NMR (75 MHz, CDCl3): l 170.39, 170.09,
169.30, 169.08, 165.97, 158.96, 155.89, 148.93,
133.53, 132.44, 128.87, 127.06, 125.60, 123.69,
122.44, 115.97, 115.31, 112.28, 99.17, 72.42,
72.13, 70.86, 68.17, 61.80, 20.61, 20.55, 20.52,
20.50, 8.12; m/z (FABMS): 626 (MH+, 24%),
331 (43), 169 (82), 105 (100). Anal. Calcd for
C31H31NO13: C, 59.52; H, 4.99; N, 2.24.
Found: C, 59.36; H, 4.93; N, 2.21.
mixture was heated under reflux for a certain
period of time. An additional amount of
trichloroimidate was then added and heating
was continued for a period of time. The sol-
vent was removed under reduced pressure and
further isolation was carried out, as specified
for each case.
For the isolation of 6a,b, 7a and 8b, the
solids were dissolved in ꢀ20 mL of warm
EtOAc, the remaining solid (benzopyran
derivative 4 or 5) was filtered off and the
filtrate was purified by column chromatogra-
phy. The eluant for 6a was first a mixture of
EtOAc/light petroleum 1:3 followed by a mix-
ture 1:2; for 6b EtOAc/light petroleum 1:3; for
7a EtOAc/light petroleum 1:2; and for 8a
EtOAc/light petroleum 1:2. For the isolation
of 7b, the solid was suspended in a minimal
3-Benzoylamino-2-oxo-2H-1-benzopyran-7-
yl 2,3,4,6-tetra-O-acetyl-i- -glucopyranoside
D
(6b). White solid, mp 116.5–119 °C (EtOAc/
light petroleum); [h]D −11.0° (c 0.5, DMSO);
amount of
a
mixture of CHCl3/light
petroleum 1:1, the crystalline product was
filtered off and the filtrate was purified by
column chromatography (eluant EtOAc/light
petroleum 1:3). Product 8b was isolated with
purification by column chromatography with
the eluant EtOAc/light petroleum 1:2. In all
cases, the products obtained by column chro-
matography were suspended in a small
amount of abs EtOH and filtered off. Details
and yields are given in Table 1.
1
IR wmax/cm−1 1755 br, 1675, 1614, 1528; H
NMR (DMSO-d6): l 1.98 (3 H, s), 2.03 (3 H,
s), 2.04 (6 H, br s) (4 Ac), 4.12 (1 H, dd, J1
2.3, J2 12, 6%-Ha), 4.21 (1 H, dd, J1 5.6, J2 12,
6%-Hb), 4.33 (1 H, deg ddd, 5%-H), 5.03 (1 H,
dd, J1=J2 9.8, 4%-H), 5.11 (1 H, dd, J1 7.9, J2
9.8, 2%-H), 5.41 (1 H, dd, J1=J2 ca. 9.8, 3%-H),
5.73 (1 H, d, J 7.9, 1%-H), 7.03 (1 H, dd, J1 9,
J2 2.3, 6-H), 7.12 (1 H, d, J 2.3, 8-H), 7.59 (3
H, m, Ph), 7.76 (1 H, d, J 9, 5-H), 7.96 (2 H,
m, Ph), 8.57 (1 H, s, 4-H), 9.63 (1 H, s, NH);
13C NMR (DMSO-d6): l 169.95, 169.60,
169.32, 169.11, 165.80, 157.86, 157.61, 151.45,
133.50, 132.20, 129.20, 129.34, 128.63, 127.88,
127.57, 122.36, 114.42, 114.08, 103.24, 96.65,
91.34, 71.92, 71.02, 70.50, 67.93, 61.62, 20.39,
20.33; m/z (FABMS): 612 (MH+, 21%), 331
(44), 169 (83), 105 (100). Anal. Calcd for
C30H29NO13: C, 58.92; H, 4.78; N, 2.29.
Found: C, 59.20; H, 4.96; N, 2.18.
General procedure for deprotection of acety-
lated deri6ati6es 6–8.—A mixture of 1 mmol
of acetylated compound in a 0.5 M Et3N soln
in MeOH (10 mL) was heated under reflux for
4 h. The starting materials dissolved within 1
h of heating and later the product began to
precipitate. The reaction mixture was left
overnight at 5 °C, the separated product was
filtered, washed with a small amount of cold
MeOH and crystallised. Yields of TLC-pure
products: 6c (from 6a) 73%, 7c (from 7a) 98%,
8c (from 8a) 77%, 8d (from 8b) 96%.
3 - Benzoylamino - 8 - methyl - 2 - oxo - 2H - 1-
benzopyran-7-yl i- -glucopyranoside (6c).
D
Analytical and spectroscopic data of products
6–8
White solid, mp 237–239 °C (dec, MeOH);
[h]D +33.4° (c 0.5, DMSO); IR wmax/cm−1
1
3 - Benzoylamino - 8 - methyl - 2 - oxo - 2H - 1-
1703, 1660, 1608, 1534; H NMR (DMSO-d6):
benzopyran-7-yl 2,3,4,6-tetra-O-acetyl-i- -
D
l 2.29 (3 H, s, Me), 3.15–3.42 (4 H, m, 2%-H,
3%-H, 4%-H, 5%-H, covered with water), 3.48 (1
H, deg ddd, 6%-Ha), 3.71 (1 H, deg ddd, 6%-Hb),
4.56 (1 H, t, J1=J2 ca. 6, 6%-OH), 4.96 (1 H,
d, J 7.2, 1%-H), 5.03 (1 H, d, J 4.9, OH), 5.09
(1 H, d, J 4.5, OH), 5.39 (1 H, d, J 4.9, OH),
7.18 (1 H, d, J 9, 6-H), 7.58 (4 H, m, 5-H, 3 H
glucopyranoside (6a). White solid, mp 188–
190 °C (from EtOAc/light petroleum); [h]D
−40.3° (c 0.8, DMSO); IR wmax/cm−1 1753,
1
1715, 1670, 1608, 1527; H NMR (DMSO-d6):
l 1.99, 2.02, 2.03 and 2.06 (12 H, 4 s, 4 Ac),
2.16 (3 H, s, Me), 4.12 (1 H, dd, J1 2.1, J2

M. Jesˇelnik et al. / Carbohydrate Research 328 (2000) 591–597
595
4.78; N, 2.29. Found: C, 59.06; H, 4.78; N,
2.30.
of Ph), 7.97 (2 H, m, Ph), 8.54 (1 H, s, 4-H),
9.61 (1 H, br s, NH); 13C NMR (DMSO-d6): l
165.74, 158.11, 156.98, 149.33, 133.56, 132.11,
128.64, 128.59, 127.52, 126.03, 121.52, 113.72,
113.52, 112.06, 100.81, 77.11, 76.51, 73.27,
69.64, 60.66, 8.10; m/z (FABMS): 458 (MH+),
295, 107, 71. Anal. Calcd for C23H23NO9·H2O:
C, 58.10; H, 5.30; N, 2.95. Found: C, 58.02;
H, 5.30; N, 2.83.
3 - Benzoylamino - 8 - methyl - 2 - oxo - 2H - 1-
benzopyran-7-yl i- -galactopyranoside (7c).
D
White solid, mp 216–219 °C (dec, MeOH/wa-
ter); [h]D −12.3° (c 0.5, DMSO); IR wmax
/
cm−1 1714, 1662, 1609, 1532; 1H NMR
(DMSO-d6): l 2.29 (3 H, s, Me), 3.41–3.75 (6
H, m, 2%-H, 3%-H, 4%-H, 5%-H, 6%-Ha, 6%-Hb),
4.53 (1 H, d, J 4.5, OH), 4.65 (1 H, t, J 5.5,
6%-OH), 4.87 (1 H, d, J 6.0, OH), 4.91 (1 H, d,
J 7.5, 1%-H), 5.23 (1 H, d, J 5.7, OH), 7.18 (1
H, d, J 8.7, 6-H), 7.58 (4 H, m, 5-H, 3 H of
Ph), 7.96 (2 H, m, Ph), 8.54 (1 H, s, 4-H), 9.61
(1 H, br s, NH); 13C NMR (DMSO-d6): l
165.73, 158.11, 157.10, 149.36, 133.57, 132.10,
128.72, 128.58, 127.52, 125.99, 121.47, 113.72,
113.44, 112.06, 101.46, 75.64, 73.18, 70.29,
68.10, 60.36, 8.11; m/z (FABMS): 458 (MH+),
295, 105, 71. Anal. Calcd for C23H23NO9: C,
60.39; H, 5.07; N, 3.06. Found: C, 60.58; H,
5.14; N, 3.07.
3 - Benzoylamino - 8 - methyl - 2 - oxo - 2H - 1-
benzopyran-7-yl 2,3,4,6-tetra-O-acetyl-i- -
D
galactopyranoside (7a). White solid, mp 178–
179 °C (EtOAc/light petroleum); [h]D −14.0°
(c 0.7, DMSO); IR wmax/cm−1 1752, 1717,
1
1674, 1609, 1529; H NMR (DMSO-d6): l
1.97, 2.04 and 2.07 (9 H, 3 s, 3 Ac), 2.16 (6 H,
br s, Me, Ac), 4.14 (2 H, m, 6%-Ha, 6%-Hb), 4.51
(1 H, pseudo t, J ca. 6.5, 5%-H), 5.32 (2 H, m,
2%-H, 3%-H), 5.38 (1 H, m, 4%-H), 5.55 (1 H, d,
J 7.7, 1%-H), 7.13 (1 H, d, J 8.8, 6-H), 7.61 (4
H, m, 5-H, 3 H of Ph), 7.97 (2 H, m, Ph), 8.56
(1 H, s, 4-H), 9.63 (1 H, s, NH); 13C NMR
(DMSO-d6): l 169.93, 169.80, 169.49, 169.33,
165.80, 157.91, 155.75, 149.27, 133.51, 132.14,
128.59, 128.05, 127.54, 126.18, 122.03, 114.34,
113.73, 111.62, 97.91, 70.54, 69.87, 68.17,
67.15, 61.25, 20.46, 20.42, 20.35, 20.29, 7.72;
m/z (FABMS): 626 (MH+, 46%), 331 (88),
169 (31), 105 (100). Anal. Calcd for
C31H31NO13: C, 59.52; H, 4.99; N, 2.24.
Found: C, 59.28; H, 5.03; N, 2.14.
3 - Benzoylamino - 8 - methyl - 2 - oxo - 2H - 1-
benzopyran-7-yl
2,3,4,6-tetra-O-acetyl-h- -
D
mannopyranoside (8a). White solid, mp 162–
164 °C (EtOAc/light petroleum); [h]D +49.3°
(c 0.3, DMSO); IR wmax/cm−1 1752, 1673,
1
1604, 1525; H NMR (DMSO-d6): l 1.94,
2.00, 2.05 and 2.17 (12 H, 4 s, 4 Ac), 2.32 (3
H, s, Me), 3.99 (2 H, dd, J1 2.3, J2 12, 6%-Ha),
4.05 (1 H, m, 5%-H), 4.19 (1 H, dd, J1 5.2, J2
12, 6%-Hb), 5.23 (1 H, m, 4%-H), 5.42 (2 H, m,
2%-H, 3%-H), 5.90 (1 H, d, J 1.6, 1%-H), 7.24 (1
H, d, J 8.7, 6-H), 7.59 (4 H, m, 5-H, 3 H of
Ph), 7.97 (2 H, m, Ph), 8.56 (1 H, s, 4-H), 9.62
(1 H, s, NH); 13C NMR (CDCl3): l 170.37,
169.92, 169.86, 169.60, 166.00, 159.03, 154.82,
149.02, 133.55, 132.43, 128.88, 127.08, 125.67,
123.78, 122.40, 115.39, 115.10, 111.59, 96.05,
69.65, 69.22, 68.77, 65.62, 62.03, 20.79 (2×
C), 20.62 (2×C), 8.41; m/z (FABMS): 626
(MH+, 13), 331 (26), 169 (48), 105 (100).
Anal. Calcd for C31H31NO13: C, 59.52; H,
4.99; N, 2.24. Found: C, 59.71; H, 5.08; N,
2.24.
3-Benzoylamino-2-oxo-2H-1-benzopyran-7-
yl
2,3,4,6-tetra-O-acetyl-i- -galactopyra-
D
noside (7b). White solid, 103–104.5 °C
(EtOH); [h]D +16.7° (c 0.6, DMSO); IR wmax
/
cm−1 1752, 1675, 1614, 1527; 1H NMR
(DMSO-d6): l 1.96, 2.03, 2.06 and 2.16 (12 H,
4 s, 4 Ac), 4.12 (2 H, d, J 6.4, 6%-CH2), 4.52 (1
H, deg dt, J ca. 6.4, 5%-H), 5.27 (2 H, m, 2%-H,
3%-H), 5.38 (1 H, deg dd, 4%-H), 5.64 (1 H, d, J
7.9, 1%-H), 7.02 (1 H, dd, J1 2.3, J2 8.7, 6-H),
7.12 (1 H, d, J 2.3, 8-H), 7.59 (3 H, m, Ph),
7.77 (1 H, d, J 8.7, 5-H), 7.96 (2 H, m, Ph),
8.57 (1 H, s, 4-H), 9.63 (1 H, br s, NH); 13C
NMR (CDCl3): l 170.38, 170.14, 170.04,
169.29, 166.06, 158.89, 157.87, 150.89, 133.53,
132.55, 128.96, 128.81, 127.10, 123.41, 122.78,
115.25, 114.93, 104.24, 99.21, 71.45, 70.69,
68.36, 66.78, 61.42, 20.70, 20.64, 20.63, 20.55;
m/z (FABMS): 612 (MH+, 28%), 154 (100).
Anal. Calcd for C30H29NO13: C, 58.92; H,
3-Benzoylamino-2-oxo-2H-1-benzopyran-7-
yl 2,3,4,6-tetra-O-acetyl-h- -mannopyranoside
D
(8b). White solid, mp 146–148.5 °C (EtOAc/
light petroleum); [h]D +76.3° (c 0.5, DMSO);
1
IR wmax/cm−1 1756 br, 1673, 1611, 1528; H
NMR (DMSO-d6): l 1.92, 1.99, 2.05 and 2.17

596
M. Jesˇelnik et al. / Carbohydrate Research 328 (2000) 591–597
Ph), 7.71 (1 H, d, J 8.7, 5-H), 7.97 (2 H, m,
Ph), 8.55 (1 H, s, 4-H), 9.63 (1 H, br s, NH);
13C NMR (DMSO-d6): l 165.74, 158.07,
158.04, 151.60, 133.53, 132.16, 129.06, 128.62,
128.49, 127.57, 121.84, 114.63, 113.57, 103.62,
98.96, 75.33, 70.56, 69.82, 66.62, 61.00; m/z
(FABMS): 444 (MH+), 281, 105, 71. Anal.
Calcd for C22H21NO9·0.5H2O: C, 58.41; H,
4.90; N, 3.10. Found: C, 58.34; H, 4.90; N,
3.08.
(12 H, 4 s, 4 Ac), 3.99 (1 H, dd, J1 2, J2 12,
6%-Ha), 4.09 (1 H, deg ddd, 5%-H), 4.18 (1 H,
dd, J1 5.6, J2 12, 6%-Hb), 5.21 (1 H, dd, J1=J2
9.6, 4%-H), 5.38 (2 H, m, 2%-H, 3%-H), 5.93 (1 H,
d, J ca. 0.8, 1%-H), 7.21 (1 H, dd, J1 2.3, J2 8.7,
6-H), 7.28 (1 H, d, J 2.3, 8-H), 7.58 (3 H, m,
Ph), 7.77 (1 H, d, J 8.7, 5-H), 7.96 (2 H, m,
Ph), 8.57 (1 H, s, 4-H), 9.63 (1 H, br s, NH);
13C NMR (CDCl3): l 170.39, 169.87, 169.85,
169.59, 165.97, 158.82, 156.70, 150.87, 133.47,
132.47, 128.88, 128.81, 127.06, 123.33, 122.72,
115.10, 114.50, 104.16, 95.97, 69.48, 69.01,
68.60, 65.70, 61.99, 20.78, 20.60, 20.59, 20.57;
m/z (FABMS): 612 (MH+, 24), 331 (49), 169
(60), 105 (100). Anal. Calcd for C30H29NO13:
C, 58.92; H, 4.78; N, 2.29. Found: C, 59.15;
H, 4.76; N, 2.31.
Acknowledgements
We thank the Ministry of Science and Tech-
nology of Slovenia for financial support (grant
no. J1-7343 and a scholarship to M.J.). Drs B.
Kralj and D. Zigon (Center for Mass Spec-
troscopy, ‘Jozef Stefan’ Institute, Ljubljana,
Slovenia) are gratefully acknowledged for
mass spectra measurements.
3-Benzoylamino-8-methyl-2-oxo-2H-1-ben-
zopyran-7-yl-h-
D
-mannopyranoside
(8c).
White solid, mp 215–218 °C (dec, MeOH);
[h]D −15.6° (c 0.5, DMSO); IR wmax/cm−1
1
1708, 1669, 1607, 1544; H NMR (DMSO-d6):
l 2.26 (3 H, s, Me), 3.38 (1 H, m, 5%-H),
3.43–3.63 (3 H, m, 4%-H, 6%-Ha, 6%-Hb), 3.76 (1
H, ddd, J1 ca. 3.4, J2 ca. 6.0, J3 ca. 9.4, 3%-H),
3.93 (1 H, m, 2%-H), 4.44 (1 H, dd, J1 =J2 6,
6%-OH), 4.79 (1 H, d, J 6.0, 3%-OH), 4.86 (1 H,
d, J 5.6, 4%-OH), 5.10 (1 H, d, J 4.5, 2%-OH),
5.55 (1 H, d, J 1.9, 1%-H), 7.27 (1 H, d, J 8.7,
6-H), 7.58 (4 H, m, 5-H, 3 H of Ph), 7.96 (2
H, m, Ph), 8.53 (1 H, s, 4-H), 9.60 (1 H, br s,
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NH); C NMR (DMSO-d6): l 165.73, 158.07,
155.79, 149.41, 133.54, 132.12, 128.73, 128.60,
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3-Benzoylamino-2-oxo-2H-1-benzopyran-7-
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D
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H, d, J 6.0, 3%-OH), 4.87 (1 H, d, J 5.6,
4%-OH), 5.11 (1 H, d, J 4.5, 2%-OH), 5.53 (1 H,
d, J 1.7, 1%-H), 7.11 (1 H, dd, J1 2.3, J2 8.7,
6-H), 7.24 (1 H, d, J 2.3, 8-H), 7.60 (3 H, m,
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