Novel ring transformation of 5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)isoxazole-4-carbaldehyde with 1,2-diaminobenzenes to 3-cyano-1,5-benzodiazepine C-nucleosides

Article abstract of DOI:10.1016/S0008-6215(00)00231-7

Syntheses of 3-cyano-7- and 8-substituted-4-(β-D-ribofuranosyl)-1H-1,5-benzodiazepines were reported. Treatment of isoxazole carbaldehyde with 1,2-diamino-4-nitrobenzene in chloroform gave a Schiff's base, 4-(2-amino-5-nitrophenyl)iminomethyl-5-(2,3,5-tri-O-benzoyl-β-D-ribofuran osyl)isoxazole in 82% yield with no trace of the other regioisomer. The cyclocondensation of the resulting Schiff's base in benzene containing trifluoroacetic acid (TFA) gave 3-cyano-8-nitro-4-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-1H-1,5-benzodia zepine in 49% yield. The same reaction of isoxazole carbaldeyde with 1,2-diamino-4-methoxy- and 4-chlorobenzenes afforded the corresponding Schiff's bases. Extending the reaction time for Schiff's base gave the corresponding cyanobenzodiazepines in good yields. Debenzoylation of the compounds with sodium methoxide produced deprotected C-nucleosides. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(00)00231-7

www.elsevier.nl/locate/carres
Carbohydrate Research 329 (2000) 681–686
Note
Novel ring transformation of
5-(2,3,5-tri-O-benzoyl-b-
D
-ribofuranosyl)-
isoxazole-4-carbaldehyde with 1,2-diaminobenzenes to
3-cyano-1,5-benzodiazepine C-nucleosides
Natsu Nishimura, Haruna Hisamitsu, Michiharu Sugiura, Isamu Maeba *
Faculty of Pharmacy, Meijo Uni6ersity, Tempaku, Nagoya 468, Japan
Received 20 June 2000; accepted 29 July 2000
Abstract
Syntheses of 3-cyano-7- and 8-substituted-4-(b-
of isoxazole carbaldehyde with 1,2-diamino-4-nitrobenzene in chloroform gave a Schiff’s base, 4-(2-amino-5-nitro-
phenyl)iminomethyl-5-(2,3,5-tri-O-benzoyl-b- -ribofuranosyl)isoxazole in 82% yield with no trace of the other
regioisomer. The cyclocondensation of the resulting Schiff’s base in benzene containing trifluoroacetic acid (TFA)
gave 3-cyano-8-nitro-4-(2,3,5-tri-O-benzoyl-b- -ribofuranosyl)-1H-1,5-benzodiazepine in 49% yield. The same reac-
D-ribofuranosyl)-1H-1,5-benzodiazepines were reported. Treatment
D
D
tion of isoxazole carbaldeyde with 1,2-diamino-4-methoxy- and 4-chlorobenzenes afforded the corresponding Schiff’s
bases. Extending the reaction time for Schiff’s base gave the corresponding cyanobenzodiazepines in good yields.
Debenzoylation of the compounds with sodium methoxide produced deprotected C-nucleosides. © 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: Synthesis; C-Nucleoside; Cyclocondensation; Isoxazole carbaldehyde; 3-Cyano-1,5-benzodiazepine; 1,5-Benzodiazepine
C-nucleoside
In a recent report from our laboratory, we
having a carbon–carbon ribosylic linkage, by
ring transformation of the isozaxole carbalde-
hyde (1), which can be obtained from an
enaminone glycoside by our previously pub-
lished procedure [2] (Scheme 1).
described the reaction of o-phenylenediamine
with 5-(2,3,5-tri-O-benzoyl-b- -ribofuranosyl)-
D
isoxazole-4-carbaldehyde (1) in chloroform at
room temperature to give 2-imino-3-[1-(2,3,5-
tri-O-benzoyl-b- -ribofuranosyl)oxo]-1H-,5H-
D
1,5-benzodiazepine (a) homo-C-nucleoside [1].
In connection with our continuing interests in
C-nucleoside chemistry, we wish to report the
synthesis of benzodiazepine C-nucleosides,
* Corresponding author. Tel.: +81-52-8321781; fax: +81-
52-8348090.
E-mail address: maeba@meijo-u.ac.jp (I. Maeba).
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00231-7

682
N. Nishimura et al. / Carbohydrate Research 329 (2000) 681–686
Treatment of isoxazole carbaldehyde (1)
4a from Schiff’s base 3a most probably pro-
ceeded by the protonation of the oxygen in
the isoxazole ring to give the ring-opened
intermediate, which was further cyclized to 4a.
Removal of protecting groups in compound
4a with sodium methoxide was readily accom-
with 1,2-diamino-4-nitrobenzene (2a) in chlo-
roform at room temperature for 5 days gave
Schiff’s base 3a in 82% yield with no trace of
the other regioisomer. High reaction tempera-
ture gave lower yields. We assume that the
condensation reaction will take place between
the aldehyde group of 1 and the more nucleo-
philic 2-amino group of 2a, as this route is
favored over reaction with 1-amino group due
to the electron-withdrawing effect of the nitro
group. The cyclocondensation of the Schiff’s
base 3a in benzene containing trifluoroacetic
acid (TFA) at room temperature for 2 h gave
plished and afforded 3-cyano-8-nitro-4-(b- -
D
ribofuranosyl)-1H-1,5-benzodiazepine (7a) in
87% yield.
Next, the reaction between 1,2-diamino-4-
methoxybenzene (2b) and 1 afforded two com-
pounds 4-(2-amino-4-methoxyphenyl)imino-
methyl-5-(2,3,5-tri-O-benzoyl-b-
osyl)isoxazole (3b) and 3-cyano-7-methoxy-4-
(2,3,5-tri-O-benzoyl-b- -ribofuranosyl)-1H-
D
-ribofuran-
3-cyano-8-nitro-4-(2,3,5-tri-O-benzoyl-b-
D
-ri-
D
bofuranosyl)-1H-1,5-benzodiazepine (4a) in
49% yield.
1,5-benzodiazepine (4b) in 76 and 14% yield,
respectively. Complete disappearance of start-
ing material 1 was observed after 22 h. Ex-
tending the reaction time for 16 days increased
the yield of the desired compound 4b (86%),
and small amounts of 2-cyano-2-(5-methoxy-
3-Cyanobenzodiazepine 4a was character-
1
ized by FABMS and H and 13C NMR spec-
tra. The NMR information indicates that the
product in dimethyl sulfoxide is actually in the
form of isomers 4 and 5 in a ratio of about 1:1
and not in other tautomeric forms such as 6.
Two single sharp peaks for the diazepine ring
hydrogens were observed at l 9.23 and 9.26,
respectively. A broad N–H absorption is in-
distinctly split into two peaks. Formation of
benzimidazolyl)-1-(2,3,5-tri-O-benzoyl-b- -
D
ribofuranosyl)ethane-1-one (8) (5%), which re-
sulted from ring contraction of 4b. In NOE
studies carried out on 8, the signal corre-
sponding to the methine proton of position 2
was not observed. The missing signal may
Scheme 1.

N. Nishimura et al. / Carbohydrate Research 329 (2000) 681–686
683
be attributed to rapid exchange occuring be-
tween tautomeric forms [3]. The ring contrac-
tion of 1,5-benzodiazepine into benzimidazole
under basic conditions has been reported by
Okamoto and Ueda [4]. A plausible explana-
tion for the formation of 4b involves nucleo-
philic attack at the hydrogen of the isoxazole
C-3 by the amino group of methoxybenzene
with subsequent cyclization to cyanobenzodi-
azepine 4b.
Fig. 1. NOE experiments for compounds 7a–c.
When the same reaction of 1 with 1,2-di-
amino-4-chlorobenzene (2c) at room tempera-
ture for 5 h was performed, an inseparable
mixture of 4-(2-amino-4- and 5-chloro-
phenyl)iminomethyl-5-(2,3,5-tri-O-benzoyl-b-
(TLC) was performed on glass plates coated
with a 0.25-mm layer of Silica Gel GF254 (E.
Merck). The compounds were detected by UV
light (254 nm).
D
-ribofuranosyl)isoxazole (3c and 3d) in a ra-
tio of about 4:1 was obtained in 68% yield.
Extending the reaction time for 2 days gave
7-chloro-3-cyano-4-(2,3,5-tri-O-benzoyl-b- -
4 - (2 - Amino - 5 - nitrophenyl)iminomethyl - 5-
(2,3,5 - tri - O - benzoyl - i -
D
- ribofuranosyl)-
D
isoxazole (3a).—To a solution of 1 (158.9 mg,
0.294 mmol) in CHCl3 (32 mL) was added
4-nitro-1,2-phenylenediamine (2a) (67.5 mg,
0.441 mmol). The mixture was stirred at rt for
5 days. Water was added, and the mixture was
then extracted with CHCl3 (3×10 mL). The
extracts were combined, washed with water
and dried over MgSO4, and evaporated to
dryness. The residual syrup was purified by
PTLC with CHCl3 as eluent to give 162.4 mg
(82%) of 3a as a yellow oil; 1H NMR (CDCl3):
l 4.67 (dd, 1 H, J4%,5%a 4.9, J5%a,5%b 13.0 Hz,
H-5%a), 4.85 (m, 2 H, H-4%, 5%b), 5.00 (s, 2 H,
NH2, exchanged with D2O), 5.84 (d, 1 H, J1%,2%
5.3 Hz, H-1%), 5.91 (dd, 1 H, J2%,3%=J3%,4% 5.3
Hz, H-3%), 5.98 (dd, 1 H, J1%,2%=J2%,3% 5.3 Hz,
H-2%), 6.63 (d, 1 H, J3,4 8.8 Hz, nitrobenzene
H-3), 7.36–7.57 (m, 9 H, Ph), 7.93–8.04 (m, 8
H, Ph), 8.72, 8.73 (each s, each 1 H, isoxazole
H-3, ꢀCHꢁNꢀ); 13C NMR (CDCl3): l 63.5
(C-5%), 72.1, 74.9, 75.9, 80.6 (C-1%, 2%, 3%, 4%),
113.1, 113.2 (Ph), 117.5 (C-4), 124.7–138.5
(Ph), 148.4 (C-3), 148.5 (Ph), 149.1 (ꢀCHꢁNꢀ),
165.2, 165.3, 166.0 (CꢁO), 167.7 (C-5).
FABMS (nitrobenzyl alcohol as matrix):
Calcd for C36H29N4O10; 677.1884 [MH].
Found: m/z 677.1926 [MH]+.
ribofuranosyl)-1H-1,5-benzodiazepine (4c) in
62% yield with no trace of the other regioiso-
mer from 3d. The position of the substituent
in compound 4c was determined by an NOE
experiment with the corresponding depro-
tected derivative 7c, prepared by deprotection
of 3b with sodium methoxide. Irradiation of
the OH signal (l 5.20) in compound 7c gave a
2.3% enhancement of the signal at l 7.69
assignable to H-6. The data indicated that the
chloro group was located at the 7-position.
The stereochemistry of the C-1% position in
compounds 7a–c was confirmed as b by NOE
experiments (Fig. 1). Thus the NOE indicates
that the b-ribofuranoside configuration has
been preserved during the reaction sequence.
1. Experimental
General.—Fast-atom bombardment mass
spectra (FABMS) were run on a JMS-HX 110
1
spectrometer. The H and 13C NMR spectra
were measured with a JNM-A-400 or an A-
600 (Jeol) spectrometer, with Me4Si as an
internal standard. The IR spectrum was mea-
sured with a FT/IR-230 (Jasco) spectrometer.
Optical rotations were measured with a Jasco
DIP-370 polarimeter (10-cm cell) at 25 °C.
Elemental analyses were carried out by the
microanalysis service of the University of
Meijo. Analytical thin-layer chromatography
3-Cyano-8-nitro-4-(2,3,5-tri-O-benzoyl-i- -
D
ribofuranosyl)-1H-1,5-benzodiazepine (4a).—
A solution of 3a (27.8 mg, 0.041 mmol) in
benzene (2 mL) containing one drop of trifl-
uoroacetic acid was stirred at rt for 2 h. Water
was added, and then the mixture was ex-

684
N. Nishimura et al. / Carbohydrate Research 329 (2000) 681–686
H, ꢀCHꢁNꢀ); 13C NMR (CDCl3): l 55.2
(OCH3), 63.8 (C-5%), 72.3, 74.8, 75.7, 80.7 (C-
1%, 2%, 3%, 4%), 100.4, 104.1, 117.3 (Ph), 118.4
(C-4), 128.4–133.7 (Ph), 142.4 (C-3), 144.0
(Ph), 149.3 (ꢀCHꢁNꢀ), 160.3 (Ph), 165.1,
165.2, 165.6, 166.2 (C-5, CꢁO), 167.7 (C-5).
FABMS (nitrobenzyl alcohol as matrix):
Calcd for C37H32N3O9; 662.2139 [MH]. Found:
m/z 662.2132 [MH]+.
tracted with CHCl3 (3×10 mL). The extracts
were combined, washed with water and dried
over MgSO4. The extracts, on evaporation,
afforded a yellow oil, which was purified by
PTLC with 99.5:0.5 CHCl3–MeOH as eluent
after four elutions.
Compound 4a: orange oil; yield 13.1 mg
1
(49%); Rf 0.27; IR (KBr) 2208 (CN) cm−1; H
NMR [(CD3)2SO]: l 4.63–4.73 (m, 2 H, H-5%),
4.92 (m, 1 H, H-4%), 6.02–6.12 (m, 2 H, H-2%,
3%), 6.41 (d, 1 H, J1%,2% 5.1 Hz, H-1%), 7.33–7.69
(m, 9.5 H, H-6, Ph), 7.74 (d, 0.5 H, J6,7 8.8
Hz, H-6), 7.80–8.09 (m, 6 H, Ph), 8.14 (m, 1
H, H-7), 8.30 (m, 1 H, H-9), 9.23, 9.26 (each s,
each 0.5 H, H-2), 13.38 (br, 1 H, NH, ex-
changed with D2O); 13C NMR (CDCl3): l
63.3 (C-5%), 71.5 (C-3%), 74.3 (C-2%), 76.4 (C-1%),
81.5 (C-4%), 110.2 (CN), 108.5, 115.9 (C-9),
111.3, 119.3 (C-6), 118.4, 119.1 (C-7), 128.3–
147.9 (C-3, 5a, 8, 9a, Ph), 150.5 (C-2), 164.4,
164.6 (C-4), 165.3, 165.6, 166.5 (CꢁO).
FABMS (nitrobenzyl alcohol as matrix):
Calcd for C36H27N4O9; 659.1778 [MH].
Found: m/z 659.1746 [MH]+.
Compound 4b: pale yellow form; yield 56.4
mg (86%); Rf 0.16; IR (KBr) 2197 (CN) cm−1
;
1H NMR [(CD3)2SO]: l 3.71, 3.79 (each s,
each 1.5 H, OCH3), 4.62–4.76 (m, 2 H, H-5%),
4.89 (m, 1 H, H-4%), 6.02 (m, 1 H, H-3%), 6.10
(m, 1 H, H-2%), 6.42, 6.46 (each d, each 0.5 H,
J1%,2% 5.1 Hz, H-1%), 6.81, 6.85 (each d, each 0.5
H, J8,9 8.8 Hz, H-9), 7.01 (s, 1 H, H-6),
7.34–8.30 (m, 16 H, H-8, Ph), 9.17, 9.18 (each
s, each 0.5 H, H-2), 12.81, 12.85 (each br, each
0.5 H, NH, exchanged with D2O); 13C NMR
[(CD3)2SO]: l 55.3, 55.5 (OCH3), 63.5 (C-5%),
72.2 (C-3%), 74.0, 74.0 (C-2%), 74.2, 74.4 (C-1%),
79.4, 79.4 (C-4%), 94.4, 100.9 (C-6), 110.8,
111.0 (CN), 111.6, 112.9 (C-9), 111.7, 119.3
(C-8), 128.3–133.8, 138.0 (C-5a, Ph), 134.7,
144.4 (C-9a), 141.2, 142.3 (C-3), 149.6, 149.7
(C-2), 155.6, 156.3 (C-7), 165.0 (C-4), 164.5,
164.5, 164.8, 165.5 (CꢁO). Anal. Calcd for
C37H29N3O8·1.4 H2O; C, 66.44; H, 4.79; N,
6.28. Found: C, 66.16; H, 4.49; N, 6.11.
4-(2-Amino-4-methoxyphenyl)iminomethyl-
5 - (2,3,5 - tri - O - benzoyl - i -
D
- ribofuranosyl)-
isoxazole (3b), 7-methoxy-3-cyano-4-(2,3,5-
tri - O - benzoyl - i - - ribofuranosyl) - 1H-1,5-
benzodiazepine (4b) and 2-cyano-2-(5-
methoxybenzimidazolyl)-1-(2,3,5-tri-O-benzoyl-
i- -ribofuranosyl)ethane-1-one (8).—To a so-
D
D
lution of 1 (55.5 mg, 0.103 mmol) in CHCl3 (8
mL) was added 4-methoxy-1,2-phenylenedi-
amine (2b) (21.2 mg, 0.154 mmol). The mix-
ture was stirred at rt for 16 days, and then the
reaction mixture was evaporated. TLC (99:1
CHCl3–MeOH) showed that the yellow syrup
contained three major components (Rf 0.25,
0.16 and 0.13). The residue was purified by
PTLC with 99.25:0.75 CHCl3–MeOH as elu-
ent after three elutions.
Compound 8: yield 3.1 mg (5%); Rf 0.13; IR
1
(KBr) 2195 (CN) cm−1; H NMR (CDCl3): l
3.72, 3.83 (each s, each 1.5 H, OCH3), 4.68
(dd, 1 H, J4%,5%a 4.9, J5%a,5%b 11.6 Hz, H-5%a), 4.79
(m, 1 H, H-4%), 4.83 (dd, 1 H, J4%,5%b 4.0, J5%a,5%b
11.6 Hz, H-5%b), 5.34 (d, 1 H, J1%,2% 3.7 Hz,
H-1%), 5.91 (dd, 1 H, J2%,3% 5.2, J3%,4% 6.4 Hz,
H-3%), 6.04 (dd, 1 H, J1%,2% 3.7, J2%,3% 5.2 Hz,
H-2%), 6.84–8.05 (m, 18 H, Ph), 12.60 (br, 1 H,
NH, exchanged with D2O); 13C NMR
(CDCl3): l 55.8 (OCH3), 64.4 (C-5%), 65.9 (C-
2), 73.1, 74.6, 79.9, 83.2 (C-1%, 2%, 3%, 4%), 96.2,
112.3, 123.8 (Ph), 119.4 (CN), 128.3–133.3
(Ph), 152.0 (benzimidazole C-2), 157.4 (Ph),
165.3, 166.2 (CꢁO), 187.4 (C-1). FABMS (ni-
trobenzyl alcohol as matrix): Calcd for
C37H30N3O9; 660.1982 [MH]. Found: m/z
660.1990 [MH]+.
Compound 3b: yellow oil; yield 2.5 mg
1
(4%); Rf 0.25; H NMR (CDCl3): l 3.75 (s, 3
H, OCH3), 4.67 (br, 2 H, NH2, exchanged
with D2O), 4.67 (dd, 1 H, J4%,5%a 3.8, J5%a,5%b 11.5
Hz, H-5%a), 4.83 (m, 2 H, H-4%, 5%b), 5.82 (d, 1
H, J1%,2% 5.1 Hz, H-1%), 5.95 (m, 2 H, H-2%, 3%),
6.19 (dd, 1 H, J3,5 2.6, J5,6 8.8 Hz, methoxy-
benzene H-5), 6.25 (d, 1 H, J3,5 2.6 Hz,
methoxybenzene H-3), 6.95 (d, 1 H, J5,6 8.8
Hz, methoxybenzene H-6), 7.36–8.06 (m, 15
H, Ph), 8.55 (s, 1 H, isoxazole H-3), 8.70 (s, 1
4-(2-Amino-4-chlorophenyl)iminomethyl-5-
(2,3,5 - tri - O - benzoyl - i -
D
- ribofuranosyl)-
isoxazole (3c) and 4-(2-amino-5-chloro-

N. Nishimura et al. / Carbohydrate Research 329 (2000) 681–686
685
phenyl)iminomethyl-5-(2,3,5-tri-O-benzoyl-i-
-ribofuranosyl)isoxazole (3d).—To a solution
63.38; H, 4.35; N, 6.21. Found: C, 63.49; H,
3.88; N, 6.12.
D
General procedure for deprotection.—
Sodium methoxide in MeOH (2 mL, 0.75
mmol) was added to the protected C-nu-
cleoside (0.05 mmol) dissolved in MeOH (2
mL). The mixture was stirred at −15 °C for 2
h, and then the mixture was neutralized with
HOAc and evaporated under reduced pres-
sure. The residue was chromatographed on a
column of silica gel with 7:3 CHCl3–MeOH as
eluent. The mixture was purified by PTLC to
afford the corresponding deprotected free C-
nucleoside.
of 1 (87.7 mg, 0.162 mmol) in CHCl3 (9 mL)
was added 4-chloro-1,2-phenylenediamine (2c)
(36.1 mg, 0.243 mmol). The mixture was
stirred at rt for 5 h, and then the reaction mix-
ture was evaporated. The residue was purified
by PTLC with 99:1 CHCl3 –MeOH as eluent
to give 73.3 mg (68%) of 3c and 3d as a yellow
form; 1H NMR (CDCl3): l 4.20 (br, 2 H, NH2,
exchanged with D2O), 4.63–4.87 (m, 3 H, H-
4%, 5%), 5.79–5.99 (m, 3 H, H-1%, 2%, 3%), 6.57
(dd, 0.8 H, J3,5 2.0, J5,6 8.5 Hz, chlorobenzene
H-5), 6.60 (d, 0.2 H, J3,4 8.1 Hz, chlorobenzene
H-3), 6.67 (d, 0.8 H, J3,5 2.0 Hz, chlorobenzene
H-3), 6.83 (d, 0.8 H, J5,6 8.5 Hz, chlorobenzene
H-6), 7.00 (m, 0.4 H, chlorobenzene H-4, 6),
7.28–8.06 (m, 15 H, Ph), 8.57 (s, 0.2 H, isoxa-
zole H-3), 8.58 (s, 0.8 H, isoxazole H-3), 8.70
(s, 0.8 H, ꢀCHꢁNꢀ), 8.71 (s, 0.2 H, ꢀCHꢁNꢀ);
13C NMR (CDCl3): l 63.6, 63.7 (C-5%), 71.6,
72.3, 74.6, 74.9, 75.9, 76.5, 80.9, 81.6 (C-1%, 2%,
3%, 4%), 115.0, 116.3, 117.1, 117.8, 117.9, 118.1
(Ph), 119.6, 122.9 (C-4), 127.9–143.2 (Ph),
146.0, 146.8 (C-3), 149.2, 149.3 (ꢀCHꢁNꢀ),
165.3, 165.8, 166.1, 166.4, 166.7, 167.0 (C-5,
CꢁO). FABMS (nitrobenzyl alcohol as ma-
trix): Calcd for C36H29ClN3O8; 666.1643 [MH].
Found: m/z 666.1636 [MH]+.
3-Cyano-8-nitro-4-(i- -ribofuranosyl)-1H-
D
1,5-benzodiazepine (7a).—Compound 7a: yel-
low oil; yield 87%; [h]D −107.8° (c 0.7,
1
CH3OH); H NMR [(CD3)2SO]: l 3.35 (br, 2
H, OH, exchanged with D2O), 3.60 (dd, 1 H,
J4%,5%a 4.4, J5%a,5%b 11.7 Hz, H-5%a), 3.67 (dd, 1 H,
J4%,5%b 4.4, J5%a,5%b 11.7 Hz, H-5%b), 3.98 (m, 1 H,
H-4%), 4.08 (m, 1 H, H-3%), 4.30 (m, 1 H, H-2%),
5.21 (br, 1 H, OH, exchanged with D2O), 5.54
(d, 1 H, J1%,2% 6.6 Hz, H-1%), 7.80 (d, 1 H, J6,7 8.8
Hz, H-6), 8.15 (dd, 1 H, J6,7 8.8, J7,9 2.2 Hz, H-
7), 8.51 (d, 1 H, J7,9 2.2 Hz, H-9), 9.22 (s, 1 H,
H-2); 13C NMR (CD3COCD3): l 62.1 (C-5%),
71.7, 76.4, 78.9, 88.1 (C-1%, 2%, 3%, 4%), 109.7
(CN), 112.0, 114.6 (C-6, 9), 118.9 (C-7), 148.2
(C-3), 151.7 (C-2), 169.1 (C-4). FABMS (ni-
trobenzyl alcohol as matrix): Calcd for
C15H15N4O6; 347.0092 [MH]. Found: m/z
347.1000 [MH]+.
7-Chloro-3-cyano-4-(2,3,5-tri-O-benzoyl-i-
-ribofuranosyl)-1H-1,5-benzodiazepine (4c).
D
—To a solution of 1 (65.3 mg, 0.121 mmol) in
CHCl3 (11.5 mL) was added 4-chloro-1,2-
phenylenediamine (2c) (26.9 mg, 0.181 mmol).
The mixture was stirred at rt for 2 days, and
then the reaction mixture was evaporated. The
residue was purified by PTLC with 1.5:1 hex-
ane–EtOAc as eluent to give 51.0 mg (62%) of
4c as a pale yellow form; IR (KBr) 2208 (CN)
3-Cyano-7-methoxy-4-(i- -ribofuranosyl)-
D
1H-1,5-benzodiazepine (7b).—Compound 7b:
yellow oil; yield 81%; [h]D −88.3° (c 1.1,
1
CH3OH); H NMR [(CD3)2SO]: l 3.59 (dd, 1
H, J4%,5%a 4.4, J5%a,5%b 10.6 Hz, H-5%a), 3.65 (dd, 1
H, J4%,5%b 3.7, J5%a,5%b 10.6 Hz, H-5%b), 3.80 (s, 3
H, OCH3), 3.95–4.30 (m, 3 H, H-2%, 3%, 4%),
5.51 (d, 1 H, J1%,2% 7.3 Hz, H-1%), 6.87 (dd, 1 H,
J6,8 2.4, J8,9 8.8 Hz, H-8), 7.11 (s, 1 H, H-6),
7.51 (d, 1 H, J8,9 8.8 Hz, H-9), 9.14 (s, 1 H, H-
2); 13C NMR (CD3COCD3): l 55.9, 5 6.1
(OCH3), 62.4 (C-5%), 72.0, 76.0, 78.6, 88.1 (C-
1%, 2%, 3%, 4%), 97.5, 97.9, 112.3, 113.3, 113.7 (C-
6, 8, 9), 110.3 (CN), 143.0 (C-3), 151.3 (C-2),
157.7 (C-7), 167.9 (C-4). Calcd for
C16H18N3O6; 348.1196 [MH]. Found: m/z
348.1203 [MH]+.
1
cm−1; H NMR (CDCl3): l 4.75 (dd, 1 H,
J4%,5%a 5.1, J5%a,5%b 12.3 Hz, H-5%a), 4.91 (m, 1 H,
H-4%), 4.96 (dd, 1 H, J4%,5%b 3.3, J5%a,5%b 12.3 Hz,
H-5%b), 5.89 (m, 2 H, H-1%, 3%), 6.06 (dd, 1 H,
J1%,2%=J2%,3% 5.1 Hz, H-2%), 7.19–7.68 (m, 12 H,
Ph), 7.96–8.86 (m, 6 H, Ph), 8.86 (s, 1 H, H-2),
13
11.00 (br, 1 H, NH, exchanged with D2O); C
NMR (CDCl3): l 63.3 (C-5%), 71.6 (C-3%), 74.5
(C-2%), 76.4 (C-1%), 81.4 (C-4%), 110.9 (CN),
111.4, 112.1, 119.2, 120.2, 123.5, 124.0 (C-6, 8,
9), 128.4–134.0, 143.0, 144.3 (C-3, Ph), 150.7
(C-2), 163.2 (C-4), 165.3, 165.7, 166.4 (CꢁO).
Anal. Calcd for C36H26ClN3O7·1.6 H2O; C,
7-Chloro-3-cyano-4-(i- -ribofuranosyl)-
D
1H-1,5-benzodiazepine (7c).—Compound 7c:
pale yellow solid; yield 51%; [h]D −95.4° (c

686
N. Nishimura et al. / Carbohydrate Research 329 (2000) 681–686
1
0.7, CH3OH); H NMR [(CD3)2SO]: l 3.36
(br, 2 H, OH, exchanged with D2O), 3.59 (dd,
1 H, J4%,5%a 4.4, J5%a,5%b 11.7 Hz, H-5%a), 3.66 (dd,
1 H, J4%,5%b 3.7, J5%a,5%b 11.7 Hz, H-5%b), 3.96 (m,
1 H, H-4%), 4.08 (m, 1 H, H-3%), 4.28 (dd, 1 H,
J1%,2%=J2%,3% 6.6 Hz, H-2%), 5.20 (br, 1 H, OH,
exchanged with D2O), 5.52 (d, 1 H, J1%,2% 6.6
Hz, H-1%), 7.24 (dd, 1 H, J6,8 1.8, J8,9 8.6 Hz,
H-8), 7.64 (d, 1 H, J8,9 8.6 Hz, H-9), 7.69 (s, 1
H, H-6), 9.17 (s, 1 H, H-2), 12.88 (br, 1 H,
NH, exchanged with D2O); 13C NMR
[(CD3)2SO]: l 61.6 (C-5%), 71.3 (C-3%), 74.5
(C-2%), 75.4 (C-1%), 86.1 (C-4%), 109.7
(CN),111.2, 112.9 (C-9), 118.1, 120.0 (C-6),
122.5, 122.9 (C-8), 126.4, 127.1, 133.0, 135.0,
139.5, 142.1, 144.1 (C-3, 5a, 7, 9a), 150.2
(C-2), 168.0 (C-4). Due to the unstable nature
of this compound an acceptable elemental
analysis could not be obtained.
Acknowledgements
This work was partly supported by the
Ministry of Education Science, Sports and
Culture of Japan (High-Tech Research Center
Project).
References
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