Synthesis of 3-β-D-ribofuranosylpyrazole-1- carboxamide

Article abstract of DOI:10.1016/S0008-6215(97)10111-2

The synthesis of 3-β-D-ribofuranosylpyrazole-1-carboxamide (12) is described. Treatment of glycosyl enaminone 4 with semicarbazide hydrochloride in dioxane afforded three cyclocondensation products, 5-(2,3,5-tri-O-benzoyl- β-D-ribofuranosyl)pyrazole-1-carboxamide (5), 3-(2,3,5-triO-benzoyl-β-D- ribofuranosyl)pyrazole-1-carboxamide (6), and 3(5)-(2,3,5-tri-O-benzoyl-β- D-ribofuranosyl)pyrazole (7), in 51, 5, and 16% yields, respectively. Compound 5 was gradually converted to 7 at room temperature as a result of the elimination of the carbamoyl group. Treatment of the 4 with hydrochloric acid in methanol at room temperature afforded 3,3-dimethoxy-1-(2,3,5-tri-O- benzoyl-β-D-ribofuranosyl)propane-1-one (9) in 90% yield. Treatment of 9 with semicarbazide afforded the corresponding semicarbazone 10, which was cyclized in trifluoroacetic acid to afford 6. Deblocking of 6 with 10% aq ammonia gave 12.

Full text of DOI:10.1016/S0008-6215(97)10111-2

Carbohydrate Research 307 (1998) 211±215
Synthesis of 3-ꢀ-d-ribofuranosylpyrazole-1-
carboxamide
Natsu Nishimura, Masashi Banno, Ayumi Maki, Yasufumi Nishiyama,
Isamu Maeba*
Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468, Japan
Received 3 October 1997; accepted 17 November 1997
Abstract
The synthesis of 3-ꢀ-d-ribofuranosylpyrazole-1-carboxamide (12) is described. Treatment of
glycosyl enaminone 4 with semicarbazide hydrochloride in dioxane a€orded three cyclocondensa-
tion products, 5-(2,3,5-tri-O-benzoyl-ꢀ-d-ribofuranosyl)pyrazole-1-carboxamide (5), 3-(2,3,5-tri-
O-benzoyl-ꢀ-d-ribofuranosyl)pyrazole-1-carboxamide (6), and 3(5)-(2,3,5-tri-O-benzoyl-ꢀ-d-ribo-
furanosyl)pyrazole (7), in 51, 5, and 16% yields, respectively. Compound 5 was gradually con-
verted to 7 at room temperature as a result of the elimination of the carbamoyl group. Treatment
of the 4 with hydrochloric acid in methanol at room temperature a€orded 3,3-dimethoxy-1-(2,3,5-
tri-O-benzoyl-ꢀ-d-ribofuranosyl)propane-1-one (9) in 90% yield. Treatment of 9 with semi-
carbazide a€orded the corresponding semicarbazone 10, which was cyclized in tri¯uoroacetic acid
to a€ord 6. Deblocking of 6 with 10% aq ammonia gave 12. # 1998 Elsevier Science Ltd. All
rights reserved
Keywords: Synthesis; C-Nucleoside; Pyrazole-1-carboxamide; glycosyl enaminone
1. Introduction
to be due to inhibition of inosine monophosphate
dehydrogenase (IMPDH), which induces the shut-
down of guanine nucleotide synthesis [3]. These
®ndings prompted us to synthesize pyrazole C-
nucleoside 12, which is structurally related to 1, 2,
and 3. During the course of our research, we
developed a preparative precursor, glycosyl enam-
inone 4, and used it in the synthesis of isoxazole [4],
pyrazolo[1,5-a]-pyrimidine [5], pyrido[2,3-d]pyr-
imidine [6] C-nucleosides and 3-ꢀ-d-ribofuranosyl-
1H-pyrazole-4-carboxamide [7]. We report herein
the synthesis of 12 from 4 (Scheme 1).
The synthetic nucleoside analogue, 1-ꢀ-d-ribo-
furanosyl-1,2,4-triazole-3-carboxamide (ribavirin,
1), possesses broad-spectrum activity against both
RNA and DNA viruses in vitro and in vivo [1].
Tiazofurin (2-ꢀ-d-ribofuranosylthiazole-4-carbox-
amide, 2) and selenazofurin (2-ꢀ-d-ribofur-
anosylselenazole-4-carboxamide, 3) [2] are two
widely studied C-nucleosides endowed with several
biological e€ects.
The biological e€ects of theses C-nucleosides,
which are structurally related to ribavirin, appear
Treatment of 4 with semicarbazide hydro-
chloride in dioxane at room temperature for 4
days a€orded three cyclocondensation products,
* Corresponding author.
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(97)10111-2

212
N. Nishimura et al./Carbohydrate Research 307 (1998) 211±215
.
.
Scheme 1. Reagents and conditions: a. dioxane, NH2NHCONH2 HCl, r.t., 4 days; b. dioxane, NH2NHCONH2 HCl, r.t., 5 days; c.
MeOH, HCl, r.t., 15 h; d. EtOH, NH2NHCONH2 HCl, r.t., 5 h; e. dioxane, HCl, r.t., 7 h; f. TFA, r.t., 30 min; g. aq NH4OH,
refrigerator, 3 days.
5-(2,3,5-tri-O-benzoyl-ꢀ-d-ribofuranosyl)pyrazole-
1-carboxamide (5), 3-(2,3,5-tri-O-benzoyl-ꢀ-d-
ribofuranosyl)pyrazole-1-carboxamide (6), and
3(5)-(2,3,5-tri-O-benzoyl-ꢀ-d-ribofuranosyl)pyr-
azole (7), in 51, 5, and 16% yields, respectively. To
ascertain the structures, the position of the ribose
group in these compounds (5 and 6) was deter-
mined by 13C NMR spectroscopy. In the 13C NMR
spectrum of compound 6, the chemical shift of C-3
was found to be 153 ppm, whilst the chemical shift
of C-5 in compound 5 was observed at 144 ppm.
These values are consistent with the observation
that the carbon (C-3 in compound 6) bonded to a
nitrogen atom is deshielded relative to benzene,
and occurs further down®eld compared with the
carbon (C-5 in compound 5) bonded to an sp2
nitrogen. In the enaminone system, ±N±C=C±
C=O, attack can occur at either the ꢀ or the
carbonyl carbon atoms. The preponderant pro-
duct 5 would result from preferential reaction at

N. Nishimura et al./Carbohydrate Research 307 (1998) 211±215
the ꢀ-carbon in the glycosyl enaminone. Com-
213
pound 5 was gradually converted to 7 [8] at room
temperature as a result of the elimination of the
carbamoyl group. Deprotection of 5 by base a€or-
ded the decarbamoylated pyrazole 8 [8], which was
also obtained by reaction of 4 with hydrazine
hydrate in good yield. Variation in the reaction
temperature, time, and solvent did not improve the
yield of compound 6.
Next, acetalization of the glycosyl enaminone 4
with hydrochloric acid in methanol at room tem-
perature for 12 h a€orded 3,3-dimethoxy-1-(2,3,5-
tri-O-benzoyl-ꢀ-d-ribofuranosyl)propane-1-one (9)
in 90% yield after puri®cation by silica gel column
chromatography. While acetal 9 gave satisfactory
1H and 13C NMR spectra, it appeared to be
unstable. Treatment of acetal 9 with semicarbazide
hydrochloride in ethanol at room temperature
a€orded the corresponding semicarbazone 10 in
67% yield. The semicarbazone 10 was treated with
hydrochloric acid in dioxane at room temperature
to a€ord two products These were readily sepa-
rated by preparative thin-layer chromatography
(PTLC) and identi®ed as 6 and its ꢁ isomer 11 in a
combined yield 32% and in a 10:1 ratio, based on
the intensities of the signal for the anomeric and
the pyrazole ring protons. The assignments of the
anomeric con®guration at C-10 to products 6 and
2. Experimental
Mass spectra were taken on a Hitachi M-80
instrument by direct insertion at 70 eV; fast-atom-
bombardment mass spectra (FABMS) were run on
a JMS-HX 110 spectrometer. The 1H and 13C
NMR spectra were measured with a JNM-GX-270
or an A-600 (Jeol) spectrometer, with tetra-
methylsilane as an internal standard. The IR spec-
trum was measured with a FT/IR-230 (Jasco)
spectrometer. UV spectra were recorded with a
Shimazu UV-31 00PC spectrophotometer. Optical
rotations were measured with a Jasco DIP-370
polarimeter (10 cm cell) at 25 ꢀC. Elemental ana-
lyses were carried out by the microanalysis service
of the University of Meijo. Analytical TLC was
performed on glass plates coated with a 0.5 mm
layer of Silica Gel GF254 (E. Merck). The com-
pounds were detected by UV light (254 nm).
1
11 were based on comparison of their H NMR
spectra. In the ꢀ isomers the H-10 signal is con-
sistently found at higher ®eld than in the corre-
sponding ꢁ isomers [9]. The chemical shift of the
anomeric proton in compound 11 (ꢂ 5.64) appeared
down®eld from that of compound 6 (ꢂ 5.38) since
the ꢀ-face location of this anomeric proton placed
it out of the shielding in¯uence of the 20-oxygen.
The anomerization was circumvented by treatment
of 10 in tri¯uoroacetic acid at room temperature.
The isolated yield of 6 was routinely 80±90% after
puri®cation by silica gel column chromatography,
with no trace of the ꢁ isomer being observed. The
removal of the sugar protecting groups in com-
pound 6 was accomplished with 10% aqueous
ammonia to produce 3-ꢀ-d-ribofuranosylpyrazole-
1-carboxamide (12) in 67% yield. The stereo-
chemistry of compound 12 was determined by a
nuclear Overhauser e€ect experiment. Irradiation
of the 10-H signal (ꢂ 4.64) in pyrazole 12 gave a 2%
enhancement of the signal at ꢂ 3.77 assignable to
the 40-H. This data indicate that the ꢀ-ribofurano-
side con®guration had been preserved during the
reaction sequence.
5- and 3-(2,3,5-Tri-O-benzoyl-b-d-ribofuranos-
yl)pyrazole-1-carboxamide (5) and (6), 3-(2,3,5-
Tri-O-benzoyl-b-d-ribofuranosyl)pyrazole (7).ÐTo
a solution of 4 (103.6 mg, 0.171 mmol) in dioxane
(5 mL) was added a solution of semicarbazide
hydrochloride (19.1 mg, 0.171 mmol) in 95:5 diox-
ane±water (5 mL). The mixture was stirred at room
temperature for 4 days, and then the reaction mix-
ture was evaporated. TLC (99:1 CHCl3±MeOH)
showed that the light yellow syrup contained three
major components (Rf 0.31, 0.25, and 0.20). The
residue was puri®ed by PTLC with 99:1 CHCl3±
MeOH as eluent after three elutions.
1
Compound 5. Yield 48.3 mg (51%); Rf 0 31; H
NMR (CDCl3): ꢂ 7.27±8.07 (m, 16 H, H-3, Ph),
7.11 (br s, 1 H, CONH2, exchanged with D2O),
0
6.60 (d, 1 H, J3,4 1.2 Hz, H-4), 6.08 (d, 1 H, J1 ,2
0
2.6 Hz, H-10), 5.94 (dd, 1 H, J1 ,2 , 2.6, J2 ,3 , 5.1 Hz,
0
0
0
0
H-20), 5.73 (dd, 1 H, J2 ,3 5.1, J3 ,4 8.1 Hz, H-30),
5.44 (br s, 1 H, CONH2, exchanged with D2O),
0
0
0
0
4.81 (dd, 1 H, J4 ,5 a 3.7, J5 a,5 b 12.0 Hz, H-50b),
4.70 (m, 1 H, H-40), 4.60 (dd, 1 H, J4 ,5 a 3.7, J5 a,5 b
12.0 Hz, H-50a); 13C NMR (CDCl3): ꢂ 78.0, 76.8,
0
0
0
0
0
0
0
0

214
N. Nishimura et al./Carbohydrate Research 307 (1998) 211±215
75.7, 71.2 (C-10, 20, 30, 40), 166.2, 165.3, 165.1
(C=O), 151.4 (CONH2), 144.10 (C-5), 141.3 (C-3),
128.3±133.3 (Ph), 109.1 (C-4), 63.6 (C-50).
Although this compound was homogeneous by
TLC, we were unable to obtain proper micro-
analytical data for it.
and then the reaction mixture was evaporated. The
residue was chromatographed on a column of silica
gel with CHCl3 as eluent. This a€orded 105.1 mg
(67%) of 10 as a colorless foam; 1H NMR
(CDCl3): ꢂ 8.90 (br s, 1 H, NH, exchanged with
D2O), 7.34±8.07 (m, 15 H, Ph), 6.19 (dd, 1 H,
1
0
J1 ,2 =J2 ,3 5.4 Hz, H-2), 5.83 (dd, 1 H, J2 ,3 =J3 ,4
0
0
0
0
0
0
0
Compound 6. Yield 4.7 mg (5%); Rf 0.25; H
5.4 Hz, H-30), 4.82 (d, 1 H, J1 ,2 5.4 Hz, H-10), 4.77
0 0
NMR (CDCl3): ꢂ 8.12 (d, 1 H, J4,5 2.7 Hz, H-5),
7.34±8.06 (m, 15 H, Ph), 6.95 (br s, 1 H, CONH2,
exchanged with D2O), 6.48 (d, 1 H, J4,5 2.7 Hz, H-
(dd, 1 H, J4 ,5 a 3.2, J5 a,5 b 12.2 Hz, H-50b), 4.68 (m,
1 H, H-40), 4.53 (t, 1 H, J2,3 4.8 Hz, H-3), 4.49 (dd,
0
0
0
0
4), 6.03 (dd, 1 H, J1 ,2 =J3 ,4 5.3 Hz, H-20), 5.88
1 H, J4 ,5 a 3.2, J5 a,5 b 12.2 Hz, H-50a), 3.35, 3.24
(each s, each 3 H, OCH3), 2.74, 2.59 (each dd, each
1 H, J2a,2b 14.0, J2,3 4.8 Hz, H-2); 13C NMR
(CDCl3): ꢂ 166.1, 165.5, 165.3 (C=O), 157.5
(CONH2), 143.9 (C-1), 128.4±133.5 (Ph), 103.1 (C-
3), 83.6, 80.0, 72.9, 72.1 (C-10, 20, 30, 40), 63.7 (C-50),
54.4, 54.3 (CH3), 32.7 (C-2). Anal. Calcd for
0
0
0
0
0
0
0
0
(dd, 1 H, J2 ,3 =J3 ,4 5.3 Hz, H-30), 5.38 (d, 1 H,
J1 ,2 5.3 Hz, H-10), 5.34 (br s, 1 H, CONH2,
0
0
0
0
0
0
0
exchanged with D2O), 4.82 (dd, 1 H, J4 ,5 a 3.7,
0
J5 a,5 b 12.0 Hz, H-50b), 4.75 (m, 1 H, H-40), 4.58
0
0
(dd, 1 H, J4 ,5 a 3.7, J5 a,5 b 12.0 Hz, H-50a); 13C
NMR (CDCl3): ꢂ 166.1, 165.4, 165.3 (C=O), 153.1
(C-3), 150.1 (CONH2), 133.5 (C-5), 128.4±133.3
(Ph), 107.6 (C-4), 80.1, 77.7, 75.3, 72.6 (C-10, 20, 30,
0
0
0
0
.
C32H33N3O10 H2O; C, 60.28; H, 5.53; N, 6.59.
Found: C, 60.36, H, 5.33; N, 6.45.
0
0
.
4 ), 63.8 (C-5 ). Anal. Calcd for C30H25N3O8 0.1
H2O: C, 64.65; H, 4.56; N, 7.54. Found: C, 64.38,
H, 4.53; N, 7.46.
3-(2,3,5-Tri-O-benzoyl-b- and a-d-ribofurano-
syl)pyrazole-1-carboxamide (6 and 11).ÐMethod
A: solution of 10 (70.8 mg, 0.114 mmol) in diox-
ane (6 mL) containing one drop of concentrated
hydrochloric acid was stirred at room tempera-
ture for 7 h. After this time, two compounds were
detected (TLC) in the reaction mixture that had
Rf values of 0.26 and 0.24 (99:1 CHCl3±MeOH),
respectively. Water was added, and the mixture
was neutralized with satd aq NaHCO3 and then
extracted with CHCl3 (3Â10 mL). The extracts
were combined, washed with water and dried
over MgSO4. The extracts, on evaporation, a€or-
ded a yellow oil which was separated by PTLC
with 99:1 CHCl3±MeOH as eluent after two elu-
tions.
Compound 6.ÐRf 0.26; colorless foam 18.4 mg
(29%); Identi®cation was con®rmed by comparing
IR and 1H NMR spectra.
Compound 11. Rf 0.24; colorless foam 1.9 mg
(3%); 1H NMR (CDCl3): ꢂ 8.14 (d, 1 H, J4,5
2.7 Hz, H-5), 7.29±8.08 (m, 15 H, Ph), 6.99 (br s, 1
H, CONH2, exchanged with D2O), 6.58 (d, 1 H,
Compound 7. Yield 14.0 mg (16%); Rf 0.20;
Identity was con®rmed by comparing the IR and
1H NMR spectra with the spectra of the product
prepared by reaction of 4 with hydrazine hydrate.
3,3-Dimethoxy-1-(2,3,5-tri-O-benzoyl-b-d-ribofur-
anosyl)propane-1-one (9).ÐTo a solution of 4
(402.2 mg, 0.663 mmol) in MeOH (34 mL) was
added concentrated hydrochloric acid (1 mL). The
mixture was stirred at room temperature for 15 h,
and then the reaction mixture was evaporated to
dryness. The residue was chromatographed on a
column of silica gel with CHCl3 as eluent. This
a€orded 335.8 mg (90%) of 9 as a colorless foam;
1H NMR (CDCl3): ꢂ 7.26±8.09 (m, 15 H, Ph), 5.91
(dd, 1 H, J1 ,2 =J2 ,3 5.4 Hz, H-20), 5.65 (dd, 1 H,
0
0
0
0
J2 ,3 =J3 ,4 5.4 Hz, H-30), 4.84 (t, 1 H, J2,3 5.5 Hz,
H-3), 4.75±4.79 (m, 2 H, H-10, 50b), 4.72 (m, 1 H,
0
0
0
0
H-40), 4.62 (dd, 1 H, J4 ,5 a 4.4, J5 a,5 b 11.7 Hz, H-
50a), 3.31, 3.29 (each s, each 3 H, CH3), 3.00 (d, 2
H, J2,3 5.5 Hz, H-2); 13C NMR (CDCl3): ꢂ 203.8
(C-1), 166.2, 164.2 (C=O), 128.2±133.5 (Ph, C-5),
101.3 (C-3), 85.9, 78.0, 72.7, 72.1 (C-10, 20, 30, 40),
64.0 (C-50), 53.69, 53.65 (CH3), 42.4 (C-2). Due to
the unstable nature of this compound, a good ele-
mental analysis could not be obtained.
0
0
0
0
0
J4 ,5 2.7 Hz, H-4), 6.10 (dd, 1 H, J1 ,2 =J2 ,3 4.8 Hz,
0
0
0
0
0
H-20), 5.93 (dd, 1 H, J2 ,3 4.8, J3 ,4 6.4 Hz, H-30),
0
0
0
0
5.64 (d, 1 H, J1 ,2 4.8 Hz, H-10), 5.07 (br s, 1 H,
CONH2, exchanged with D2O), 4.87 (m, 1 H, H-
0
0
40), 4.76 (dd, 1 H, J4 ,5 a 4.1, J5 a,5 b 11.8 Hz, H-50b),
0
0
0
0
4.63 (dd, 1 H, J4 ,5 a 4.1, J5 a,5 b 11.8 Hz, H-50a); 13
C
0 0 0 0
3,3-Dimethoxy-1-(2,3,5-tri-O-benzoyl-b-d-ribofur-
anosyl)propane-1-one semicarbazone (10).ÐTo a
solution of 9 (141.6 mg, 0.252 mmol) in EtOH
(11 mL) was added semicarbazide hydrochloride
(33.7 mg, 0.302 mmol) at room temperature for 5 h,
NMR (CDCl3): ꢂ 166.4, 165.6, 165.3 (C=O), 152.4
(C-3), 150.3 (CONH2), 128.6±133.7 (Ph, C-5),
108.6 (C-4), 79.0, 77.2, 76.5, 73.1 (C-10, 20, 30, 40),
64.5 (C-50).

N. Nishimura et al./Carbohydrate Research 307 (1998) 211±215
215
Method B:
A
solution of 10 (21.6 mg,
R.W. Sidwell, and L.N. Simon, J. Med. Chem., 15
(1972) 1150±1154.
0.035 mmol) in tri¯uoroacetic acid (0.5 mL) was
stirred at room temperature for 30 min. Water was
added, and the mixture was neutralized with satd
aq NaHCO3 and then extracted with CHCl3
(3Â10 mL). The extracts were combined, washed
with water, and dried over MgSO4. The extracts
upon evaporation a€orded an oil that was chro-
matographed on a column of silica gel with CHCl3
as eluent. This a€orded 16.1 mg (83%) of 6 as a
colorless foam. Identi®cation was con®rmed by
comparing IR and 1H NMR spectra.
[2] P.C. Srivastava, M.V. Pickering, L.B. Allen, D.G.
Streeter, M.T. Campbell, J.T. Witkowski, R.W.
Sidwell, and R.K. Robins, J. Med. Chem., 20
(1977) 256±262; P.C. Srivastava and R.K. Robins,
J. Med. Chem., 26 (1983) 445±448; R.K. Robins,
P.C. Srivastava, V.L. Narayanan, J. Powman, and
K.D. Paull, J. Med. Chem., 25 (1982) 107±108;
H.N. Jayaram, A.L. Smith, R.I. Glazer, D.G.
Johns, and D.A. Cooney, Biochem. Pharmacol., 31
(1982) 3839±3845; W. Zhen, H.N. Jayaram, and G.
Weber, Cancer Invest., 10 (1992) 505±511; H.N.
Jayaram, G.S. Ahluwalia, R.L. Dion, G.
Gebeyehu, V.E. Marquez, J.A. Kelley, R.K.
Robins, D.A. Cooney, and D.G. Johns, Biochem.
Pharmacol., 32 (1983) 2633±2636; B.M. Goldstein,
J.F. Leary, B.A. Farley, V.E. Marquez, and P.T.
Rowley, Blood, 78 (1991) 593±598; Z. Parandoosh,
B. Rubalcava, S.S. Matsumoto, W.B. Jolley, and
R.K. Robins, Life Sci., 46 (1990) 315±329; S.M.
Kharbanda, M.L. Sherman, D.R. Springs, and
D.W. Kufe, Cancer Res., 48 (1988) 5965±5968.
[3] D.A. Cooney, H.N. Jayaram, G. Gebeyehu, C.R.
Betts, J.A. Kelley, V.E. Marquez, and D.G. Johns,
Biochem. Pharmacol., 31 (1982) 2133±2136; H.N.
Jayaram, R.L. Dion, R.I. Glazer, D.G. Johns,
R.K. Robins, P.C. Srivastava, and D.A. Cooney,
Biochem. Pharmacol., 31 (1982) 2371±2380; R.
Kuttan, R.K. Robins, and P.P. Saunders, Biochem.
Biophys. Res. Commun., 107 (1982) 862±868.
[4] I. Maeba, Y. Ito, M. Wakimura, and C. Ito, Het-
erocycles, 36 (1993) 1617±1623.
[5] I. Maeba, Y. Nishiyama, S. Kanazawa, and A.
Sato, Heterocycles, 41 (1995) 507±513.
[6] I. Maeba, Y. Nishiyama, M, Wakimura, and T.
Tabata, Carbohydr. Res., 290 (1996) 71±77.
[7] Y. Nishiyama, N. Nishimura, N. Kuroyanagi, and
I. Maeba, Carbohydr. Res., 300 (1997) 283±288.
[8] J.G. Buchanan, A.R. Edgar, M.J. Power, and G.C.
Williams, Carbohydr. Res., 55 (1977) 225±238.
[9] I. Maeba, T. Takeuchi, T. Iijima, and H. Furukawa,
J. Org. Chem., 53 (1988) 1401±1405; C.K. Chu,
F.M. El-Kabbani, and B.B. Thompson, Nucleo-
sides, Nucleotides, 3 (1984) 1±31.
3-b-d-Ribofuranosylpyrazole-1-carboxamide (12).Ð
To a solution of 6 (55.2 mg, 0.099 mmol) in MeOH
(4 mL) was added 10% aq NH4OH (1 mL) at 10 ꢀC
for 3 days, and then the reaction mixture was eva-
porated to dryness. The solid was recrystallized
from 2-propanol to give colorless needles of 12,
16.1 mg (67%); mp 123±124 ꢀC. [ꢁ]d 4.5ꢀ (c 0.8,
1
MeOH); H NMR [(CD3)2SO]: ꢂ 8.18 (d, 1 H, J4,5
2.6 Hz, H-5), 7.75 (s, 2 H, CONH2, exchanged with
D2O), 6.53 (d, 1 H, J4,5 2.6 Hz, H-4), 4.73±5.01 (br,
0
0
3 H, OH, exchanged with D2O), 4.64 (d, 1 H, J1 ,2
5.7 Hz, H-10), 4.01 (dd, 1 H, J1 ,2 5.7, J2 ,3 10.6 Hz,
0
0
0
0
H-20), 3.91 (dd, 1 H, J2 ,3 10.6, J3 ,4 5.7 Hz, H-30),
0
0
0
0
3.77 (m, 1 H, H-40), 3.54 (dd, 1 H, J4 ,5 a 5.3, J5 a,5 b
0
0
0
0
11.2 Hz, H-50b), 3.46 (dd, 1 H, J4 ,5 a 5.3, J5 a,5 b
11.2 Hz, H-50a); 13C NMR (CD3OD): ꢂ 156.9 (C-
3), 153.0 (CONH2), 130.5 (C-5), 108.0 (C-4), 86.4,
80.5, 77.3, 72.9 (C-10, 20, 30, 40), 63.5 (C-50).
FABMS (nitrobenzyl alcohol as matrix). Found:
[M+H]+ m/z 244.0933. Calcd for C9H14N3O5
0
0
0
0
.
[M+H] 244.0948. Anal. Calcd for C9H13N3O5 0.75
H2O: C, 42.11; H, 5.69; N, 16.37. Found: C, 42.49,
H, 5.39; N, 15.80.
References
[1] R.W. Sidwell, J.H. Hu€man, G.P. Khare, L.B.
Allen, J.T. Witkowski, and R.K. Robins, Science,
177 (1972) 705±706; J.T. Witkowski, R.K. Robins,