Synthesis of new pseudo-C-nucleosides containing pyrazole rings in their structure

Article abstract of DOI:10.1081/CAR-200044574

Synthetic approaches to new 4-(furanos-4- C -yl)-1 H -pyrazole and 3-(furanos-4- C -yl)-1 H -pyrazole derivatives are described, including its pyrazole-5-carboxylate derivative, which is a pyrazofurin analogue. Preparation of related 5-acetoxy-1-acetyl-1

Full text of DOI:10.1081/CAR-200044574

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Synthesis of New Pseudo‐C‐Nucleosides
Containing Pyrazole Rings in their
Structure
Amélia P. Rauter a , José A. Figueiredo b , Maria I. Ismael b & Jorge
Justino c
a Departamento de Química e Bioquímica, Faculdade de Ciências
da Universidade de Lisboa, Edifício C8, 5° Piso, Campo Grande,
1749‐016, Lisboa, Portugal
b Departamento de Química, Universidade da Beira Interior, Unidade
I&D de Materiais Têxteis e Papeleiros, Covilhã, Portugal
c Escola Superior Agrária‐Instituto Politécnico de Santarém,
Santarém, Portugal
Published online: 09 Aug 2006.
To cite this article: Amélia P. Rauter , José A. Figueiredo , Maria I. Ismael & Jorge Justino (2004):
Synthesis of New Pseudo‐C‐Nucleosides Containing Pyrazole Rings in their Structure, Journal of
Carbohydrate Chemistry, 23:8-9, 513-528
To link to this article: http://dx.doi.org/10.1081/CAR-200044574
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 23, No. 8–9, pp. 513–528, 2004
Synthesis of New Pseudo-C-Nucleosides Containing
Pyrazole Rings in their Structure
1,
Amelia P. Rauter, Jose A. Figueiredo, Maria I. Ismael,
2
2
*
´
´
and Jorge Justino3
1
´ ´ ˆ
Departamento de Quımica e Bioquımica, Faculdade de Ciencias da
Universidade de Lisboa, Lisboa, Portugal
´
Departamento de Quımica, Universidade da Beira Interior, Unidade I&D
2
ˆ
de Materiais Texteis e Papeleiros, Covilha˜, Portugal
´
3
´ ´
Escola Superior Agraria-Instituto Politecnico de Santarem, Santarem, Portugal
´
CONTENTS
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
I. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
II. RESULTS AND DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . 515
III. EXPERIMENTAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 518
A. General Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 518
B. General Procedure for the Reformatsky Reaction . . . . . . . . . . . 520
C. General Procedure for the Reaction of Keto Sugars
with Hydrazine Derivatives . . . . . . . . . . . . . . . . . . . . . . . 521
D. General Procedure for the Cyclisation of Hydrazones to Pyrazoles . 523
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526
*
´ ´ ´ ˆ
Correspondence: Amelia P. Rauter, Departamento de Quımica e Bioquımica, Faculdade de Cien-
´
cias da Universidade de Lisboa, Edifıcio C8, 58 Piso, Campo Grande, 1749-016 Lisboa, Portugal.
513
DOI: 10.1081/CAR-200044574
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

514
Rauter et al.
ABSTRACT
Synthetic approaches to new 4-(furanos-4-C-yl)-1H-pyrazole and 3-(furanos-4-C-yl)-
1H-pyrazole derivatives are described, including its pyrazole-5-carboxylate derivative,
which is a pyrazofurin analogue. Preparation of related 5-acetoxy-1-acetyl-1H-pyrazole,
5-acetoxy-1H-pyrazole-1-carboxylate, and 4,5-dihydro-1-phenyl-1H-pyrazol-5-one
derivatives is also reported. The formation of the pyrazole rings was accomplished
either by reaction of enones and of 1,3-diketones with N-nucleophiles or by ring
closure of a diazoketone.
Key Words: Pyrazoles; Pseudo-C-Nucleosides; 1,3-Diketones; Hydrazones.
INTRODUCTION
The pyrazole ring system is of some practical importance, because many drugs
contain a pyrazole unit in their structure. 1-Phenylpyrazoles were evaluated for inhibitory
activity against xanthine oxidase, some of them being potent inhibitors, displaying long-
lasting hypouricemic action.[1] 1-Naphthylpyrazole-5-carboxamides were found to be
nonbasic factor Xa inhibitors, showing significantly increased enzyme specificity and
oral bioavailability than related lead structures.[2]Antagonists of the CB1 cannabinoid
receptor were described as possessing the pyrazole-3-carboxamide moiety in their struc-
ture.[3] Pyrazole derivatives were also evaluated as antitumor and antiangiogenic
agents.[4] The antipyretic action of a pyrazole derivative has been known since 1884,[5]
and since then a diversity of bioactivities has been reported for this type of compounds.
Pyrethroid acid oxime-esters containing a pyrazole ring were found to possess plant
antiviral activities.[6] The herbicidal activity of substituted phenyl pyrazoles,[7] the acari-
cidal activity of pyrazole-5-carboxamides,[8] and the fungicidal activity of 1H-pyrazole
derivatives make these types of compounds important for pest management.[9,10] Recently,
the interest on the synthesis of new substituted pyrazole derivatives has increased.
Reaction of 1,3-diketones with N-nucleophiles[11] reaction of Baylis-Hillman adducts
with hydrazine hydrochlorides,[12] and the microwave-assisted synthesis of pyrazoles by
Vilsmeier cyclization of hydrazones[13] and of pyrazole libraries by means of cellulose
beads as solid support[14] are some of the reported achievements in this field. Pyrazole
C-nucleosides have been frequently mentioned in the literature. Since the isolation from
S. Candidus of the pyrazole C-nucleoside pyrazofurin,[15] which has a broad spectrum
of antiviral and antitumor activities, there has been considerable interest in synthetic
approaches to new analogues of this compound. Synthesis and antiviral activity of
50-deoxypyrazofurin was reported in the literature, being more selective and less toxic
than pyrazofurin.[16] Isothiazole derivative analogues to this C-nucleoside antibiotic
were synthesized, but no significant inhibition of tumor cell growth or of viral replication
was detected.[15]
A variety of strategies is known for the synthesis of pyrazole C-nucleosides, namely
the reaction of an alkyne acetal with acetic acid and aqueous HCl, followed by addition
of hydrazine hydrate,[17] palladium catalyzed glycal coupling with iodopyrazoles,[18]
and metal catalyzed reaction of keto esters with alkyl cyanoformates.[19] Recently the prepa-
ration of pyrazole C-nucleosides was described via reaction of ribofuranosyl cyanides with

Pseudo-C-Nucleosides Containing Pyrazole Rings
515
b-dicarbonyl compounds promoted by tin (IV) chloride.[20] Heptenuloses underwent ring
closure reactions with various N-nucleophiles to give acyclic pyrazole C-nucleosides.[21]
We report now synthetic approaches leading to new C-nucleoside analogues, which
contain the pyrazole ring bonded to C-4 of the furanosyl moiety, therefore being known
as pseudo-C-nucleosides. A goal of the investigation is the preparation of new sugar deriva-
tives possessing the pyrazole unit bonded to C-4 for further evaluation of their bioactivity in
various domains, namely as pesticides, due to the bioactivity found for other pseudo-
C-nucleosides and analogues containing thiazole and thiazolidinone moieties in their
structure.[22]
RESULTS AND DISCUSSION
Synthesis of the ethyl 4-[(4R)-a-D-erythrofuranos-4-C-yl]pyrazole-5-carboxylate
derivative 5 was accomplished by Wittig reaction of 3-O-benzyl-1,2-O-isopropylidene-
a-D-ribo-pentodialdo-1,4-furanose (1)[23] with [(ethoxycarbonyl)methylene]triphenyl-
phosphorane to give the E- and Z-isomers 2 and 3 in 74% and 10% yield, respectively.
Treatment of 2 with diazomethane in diethyl ether at 08C[24] for 2 h and dehydrogenation
of the intermediate pyrazoline 4 with Cl2/CCl4 gave the target molecule in 84% yield
(Sch. 1). The evidence that helped to elucidate the stereochemistry of 2 and 3 is based
Scheme 1. i) Ph3P ¼ CHCO2Et, CHCl3, rt, 30 min, 74% for 2, 10% for 3; ii) CH2N2, Et2O, 08C,
2 h; iii) Cl2/CCl4, rt, 3 h, 84%.

516
Rauter et al.
on their NMR data. The signal of H-4 of the Z-isomer appears in a multiplet at d 5.76–
5.73, due to the neighbourhood of the carbonyl group, while the resonance of H-4 of
the E-isomer is included in the multiplet at d 4.63–4.54. This effect has also been
found in Z-alkenes bonded to pyranosidic moieties.[25] The same effect justifies that
H-5 of the E-isomer appears at lower field (d 6.92) than H-5 of the Z-isomer (included
in the multiplet at d 5.97–5.95). The coupling constant J5,6 ¼ 16 Hz for 2 is also in agree-
ment with the stereochemistry assigned. Compound 5 is analogous to C-nucleosides con-
taining 5-carboxamido-4-(b-D-ribofuranosyl)pyrazole moieties, which were moderate
inhibitors of the in vitro growth of tumor cell lines, and showed a moderate in vitro anti-
viral activity towards the rabies virus.[26]
Reformatsky reaction of 1 with ethyl bromoacetate in THF in the presence of acti-
vated zinc at 458C gave the ethyl allo-/talo-heptofuranuronate 6a,b in 65% yield in a
1 : 1 ratio (Sch. 2). Its oxidation with pyridinium dichromate in the presence of powdered
˚
molecular sieve (3 A) and acetic acid in dichloromethane at rt for 30 min gave 7 in 75%
˚
Scheme 2. i) BrCH2CO2Et, Zn, THF, 458C, 1 hr, 65%; ii) PDC, molecular sieves powder 3 A,
CH2Cl2, AcOH, 258C, 30 min, 75%; iii) H2NNHC6H3(NO2)2, EtOH, AcOH, 808C, 5 hr, 46% for
8, 47% for 9; iv) H2NNHCO2Me, EtOH, AcOH, 808C, 5 hr, 80%; v) H2NNHCOPh, EtOH,
AcOH, 808C, 5 hr, 80%; vi) Ac2O, NaOAc, 1008C, 4 hr, 72% for 12, 16% for 13 starting from
10a,b; 85% for 13 starting from 11a,b.

Pseudo-C-Nucleosides Containing Pyrazole Rings
517
yield. This derivative contains a 2-methylene-1,3-dicarbonyl moiety, which, after
reaction with hydrazine derivatives, afforded the corresponding hydrazones 8, 9, 10a,b,
and 11a,b, when 2,4-dinitrophenyl hydrazine, methyl hydrazinocarboxylate, and
benzoyl hydrazine were used. Separation by column chromatography of the Z/E
isomers was only possible with the 2,4-dinitrophenylhydrazono derivatives 8 and 9,
which were isolated in 46% and 47% yield, respectively. The Z/E stereochemistry was
assigned by means of the chemical shift of H-4, which appeared at a lower field for the
Z-isomer, due to the neighborhood of NH, than the corresponding signals of the
E-isomer (d 4.80) and of the 1,3-dicarbonyl starting material (included in the multiplet
at d 4.67–4.57). Intramolecular cyclization of 10a,b promoted by acetic anhydride and
sodium acetate at 1008C for 4 hr gave the expected pyrazole 12 in 72% yield, together
with the 1-acetyl-1H-pyrazole derivative 13 in 16% yield. The formation of the pyrazole
ring was confirmed by NMR data. The signal of the olefinic H-4 appeared at d 6.09 (for 12)
and d 6.52 (for 13) and the signals of C-3, C-4, and C-5 appeared at d 153.0, 98.1, and
148.8 (for 12) and at d 155.7, 103.4, and 144.4 (for 13). The presence of the methoxy
1
group was detected in 12 by the H- and 13C NMR signals at d 4.02 and d 54.7, respec-
tively, which were absent in the corresponding spectra of 13. They also exhibited the
resonances due to the methyl group of two acetyl groups at d 2.51, and 2.25 and d 23.3
and 20.9, confirming the proposed structure for 13, which was also obtained by treatment
of 12 with acetic anhydride and sodium acetate. When the hydrazone 11a,b was treated
with acetic anhydride and sodium acetate under the same conditions, only compound
13 was obtained in 85% yield. Replacement of the methoxycarbonyl group or of the
benzoyl group by the acetyl group in 13 was caused by reaction with acetic anhydride
present in a large excess.
Reaction of 1,3-dicarbonyl compound 7 with phenyl hydrazine gave the 1-phenyl-1H-
pyrazole derivative 14 in 72% yield. The structure of the pyrazole ring was confirmed by
1H NMR due to the presence of the expected phenyl protons and of the methylene group,
which appeared at d 3.28 and 2.79, as an AB system with JA,B ¼ 24. 13C NMR spectrum
showed the signals corresponding to C-3 at d 155.5, C-4 at d 38.7, C-5 at d 170.2, and the
resonances of the aromatic ring, which appear with those of the phenyl ring of the benzyl
group.
Synthesis of 3-O-benzyl-5-deoxy-1,2-O-isopropylidene-a-D-ribo-hexodialdo-1,4-
furanose (16) was accomplished by oxidation of 3-O-benzyl-5-deoxy-1,2-O-isopropyli-
˚
dene-a-D-ribo-hexofuranose (15b) with PCC and powdered molecular sieves (4 A) in
CH2Cl2 at rt for 15 min in 80% yield. The starting material 15b was obtained by reac-
tion of 1[23] with N,N0- thiocarbonyldiimidazole[27] to give the intermediate thiocarbo-
nate 15a, which was treated with tributyltin hydride and azoisobutyronitrile in
toluene,[28] a reaction that also gave compound 15c (Sch. 3). An alternative procedure
consisted of a classic approach based on tritylation of 1, followed by iodination
with triphenylphosphine/iodine/imidazole, detritylation, and reduction with lithium
aluminium hydride to give 15b in 55% overall yield.[29] Reformatsky reaction of 16
with ethyl bromoacetate and zinc gave 17a,b in 60% yield, which oxidation with
PCC for 40 min under the reaction conditions previously described for 15, gave the
ketoester 18 in 92% yield. Its reaction with tosyl azide and triethylamine in acetonitrile
at rt for 30 min afforded the diazoester 19 in 93.5% yield. The pyrazofurin analogue 20
was synthesized by intramolecular cyclization of 19 with NaH in 20% yield, according
to the procedure described by Chen and Schneller.[16]

518
Rauter et al.
˚
Scheme 3. i) PCC, molecular sieves powder 4 A, CH2Cl2, rt, 15 min, 80%; ii) BrCH2CO2Et, Zn,
˚
THF, 558C, 40 min, 60%; iii) PCC, molecular sieve powder 4 A, CH2Cl2, rt, 40 min, 92%;
iv) TsN3, Et3N, MeCN, rt, 30 min, 93.5%; v) NaH, THF, rt, 20 hr, 20%.
EXPERIMENTAL
General Methods
Melting points were determined with a melting point apparatus (Leitz-Biomed)
with platinium plate and are uncorrected. Optical rotations were measured with an
Atago Polax-D polarimeter and IR spectra were recorded with a Biorad FTS 25 PC
1
spectrophotometer. H NMR spectra were run with a Bruker AC-250 P spectrometer.
Chemical shifts are expressed in parts per million (ppm) downfield from TMS and
the coupling constants J in Hz. The 13C NMR spectra were run at 62.90 MHz in the
same spectrometer. The experiments were performed in chloroform-d. The progress
of all reactions was monitored by thin layer chromatography (TLC) using aluminium
sheets precoated with silica gel 60F254 to a thickness of 0.2 mm (Merck). Preparative
TLC was performed with aluminium plates coated with silica gel 60F254 to a thickness
of 0.5 mm (Merck). Compounds were detected with UV light (254 nm) and/or by
spraying the sheets with a 3% vanillin-sulfuric acid solution. Column chromatography
(CC) was conducted under low pressure by elution of the columns filled with silica gel
(0.040–0.063 mm, Merck).

Pseudo-C-Nucleosides Containing Pyrazole Rings
519
Ethyl 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-a-D-ribo-hept-5(E)-enefura-
nuronate (2) and ethyl 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-a-D-ribo-hept-
5(Z)-enefuranuronate (3). A solution of 1[23](2.0 g, 7.2 mmol) in chloroform (35 mL)
was added to a solution of [(ethoxycarbonyl)methylene]triphenylphosphorane (5.1 g,
14.6 mmol) in chloroform (35 mL). The mixture was stirred at rt for 30 min. After concen-
tration under reduced pressure the residue was purified by CC eluted with ethyl acetate/
toluene (1 : 4) to give 2 (1.85 g, 74%) and 3 (0.25 g, 10%). Physical and spectroscopic data
for 2: Rf 0.78 (ethyl acetate/toluene 1 : 1); [a] 2D5 ¼ þ47.58 (c 2, CHCl3); IR (neat) (cm21):
1
1725 (C ¼ O), 1660 (C ¼ C); UV (lmax. nm) ethanol: 203 (1 ¼ 12320); H NMR: 7.34
´
(s, 5H, Ph), 6.92 (dd, 1H, H-5, J4,5 ¼ 5, J5,6 ¼ 16), 6.12 (d, 1H, H-6), 5.76 (d, 1H, H-1,
J1,2 ¼ 3.4), 4.72 (part A of AB system, 1H, CH2, Bn, JAB ¼ 12), 4.63–4.56 (m, 3H,
H-2, H-4 and part B of AB system, CH2, Bn), 4.19 (q, 2H, CH2, Et, JCH2,CH3 ¼ 7), 3.53
(dd, 1H, H-3, J2,3 ¼ 4, J3,4 ¼ 9), 1.61 (s, 3H, CH3, isop), 1.36 (s, 3H, CH3, isop), 1.29
(t, 3H, CH3,Et); 13C NMR: 166.4 (C-7), 143.9 (C-5), 137.5 (Cq, Ph), 128.9, 128.5,
128.4 (CH, Ph), 122.9 (C-6), 113.6 (Cq, isop), 104.4 (C-1), 82.3 (C-3), 77.9 (C-2), 77.4
(C-4), 72.9 (CH2, Bn), 60.9 (CH2, Et), 27.2 (CH3, isop), 26.8 (CH3, isop), 14.6 (CH3, Et).
Anal. Calcd for C19H24O6: C 65.50, H 6.94; Found: C 65.83, H 6.57.
Data for 3: Rf 0.74 (ethyl acetate/toluene 1 : 1); [a]2D5 ¼ 288 (c 1.25, CHCl3); IR
(neat) (cm21): 1730 (C ¼ O), 1680 (C ¼ C); UV (lmax. nm) (ethanol): 204
´
(1 ¼ 16759); 1H NMR: 7.32 (s, 5H, Ph), 5.97–5.95 (m, 2H, H-5, H-6), 5.76–5.73
(m, 2H, H-1, H-4), 4.74–4.56 (m, 3H, H-2, CH2, Bn), 4.18 (q, 2H, CH2, Et,
JCH CH ¼ 7), 3.53 (dd, 1H, H-3, J2,3 ¼ 4.2, J3,4 ¼ 9), 1.66 (s, 3H, CH3, isop), 1.37
2
3
(s, 3H, CH3, isop), 1.29 (t, 3H, CH3, Et); 13C-NMR: 165.3 (C-7), 142.9 (C-5), 137.4
(Cq, Ph), 128.3, 128.0, 127.8 (CH, Ph), 124.4 (C-6), 113.3 (Cq, isop), 103.9 (C-1), 82.0
(C-3), 77.8 (C-2), 73.2 (C-4), 72.0 (CH2, Bn), 60.5 (CH2, Et), 26.8 (CH3, isop), 26.7
(CH3, isop), 14.1 (CH3, Et).
Anal. Calcd for C19H24O6: C 65.50, H 6.94; Found: C 65.80, H 6.75.
Ethyl 4-[(4R)-3-O-benzyl-1,2-O-isopropylidene-a-D-erythrofuranos-4-C-yl]-1H-
pyrazole-5-carboxylate (5). A solution of 2 (2.79 g, 8 mmol) in diethyl ether (60 mL)
was cooled to 08C and added dropwise to a solution of diazomethane in diethyl ether
(32 mmol, 500 mL). The mixture was stirred at 08C for 2 hr. Glacial acetic acid was
added dropwise to get a colorless reaction mixture, due to the elimination of the diazo-
methane that did not react. Concentration in vacuum gave a residue, which was dissolved
in carbon tetrachloride (40 mL). A saturated chlorine solution in carbon tetrachloride
(200 mL) was added dropwise, and the mixture was stirred at rt for 3 hr. The solvent
was removed by evaporation under reduced pressure, and the residue was dissolved in
diethyl ether (50 mL), extracted with a saturated solution of sodium hydrogen carbonate
(50 mL), and washed with water (50 mL). The organic phase was dried (Na2SO4) and con-
centrated under reduced pressure. The residue was purified by CC with ethyl acetate/
toluene (3 : 2) to give 5 (2.5 g, 84%). Rf 0.43 (ethyl acetate/toluene 2 : 1);
[a]2D5 ¼ þ43.88 (c 1.6, CHCl3); IR (neat) (cm21): 3443 (N-H), 1722 (C ¼ O), 1592
1
(C ¼ C); UV (lmax. nm) ethanol: 237 (1 ¼ 12903), 209 (1 ¼ 12974); H NMR: 13.80
´
(s, 1H, N-H), 7.75 (s, 1H, H-3), 7.30–7.15 (m, 5H, Ph), 5.86 (d, 1H, H-10, J1 ,2 ¼ 3.7),
0
0
5.56 (d, 1H, H-40, J3 ,4 ¼ 9), 4.70 (t, 1H, H-20, J2 ,3 ¼ 3.9), 4.62, 4.50 (2 H, AB system,
0
0
0
0
CH2, Bn, JAB ¼ 12), 4.35 (q, 2H, CH2, Et, JCH CH ¼ 7), 3.95 (dd, 1H, H-30), 1.70
2
3
(s, 3H, CH3, isop), 1.42 (s, 3H, CH3, isop), 1.36 (t, 3H, CH3, Et);13C NMR: 162.1
(C ¼ O), 139.5 (C-5), 137.2 (Cq, Ph), 132.0 (C-3), 128.5, 128.2, 127.8 (CH, Ph), 120.5

520
Rauter et al.
(C-4), 112.8 (Cq, isop), 103.6 (C-10), 82.3 (C-30), 77.6 (C-20), 72.0 (CH2, Bn), 71.7 (C-40),
61.0 (CH2, Et), 26.8 (CH3, isop), 26.5 (CH3, isop), 14.2 (CH3, Et).
Anal. Calcd for C20H24N2O6: C 61.84, H 6.23, N 7.21; Found: C 62.15, H 6.53, N 7.45.
General Procedure for the Reformatsky Reaction
A solution of ethyl bromoacetate (10 mmol) in anhydrous THF (4 mL) was added at rt
under nitrogen to the suspension of activated granulated zinc 20 mesh (0.34 g, 5.32 mmol)
in the solution of the carbonyl compound (3.6 mmol) in anhydrous THF (2 mL). The reac-
tion mixture was heated under nitrogen. After cooling to rt, a 10% hydrochloric acid sol-
ution (25 mL), previously cooled to 08C, was added. The organic phase was extracted with
dichloromethane (3 ꢀ 25 mL), neutralized with a 2.5% sodium hydrogen carbonate sol-
ution (25 mL), and then dried (Na2SO4). Concentration under reduced pressure afforded
a residue, which was purified by CC eluted with ethyl acetate/toluene (1 : 5).
Ethyl 3-O-benzyl-6-deoxy-1,2-O-isopropylidene-a-D-allo/talo-heptofuranuro-
nate (6a,b). Starting from 1[23] (1 g, 3.6 mmol), the reaction mixture was heated at 458C
for1 hr to give 6a,b, (0.86 g, 65%). Rf 0.53 (ethyl acetate/toluene 1 : 1); IR (cm21
)
1
3460 (O-H), 1730 (C ¼ O); H NMR: 7.37–7.17 (m, 10 H, Ph), 5.69 (t, 2H, H-1a,
H-1b, J1,2 ¼ 3.4), 4.69 (part A of AB system, 2H, CH2a and CH2b, Bn, JAB ¼ 12),
4.53–4.48 (m, 4H, H-2a, H-2b and part B of AB system, CH2a, CH2b, Bn), 4.34–4.31
(m, 1H, H-5a); 4.14–4.03 (m, 7H, H-4a, H-4b, H-5b, CH2a, CH2b, Et), 3.95–3.90
(m, 2H, H-3a, H-3b), 3.47 (brs, 1H, OH-5a), 3.29 (d, 1H, OH-5b, J5b,OH-5b ¼ 7), 2.64–
2.49 (m, 4H, CH2-6a, CH2-6b), 1.53 (s, 6H, CH3, isop), 1.30 (s, 6H, CH3, isop), 1.18
(t, 6H, CH3, Et, JCH CH3 ¼ 7); 13C NMR: 172.0, 171.8 (C ¼ O, C-7a, C-7b), 137.8,
2
137.7 (Cq, Ph), 129.0, 128.4, 128.2, 127.9, 127.9 (CH, Ph), 112.8 (Cq, isop), 104.3,
104.2 (C-1a, C-1b), 80.8, 80.5 (C-4a, C-4b), 78.2, 77.8 (C-2a, C-2b), 77.7, 77.1 (C-3a,
C-3b), 72.0, 71.8 (CH2-a, CH2-b, Bn), 67.0, 66.5 (C-5a, C-5b), 60.5, 60.5 (CH2-a, CH2-
b, Et), 39.1, 37.3 (C-6a, C-6b), 26.9 (CH3, isop), 26.7 (CH3, isop), 14.1 (CH3, Et).
Anal. Calcd for C19H26O7: C 62.28, H 7.15; Found: C 62.15, H 7.20.
Ethyl 3-O-benzyl-5,7-dideoxy-1,2-O-isopropylidene-a-D-allo/talo-octofuranuro-
nate (17a,b). Starting from 16 (1.05 g, 3.60 mmol), the reaction mixture was heated at
558C for 40 min to give 17a,b (0.82 g, 60%); Rf 0.53 (ethyl acetate/toluene 1 : 1); IR
(neat) (cm21) 3500 (OH), 1740 (C ¼ O); 1H NMR: 7.32–7.28 (m, 5H, Ph), 5.69
(d, 1H, H-1, J1,2 ¼ 3.5), 4.76 (part A of AB system, 1H, CH2, Bn, JAB ¼ 11.8), 4.54–
4.49 (m, 2H, H-2, part B of AB system, CH2, Bn), 4.25–4.08 (m, 4H, H-4, H-6, CH2,
Et), 3.45 (dd, 1H, H-3, J2,3 ¼ 3.9, J3,4 ¼ 8.2), 3.32 (brs, 1H, OH-6), 2.48–2.45 (m, H,
H-7) 1.90–1.65 (m, H, H-5), 1.58 (s, 3H, CH3, isop), 1.33 (s, 3H, CH3, isop), 1.25
(t, 3H, CH3, Et, JCH CH ¼ 7.2); 13C NMR: 171.8, 171.71 (C-8), 137.0 (Cq, Ph), 128.7,
2
3
128.2, 127.8 (CH, Ph), 112.5 (Cq, isop), 103.8, 103.6 (C-1), 81.6, 81.3 (C-3), 76.6, 76.4
(C-2), 76.0, 75.2 (C-4), 71.8 (CH2, Bn), 66.1, 65.3 (C-6), 60.2 (CH2, Et), 41.6, 41.3
(C-7), 38.6, 38.4 (C-5).
Anal. Calcd for C20H28O7: C 63.14, H 7.42; Found: C 63.15, H 7.25.
Ethyl 3-O-benzyl-6-deoxy-1,2-O-isopropylidene-a-D-ribo-hept-5-ulofuranuro-
˚
nate (7). Compounds 6a,b (1.83 g, 5 mmol), activated powdered molecular sieves (4 A,
5.0 g) and pyridinium dichromate (3.2 g, 15 mmol) were added to dichloromethane
˚
(24 mL), previously dried over molecular sieves 4 A, and cooled at 58C. The mixture

Pseudo-C-Nucleosides Containing Pyrazole Rings
521
was cooled at 08C and stirred for 5 min. Glacial acetic acid (0.49 mL) was added dropwise.
The reaction mixture was warmed at 258C and stirred for 30 min. Ethyl acetate (30 mL)
was then added, and the suspension was filtered and concentrated under reduced pressure.
Toluene (3 ꢀ 20 mL) was added to the slushy mixture and concentrated. The residue was
purified by CC eluted with ethyl acetate/toluene (1 : 1) to give 7 (1.36 g, 75%). Rf 0.62
(ethyl acetate/toluene 1 : 2); [a]2D5 ¼ þ5028 (c 2.5, CHCl3); IR (neat) (cm21) 1737
1
(C ¼ O); H NMR: 7.37–7.27 (m, 5H, Ph), 5.77 (d, 1H, H-1, J1,2 ¼ 3.1), 4.73 (1H, part
A of the AB system, CH2, Bn, JAB ¼ 11.9), 4.67–4.57 (m, 3H, H-2, H-4, part B of the
AB system, Bn), 4.12 (q, 2H, CH2, Et, J ¼ 7,3), 3.93 (dd, 1H, H-3, J2,3 ¼ 2,8,
J3,4 ¼ 7.6), 3.61, 3.51 (AB system, 2H, H-6, H-60, JAB ¼ 16), 1.56 (s, 3H, CH3, isop),
1.34 (s, 3H, CH3, isop), 1.21 (t, 3H, CH3, Et); 13C NMR: 200.3 (C-5), 171.7 (C-7),
136.6 (Cq, Ph), 128.0, 127.5 (CH, Ph), 113.1 (Cq, isop), 103.9 (C-1), 82.1 (C-3), 78.8
(C-2), 77.5 (C-4), 71.8 (CH2, Bn), 60.8 (CH2, Et), 45.5 (C-6), 26.5 (CH3, isop), 26.1
(CH3, isop), 13.6 (CH3, Et).
Anal. Calcd for C19H24O7: C 62.63, H 6.64; Found: C 62.52, H 6.81.
General Procedure for the Reaction of Keto Sugars
with Hydrazine Derivatives
A mixture of the keto sugar 7 (1 g, 2.75 mmol) and the hydrazine derivative (3.0–
4.78 mmol) in ethanol (10 mL) was stirred for 5 min at rt. Glacial acetic acid (0.1 mL)
was added dropwise. The reaction mixture was heated at 808C for 5 hr, then cooled and
concentrated. The residue was purified by CC.
Ethyl
3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-5(Z)-(2,4-dinitrophenyl)
hydrazono-a-D-ribo-heptofuranuronate (8) and ethyl 3-O-benzyl-5,6-dideoxy-1,2-O-
isopropylidene-5(E)-(2,4-dinitrophenyl)hydrazono-a-D-ribo-heptofuranuronate (9).
Reaction with 2,4-dinitrophenyl hydrazine (0.6 g, 3.0 mmol) and purification of the
residue with ethyl acetate/toluene (1 : 10) gave 8 (0.69 g, 46%) and 9 (0.70 g, 47%).
Data for 8: Rf 0.57 (ethyl acetate/toluene 1 : 5); [a]2D5 ¼ þ56.68 (c 1.7, CHCl3); IR
(neat) (cm21) 3230 (N-H), 1728 (C ¼ O); UV (lmax. nm) ethanol: 354 (1 ¼ 19306),
´
1
202 (1 ¼ 45054); H NMR: 12.32 (s, 1H, N-H), 9.07 (d, 1H, H-30, J3 ,5 ¼ 2.9), 8.30
0
0
(dd, 1H, H-50), 7.90 (d, 1H, H-60, J5 ,6 ¼ 9.7), 7.28 (s, 5H, Ph), 5.98 (d, 1H, H-1,
J1,2 ¼ 3.5), 5.04 (d, 1H, H-4, J3,4 ¼ 9), 4.82, 4.57 (AB system, 2H, CH2, Bn,
JAB ¼ 12), 4.63 (t, 1H, H-2, J2,3 ¼ 3.7), 4.22–4.13 (m, 3H, H-3, CH2, Et), 3.58, 3.42
(AB system, 2H, H-6a, H-6b, JAB ¼ 16), 1.63 (s, 3H, CH3, isop), 1.39 (s, 3H, CH3,
isop), 1.26 (t, 3H, CH3, Et, JCH CH ¼ 7); 13C NMR: 164.5 (C-7), 149.0 (C-5), 144.9
0
0
2
3
(C-40, Ph-NO2), 138.1 (C-20, PhNO2), 136.3 (Cq, Ph), 129.6 (C-50), 128.5, 128.3, 128.2
(CH, Ph), 123.2 (C-30), 116.2 (C-60), 114.1 (Cq, isop), 104.7 (C-1), 80.5 (C-3), 76.7
(C-2 and C-4), 72.5 (CH2, Bn), 61.2 (CH2, Et), 40.6 (C-6), 26.7 (CH3, isop), 26.5 (CH3,
isop), 14.1 (CH3, Et).
Anal. Calcd for C25H28O10N4: C 55.15, H 5.18, N 10.29; Found C 55.40, H 5.04, N
10.46.
Data for 9: Rf 0.51 (ethyl acetate/toluene 1 : 5); [a]2D5 ¼ 26.78C (c 1.5, CHCl3); IR
(neat) (cm21) 3266 (N-H), 1730 (C ¼ O); UV (lmax. nm) ethanol: 351 (1 ¼ 4571), 206
´
1
(1 ¼ 6656); H NMR: 11.60 (s, 1H, N-H), 9.14 (d, 1H, H-30, J3 ,5 ¼ 2.2), 8.31 (dd, 1H,
0
0
H-500), 7.98 (d, 1H, H-60, J5 ,6 ¼ 9.4), 7.28 (s, 5H, Ph), 5.85 (d, 1H, H-1, J1,2 ¼ 3.5),
0
0

522
Rauter et al.
4.80 (d, 1H, H-4, J3,4 ¼ 9.2), 4.74, 4.58 (AB system, 2H, CH2, Bn, JAB ¼ 12.2), 4.65
(t, 1H, H-2, J2,3 ¼ 3.7), 4.19 (q, 2H, CH2, Et, J ¼ 7), 3.96 (dd, 1H, H-3), 3.47, 3.36
(AB system, 2H, H-6a, H-6b, JAB ¼ 15.4), 1.67 (s, 3H, CH3, isop), 1.40 (s, 3H, CH3,
isop), 1.26 (t, 3H, CH3, Et, JCH CH ¼ 7); 13C NMR: 167.1 (C-7), 147.9 (C-5), 145.0
2
3
(C-40, PhNO2), 138.7 (C-20, PhNO2), 137.0 (Cq, Ph), 129.8 (C-50), 128.3, 128.0, 127.9
(CH, Ph), 123.0 (C-30), 117.1 (C-60), 113.6 (Cq, isop), 104.1 (C-1), 80.9 (C-3), 79.2
(C-4), 76.9 (C-2), 72.5 (CH2, Bn), 62.4 (CH2, Et), 32.9 (C-6), 26.8 (CH3, isop), 26.4
(CH3, isop), 14.0 (CH3, Et).
Anal. Calcd for C25H28O10N4: C 55.15, H 5.18, N 10.29; Found: C 54.95, H 5.30, N
10.04.
Ethyl 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-5(E)/5(Z)-methoxycarbonyl-
hydrazono-a-D-ribo-heptofuranuronate (10a,b). Reaction with methyl hydrazino-
carboxylate (0.18 g, 3.02 mmol) and purification of the residue by CC eluted with ethyl
acetate/toluene (1 : 5) gave 10a,b (0.96 g, 80%). Rf 0.45 (ethyl acetate/toluene 1 : 3);
1
IR (cm21) 3626 (N-H), 1725 (C ¼ O), 1720 (C ¼ O); H NMR: 8.15 (s, 1H, N-H),
7.73 (s, 1H, N-H), 7.36–7.16 (m, 10 H, Ph), 5.74, 5.73 (each d, 1H, H-1, J1,2 ¼ 3.8,
J1,2 ¼ 3.7), 4.95 (d, 1H, H-4, J3,4 ¼ 8.7), 4.82–4.72 (m, 3H, H-2, part A of AB
system, Bn), 4.64–4.52 (m, 3H, H-2, H-4, part B of AB system, CH2, Bn), 4.08 (q, 4H,
CH2, Et, J ¼ 7.1), 4.40, 3.93 (2 dd, 1H, H-3, J2,3 ¼ 4.3, J3,4 ¼ 8.9), 3.83 (s, 3H, OCH3),
3.65 (s, 3H, OCH3), 3.62, 3.38 (AB system, 2H, H-6, H-60, JAB ¼ 17), 3.28, 3.22 (AB
system, 2H, H-6, H-60, JAB ¼ 14), 1.60, 1.59 (s, each 3H, CH3, isop), 1.42, 1.37 (2s,
each 3H, CH3, isop), 1.21 (t, 6H, CH3, Et); 13C NMR: 170.6 (C-7), 168.3 (Cq,
COOMe), 154.5, 148.4 (C-5), 137.5, 135.7 (Cq, Ph), 128.8, 128.4, 128.3, 128.2, 128.0,
127.8 (CH, Ph), 113.7, 113.3 (Cq, isop), 104.9, 103.7 (C-1), 81.3, 78.7 (C-3), 80.8, 77.7
(C-2), 77.3, 76.3 (C-4), 72.7, 72.1 (CH2, Bn), 62.1, 60.7 (CH2, Et), 52.8, 52.4 (OCH3),
39.6, 33.2 (C-6), 26.8, 26.68 (CH3, isop), 26.5, 26.3 (CH3, isop), 14.0, 13.8 (CH3, Et).
Anal. Calcd for C21H28N2O8: C 57.79, H 6.47, N 6.42; Found: C 57.55, H 6.90,
N 6.39.
Ethyl
5(E)/5(Z)-benzoylhydrazono-3-O-benzyl-5,6-dideoxy-1,2-O-isopropyli-
dene-a-D-ribo-heptofuranuronate (11a,b). Reaction with benzoyl hydrazine (0.65 g,
4.78 mmol) and CC eluted with ethyl acetate/toluene (1 : 2) gave 11a,b (1.06 g, 80%).
Rf 0.27 (ethyl acetate/toluene 1 : 2); IR (cm21)3450 (N-H), 1730 (C ¼ O), 1690
1
(C ¼ O); H NMR (C3D6O): 10.81, 9.75 (each s, 1H, N-H), 7.84 (dd, 4H, H-2, Ph, H-4,
Ph) 7.53–7.12 (m, 16H, Ph), 5.90, 5.88 (each d, 1H, H-1, J1,2 ¼ 3.6, J1,2 ¼ 3.7), 5.17
(d, 1H, H-4, J3,4 ¼ 9.1), 4.98 (t, 1H, H-2, J2,3 ¼ 3.9), 4.87–4.63 (m, 6H, CH2, Bn, H-2,
H-4), 4.67 (dd, 1H, H-3, J2,3 ¼ 4, J3,4 ¼ 9), 4.17–4.07 (m, 5H, H-3, CH2, Et,), 3.66
(s, 2H, H-6, H-60), 3.54, 3.36 (AB system, 2H, H-6, H-60, JAB ¼ 16.5), 1.57, 1.52 (each
s, 3H, CH3, isop), 1.37, 1.32 (each s, 3H, CH3, isop), 1.19 (t, 6H, CH3, Et); 13C-NMR:
170.7 (C-7), 164.3 (C ¼ O), 152.5 (C-5), 135.4 (Cq, Ph), 132.4 (Cq, Ph, Bz), 131.8,
128.6, 128.4, 128.1, 128.0, 127.8, 127.2 (CH, Ph), 114.0 (Cq, isop), 105.0 (C-1), 81.6
(C-3), 77.2 (C-2), 76.3 (C-4), 73.0 (CH2, Bn), 60.9 (CH2, Et), 40.0 (C-6), 26.9 (CH3,
isop), 26.7 (CH3, isop), 14.1 (CH3, Et).
Anal. Calcd for C26H30N2O7: C 64.72, H 6.27, N 5.81; Found: C 64.35, H 7.56,
N 5.49.
3-[(4R)-3-O-Benzyl-1,2-O-isopropylidene-a-D-erythrofuranos-4-C-yl]-4,5-dihydro-
,1-phenyl-1H-pyrazol-5-one (14). Reaction with phenyl hydrazine (0.5 g, 4.6 mmol) and
purification by CC eluted with ethyl acetate/toluene (1 : 4 v/v) gave 14 (0.81 g, 72%).

Pseudo-C-Nucleosides Containing Pyrazole Rings
523
Rf ¼ 0.49 (ethyl acetate/toluene 1/1);[a]2D5 ¼ þ808 (c 1.5, CHCl3); IR 1714 (C ¼ O)
cm21 1H NMR: 7.84 (d, 2H, Ph), 7.45–7.18 (m, 8H, Ph), 5.79 (d, 1H, H-10,
;
J1 ,2 ¼ 3.5), 4.83 (d, 1H, H-40, J3 ,4 ¼ 9.1), 4.87, 4.54 (AB system, 2H, CH2, Bn,
0
0
0
0
JAB ¼ 12.4), 4.70 (t, 1H, H-20, J2 ,3 ¼ 3,9), 3.85 (dd, 1H, H-30), 3.28, 2.79 (AB
system, 2H, CH2-4, JAB ¼ 24), 1.66 (s, 3H, CH3, isop), 1.40 (s, 3H, CH3, isop);
13C-NMR: 170.2 (C-5), 155.5 (C-3), 138.8, 137.7 (Cq, Ph), 129.1, 128.8, 128.6, 128.3,
125.3, 118.9 (CH, Ph), 113.6 (Cq, isop), 104.1 (C-10), 79.1 (C-30), 77.2 (C-20), 76.5
(C-40), 72.5 (CH2, Bn), 38.7 (C-4), 26.7 (CH3, isop), 26.4 (CH3, isop).
0
0
Anal. Calcd for C23H24N2O5: C 67.63, H 5.92; Found: C 67.58, H 6.20, N 5.80.
General Procedure for the Cyclisation of Hydrazones to Pyrazoles
The solution of the hydrazone (1.1 mmol) in chloroform (2 mL) was added to the
mixture of sodium acetate (164 mg, 2 mmol) and acetic anhydride (2.8 mL, 30 mmol).
The reaction mixture was stirred at 1008C for 4 hr. Concentration in vacuum gave a
residue, which was extracted with chloroform (3 ꢀ 50 mL), the organic phase was
washed with water, dried (Na2SO4), and concentrated under reduced pressure to give a
residue, which was purified by CC eluted with ethyl acetate/toluene (1 : 6).
Methyl 5-acetoxy-3-[(4R)-3-O-benzyl-1,2-O-isopropylidene-a-D-erythrofuranos-
4-C-yl]-1H-pyrazole-1-carboxylate (12) and 5-acetoxy-1-acetyl-3-[(4R)-3-O-benzyl-
1,2-O-isopropylidene-a-D-erythrofuranos-4-C-yl]-1H-pyrazole (13). Starting from
10a,b (0.48 g, 1.1 mmol), the residue obtained was subjected to CC to give 12 (0.34 g,
72%) and 13 (0.073 g, 16%). Starting from 11a,b (0.53 g, 1.1 mmol) only 13 (0.39 g,
85%) was obtained.
Data for 12: Rf 0.54 (ethyl acetate/toluene 1 : 1); [a]2D5 ¼ þ178 (c 1.8, CHCl3); IR
(neat) (cm21): 1798, 1766 (C ¼ O), 1591 (C ¼ C); UV (lmax. nm) ethanol: 228
´
1
(1 ¼ 7424), 209 (1 ¼ 8398); H NMR: 7.28 (s, 5H, Ph), 6.09 (s, 1H, H-4), 5.83 (d, 1 H,
H-10, J1 ,2 ¼ 3.6), 5.06 (d, 1H, H-40, J3 ,4 ¼ 9), 4.67-4.60 (m, 3H, H-20, CH2, Bn), 4.02
0
0
0
0
(s, 3H, OCH3), 3.90 (dd, 1H, H-30, J2 ,3 ¼ 4), 2.36 (s, 3H, CH3, Ac), 1.64 (s, 3H, CH3,
isop), 1.25 (s, 3H, CH3, isop); 13C NMR: 171.2 (C ¼ O), 166.9 (C ¼ O, Ac), 153.0 (C-
3), 148.8 (C-5), 137.1 (Cq, Ph), 128.3, 128.1, 127.8 (CH, Ph), 113.2 (Cq, isop), 104.0
(C-10), 98.1 (C-4), 81.1 (C-30), 77.7 (C-20), 74.8 (C-40), 72.1 (CH2, Ph), 54.7 (CH3,
OCH3), 26.7 (CH3, isop), 26.5 (CH3, isop), 20.4 (CH3, Ac).
0
0
Anal. Calcd for (C21H24O8N2): C 58.33, H 5.59, N 6.48; Found C 57.95, H 5.45, N
6.93.
Data for 13: Rf 0.69 (ethyl acetate/toluene 1 : 1); [a]2D5 ¼ þ258 (c 2.3, CHCl3); IR
(neat)(cm21): 1780, 1755 (C ¼ O), 1579 (C ¼ C); UV (lmax. nm) ethanol: 240
´
1
(1 ¼ 8693), 208 (1 ¼ 8861); H NMR: 7.30–7.15 (m, 5H, Ph), 6.52 (s, 1H, H-4), 5.74
(d, 1H, H-10, J1 ,2 ¼ 3.5), 5.65 (d, 1H, H-40, J3 ,4 ¼ 8.9), 4.67, 4.45 (AB system, 2H,
0
0
0
0
CH2, Bn, JAB ¼ 12), 4.63 (t, 1H, H-20, J2 ,3 ¼ 3.8), 3.98 (dd, 1H, H-30), 2.51 (s, 3H,
CH3, Ac), 2.25 (s, 3H, CH3, Ac), 1.62 (s, 3H, CH3, isop), 1.34 (s, 3H, CH3, isop); 13C
NMR: 170.0, 167.1 (C ¼ O), 155.7 (C-3), 144.4 (C-5), 137.0 (Cq, Ph), 129.0, 128.4,
128.0 (CH, Ph), 113.6 (Cq, isop), 104.2 (C-10), 103.4 (C-4), 82.2 (C-30), 77.6 (C-20),
72.5 (C-40), 72.1 (CH2, Bn), 27.0 (CH3, isop), 26.9 (CH3, isop), 23.3 (CH3, Ac), 20.9
(CH3, Ac).
0
0

524
Rauter et al.
Anal. Calcd for (C21H24O7N2): C 60.57, H 5.81, N 6.73; Found C 60.67, H 5.50, N
7.12.
3-O-benzyl-5-deoxy-1,2-O-isopropylidene-a-D-ribo-hexofuranose (15b) and 3-O-
benzyl-6-deoxy-1,2-O-isopropylidene-a-D-allofuranose (15c). N,N0-thiocarbonyldiimi-
dazole (1.9 g, 10 mmol) was added to a solution of 123 (3.0 g, 9.7 mmol) in THF
(20 mL). The reaction mixture was refluxed for 30 min under nitrogen. Evaporation of
the solvent under reduced pressure gave a residue that was dissolved in dichloromethane
(90 mL) and washed with cold HCl 2M (11 mL) to which cold water was added (2 mL).
The organic layer was dried with sodium sulphate and the solvent evaporated to give
the intermediate 3-O-benzyl-1,2-O-isopropylidene-5,6-O-thiocarbonyl-a-D-allofuranose
(15a) (2.7 g, 80%). The thiocarbonate (2.7 g, 7.7 mmol), Bu3SnH (4.5 g, 15.3 mmol),
and AIBN (0.11 g, 0.67 mmol) in dry toluene (150 mL) was added dropwise to refluxing
toluene (80 mL) under argon for 45 min. Subsequent addition of the Bu3SnH (2 ꢀ 2.2 g,
7.5 mmol) together with AIBN (2 ꢀ 0.06 g, 0.37 mmol) after 2 hr and 4 hr was necessary.
The reaction was complete in 6 hr. The solution was then treated with aqueous NaOH
(10%, 80 mL) and stirred at 408C for 12 hr. The organic layer was separated and the
aqueous layer was reextracted with diethyl ether. The combined organic phases were
washed repeatedly with water until free of base and dried with sodium sulfate. Concen-
tration to a syrup, followed by CC eluted with ethyl acetate/toluene (1 : 5) gave 15b
(2.34 g, 30%) and 15c (2.34 g, 30%).
Data for 15b: Rf 0.37 (ethyl acetate/toluene 1 : 1); [a]2D5 ¼ þ1208 (c 1.3, CHCl3); IR
(neat) (cm21): 3430 (OH); 1H NMR: 7.37–7.28 (m, 5H, Ph), 5.72 (d, 1H, H-1, J1,2 ¼ 3.7),
4.79 (part A of AB system, 1H, CH2, Bn, JAB ¼ 11.8), 4.59–4.51 (m, 2H, H-2, part B of
AB system), 4.13 (ddd, 1H, H-4, J3,4 ¼ 9, J4,5 ¼ 4.7), 3.71 (t, 2H, H-6, J5,6 ¼ 5.7), 3.48
(dd, 1H, H-3, J2,3 ¼ 4.3), 2.78 (brs, 1H, OH-6), 1.99-1.87 (m, 1H, H-5a), 1.84–1.68
(m, 1H, H-5b), 1.59 (s, 3H, CH3, isop), 1.35 (s, 3H, CH3, isop); 13C NMR: 136.9 (Cq,
Ph), 128.2, 128.0, 127.9 (CH, Ph), 112.6 (Cq, isop), 103.7 (C-1), 81.4 (C-3), 76.7 (C-
4), 76.5 (C-2), 71.8 (CH2, Bn), 59.8 (C-6), 34.6 (C-5), 26.4 (CH3, isop), 26.2 (CH3, isop).
Anal. Calcd for (C16H22O5): C 65.29, H 7.53; Found C 65.43, H 7.50.
Data for 15c: Rf 0.66 (ethyl acetate/toluene 1 : 1); [a]2D5 ¼ þ107.48 (c 1.5, CHCl3); IR
(neat) (cm21): 3460 (OH); 1H NMR: 7.39–7.31 (m, 5H, Ph), 5.71 (d, 1H, H-1, J1,2 ¼ 3.7),
4.75 (part A of AB system, 1H, CH2, Bn, JAB ¼ 11.6), 4.58–4.54 (m, 2H, H-2, part B of
AB system), 4.05–3.99 (m, 2H, H-4, H-5), 3.89 (dd, 1H, H-3, J2,3 ¼ 4.3, J3,4 ¼ 8.4), 2.54
(brs, 1H, OH-5), 1.59 (s, 3H, CH3, isop), 1.35 (s, 3H, CH3, isop), 1.21 (d, 3H, H-6,
J5,6 ¼ 6.5); 13C NMR: 137.2 (Cq, Ph), 128.3, 128.0, 127.9 (CH, Ph), 112.8 (Cq, isop),
103.8 (C-1), 81.3 (C-4), 77.6 (C-2), 76.9 (C-3), 71.8 (CH2, Bn), 66.3 (C-5), 26.7 (CH3,
isop), 26.5 (CH3, isop), 17.4 (C-56).
Anal. Calcd for (C16H22O5): C 65.29, H 7.53; Found C 65.38, H 7.49.
3-O-benzyl-5-deoxy-1,2-O-isopropylidene-a-D-ribo-hexodialdo-1,4-furanose (16).
3-O-benzyl-5-deoxy-1,2-O-isopropylidene-a-D-ribo-hexofuranose (15b) (1.2g, 4.1 mmol)
was added to a suspension of pyridinium chlorochromate (2 g, 9.2 mmol) and molecular
˚
sieve powder 4 A (4 g) in dichloromethane (20 mL). The reaction mixture was stirred at rt
for 15min. Ethyl acetate was then added (30 mL) and the mixture stirred at rt for 10min.
The suspension was filtered and concentrated under reduced pressure. The residue was
purified by CC eluted with ethyl acetate/toluene (1: 4) to give 16 (0.96 g, 80%); Rf 0.65
(ethyl acetate/toluene 1 : 1); [a]2D5 ¼ þ808 (c 1.5, CHCl3); IR(cm21): 1726 (C ¼ O); H
1
NMR: 9.72 (t, 1H, H-6, J5,6 ¼ 2), 7.35–7.32 (m, 5H, Ph), 5.73 (d, 1H, H-1, J1,2 ¼ 3,7),

Pseudo-C-Nucleosides Containing Pyrazole Rings
525
4.78 (part A of AB system, 1H, CH2,Bn, JAB ¼ 11.8), 4.59–4.45 (m, 3H, H-2, H-4, part B of
AB system), 3.51 (dd, 1H, H-3, J2,3 ¼ 4.2, J3,4 ¼ 9), 2.73–2.43 (m, 2H, H-5, H-50), 1.61
(s, 3H, CH3, isop), 1.36 (s, 3H, CH3, isop); 13C NMR: 199.8 (Cq, C-6), 137.0 (Cq, Ph),
128.4, 128.3, 127.9 (CH, Ph), 112.9 (Cq, isop), 104.0 (C-1), 81.0 (C-3), 76.3 (C-4), 72.9
(C-2), 72.0 (CH2, Bn), 45.5 (C-6), 26.5 (CH3, isop), 26.2 (CH3, isop).
Anal. Calcd for C16H20O5: C 65.74, H 6.90; Found C 66.05, H 6.78.
Ethyl 3-O-benzyl-5,7-dideoxy-1,2-O-isopropylidene-a-D-ribo-oct-6-ulofuranuro-
nate (18). A solution of 17a,b (1.3 g, 3.4 mmol) in dry dichloromethane (3 mL) was
˚
added to a suspension of PCC (2.45 g, 11.4 mmol) and powdered molecular sieves (4 A,
3.42 g) in dry dichloromethane (17 mL). The mixture remained under stirring at rt for
40 min. Absolute ethyl acetate was added (30 mL), and the mixture was stirred for
10 min. After filtration, the filtrate was concentrated under reduced pressure at rt to give
18 (1.2 g, 92%); Rf 0.66 (ethyl acetate/toluene 1 : 1); [a]2D5 ¼ þ468 (c 2.5, CHCl3); IR
(neat) (cm21): 1744 (C ¼ O), 1720 (C ¼ O); UV (lmax. nm) ethanol: 230 (1 ¼ 7222),
´
1
204 (1 ¼ 6476); H NMR: 7.36–7.30 (m, 5H, Ph), 5.70 (d, 1H, H-1, J1,2 ¼ 3,7), 4.78
(part A of AB system, 1H, CH2, Bn, JAB ¼ 11.9), 4.56–4.51 (m, 2H, H-2, part B of AB
system of CH2, Bn), 4.37 (ddd, 1H, H-4), 4.17 (q, 2H, CH2, Et, JCH CH ¼ 7.2), 3.55
2
3
(dd, 1H, H-3, J2,3 ¼ 4.2, J3,4 ¼ 9), 3.49 (s, 2H, H-7, H-70), 2.90–2.58 (m, 2H, H-5,
H-50), 1.60 (s, 3H, CH3, isop), 1.35 (s, 3H, CH3, isop), 1.26 (t, 3H, CH3, Et); 13C NMR:
200,4 (C-6), 167.0 (C-8), 137,2 (Cq, Ph), 128.4, 128.0 (CH, Ph), 113.1 (Cq, isop),
104.0 (C-1), 80.8 (C-3), 76.6 (C-2), 74.1 (C-4), 72.2 (CH2, Bn), 61.3 (CH2, Et), 49.9
(C-7), 44.7 (C-5), 26.7 (CH3, isop), 26.5 (CH3, isop), 14.0 (CH3, Et).
Anal. Calcd for C20H26O7: C 63.48, H 6.92; Found C 64.04, H 6.45.
Ethyl 3-O-benzyl-7-diazo-5,7-dideoxy-1,2-O-isopropylidene-a-D-ribo-oct-6-ulo-
furanuronate (19). Tosyl azide (2.14 g, 10.8 mmol) and triethylamine (0.56 mL,
4.06 mmol) were added to a solution of 18 (1.5 g, 3.97 mmol) in anhydrous acetonitrile
(18 mL). The mixture was kept under stirring at rt for 30 min. The mixture was filtered
and concentrated under reduced pressure. The residue was purified by CC eluted with
ethyl acetate/toluene (1 : 6) to give 19 (1.5 g, 93.5%); Rf 0.60 (ethyl acetate/toluene
1 : 2); [a]2D5 ¼ þ698 (c 1.45, CHCl3); IR (neat) (cm21): 2150 (C ¼ N2), 1730 (C ¼ O),
1
1660 (C ¼ O); UV (lmax. nm) ethanol: 257 (1 ¼ 7855), 216 (1 ¼ 12535); H NMR:
´
7.37–7.23 (m, 5H, Ph), 5,71 (d, 1H, H-1, J1,2 ¼ 3.7), 4.78 (part A of AB system, 1H,
CH2, Bn, JAB ¼ 11.8), 4.57–4.50 (m, 3H, H-2, H-4, part B of AB system of CH2, Bn),
4.27 (q, 2H, CH2, Et, JCH CH ¼ 7.1), 3.63 (dd, 1H, H-3, J2,3 ¼ 4.2, J3,4 ¼ 9), 3.16–3.13
2
3
(m, 2H, H-5), 1.60 (s, 3H, CH3, isop), 1.35 (s, 3H, CH3, isop), 1,31 (t, 3H, CH3, Et);
13C NMR (C3D6O): 189.3 (C-6), 161.1 (C-8), 137.4 (Cq, Ph), 128.4, 127.9 (CH, Ph),
113.1 (Cq, isop), 104.0 (C-1), 81,3 (C-3), 76,8 (C-4), 76.7 (Cq, C-7), 74.2 (C-2), 72.2
(CH2, Bn), 61.4 (CH2, Et), 42.0 (C-5), 26.7 (CH3, isop), 26.4 (CH3, isop), 14.3 (CH3, Et).
Anal. Calcd for (C20H24O7N2): C 59.40, H 5.98, N 6.93; Found: C, 59.65; H, 5.78; N, 7.28.
Ethyl 3-[(4R)-3-O-benzyl-1,2-O-isopropylidene-a-D-erythrofuranos-4-C-yl]-4-
hydroxy-1H-pyrazole-5-carboxylate (20). A solution of 19 (1 g, 2.48 mmol) in dry
THF (13.5 mL) was added dropwise to a suspension of 95% sodium hydride (0.3 g,
12.4 mmol) in dry THF (13.5 mL) under nitrogen at 08C. After complete addition, the
reaction mixture was stirred at 208C for 20 hr. The mixture was cooled to 08C, a solution
of glacial acetic acid (0.71 mL, 12.4 mmol) in THF (2 mL) was added dropwise, and the
mixture was concentrated under reduced pressure. The residue was extracted with
CHCl3 (2 ꢀ 50 mL) and water (50 mL). THF (20 mL) was added to the aqueous phase,

526
Rauter et al.
and the solution was extracted with CHCl3 (50 mL). The organic phases were dried
(Na2SO4) and concentrated. The residue was purified by CC eluted with ethyl acetate/
toluene (1 : 10) to give 20 (0.2 g, 20%); mp 161–161.58C; Rf 0.57 (n-hexane/ethyl
acetate 1 : 3); [a]2D5 ¼ þ158 (c 2.0, CHCl3); IR (KBr) (cm21): 3431 (N-H), 3300 (O-H),
1724 (C ¼ O), 1691 (C ¼ C); UV (lmax. nm) ethanol: 230 (1 ¼ 7635), 207 (1 ¼ 8938);
´
1
H NMR: 7.30–7.25 (m, 5H, Ph), 6.87 (s, 1H, N-H), 5.85 (d, 1H, H-10, J1 ,2 ¼ 3.6),
0
0
5.17 (d, 1H, H-40, J3 ,4 ¼ 9.2), 4.67–4.24 (m, 3H, H-20, CH2, Bn), 4.44 (q, 2H, CH2,
0
0
Et, JCH CH ¼ 7.1), 4.30 (dd, 1H, H-30, J2 ,3 ¼ 4.2), 1.67 (s, 3H, CH3, isop), 1.39 (s, 3H,
0
0
2
3
CH3, isop), 1.43 (t, 3H, CH3, Et); 13C NMR: 161.8 (C ¼ O), 144.6 (C-3), 137.3 (Cq,
Ph), 131.5 (C-5), 128.5, 128.2, 127.9 (CH, Ph), 122.7 (C-4), 113.2 (Cq, isop), 103.8 (C-
1), 79.6 (C-3), 77.5 (C-2), 72.5 (CH2, Bn), 72.1 (C-4), 61.4 (CH2, Et), 26.7 (CH3, isop),
26.4 (CH3, isop), 14.3 (CH3, Et).
Anal. Calcd for C20H24O7N2: C 59.40, H 5.98, N 6.93; Found: C 59.34, H 5.81, N 7.14.
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