Synthesis of iso-C-nucleoside analogues from 1-(methyl 2-O-benzyl-4,6-O- benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-ones

Article abstract of DOI:10.1515/znb-2005-1110

1-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3- yl)but-3-yn-2-one (3a) reacted with 3-amino-1H-1,2,4-triazole and 5-aminopyrazole-4-carboxylic acid derivatives in the presence of base to furnish the triazolo[1,5-a]pyrimidine (5) and t

Full text of DOI:10.1515/znb-2005-1110

Synthesis of Iso-C-nucleoside Analogues from 1-(Methyl 2-O-benzyl-4,6-
O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-ones
Iran Oteroa,b, Holger Feista, Dirk Michalikc, Manfred Michalikc, Jose´ Quincocesd, and
Klaus Pesekea
a Institut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Str. 3a, D-18051 Rostock
b Facultad de Qu´ımica y Farmacia, Universidad Central de Las Villas, Carretera a Camajuan´ı,
km 5.5. Santa Clara, Cuba
c Leibniz-Institut fu¨r Organische Katalyse, Albert-Einstein-Str. 29a, D-18059 Rostock
d Universidade Bandeirante de Sao Paulo, Rua Maria Candida, 1813, Vila Guilherme, Sao Paulo,
CEP: 02071-013, Brazil
Reprint requests to Prof. Dr. K. Peseke. Fax +49(381)4986412. E-mail: klaus.peseke@uni-rostock.de
Z. Naturforsch. 60b, 1175 – 1185 (2005); received July 7, 2005
Dedicated to Prof. Dr. Istva´n Farkas on the occasion of his 80th birthday
1-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-one (3a)
reacted with 3-amino-1H-1,2,4-triazole and 5-aminopyrazole-4-carboxylic acid derivatives in
the presence of base to furnish the triazolo[1,5-a]pyrimidine (5) and the pyrazolo[1,5-
a]pyrimidines (8a – d), respectively. Treatment of 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-
deoxy-α-D-altropyranosid-3-yl)-4-phenyl-but-3-yn-2-one (3b) with cyanacetamide, 2-cyano-N-
(4-methoxyphenyl)acetamide und N-aryl-3-oxo-butyramides afforded the substituted nicotino-
nitriles (11a – d). Furthermore, reaction of 3b with 2-benzimidazolyl-acetonitrile yielded the
benz[4,5]imidazo[1,2-a]pyridine-4-carbonitrile (13). Deprotection of 8d in two steps afforded the
2-amino-N-benzyl-5-(methyl 3-deoxy-α-D-altropyranosid-3-yl-methyl)pyrazolo[1,5-a]pyrimidine-
3-carboxamide (10). Compounds 5 and 11d were treated with AcOH/H2O to furnish the 5-(methyl
2-O-benzyl-3-deoxy-α-D-altropyranosid-3-yl-methyl)[1,2,4]triazolo[1,5-a]pyrimidine (6) and the
3-acetyl-1,2-dihydro-1-(4-methoxyphenyl)-6-(methyl 2-O-benzyl-3-deoxy-α-D-altropyranosid-3-yl-
methyl)-4-phenylpyridin-2-one (12), respectively.
Key words: C-Nucleoside Analogues, Glycosylalkynone, Pyrazolo[1,5-a]pyrimidine,
1,2-Dihydropyridin-2-one, Benz[4,5]imidazo[1,2-a]pyridine
Introduction
thesized [10, 11]. In this paper we report the synthe-
sis of spacered pyridine-, pyrazolo[1-5a]pyrimidine-,
[1,2,4]triazolo[1,5-a]pyrimidine- and benz[4,5]imid-
azo[1,2-a]pyridine-iso-C-nucleoside analogues from
1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-
D-altropyranosid-3-yl)but-3-yn-2-ones (3).
Iso- or “reversed” nucleosides represent a class
of nucleoside analogues in which the nucleobase is
linked to the sugar moiety with a carbon atom other
than C-1. The syntheses of isonucleosides are inter-
esting because compounds having anticancer and an-
tiviral activities can result [1, 2]. Examples of such
nucleosides are relatively rare in the literature but,
Results and Discussion
Recently, we have described the synthesis of the
in the recent years intensified activities could be ob- 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-
served on this field [3, 4]. Like C-nucleosides [5 – D-altropyranosid-3-yl)but-3-yn-2-ones (3a and 3b) in
7] also iso-C-nucleosides show often different bi- five reaction steps from 2,3-anhydro-4,6-O-benzyl-
ological activities frequently caused by their in- idene-α-D-mannopyranoside 1 with the (pyranosid-3-
creased hydrolytic and enzymatic stability [8, 9]. Fur- yl)ethanal 2 as an intermediate (Scheme 1) [12]. These
thermore, nucleoside derivatives possessing a het- acetylenic ketones can be used as valuable synthetic
eroatom or a methylene group as spacer between intermediates for the preparation of nitrogen hetero-
the sugar unit and the heterocycle have been syn- cycles.
c
0932–0776 / 05 / 1100–1175 $ 06.00 ꢀ 2005 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com

1176
I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
Scheme 1. 1-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-ones 3a, b.
Scheme 2. (i) 3-Amino-1H-1,2,4-triazole, EtOH, reflux, 4 h; (ii) NaOEt, r. t. 1 h; (iii) AcOH/H2O, 70 ◦C, 5 h.
In order to prepare fused heterocyclic compounds Reaction of compound 5 with aqueous acetic acid
having a spacered monosaccharide unit, ynone 3a was afforded the 5-(methyl 2-O-benzyl-3-deoxy-α-D-
refluxed with 3-amino-1H-1,2,4-triazole in ethanol altropyranosid-3-yl-methyl)[1,2,4]triazolo[1,5-a]pyr-
to furnish (3E)-4-(5-amino-1H-1,2,4-triazol-1-yl)-1- imidine (6) in 92% yield. Unfortunately, attempts
(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D- to split off the benzyl group in compound 6 by
altropyranosid-3-yl)-3-buten-2-one (4) as an addition catalytic hydrogenation or with iodotrimethylsilane
product in 55% yield (Scheme 2). As expected, for the [13, 14], respectively, under several conditions were
compound 4 no signals of the acetylenic carbon atoms unsuccessful.
were observed in the 13C NMR spectrum, but reso-
Similarly, polycyclic spacered iso-C-nucleosides
nances were visible belonging to the triazole ring (at
δ = 151.4 for C-3” and δ = 155.6 for C-5”, respec-
tively). In the 1H NMR spectrum besides the signals of
the sugar part, the signals of the NH2 group and 3-H”
at δ = 5.40 and δ = 7.49, respectively, were found. A
large coupling constant (J = 13.0 Hz) for the coupling
between 3-H and 4-H confirmed the (E)-configuration
of the addition product.
could be obtained by reaction of ynone 3a with
various 5-aminopyrazole-4-carboxylic acid derivatives
in ethanol under reflux followed by treatment with
sodium ethanolate at room temperature to afford
2-amino-5-(methyl 2-O-benzyl-4,6-O-benzylidene-
3-deoxy-α-D-altropyranosid-3-yl-methyl)pyrazolo-
[1,5-a]pyrimidine-3-carboxylic acid derivatives 8a – d
in good yields (Scheme 3). In the first step of this
Subsequent treatment of enone 4 with sodium reaction as intermediates the 5-amino-3-(amino and 4-
ethanolate at room temperature led to the desired spac- methoxyphenylamino, respectively)-1-[(1E)-4-(meth-
ered triazolo[1,5-a]pyrimidine-iso-C-nucleoside 5 in yl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altro-
78% yield. The absence of the carbonyl and the amino pyranosid-3-yl)-3-oxo-1-butenyl]-1H-pyrazole-4-carb-
signals in the IR and NMR spectra clearly demon- oxylic acid derivatives 7 were formed. Compounds
strated the successful course of the cyclization reac- 7a, b were isolated in a pure form and completely
1
tion. Moreover, the molecular peak at m/z = 488 and characterized. In the H NMR spectra of 7a and 7b
the 1H NMR signals of 6-H, 2-H and 7-H at δ = 6.61, the signals for 1’-H (7a: δ = 7.85, 7b: δ = 8.08)
8.40 and 8.44, respectively, with the coupling between and 2’-H (7a: δ = 6.54, 7b: δ = 6.41) and the
3
6-H and 7-H (J = 7.0 Hz) confirmed the structure coupling constants J1ꢀ,2ꢀ = 12.8 Hz and 13.2 Hz,
of 5.
respectively, proved that the addition of the 5-amino-

I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
1177
Scheme 3. (i) EtOH, reflux; (ii) NaOEt, r. t. 1 h; (iii) AcOH/H2O, 70 ◦C, 5 h; (iv) HCOONH4/Pd(H2), MeOH, reflux.
pyrazole-4-carboxylic acid derivatives to the ynone
Treatment of acetylenic ketone 3b with cyanac-
3a yielded compounds 7a, b in the (E)-configuration. etamide, 2-cyano-N-(4-methoxyphenyl)acetamide, 3-
Additionally, no signals of acetylenic carbon atoms oxo-N-phenyl-butyramide und N-(4-methoxyphenyl)-
were observed in the 13C NMR spectra.
3-oxo-butyramide in the presence of potassium car-
bonate and 18-crown-6 provided the substituted 1,2-
dihydropyridin-2-ones 11a– d in yields of 44 – 77%
(Scheme 4). In order to verify the regiochemistry of
the reactions, NOESY spectra were measured. For
11b a correlation was observed between ortho-protons
of phenyl at N-1 and the methylene spacer. In the
NOESY spectra of compounds 11c, d cross peaks were
found not only between the ortho protons of aryl at
N-1 with the exocyclic methylene group but also be-
tween the acetyl group and the ortho-protons of the
4-phenyl ring. According to these results, the nucle-
ophilic attack of the carbanionic carbon atom aris-
ing from the used carboxamides occurred at C-4 of
ynone 3b and was followed by cyclization through
attack of the amide nitrogen atom on the carbonyl
group. All the other spectroscopic data including
mass spectra were in accordance with the proposed
structures.
The 13C NMR spectra of compounds 8a– d showed
no signals for a carbonyl group. In addition, the ex-
pected molecular peaks and the 1H NMR signals of
6-H and 7-H in the range of δ = 6.45 − 6.62 and
δ = 8.04 − 8.24, respectively, with the coupling con-
stants between 6-H and 7-H of J = 5.0 − 7.0 Hz con-
firmed the structures of the compounds 8.
On compound 8d deprotection was examined exem-
plarily. The cleavage of the benzylidene group could
be performed in a mixture of acetic acid and water
to provide the 2-amino-N-benzyl-5-(methyl 2-O-benz-
yl-3-deoxy-α-D-altropyranosid-3-y l-methyl) pyrazo-
lo[1,5-a]pyrimidine-3-carboxamide (9) in 73% yield.
Furthermore, the 2-O-benzyl group of compound 9
was removed by catalytic transfer hydrogenation us-
ing 10% palladium on carbon and ammonium formate
as the hydrogen donor providing the iso-C-nucleoside
10 as a white solid in 79% yield. The values of 8.0–
8.5 Hz for the coupling constants 3J4 ,5 for compounds
9 and 10 indicated an axial-axial disposition of 4’-H
and 5’-H. This observation and the small values of
ꢀ
ꢀ
The deprotection of compound 11d by treatment
with aqueous acetic acid afforded the 3-acetyl-1,2-
dihydro-1-(4-methoxyphenyl)-6-(methyl 2-O-benz-
yl-3-deoxy-α-D-altropyranosid-3-yl-methyl)-4-phen-
3J1ꢀ,2ꢀ and 3J2ꢀ,3ꢀ (∼ 2 − 5 Hz) in compounds 9 and 10
4
were strong clues that the C1 conformation had been ylpyridin-2-one (12) in 87% yield. Unfortunately,
retained.
catalytic hydrogenation of compound 12 afforded a

1178
I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
Scheme 4. (i) XCH2CONHR3
(X = CN, COMe; R3 = H,
Ph,
C6H4OMe-p),
THF,
K2CO3,
reflux;
18-crown-6,
(ii) AcOH/H2O, 70 ◦C, 7 h.
Scheme 5. (i) K2CO3, 18-crown-6, THF, reflux.

I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
1179
mixture of products, which could not be separated. (3E)-4-(5-Amino-1H-1,2,4-triazol-1-yl)-1-(methyl 2-O-benz-
yl-4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl)-3-
buten-2-one (4)
The NMR spectra of the mixture showed that the
removal of the benzyl group along with the re-
duction of the acetyl group at pyridone ring took
place.
A mixture of 3a (0.210 g, 0.5 mmol), 3-amino-1H-1,2,4-
triazole (0.050 g, 0.6 mmol) and ethanol (5 ml) was heated
Similarly, the ynone 3b was allowed to react under reflux for 4 h. The solvent was removed under re-
duced pressure and the residue was purified by column chro-
matography (EtOAc). Yield 0.140 g (55%), white solid. –
M. p. 82 – 84 ◦C. – [α]D22 = +102.2 (c 1.5, CHCl3). – Rf =
0.45 (EtOAc). – IR (KBr): ν = 3376, 3353 (NH2), 1690
(C=O) cm−1. – 1H NMR (250 MHz, CDCl3): δ = 7.66
with 2-benzimidazolyl-acetonitrile in the presence
of potassium carbonate and 18-crown-6 in order to
synthesize 3-(methyl 2-O-benzyl-4,6-O-benzylidene-
3-deoxy-α-D-altropyranosid-3-yl-methyl)-1-phenyl-
benz[4,5]imidazo[1,2-a]pyridine-4-carbonitrile (13)
which could be isolated as an amorphous dark yellow
solid in 57% yield (Scheme 5). In dependency on the
preferred direction of attack of the 2-benzimidazolyl-
acetonitrile on the ynone isomers 13 and 14 could
be formed. In a NOESY experiment of the isolated
compound the expected cross peaks were found for
the ortho protons of the 1-phenyl ring with 2-H and
9-H. These ortho hydrogen atoms showed different
chemical shifts indicating a hindered rotation of the
phenyl ring around the bond axis. A HMBC spec-
trum of 13 allowed the assignment of all 13C NMR
signals.
3
5
ꢀꢀ
(dd, 1H, J3,4 ∼ 13.0 Hz, J3 ,4 ∼ 1.0 Hz, H-4), 7.49 (br
s, 1H, H-3”), 7.40 – 7.12 (m, 10H, 2 × Ph), 6.64 (d, 1H,
H-3), 5.53 (s, 1H, CHPh), 5.40 (br s, NH2), 4.61 (q(AB),
2
2H, JCH ∼ 12.0 Hz, CH2Ph), 4.58 (br s, 1H, H-1’), 4.22
2
2
3
ꢀ
ꢀ
ꢀ
ꢀ
(dd, 1H, J6 ax,6 eq ∼ 10.0 Hz, J5 ,6 eq ∼ 4.0 Hz, H-6’eq),
3
ꢀ
ꢀ
4.16 – 4.07 (m, 1H, H-4’), 3.84 (dt, 1H, J4 ,5 ∼ 10.0 Hz,
3
ꢀ
ꢀ
H-5’), 3.74 (t, 1H, J5 ,6 ax ∼ 10.0 Hz, H-6’ax), 3.52 (br
m, 1H, H-2’), 3.28 (s, 3H, OMe), 3.05 – 2.98 (m, 3H, H-1,
H-3’). – 13C NMR (125 MHz, CDCl3): δ = 198.9 (C-2),
155.6 (C-5”), 151.4 (C-3”), 137.9, 137.6 (2 × i-Ph), 131.3
(C-4), 129.1, 128.4, 128.2, 127.79, 127.82, 126.2 (o-, m-, p-
Ph), 114.4 (C-3), 101.9 (CH-Ph), 100.6 (C-1’), 76.9 (C-2’),
75.4 (C-4’), 71.8 (CH2-Ph), 69.4 (C-6’), 59.7 (C-5’), 55.2
(OMe), 38.0 (C-1), 34.8 (C-3’). – MS (EI): m/z (%) = 506 (5)
[M]+. – C27H30N4O6 (506.22): calcd. C 64.02, H 5.97,
N 11.06; found C 63.50, H 5.92, N 10.42.
Experimental Section
General procedures
5-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-
altropyranosid-3-yl-methyl)-[1,2,4]triazolo[1,5-a]py-
rimidine (5)
Solvents were distilled and, if necessary, dried using
standard procedures. Melting points were measured with a
Boe¨tius apparatus and are corrected. Specific rotations were
determined with a Gyromat HP (Dr. Kernchen Ltd.). IR spec-
tra were recorded with a Nicolet 205 FT-IR spectrometer.
1H NMR (500.13, 300.13 and 250.13 MHz, respectively) and
13C NMR (125.7, 75.5 MHz and 62.9 MHz) spectra were
recorded on Bruker instruments AVANCE 500, ARX 300 and
AC 250. The calibration of spectra was carried out on TMS
Compound 4 (0.253 g, 0.5 mmol) was added to a solu-
tion of sodium ethanolate (1.5 mmol) in ethanol (5 ml) and
the mixture stirred for 1 h. After neutralization with amber-
lite IR-120 (Fluka-Chemie GmbH) the solvent was removed
under reduced pressure and the residue was purified by col-
umn chromatography (toluene/EtOAc 1:1). Yield 190 mg
◦
1
(78%), white solid. – M. p. 65 – 67 C. – [α]2D2 = +33.5
(internal H) and on solvent signals CDCl3: δ(1H) = 7.25,
(c 1.0, CHCl3). – Rf = 0.46 (toluene/EtOAc 1:1). – 1H NMR
δ(13C) = 77.0; [D6]-DMSO: δ(1H) = 2.50; δ(13C) = 39.7.
The 13C NMR signals were assigned by DEPT and/or two-
dimensional 13C,1H correlation spectra. HMBC spectra were
recorded for the compounds 8d, 11c and 13 in order to
assign the quaternary carbon signals. The two-dimensional
NOESY spectra for structure elucidation of 11a – d and 13
3
(250 MHz, CDCl3): δ = 8.44 (d, 1H, J6,7 ∼ 7.0 Hz, H-7),
8.40 (s, 1H, H-2), 7.33 – 7.06 (m, 10H, 2 ×Ph), 6.81 (d, 1H,
H-6), 5.55 (s, 1H, CHPh), 4.59 (br s, 1H, H-1’), 4.58 (q(AB),
2
2
ꢀ
ꢀ
2H, JCH ∼ 12.0 Hz, CH2Ph), 4.27 (dd, 1H, J6 ax,6 eq
∼
2
10.0 Hz, 3J5 ,6 eq ∼ 5.0 Hz, H-6’eq), 4.20 (dd, 1H, 3J4 ,5
∼
ꢀ
ꢀ
ꢀ
ꢀ
were recorded with an AVANCE 500 spectrometer using a 10.0 Hz, 3J3 ,4 ∼ 5.0 Hz, H-4’), 3.97 (dt, 1H, H-5’), 3.78 (t,
ꢀ
ꢀ
mixing time of 1 sec. The mass spectra were measured on an 1H, 3J5 ,6 ax ∼ 10.0 Hz, H-6’ax), 3.48 (br s, 1H, H-2’), 3.32
ꢀ
ꢀ
2
AMD 402/3 spectrometer (AMD Intectra GmbH). For chro- (s, 3H, OMe), 3.29 (q(AB), 2H, JCH ∼ 14.3 Hz, 5-CH2),
2
matography, Merck silica gel 60 (230 – 400 mesh) was used. 3.24 – 3.14 (m, 1H, H-3’). – 13C NMR (125 MHz, CDCl3):
TLC was performed on silica gel 60 GF254 (Merck) with de- δ = 168.4 (C-5), 155.9 (C-2), 155.1 (C-3a), 137.53, 137.50
tection by using UV-light and charring with sulfuric acid. El- (2 × i-Ph), 134.4 (C-7), 128.9, 128.2, 128.1, 128.0, 127.6,
emental analysis were performed on a CHNS automatic ele- 125.9 (o-, m-, p-Ph), 112.0 (C-6), 101.6 (CHPh), 100.8 (C-
mental Flash EA 1112 (ThermoQuest).
1’), 75.8 (C-4’), 75.1 (C-2’), 71.4 (CH2Ph), 69.4 (C-6’), 59.7

1180
I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
3
3
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
(C-5’), 55.2 (OMe), 37.8 (C-3’), 33.4 (5-CH2). – MS (EI): 1H, J4 ,5 ∼ 10.0 Hz, J3 ,4 ∼ 4.5 Hz, H-4”), 3.87 (dt,
m/z (%) = 488 (1) [M]+. – C27H28N4O5 (488.21): calcd. 1H, H-5”), 3.74 (t, 1H, J5 ,6 ax ∼ 10.0 Hz, H-6”ax), 3.71
3
ꢀꢀ ꢀꢀ
C 66.38, H 5.78, N 11.47; found C 66.38, H 5.75, N 10.89.
(p-OMe), 3.53 (br m, 1H, H-2”), 3.31 (s, 3H, OMe), 3.06 –
2.90 (m, 3H, H-3”, H-4’). – 13C NMR (75.5 MHz, CDCl3):
δ = 199.9 (C-3’), 155.1 (Cp-NHC6H4), 152.9, 152.0 (C-3,
C-5), 137.6, 137.5 (2 × i-Ph), 132.9 (Ci-NHC6H4), 132.4
(C-1’), 129.1, 128.4, 128.3, 127.9, 126.2 (o-, m-, p-Ph),
119.6 (Co-NHC6H4), 114.3 (Cm-NHC6H4), 113.3 (CN),
111.3 (C-2’), 101.8 (CH-Ph), 100.4 (C-1”), 76.7 (C-2”), 75.3
(C-4”), 71.8 (CH2-Ph), 69.4 (C-6”), 66.8 (C-4), 59.7 (C-5”),
55.5, 55.2 (OMe, p-OMe), 38.1 (C-4’), 34.9 (C-3”). –
MS (FAB+): m/z (%) = 652 (20) [MH]+. – C36H37N5O7
(651.27): calcd. C 66.35, H 5.72, N 10.75; found C 66.15,
H 5.71, N 10.24.
5-(Methyl 2-O-benzyl-3-deoxy-α-D-altropyranosid-3-yl-
methyl)[1,2,4]triazolo[1,5-a]pyrimidine (6)
A solution of compound 5 (0.245 g, 0.5 mmol) in acetic
acid (5 ml) and water (0.5 ml) was heated at 70 ◦C for 5 h.
Water (10 ml) and NaHCO3 were added until neutraliza-
tion of the solution. The mixture was extracted with EtOAc
(3 × 50 ml), the organic phases were washed with water
(2 × 50 ml), dried (Na2SO4) and evaporated under reduced
pressure. The residue was purified by column chromatog-
raphy (EtOAc/MeOH 10:1). Yield 0.185 g (92%), white
foam. – M. p. 43 – 45 ◦C. – [α]2D1 = +75.8 (c 0.4, MeOH). –
Rf = 0.39 (EtOAc/MeOH 10:1). – IR (KBr): ν = 3382 (OH)
cm−1. – 1H NMR (500 MHz, [D6]-DMSO): δ = 9.15 (d, 1H,
3J6,7 ∼ 7.0 Hz, H-7), 8.59 (s, 1H, H-2), 7.16 (d, 1H, H-6),
7.17 – 7.09 (m, 5H, Ph), 5.04 (br s, 1H, OH-4’), 4.62 (br s,
3,5-Diamino-1-[(1E)-4-(methyl 2-O-benzyl-4,6-O-benzylid-
ene-3-deoxy-α-D-altropyranosid-3-yl)-3-oxo-but-1-enyl]-
1H-pyrazole-4-carboxamide (7b)
The reaction of 3a (0.210 g, 0.5 mmol) with 3,5-diamino-
1H-pyrazole-4-carboxamide (70 mg, 0.5 mmol) [15, 16]
was carried out as described above for the preparation
of 4. The product was purified by column chromatography
(CHCl3/MeOH 10:1). Yield 0.197 g (70%), yellow solid. –
M. p. 147 – 149 ◦C. – [α]D24 = +127.0 (c 0.5, CHCl3). – Rf =
0.29 (CHCl3/MeOH 10:1). – IR (KBr): ν = 3449, 3437,
1H, OH-6’), 4.59 (d, 1H, 3J1 ,2 ∼ 2.5 Hz, H-1’), 4.48 (q(AB),
ꢀ
ꢀ
2
2H, JCH ∼ 12.0 Hz, CH2Ph), 3.80 (br m, 1H, H-4’), 3.65
2
(br d, 1H, 2J6 a,6 b ∼ 11.0 Hz, H-6’a), 3.54 (ddd, 1H, 3J4 ,5
∼
ꢀ
ꢀ
ꢀ
ꢀ
8.5 Hz, 3J5 ,6 a ∼ 2.0 Hz, 3J5 ,6 b ∼ 6.5 Hz, H-5’), 3.52 – 3.46
ꢀ
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
(m, 1H, H-6’b), 3.35 (dd, 1H, J2 ,3 ∼ 5.5 Hz, H-2’), 3.34
(s, 3H, OMe), 3.19 – 3.10 (m, 2H, 5-CH2), 2.68 – 2.61 (m,
1H, H-3’). – 13C NMR (75.5 MHz, [D6]-DMSO): δ = 169.1
(C-5), 155.7 (C-2), 154.7 (C-3a), 138.3 (i-Ph), 136.1 (C-7),
128.1, 127.6 (o-, m-Ph), 127.4 (p-Ph), 112.2 (C-6), 100.8 (C-
1’), 75.9 (C-2’), 72.2 (C-5’), 70.8 (CH2Ph), 64.2 (C-4’), 61.7
(C-6’), 54.5 (OMe), 40.9 (C-3’), 33.6 (5-CH2). – MS (CI):
m/z (%) = 401 (66) [MH]+. – C20H24N4O5 (400.17): calcd.
C 59.99, H 6.04, N 13.99; found C 59.68, H 5.98, N 13.56.
3416, 3396, 3388, 3377, 3368 (NH2), 1670 (C=O) cm−1. –
1H NMR (250 MHz, CDCl3): δ = 8.08 (d, 1H, J1 ,2
∼
3
ꢀ
ꢀ
13.2 Hz, H-1’), 7.39 – 7.03 (m, 10H, 2 × Ph), 6.65 (br s,
2H, NH2), 6.41 (d, 1H, H-2’), 6.38 (br s, 2H, NH2), 5.50
(s, 1H, CHPh), 4.59 [q(AB), 2H, 2JCH22 ∼ 12.0 Hz, CH2Ph],
ꢀꢀ
ꢀꢀ
4.54 (s, 1H, H-1”), 4.19 (dd, 1H, J6 ax,6 eq ∼ 10.0 Hz,
J5 ,6 eq ∼ 4.0 Hz, H-6”eq), 4.09 (dd, 1H, 3J4 ,5 ∼ 9.5 Hz,
3
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
3
ꢀꢀ ꢀꢀ
J3 ,4 ∼ 4.5 Hz, H-4”), 3.88 – 3.73 (m, 3H, H-5”, NH2),
5-Amino-3-(4-methoxyphenylamino)-1-[(1E)-4-(methyl
2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyr-
anosid-3-yl)-3-oxo-but-1-enyl]-1H-pyrazole-4-carbo-
nitrile (7a)
3.71 (t, 1H, 3J5 ,6 ax ∼ 10.0 Hz, H-6”ax), 3.53 (br s, 1H, H-
2”), 3.23 (s, 3H, OMe), 3.13 – 2.92 (m, 3H, H-3”, H-4’). –
13C NMR (125 MHz, CDCl3): δ = 199.4 (C-3’), 166.9
(CONH2), 154.5, 152.6 (C-3, C-5), 138.0, 137.5 (2 × i-Ph),
132.8 (C-1’), 128.9, 128.4, 128.2, 127.7, 126.2, 125.2 (o-, m-,
p-Ph), 110.0 (C-2’), 101.8 (CHPh), 100.7 (C-1”), 88.3 (C-4),
77.0 (C-2”), 75.4 (C-4”), 71.6 (CH2Ph), 69.4 (C-6”), 59.7
(C-5”), 55.1 (OMe), 38.0 (C-4’), 34.4 (C-3”). – MS (FAB+):
m/z (%) = 564 (10) [MH]+. – C29H33N5O7 (563.24): calcd.
C 61.80, H 5.90, N 12.43; found C 61.26, H 5.96, N 11.65.
ꢀꢀ ꢀꢀ
The reaction of 3a (0.210 g, 0.5 mmol) with 5-amino-
3-(4-methoxyphenylamino)-1H-pyrazole-4-carbonitrile
(115 mg, 0.5 mmol) prepared according to lit. [15, 16]
was carried out as described above for the preparation
of 4. The product was purified by column chromatography
(toluene/EtOAc 3:1). Yield 0.221 g (68%), yellow solid. –
M. p. 129 – 132 ◦C. – [α]D23 = +69.0 (c 1.0, CHCl3). –
Rf = 0.21 (toluene/EtOAc 3:1). – IR (KBr): ν = 3421, 3342
2-(4-Methoxyphenyl)-5-(methyl 2-O-benzyl-4,6-O-benzyl-
idene-3-deoxy-α-D-altropyranosid-3-yl-methyl)pyrazolo-
[1,5-a]pyrimidine-3-carbonitrile (8a)
(NH), 2210 (CN), 1671 (C=O) cm−1. – 1H NMR (250 MHz,
3
ꢀ
ꢀ
CDCl3): δ = 7.85 (d, 1H, J1 ,2 ∼ 12.8 Hz, H-1’), 7.43 –
7.08 (m, 12H, 2 × Ph, Ho-NHC6H4), 6.86 – 6.77 (m, 2H,
Hm-NHC6H4), 6.54 (d, 1H, H-2’), 6.21 (s, 1H, NH), 5.58
Method A:
(s, 1H, CHPh), 5.56 (s, 2H, NH2), 4.60 (s, 1H, H-1”), 4.56
The reaction of 7a (0.162 g, 0.25 mmol) with a solution of
2
[q(AB), 2H, JCH ∼ 12.0 Hz, CH2-Ph], 4.23 (dd, 1H, sodium ethanolate (1.5 mmol) in ethanol (5 ml) was carried
2
J6 ax,6 eq ∼ 10.0 Hz, 3J5 ,6 eq ∼ 4.5 Hz, H-6”eq), 4.14 (m, out as described above for the preparation of 5.
2
ꢀꢀ
ꢀꢀ
ꢀꢀ ꢀꢀ

I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
1181
Method B:
1H, H-1’), 4.40 [q(AB), 2H, 2JCH3 2 ∼ 12.0 Hz, CH2Ph], 4.26
2
ꢀ
ꢀ
ꢀ
ꢀ
(dd, 1H, J6 ax,6 eq ∼ 10.0 Hz, J5 ,6 eq ∼ 4.8 Hz, H-6’eq),
A mixture of 3a (0.210 g, 0.5 mmol), 5-amino-3-(4-
methoxyphenylamino)-1H-pyrazole-4-carbonitrile (115 mg,
0.5 mmol) [15, 16] and ethanol (5 ml) was heated under re-
flux for 4 h. After cooling to 20 ◦C, the mixture was treated
with sodium ethanolate (1.5 mmol) in ethanol (5 ml) for 1 h
under stirring. Neutralization with amberlite IR-120 (Fluka-
Chemie GmbH) was followed by evaporation of the solvent
under reduced pressure and purification of the residue by col-
umn chromatography (toluene/EtOAc 6:1).
4.17 (dd, 1H, 3J4 ,5 ∼ 10.0 Hz, 3J3 ,4 ∼ 5.5 Hz, H-4’), 3.96
ꢀ
ꢀ
ꢀ
ꢀ
(dt, 1H, H-5’), 3.77 (t, 1H, 3J5 ,6 ax ∼ 10.0 Hz, H-6’ax), 3.35
(s, 3H, OMe), 3.33 (br m, 1H, H-2’), 3.18 – 3.08 (m, 2H, 5-
CH2), 2.91 – 2.79 (m, 1H, H-3’). – 13C NMR (125 MHz,
CDCl3): δ = 166.2 (CONH2), 162.8 (C-5), 161.5 (C-2),
147.2 (C-3a), 137.5, 136.9 (2 × i-Ph), 133.6 (C-7), 129.1,
128.2, 127.8, 127.7, 126.1 (o-, m-, p-Ph), 108.7 (C-6), 101.9
(CH-Ph), 100.2 (C-1’), 87.3 (C-3), 75.8 (C-4’), 74.6 (C-2’),
71.5 (CH2-Ph), 69.4 (C-6’), 59.5 (C-5’), 55.2 (OMe), 39.2
(C-3’), 32.9 (5-CH2). – MS (EI): m/z (%) = 545 (11) [M]+. –
C29H31N5O6 (545.23): calcd. C 63.84, H 5.73, N 12.84;
found C 63.93, H 5.90, N 12.01.
ꢀ
ꢀ
Yield 0.135 g (85%, method A), 0.250 g (80%, method
B), yellow solid. – M. p. 108 – 110 ◦C. – [α]D21 = +29.1
(c 1.5, CHCl3). – Rf = 0.35 (toluene/EtOAc 6:1). – IR
(KBr): ν = 3414 (NH), 2215 (CN) cm−1. – 1H NMR
(250 MHz, CDCl3): δ = 8.13 (d, 1H, 3J6,7 ∼ 7.0 Hz, H-7),
7.46 – 7.38 (m, 2H, Ho-NHC6H4), 7.38 – 7.06 (m, 10H, 2 ×
Ph), 6.87 – 6.80 (m, 2H, Hm-NHC6H4), 6.57 (d, 1H, H-6),
6.56 (s, 1H, NH), 5.55 (s, 1H, CHPh), 4.64 (q(AB), 2H,
Ethyl 2-(4-chlorophenylamino)-5-(methyl-2-O-benzyl-4,6-
O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl-methyl)-
pyrazolo[1,5-a]pyrimidine-3-carboxylate (8c)
2JCH ∼ 12.0 Hz, CH2Ph), 4.60 (s, 1H, H-1’), 4.26 (dd,
The reaction of 3a (0.210 g, 0.5 mmol) with ethyl 5-
amino-3-(4-chlorophenylamino)-1H-pyrazole-4-carboxylate
(140 mg, 0.5 mmol) [15, 16] was carried out as described
above under method B for the preparation of 8a. The product
was purified by column chromatography (toluene/EtOAc
3:1). Yield 0.290 g (85%), white solid. – M. p. 88 – 90 ◦C. –
[α]2D1 = +17.5 (c 0.5, CHCl3). – Rf = 0.63 (toluene/EtOAc
3:1). – IR (KBr): ν = 3440 (NH), 1668 (C=O) cm−1. –
1H NMR (250 MHz, CDCl3): δ = 9.01 (s, 1H NH),
2
2
3
ꢀ
ꢀ
ꢀ
3
ꢀ
1H, J6 ax,6 eq ∼ 10.0 Hz, J5 ,6 eq ∼ 4.7 Hz, H-6’eq), 4.19
3
ꢀ
ꢀ
ꢀ
ꢀ
(dd, 1H, J4 ,5 ∼ 10.0 Hz, J3 ,4 ∼ 4.4 Hz, H-4’), 3.95
3
ꢀ
ꢀ
(dt, 1H, H-5’), 3.78 (t, 1H, J5 ,6 ax ∼ 10.0 Hz, H-6’ax),
3.73 (p-OMe), 3.52 (br m, 1H, H-2’), 3.32 (s, 3H, OMe),
3.25 – 3.10 (m, 3H, 5-CH2, H-3’). – 13C NMR (125 MHz,
CDCl3): δ = 165.4 (C-5), 158.1 (C-2), 150.1 (C-3a), 155.7
(Cp-NHC6H4), 137.8, 137.6 (2 × i-Ph), 134.1 (C-7), 132.5
(Ci-NHC6H4), 128.9, 128.2, 128.1, 127.8, 127.6, 126.0 (o-,
m-, p-Ph), 120.7 (Co-NHC6H4), 114.5 (Cm-NHC6H4), 113.5
(CN), 110.3 (C-6), 101.7 (CHPh), 100.9 (C-1’), 75.8 (C-4’),
75.4 (C-2’), 71.6 (CH2Ph), 69.5 (C-6’), 67.9 (C-3), 59.7
(C-5’), 55.5, 55.2 (p-OMe, OMe), 37.4 (C-3’), 32.7 (5-
CH2). – MS (EI): m/z (%) = 633 (40) [M]+. – C36H35N5O6
(633.26): calcd. C 68.23, H 5.57, N 11.05; found C 68.06,
H 5.61, N 10.58.
3
8.24 (d, 1H, J6,7 ∼ 6.9 Hz, H-7), 7.62 – 7.54 (m, 2H,
Ho-NHC6H4), 7.40 – 7.05 (m, 12H, Hm-NHC6H4, 2 × Ph),
6.62 (d, 1H, H-6), 5.58 (s, 1H, CHPh), 4.58 (s, 1H, H-1’),
2
4.54 [q(AB), 2H, JCH ∼ 12.0 Hz, CH2-Ph], 4.39 – 4.18
2
3
ꢀ
ꢀ
(m, 3H, OCH2CH3, H-6’), 4.21 (dd, 1H, J4 ,5 ∼ 10.0 Hz,
3
3
ꢀ
ꢀ
ꢀ
ꢀ
J3 ,4 ∼ 4.4 Hz, H-4’), 3.98 (dt, 1H, J5 ,6 eq ∼ 4.8 Hz,
H-5’), 3.79 (t, 1H, 3J5 ,6 ax ∼ J6 ax,6 eq ∼ 10.0 Hz, H-6’ax),
2
ꢀ
ꢀ
ꢀ
ꢀ
3.49 (br m, 1H, H-2’), 3.32 (s, 3H, OMe), 3.29 – 3.18 (m,
2-Amino-5-(methyl-2-O-benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-yl-methyl)pyrazolo[1,5-a]pyrimidine-
3-carboxamide (8b)
3
3H, 5-CH2, H-3’), 1.32 (t, 3H, J ∼ 7.0 Hz, OCH2CH3). –
13C NMR (125 MHz, CDCl3): δ = 165.4, 165.1 (COOEt,
C-5), 157.9 (C-2), 147.4 (C-3a), 138.9 (Ci-NHC6H4),
137.7, 137.6 (2 × i-Ph), 134.1 (C-7), 128.9, 128.24, 128.17,
127.8, 127.7, 126.1 (o-, m-, p-Ph, Cm-NHC6H4), 126.3
(Cp-NHC6H4), 119.2 (Co-NHC6H4), 109.9 (C-6), 101.8
(CH-Ph), 100.9 (C-1’), 86.4 (C-3), 75.9 (C-4’), 75.1 (C-2’),
71.2 (CH2Ph), 69.5 (C-6’), 60.2 (OCH2CH3), 59.7 (C-5’),
Method A:
Compound 7b (0.140 g, 0.25 mmol) was reacted as de-
scribed above under method A for the preparation of 8a.
Method B:
Compound 3a (0.210 g, 0.5 mmol) and 3,5-diamino-1H- 55.2 (OMe), 37.7 (C-3’), 33.1 (5-CH2), 14.5 (OCH2CH3).
pyrazole-4-carboxamide (70 mg, 0.5 mmol) [15, 16] were re- MS (EI): m/z (%) = 685 (17) [MH]+. – C37H37ClN4O7
acted as described above under method B for the prepara- (684.24): calcd. C 64.86, H 5.44, N 8.18; found C 64.75,
tion of 8a. Yield 0.120 g (88%, method A), ◦0.220 g (82%, H 5.56, N 7.63.
method B), white solid. – M. p. 105 – 107 C. – [α]D22
=
2-Amino-N-benzyl-5-(methyl 2-O-benzyl-4,6-O-benzylidene-
3-deoxy-α-D-altropyranosid-3-yl-methyl)pyrazolo[1,5-a]-
pyrimidine-3-carboxamide (8d)
+28.7 (c 1.0, CHCl3). – Rf = 0.40 (EtOAc). – IR (KBr): ν =
3438, 3425 (NH2) cm−1. – 1H NMR (250 MHz, CDCl3):
3
δ = 8.07 (d, 1H, J6,7 ∼ 6.8 Hz, H-7), 7.54 (br s, NH2),
7.42 – 7.24 (m, 5H, Ph), 7.09 – 6.98 (m, 5H, Ph), 6.48 (d,
The reaction of 3a (0.210 g, 0.5 mmol) with 3,5-diamino-
1H, H-6), 5.63 (br s, NH2), 5.56 (s, 1H, CHPh), 4.61 (s, N-benzyl-1H-pyrazole-4-carboxamide (115 mg, 0.5 mmol)

1182
I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
[15, 16] was carried out as described above under method B (C-7), 128.6, 127.9, 127.5, 127.3, 127.0, 126.9 (o-, m-, p-
for the preparation of 8a. The product was purified by col- Ph), 108.6 (C-6), 100.5 (C-1’), 86.1 (C-3), 75.2 (C-2’),
umn chromatography (toluene/EtOA◦c 1:1). Yield 0.290 g 71.9 (C-5’), 70.7 (CH2Ph), 64.1 (C-4’), 61.7 (C-6’), 54.4
(91%), white solid. – M. p. 72 – 74 C. – [α]2D2 = +35.8 (OMe), 41.6 (NHCH2Ph), 41.2 (C-3’), 32.8 (5-CH2). – MS
(c 0.5, CHCl3). – Rf = 0.37 (toluene/EtOAc 1:1). – IR (EI): m/z (%) = 547 (8) [M]+. – C29H33N5O6 (547.24):
(KBr): ν = 3442, 3344 (NH), 1647 (C=O) cm−1. – 1H NMR
calcd. C 63.61, H 6.07, N 12.79; found C 62.97, H 6.12,
N 12.32.
(250 MHz, CDCl3): δ = 8.14 – 8.04 (m, 2H, H-7, NH),
3
7.40 – 6.86 (m, 15H, 3 × Ph), 6.45 (d, 1H, J6,7 ∼ 5.0 Hz,
H-6), 5.55 (s, 1H, CHPh), 4.66 (dd, 1H, 3JNH,NCH ∼ 6.0 Hz,
2-Amino-N-benzyl-5-(methyl 3-deoxy-α-D-altropyranosid-
3-yl-methyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (10)
2
3
2JNCH ∼ 15.0 Hz, NCH2), 4.54 (dd, 1H, JNH,NCH
∼
2
2
6.0 Hz, NCH2), 4.51 (s, 1H, H-1’), 4.30 – 4.18 (m, 3H,
A mixture of 9 (0.135 g, 0.25 mmol), ammonium for-
mate (0.1 g), 10% palladium on carbon (0.200 g, Lancaster)
in dry MeOH (10 ml) was refluxed for 2 h. The catalyst
was filtered off and washed with the solvent. The filtrate
was evaporated under reduced pressure and the residue was
purified by column chromatography (EtOAc/MeOH 5:1).
Yield 0.090 g (79%), white solid. – M. p. 84 – 86 ◦C. –
[α]2D1 = +52.9 (c 0.5, MeOH). – Rf = 0.46 (EtOAc/MeOH
5:1). – IR (KBr): ν = 3576, 3462, 3315, 3199 (OH, NH2)
cm−1. – 1H NMR (500 MHz, [D6]-DMSO): δ = 8.75 (d,
3
3
ꢀ
ꢀ
ꢀ
ꢀ
CH2Ph, H-6’eq), 4.10 (dd, 1H, J4 ,5 ∼ 10.0 Hz, J3 ,4
∼
3
ꢀ
ꢀ
5.3 Hz, H-4’), 3.91 (dt, 1H, J5 ,6 eq ∼ 4.7 Hz, H-5’), 3.76
(t, 1H, 3J5 ,6 ax ∼ J6 ax,6 eq ∼ 10.0 Hz, H-6’ax), 3.28 (br m,
1H, H-2’), 3.24 (s, 3H, OMe), 3.11 – 3.02 (m, 2H, 5-CH2),
2.73 – 2.59 (m, 1H, H-3’). – 13C NMR (125 MHz, CDCl3):
δ = 164.5 (CONH2), 162.8 (C-5), 161.3 (C-2), 146.7 (C-3a),
139.1, 137.5, 136.8 (3 × i-Ph), 133.6 (C-7), 129.1, 128.6,
128.3, 128.1, 127.8, 127.7, 127.2, 127.1, 126.1 (o-, m-, p-
Ph), 108.5 (C-6), 101.9 (CH-Ph), 100.3 (C-1’), 87.5 (C-3),
75.7 (C-4’), 73.9 (C-2’), 71.3 (CH2-Ph), 69.4 (C-6’), 59.4
(C-5’), 55.1 (OMe), 42.5 (NCH2Ph), 39.3 (C-3’), 32.8 (5-
CH2). – MS (EI): m/z (%) = 635 (24) [M]+. – C36H37N5O6
(635.27): calcd. C 68.02, H 5.87, N 11.02; found C 67.78,
H 5.81, N 10.67.
2
ꢀ
ꢀ
ꢀ
ꢀ
3
3
1H, J6,7 ∼ 7.0 Hz, H-7), 8.29 (t, 1H, JNH,NCH ∼ 6.0 Hz,
NHCH2), 7.38 – 7.22 (m, 5H, Ph), 6.85 (d, 1H,2 H-6), 6.40
3
ꢀ
ꢀ
(s, 2H, NH2), 5.04 (d, 1H, J2 ,OH−2 ∼ 5.2 Hz, OH-2’),
3
ꢀ
ꢀ
4.86 (d, 1H, J4 ,OH−4 ∼ 5.3 Hz, OH-4’), 4.59 (dd, 1H,
JCH ∼ 15.5 Hz, NHCH2), 4.56 (t, 1H, 3J6 ,OH−6 ∼ 6.0 Hz,
2
ꢀ
ꢀ
2
OH-6’), 4.55 (dd, 1H, NHCH2), 4.35 (d, 1H, 3J1 ,2 ∼ 3.0 Hz,
ꢀ
ꢀ
3
3
2-Amino-N-benzyl-5-(methyl 2-O-benzyl-3-deoxy-α-D-
altropyranosid-3-yl-methyl)pyrazolo[1,5-a]pyrimidine-3-
carboxamide (9)
ꢀ
ꢀ
ꢀ
ꢀ
H-1’), 3.76 (dt, 1H, J3 ,4 ∼ 5.2, J4 ,5 ∼ 8.0 Hz, H-4’),
3.59 (ddd, 1H, 3J5 ,6 a ∼ 3.0 Hz, 2J6 a,6 b ∼ 11.0 Hz, H-6’a),
ꢀ
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
3.55 – 3.46 (m, 2H, H-5’, H-2’), 3.43 (ddd, 1H, J5 ,6 a
∼
∼
∼
6.0 Hz, H-6’a), 3.26 (s, 3H, OMe), 3.07 (dd, 1H, 3JCH ,3
ꢀ
2
The deprotection of compound 8d (0.315 g, 0.5 mmol)
was carried out as described above for the preparation of
6 (reaction time 7 h). The product was purified by col-
umn chromatography (EtOAc/MeOH 10:1). Yield 0.200 g
(73%), white solid. – M. p. 75 – 78 ◦C. – [α]D21 = +60.6
(c 0.4, MeOH). – Rf = 0.41 (EtOAc/MeOH 10:1). – IR
(KBr): ν = 3456, 3313, 3200 (OH, NH2) cm−1. – 1H NMR
2
3
ꢀ
8.5 Hz, JCH ∼ 14.5 Hz, 5-CH2), 3.01 (dd, 1H, JCH ,3
2
2
6.5 Hz, 5-CH2), 2.38 – 2.31 (m, 1H, H-3’). – 13C NMR
(75.5 MHz, [D6]-DMSO): δ = 163.9 (CONH2), 163.8 (C-5),
161.2 (C-2), 146.4 (C-3a), 139.9 (i-Ph), 134.8 (C-7), 128.6,
127.1, 126.9 (o-, m-, p-Ph), 108.7 (C-6), 102.9 (C-1’), 86.0
(C-3), 72.9 (C-5’), 68.5 (C-2’), 64.1 (C-4’), 61.7 (C-6’), 54.6
(OMe), 42.9 (C-3’), 41.7 (NHCH2Ph), 32.9 (5-CH2). – MS
(EI): m/z (%) = 457 (12) [M]+. – C22H27N5O6 (457.19):
calcd. C 57.76, H 5.95, N 15.31; found C 57.56, H 5.89,
N 15.02.
3
(500 MHz, [D6]-DMSO): δ = 8.68 (d, 1H, J6,7 ∼ 7.0 Hz,
3
H-7), 8.22 (t, 1H, JNH,NCH ∼ 6.0 Hz, NHCH2), 7.33 –
7.20 (m, 5H, Ph), 7.13 – 6.982(m, 5H, Ph), 6.75 (d, 1H, H-
3
ꢀ
ꢀ
6), 6.42 (s, 2H, NH2), 4.98 (d, 1H, J4 ,OH−4 ∼ 5.2 Hz,
OH-4’), 4.59 (dd, 1H, 2JNCH ∼ 15.5 Hz, NHCH2), 4.58 (t,
2
1,2-Dihydro-6-(methyl 2-O-benzyl-4,6-O-benzylidene-3-de-
oxy-α-D-altropyranosid-3-yl-methyl)-2-oxo-4-phenylpyr-
idine-3-carbonitrile (11a)
3
ꢀ
ꢀ
1H, J6 ,OH−6 ∼ 6.0 Hz, OH-6’), 4.51 (dd, 1H, NHCH2),
3
ꢀ
ꢀ
4.50 (d, 1H, J1 ,2 ∼ 2.4 Hz, H-1’), 4.33 (q (AB), 2H,
2
3
2
3
ꢀ
ꢀ
JCH ∼ 12.0 Hz, CH2Ph), 3.83 (dt, 1H, J3 ,4 ∼ 5.2 Hz,
2
3
ꢀ
ꢀ
ꢀ
ꢀ
J4 ,5 ∼ 8.5 Hz, H-4’), 3.63 (ddd, 1H, J5 ,6 a ∼ 2.0 Hz,
A mixture of 3b (0.250 g, 0.5 mmol), cyanacetamide
(0.063 g, 0.75 mmol), K2CO3 (0.120 g, 0.87 mmol), 18-
crown-6 (100 mg, 0.38 mmol) in THF (15 ml) was re-
fluxed up to the disappearance of 3b (8 h, TLC control).
The suspension was filtered and the filtrate was concen-
J6 a,6 b ∼ 11.0 Hz, H-6’a), 3.50 (ddd, 1H, 3J5 ,6 b ∼ 6.0 Hz,
ꢀ
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
H-5’), 3.47 (dt, 1H, H-6’b), 3.29 (dd, 1H, J2 ,3 ∼ 4.8 Hz,
H-2’), 3.24 (s, 3H, OMe), 3.02 (dd, 1H, 3J5−CH ,3 ∼ 6.0 Hz,
ꢀ
2
2J5−CH ∼ 14.0 Hz, 5-CH2), 2.98 (dd, 1H, JCH
∼
3
ꢀ
2
2a,3
9.0 Hz, 5-CH2b), 2.52 – 2.44 (m, 1H, H-3’). – 13C NMR trated. The residue was purified by column chromatography
(75.5 MHz, [D6]-DMSO): δ = 163.9 (CONH2), 163.3 (C- (toluene/EtOAc 1:1). Yield 0.124 g (44%), white solid. –
5), 161.3 (C-2), 146.4 (C-3a), 139.9, 138.0 (2×i-Ph), 134.8 M. p. 104 – 107 ◦C. – [α]D21 = +26.6 (c 1.0, CHCl3). –

I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
1183
Rf = 0.51 (toluene/EtOAc 1:1). – IR (KBr): ν = 3298 (NH), 3-Acetyl-1,2-dihydro-6-(methyl 2-O-benzyl-4,6-O-benzyl-
2221 (CN), 1644 (C=O) cm−1. – 1H NMR (250 MHz,
CDCl3): δ = 12.80 (br s, NH), 7.51 – 7.18 (m, 15H, 3×Ph),
6.16 (s, 1H, H-5), 5.51 (s, 1H, CHPh), 4.72 (s, 1H, H-1’),
idene-3-deoxy-α-D-altropyranosid-3-yl-methyl)-1,4-di-
phenylpyridin-2-one (11c)
The reaction of 3b (0.250 g, 0.5 mmol) with 3-oxo-N-
phenyl-butyramide (0.130 g, 0.75 mmol) was carried out
as described above for the preparation of 11a. The prod-
uct was purified by column chromatography (toluene/EtOAc
1:1). Yield 0.255 g (77%), white solid. – M. p. 99 – 102 ◦C. –
[α]2D2 = +5.8 (c 0.5, CHCl3). – Rf = 0.23 (toluene/EtOAc
2
4.70 [q(AB), 2H, JCH ∼ 12.0 Hz, CH2-Ph], 4.35 (dd, 1H,
2
3
2
ꢀ
ꢀ
ꢀ
ꢀ
J6 ax,6 eq ∼ 10.0 Hz, J5 ,6 eq ∼ 4.6 Hz, H-6’eq), 4.20 (dd,
3
3
ꢀ
ꢀ
ꢀ
ꢀ
1H, J4 ,5 ∼ 10.0 Hz, J3 ,4 ∼ 4.6 Hz, H-4’), 4.13 (dt, 1H,
3
ꢀ
ꢀ
H-5’), 3.79 (t, 1H, J5 ,6 ax ∼ 10.0 Hz, H-6’ax), 3.69 (br s,
1H, H-2’), 3.47 (s, 3H, OMe), 3.18 (dd, 1H, 2JCH ∼ 14.0 Hz,
2
3
ꢀ
JCH ,3 ∼ 7.9 Hz, CH2), 2.90 – 2.75 (m, 1H, H-3’), 2.75 (dd,
1:1). – IR (KBr): ν = 1699, 1647 (C=O) cm−1. – H NMR
2
1
1H, 2JCH ∼ 14.0 Hz, 3JCH ,3 ∼ 5.2 Hz, CH2). – 13C NMR
ꢀ
(62.9 MHz, CDCl3): δ =2163.7, 160.8 (C-2, C-4), 154.4
2
(500 MHz, CDCl3): δ = 7.50 – 7.10 (m, 20H, 3 × Ph,
CH2C6H5), 6.23 (s, 1H, H-5), 5.41 (s, 1H, CHPh), 4.61 (s,
(C-6), 137.7, 137.3, 135.9 (3×i-Ph), 130.4, 128.84, 128.76,
128.4, 128.1, 128.0, 127.93, 127.85, 125.5 (o-, m-, p-Ph),
115.9 (CN), 108.4 (C-5), 101.4 (CH-Ph), 99.8 (C-1’), 98.7
(C-3), 77.5 (C-4’), 76.1 (C-2’), 72.4 (CH2-Ph), 69.3 (C-6’),
59.0 (C-5’), 55.4 (OMe), 39.5 (C-3’), 31.3 (6-CH2). – MS
(EI): m/z (%) = 564 (7) [M]+. – C34H32N2O6 (564.23):
calcd. C 72.32, H 5.71, N 4.96; found C 72.08, H 5.68,
N 4.66.
1H, H-1’), 4.48 [q(AB), 2H, 2JCH ∼ 12.0 Hz, CH2Ph], 4.20
2
3
3
ꢀ
ꢀ
2
ꢀ
ꢀ
(m, 1H, H-6’eq), 3.96 (dd, 1H, J4 ,5 ∼ 9.5 Hz, J3 ,4
∼
3
ꢀ
ꢀ
ꢀ
ꢀ
5.2 Hz, H-4’), 3.69 (t, 1H, J5 ,6 ax ∼ J6 ax,6 eq ∼ 10.0 Hz,
H-6’ax), 3.74 – 3.61 (m, 1H, H-5’), 3.44 (br s, 1H, H-
2’), 3.27 (s, 3H, OMe), 2.91 – 2.77 (m, 2H, 6-CH2), 2.40
(s, 3H, COMe), 2.36 – 2.28 (m, 1H, H-3’). – 13C NMR
(62.9 MHz, CDCl3): δ = 202.1 (COMe), 161.5 (C-2), 150.5
(C-4), 149.2 (C-6), 137.9, 137.19, 137.16, 137.1 (3 × i-Ph,
Ci-NC6H5), 129.6, 129.5, 128.90, 128.85, 128.80, 128.62,
128.58, 128.5, 128.2, 128.0, 127.9, 127.8, 125.9 (o-, m-, p-
Ph), 128.3 (C-3), 109.5 (C-5), 101.2 (CHPh), 99.7 (C-1’),
75.3 (C-4’), 74.8 (C-2’), 71.9 (CH2Ph), 69.2 (C-6’), 58.9 (C-
5’), 54.9 (OMe), 37.8 (C-3’), 31.7 (COMe), 28.7 (6-CH2). –
MS (EI): m/z (%) = 657 (55) [M]+. – C41H39NO7 (657.27):
calcd. C 74.87, H 5.98, N 2.13; found C 74.89, H 6.18,
N 1.99.
1,2-Dihydro-1-(4-methoxyphenyl)-6-(methyl 2-O-benzyl-
4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl-
methyl)-2-oxo-4-phenylpyridine-3-carbonitrile (11b)
The reaction of 3b (0.250 g, 0.5 mmol) with 2-cyano-
N-(4-methoxy-phenyl)acetamide (0.140 g, 0.75 mmol) was
carried out as described above for the preparation of
11a. The product was purified by column chromatography
(toluene/EtOAc 2:1). Yield 0.218 g (65%), white solid. –
M. p. 117 – 120 ◦C. – [α]D20 = +11.3 (c 0.5, CHCl3). –
Rf = 0.43 (toluene/EtOAc 2:1). – IR (KBr): ν = 2219
(CN), 1660 (C=O) cm−1. – 1H NMR (500 MHz, CDCl3):
3-Acetyl-1,2-dihydro-1-(4-methoxyphenyl)-6-(methyl
2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyrano-
sid-3-yl-methyl)-4-phenylpyridin-2-one (11d)
The reaction of 3b (0.250 g, 0.5 mmol) with N-(4-
δ = 7.54 – 7.48 (m, 4H, 2 × Ph, C6H5CH2, C6H4), 7.35 – methoxyphenyl)-3-oxo-butyramide (0.155 g, 0.75 mmol)
7.14 (m, 13H, 2 × Ph, C6H5CH2, C6H4), 7.05 – 7.01 (m, was carried out as described above for the preparation of
2H, 2 × Ph, C6H5CH2, C6H4), 6.29 (s, 1H, H-5), 5.44 (s, 11a. The product was purified by column chromatography
2
1H, CHPh), 4.64 (s, 1H, H-1’), 4.48 [q(AB), 2H, JCH
∼
(toluene/EtOAc 2:1). Yield 0.245 g (71%), white solid. –
2
12.0 Hz, CH2Ph], 4.23 (m, 1H, H-6’eq), 3.99 (dd, 1H, M. p. 92–94 ◦C. – [α]D23 = +29.9 (c 1.0, CHCl3). – Rf = 0.27
3
3
ꢀ
ꢀ
ꢀ
ꢀ
J4 ,5 ∼ 9.2 Hz, J3 ,4 ∼ 5.5 Hz, H-4’), 3.74 (s, 3H, p-OMe), (toluene/EtOAc 2:1). – IR (KBr): ν = 1699, 1645 (C=O)
3.73 – 3.68 (m, 2H, H-5’, H-6’ax), 3.39 (br s, 1H, H-2’), 3.31 cm−1. – H NMR (500 MHz, CDCl3): δ = 7.43 – 6.90 (m,
1
(s, 3H, OMe), 2.98 – 2.80 (m, 2H, 6-CH2), 2.35 – 2.28 (m, 19H, 2 × Ph, C6H5CH2, C6H4), 6.21 (s, 1H, H-5), 5.44 (s,
2
1H, H-3’). – 13C NMR (62.9 MHz, CDCl3): δ = 162.0, 1H, CHPh), 4.62 (s, 1H, H-1’), 4.48 [q(AB), 2H, JCH
∼
2
160.0 (C-2, C-4), 158.4 (Cp-NC6H4), 154.0 (C-6), 137.1, 12.0 Hz, CH2-Ph], 4.21 (m, 1H, H-6’eq), 3.98 (m, 1H, H-
136.9, 135.8 (3 × i-Ph), 130.5, 129.2, 128.7, 128.4, 128.2, 4’), 3.73 (s, 3H, p-OMe), 3.75 – 3.68 (m, 2H, H-5’, H-6’ax),
128.1, 128.0, 127.8, 125.7, 125.3 (o-, m-, p-Ph), 128.9 (Ci- 3.47 (br s, 1H, H-2’), 3.29 (s, 3H, OMe), 2.94 – 2.82 (m, 2H,
NC6H4), 115.8 (CN), 115.5, 114.4 (Co, Cm-NC6H4), 108.9 6-CH2), 2.32 – 2.29 (m, 1H, H-3’), 2.40 (s, 3H, COMe). –
(C-5), 101.2 (CH-Ph), 100.1 (C-3), 99.5 (C-1’), 75.2 (C- 13C NMR (62.9 MHz, CDCl3): δ = 202.1 (COMe), 161.8
4’), 74.3 (C-2’), 71.9 (CH2-Ph), 69.2 (C-6’), 59.0 (C-5’), (C-2), 159.7 (Cp-NC6H4), 150.3 (C-4), 149.6 (C-6), 138.0,
55.4, 55.1 (OMe, p-OMe), 38.1 (C-3’), 29.6 (6-CH2). – MS 137.3, 137.1 (3 × i-Ph), 129.7, 128.8 (C-3, Ci-NC6H4),
(EI): m/z (%) = 670 (14) [M]+. – C41H38N2O7 (670.27): 129.5, 129.1, 128.8, 128.7, 128.6, 128.3, 128.1, 127.8, 125.8
calcd. C 73.42, H 5.71, N 4.18; found C 73.47, H 5.83, (o-, m-, p-Ph), 115.5, 114.3 (Co, Cm-NC6H4), 109.5 (C-5),
N 3.83.
101.2 (CH-Ph), 99.8 (C-1’), 75.3 (C-4’), 74.7 (C-2’), 72.0

1184
I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
(CH2Ph), 69.3 (C-6’), 59.0 (C-5’), 55.4, 55.0 (OMe, p- 3-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-
OMe), 37.8 (C-3’), 31.7 (COMe), 28.8 (6-CH2). – MS altropyranosid-3-yl-methyl)-1-phenyl-benz[4,5]imidazo-
(EI): m/z (%) = 687 (50) [M]+. – C42H41NO8 (687.28): [1,2-a]pyridine-4-carbonitrile (13)
calcd. C 73.34, H 6.01, N 2.04; found C 73.02, H 6.28,
The reaction of 3b (0.250 g, 0.5 mmol) with 2-
N 1.87.
benzimidazolyl-acetonitrile (0.115 g, 0.75 mmol) was car-
ried out as described above for the preparation of 11a.
The product was purified by column chromatography
(toluene/EtOAc 8:1). Yield 0.180 g (57%), yellow solid. –
M. p. 112 – 114 ◦C. – [α]D23 = +10.7 (c 1.0, CHCl3). –
Rf = 0.14 (toluene/EtOAc 8:1). – IR (KBr): ν = 2224 (CN)
cm−1. – 1H NMR (250 MHz, CDCl3): δ = 8.03 (dd, 1H,
3J6,7 ∼ 8.0 Hz, H-6), 7.67 – 7.52 (m, 3H, Ph), 7.47 (dt, 1H,
3-Acetyl-1,2-dihydro-1-(4-methoxyphenyl)-6-(methyl
2-O-benzyl-3-deoxy-α-D-altropyranosid-3-yl-methyl)-
4-phenylpyridin-2-one (12)
The deprotection of compound 11d (0.170 g, 0.25 mmol)
using acetic acid (5 ml) and water (0.5 ml) was carried
out as described above for the preparation of 6 (reaction
time 7 h). The product was purified by column chromatog-
raphy (EtOAc). Yield 0.130 g (87%), white solid. – M. p.
4
3J7,8 ∼ 8.0 Hz, J7,9 ∼ 1.0 Hz, H-7), 7.36 – 7.04 (m, 11H,
4
Ph), 7.02 (dt, 1H, J6,8 ∼ 1.0 Hz, H-8), 6.9. – 6.91 (m, 1H,
3
Ph), 6.57 (s, 1H, H-2), 6.51 (dd, 1H, J8,9 ∼ 8.0 Hz, H-9),
◦
91 – 93 C. – [α]2D1 = +38.7 (c 0.4, MeOH). – Rf = 0.26
5.58 (s, 1H, CHPh), 4.73 (s, 1H, H-1’), 4.57 (s, 2H, CH2Ph),
2
3
ꢀ
ꢀ
3
ꢀ
3
ꢀ
4.35 (dd, 1H, J6 ax,6 eq ∼ 10.0 Hz, J5 ,6 eq ∼ 4.9 Hz, H-
(EtOAc). – IR (KBr): ν = 3427 (OH), 1699, 1637 (C=O)
cm−1. – 1H NMR (500 MHz, [D6]-DMSO): δ = 7.47 – 7.43
(m, 3H, Ph), 7.35 – 7.32 (m, 2H, Ho-NHC6H4), 7.30 – 7.10
ꢀ
ꢀ
ꢀ
ꢀ
6’eq), 4.25 (dd, 1H, J4 ,5 ∼ 10.0 Hz, J3 ,4 ∼ 5.2 Hz, H-
3
ꢀ
ꢀ
4’), 4.12 (dt, 1H, H-5’), 3.84 (t, 1H, J5 ,6 ax ∼ 10.0 Hz, H-
6’ax), 3.55 (br s, 1H, H-2’), 3.48 (dd, 1H, 2JCH ∼ 14.0 Hz,
(m, 7H, Ph), 7.07 – 7.04 (m, 2H, Hm-NHC6H4), 6.28 (s, 1H,
2
3
3
ꢀ
ꢀ
H-5), 4.85 (d, 1H, J4 ,OH−4 ∼ 5.5 Hz, OH-4’), 4.58 (t,
ꢀ
JCH ,3 ∼ 6.5 Hz, CH2), 3.45 (s, 3H, OMe), 3.34 (dd,
2
3
3
ꢀ
ꢀ
1H, J6 ,OH−6 ∼ 6.0 Hz, OH-6’), 4.47 (s, 1H, H-1’), 4.42
ꢀ
1H, JCH ,3 ∼ 8.9 Hz, CH2), 2.95 – 2.88 (m, 1H, H-3’). –
2
2
13C NMR (62.9 MHz, CDCl3): δ = 151.9 (C-3), 147.6
[q (AB), 2H, JCH ∼ 12.0 Hz, CH2Ph], 3.80 (s, 3H, p-
2
OMe), 3.62 (dt, 1H, 3J3 ,4 ∼ 5.0 Hz, 3J4 ,5 ∼ 7.5 Hz, H-4’),
ꢀ
ꢀ
ꢀ
ꢀ
(C-4a), 143.9 (C-5a), 143.4 (C-1), 137.4, 137.2, 132.9 (3×i-
Ph), 129.3 (C-9a), 130.7, 129.21, 129.17, 128.8, 128.41,
128.38, 128.2, 128.0, 127.8, 127.7, 126.1, 125.9 (o-, m-,
p-Ph, C-7), 121.3 (C-8), 120.3 (C-6), 114.6 (CN), 114.4
(C-9), 114.0 (C-2), 101.7 (CH-Ph), 100.1 (C-4), 99.9 (C-1’),
75.95 (C-4’), 75.89 (C-2’), 71.8 (CH2Ph), 69.4 (C-6’), 59.3
(C-5’), 55.2 (OMe), 40.2 (C-3’), 30.8 (3-CH2). – MS (EI):
m/z (%) = 637 (76) [M]+. – C40H35N3O5 (637.26): calcd.
C 75.33, H 5.53, N 6.59; found C 74.99, H 5.75, N 6.25.
3.52 (ddd, 1H, 3J5 ,6 a ∼ 3.5 Hz, 2J6 a,6 b ∼ 12.0 Hz, H-6’a),
ꢀ
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
3.38 (ddd, 1H, J5 ,6 b ∼ 6.0 Hz, H-5’), 3.32 – 3.28 (m, 1H,
3
ꢀ
ꢀ
H-6’b), 3.22 (s, 3H, OMe), 3.21 (dd, 1H, J2 ,3 ∼ 6.0 Hz,
H-2’), 2.67 (dd, 1H, 3JCH ,3 ∼ 8.0 Hz, 2JCH ∼ 15.5 Hz, 6-
ꢀ
2
2
CH2), 2.61 (dd, 1H, 3JCH ,3 ∼ 7.0 Hz, 6-CH2), 2.33 (s, 3H,
ꢀ
2
COMe), 2.08 – 2.02 (m, 1H, H-3’). – 13C NMR (62.9 MHz,
[D6]-DMSO): δ = 202.2 (COMe), 161.1 (C-2), 159.3 (Cp-
NC6H4), 151.1 (C-4), 149.6 (C-6), 138.4, 138.1 (2 × i-Ph),
130.2, 127.3 (C-3, Ci-NC6H4), 129.7, 128.9, 128.8, 128.4,
127.9, 127.6, 127.5 (Co-NC6H4, o-, m-, p-Ph), 114.6, 114.7
(Cm-NC6H4), 107.7 (C-5), 100.6 (C-1’), 76.1 (C-2’), 72.9
(C-5’), 71.1 (CH2Ph), 63.8 (C-4’), 61.5 (C-6’), 55.6, 54.5
(OMe, p-OMe), 39.2 (C-3’), 31.8 (COMe), 29.4 (6-CH2). –
MS (EI): m/z (%) = 599 (45) [M]+. – C35H37NO8 (599.25):
HRMS calcd. 599.25189; found 599.25203.
Acknowledgements
The authors would like to thank the Fonds der Chemi-
schen Industrie for financial support. J. Q. is grateful to
the Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o
Paulo (FAPESP, Brasil). I. O. is grateful to the Deutscher
Akademischer Austauschdienst for a scholarship.
[1] H. W. Yu, H. Y. Zhang, Z. J. Yang, J. M. Min, L. T. Ma,
L. H. Zhang, Pure Appl. Chem. 70, 435 (1998).
[2] Z. J. Yang, H. W. Yu, J. M. Min, L. T. Ma, L. H. Zhang,
Tetrahedron Asym. 8, 2739 (1997).
[6] M. A. E. Shaban, A. Z. Nasr, Adv. Heterocycl. Chem.
68, 223 (1997).
[7] M. A. E. Shaban, Adv. Heterocycl. Chem. 70, 163
(1998).
[3] M. E. Jung, C. J. Nichols, J. Org. Chem. 63, 347 (1998).
[4] J. Marco-Contelles, C. A. Jime´nez, Tetrahedron 55,
10511 (1999).
[8] M. Zhang, H. Zhang, Z. Yang, L. Ma, J. Min, L. Zhang,
Carbohydr. Res. 318, 157 (1999).
[9] J. M. J. Tronchet, S. Zerelli, G. Bernardinelli, J. Carbo-
hydr. Chem. 18, 343 (1999).
[5] D. E. Levy, C. Tang, in J. E. Baldwin, P. D. Mag-
nus (eds): The Chemistry of C-Glycosides, Pergamon [10] Y. Toyooka, T. Matsuzawa, T. Eguchi, K. Kakinuma,
Press, Oxford (1995). Tetrahedron 51, 6459 (1995).

I. Otero et al. · Synthesis of Iso-C-nucleoside Analogues
1185
[11] C.-H. Wong, L. Provencher, J. A. Porco, S.-H. Jung,
Y.-F. Wang, L. Chen, R. Wang, D. H. Steensma, J. Org.
Chem. 60, 1492 (1995).
[12] I. Otero, H. Feist, L. Herrera, M. Michalik, J. Quinco-
ces, K. Peseke, Aust. J. Chem. 58, 104 (2005).
[13] M. E. Jung, M. A. Lyster, J. Org. Chem. 42, 3761
(1977).
[14] G. A. Olah, S. C. Narang, B. G. Gupta, R. Malhotra, J.
Org. Chem. 44, 1247 (1979).
[15] K. Peseke, Pharmazie 31, 532 (1976).
[16] Y. Tominaga, Y. Honkawa, M. Hara, A. Hosomi, J. Het-
erocycl. Chem. 27, 775 (1990).