Nucleoside analogues from branched-chain pyranosides

Article abstract of DOI:10.1071/CH04168

Reaction of (pyranosid-3-yl)ethanal 2 with ethynylmagnesium bromide or lithium phenylacetylide in THF afforded (2R, S)-1-(methyl 2-O-benzyl-4,6-O- benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-ols 3a and 3b, respectively. Oxidation of 3a and 3b y

Full text of DOI:10.1071/CH04168

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2005, 58, 104–111
www.publish.csiro.au/journals/ajc
Nucleoside Analogues from Branched-Chain Pyranosides
Iran Otero,A,B Holger Feist,A Lidcay Herrera,A Manfred Michalik,C
José Quincoces,D and Klaus PesekeA,E
A Universität Rostock, Fachbereich Chemie, 18051 Rostock, Germany.
B Facultad de Química y Farmacia, Universidad Central de Las Villas, Cuba.
C Leibniz-Institut für Organische Katalyse, 18055 Rostock, Germany.
D Universidade Bandeirante de São Paolo, São Paolo, CEP: 02071-013, Brazil.
E Corresponding author. Email: klaus.peseke@chemie.uni-rostock.de
Reaction of (pyranosid-3-yl)ethanal 2 with ethynylmagnesium bromide or lithium phenylacetylide in THF
afforded (2R,S)-1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)but-3-yn-2-ols 3a and
3b, respectively. Oxidation of 3a and 3b yielded the 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-
α-d-altropyranosid-3-yl)but-3-yn-2-ones 4a and 4b, which upon treatment with hydrazine and hydrazine derivatives
formed the 3-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)pyrazoles 5a–5d.
Compounds 4a and 4b also underwent reaction with amidinium and guanidinium salts under basic condi-
tions to furnish the 4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)pyrimidines
8a–8f. Furthermore, treatment of 4a and 4b with 2-aminobenzimidazole yielded the 2-(methyl 2-O-benzyl-
4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)benzo[4,5]imidazo[1,2-a]pyrimidines 11a and 11b.
Deprotection of 5a and 8b in two steps afforded 3(5)-(methyl 3-deoxy-α-d-altropyranosid-3-ylmethyl)-1H(2H)-
pyrazole 7 and 4-(methyl 3-deoxy-α-d-altropyranosid-3-ylmethyl)-2-phenylpyrimidine 10, respectively. Compound
11a was treated with AcOH/H2O to furnish 2-(methyl 2-O-benzyl-3-deoxy-α-d-altropyranosid-3-ylmethyl)benzo-
[4,5]imidazo[1,2-a]pyrimidine 13.
Manuscript received: 7 July 2004.
Final version: 9 December 2004.
Introduction
O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)ethanal
2
The development of strategies for the formation of
C-nucleoside analogues is a topic of current interest in
organic synthesis.[1] Iso-C-nucleosides constitute a class of
nucleoside analogues in which the nucleobase is linked
by a carbon–carbon bond to the sugar moiety through a
carbon atom other than C1. Interest in the synthesis of iso-
C-nucleosides as compounds that possess anticancer and
antiviral activities is growing.[2,3] Examples of this sub-
class of nucleosides are relatively rare in the literature,
but recently, intensified efforts have been observed.[4–9]
Like C-nucleosides, iso-C-nucleosides often display numer-
ous biological activities that are frequently connected with
theirincreasedhydrolyticandenzymaticstability. Nucleoside
derivatives that contain a heteroatom or a methylene group as
a spacer between the sugar unit and the heterocycle have been
synthesized. Among these analogues, carbon-bridge deriva-
tives have been found to act as glycosidase inhibitors.[10,11]
Furthermore, connecting the sugar to the heterocyclic sys-
tems through carbon may have interesting pharmacological
implications.[12–15]
that contain spacers.
Results and Discussion
Compound 2 could be obtained in three steps from methyl
2,3-anhydro-4,6-O-benzylidene-α-d-mannopyranoside 1 by
reaction with allylmagnesium bromide,[16,17] benzylation of
the 2-hydroxy group with benzyl bromide, sodium hydride,
and tetrabutylammonium iodide[18,19] in THF, and oxida-
tion of the resultant product with osmium tetraoxide/sodium
periodate in 1,4-dioxan/water (10 : 1).[20]
Reaction of the branched-chain monosaccharide 2 with
ethynylmagnesium bromide or lithium phenylacetylide in
THF afforded, after 4 h at room temperature, butynols 3a
and 3b as an inseparable mixture of diastereoisomers in
85 and 87% yield, respectively (Scheme 1). Disappearance
of the aldehyde signals concurrently with the appearance
of the new resonances for the alkyne carbon atoms in the
13C NMR spectra clearly demonstrated the formation of the
expected alcohols as R,S mixtures. A typical long-range cou-
pling of 2.1 Hz between the acetylenic proton and H2 could
In this paper we report the synthesis of a new
series of iso-C-nucleosides from 2-(methyl 2-O-benzyl-4,6-
1
be observed in the H NMR spectrum of 3a. Moreover, a
© CSIRO 2005
10.1071/CH04168
0004-9425/05/020104

Nucleoside Analogues from Branched-Chain Pyranosides
105
OBn
O
O
O
O
Ph
Ph
O
O
O
OMe
OMe
O
1
2
6؅
6؅
R
M,
OBn
O
OBn
O
4؅
O
4؅
Ph
5؅
THF, room temp.
Ph
5؅
O
3a, MnO2, Et2O, room temp.
3b, PCC, CH2Cl2, room temp.
O
O
O
1؅
1؅
2؅
R ϭ H, Ph
2؅
3؅
3؅
HO
1
M ϭ MgBr, Li
1
OMe
OMe
2
2
3
3
4
4
R
R
3a
3b
4a
R ϭ H 57%
R ϭ H 85%
R ϭ Ph 87%
4b
R ϭ Ph 55%
Scheme 1. Synthesis of 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)but-3-yn-
2-ones 4a and 4b.
strong Csp-H absorption at 3257 cm−1 was observed in the IR
spectrum of this compound.
pyrazoles 5c and 5d was determined by NOESY experi-
ments. In the NOESY spectrum of 5c a correlation was found
between the N-methyl group and the ortho protons of the
phenyl ring attached to the pyrazole system. The analogous
ortho phenyl protons in 5d gave a similar correlation with
the four methylene hydrogen atoms of the 2-hydroxyethyl
substituent.
Acetylenic ketones are a versatile class of compounds
which can be used as starting materials for the synthe-
sis of numerous heterocycles.[21] In order to obtain the
desired (pyranosid-3-yl)butynones, butynols 3a and 3b
were oxidized with pyridinium chlorochromate (PCC) in
dichloromethane to yield compounds 4a and 4b in 35 and
55% yield, respectively. The low yield of 4a could be
increased to 57% by using MnO2 as the oxidizing agent in
diethyl ether. All the analytical data were in accordance with
the proposed structures. In particular, OH bands were absent
in the IR spectra, while typical C O signals appeared in the
13C NMR spectra.
Treatment of 4a and 4b with hydrazine, methylhydrazine,
and 2-hydrazinoethanol at room temperature in methanol
resulted, after short reaction times, in the formation of
the 3-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-
altropyranosid-3-ylmethyl)pyrazoles 5a–5d in good to excel-
lent yields (70–90%, Scheme 2).
We examined the deprotection of compound 5a over
two steps. Cleavage of the benzylidene group was per-
formed in a mixture of acetic acid and water to afford
the 3(5)-(methyl 2-O-benzyl-3-deoxy-α-d-altropyranosid-3-
ylmethyl)-1H(2H)-pyrazole 6 in 90% yield. The NMR spec-
tra showed the absence of the benzylidene group, while
the mass spectrum displayed a molecular peak that cor-
responded with the proposed structure. Subsequently, the
2-O-benzyl group in compound 6 could be removed by cat-
alytic transfer hydrogenation using 10% palladium on carbon
and ammonium formate as the hydrogen donor.[26] The iso-
C-nucleoside 7 was thus obtained as a white solid in 90%
yield. The value determined for the 3J4 ,5 coupling constant
ꢀ
ꢀ
In accordance with literature,[22–24] the preferred posi-
tion for the first nucleophilic attack at the acetylenic
ketone should be the β-carbon atom. Nevertheless, this
does not indicate the manner by which ynones will cyclize
when allowed to react with unsymmetrical dinucleophiles.
Bishop et al.[25] described a highly regioselective cycliza-
tion reaction of hydrazine derivatives with aryl-substituted
acetylenic ketones. In our hands, with methylhydrazine and
2-hydrazinoethanol, 4a gave a mixture of two possible regio-
isomeric pyrazoles that could not be separated. In contrast,
reaction of the phenyl substituted ynone 4b with these
hydrazine derivatives followed a highly regioselective reac-
tion pathway that resulted in the formation of pyrazoles 5c
and 5d in good yields.Thestructuresof pyrazoles 5a–5d were
confirmed from spectroscopic data. In particular, signals for
a carbonyl group or the acetylenic carbon atoms could not be
observed in the IR and 13C NMR spectra. The position of the
methyl and 2-hydroxyethyl substituents in the N-substituted
(approx. 8 Hz), which suggests an axial–axial disposition,
3
3
ꢀ
ꢀ
ꢀ
ꢀ
along with the small J1 ,2 and J2 ,3 values (approx. 2–
1
5 Hz) clearly indicated the presence of the preferred C4
conformation in compounds 6 and 7.
Addlington et al.[27] reported the reaction of acetylenic
ketoneswithamidiniumsaltsusingethylacetate/waterorace-
tonitrile as solvent and sodium carbonate as base to obtain the
corresponding pyrimidines. Following this strategy, ynones
4a and 4b were allowed to react with acetamidinium chlo-
ride, benzamidinium chloride, S-methylisothiouronium sul-
fate, and guanidinium chloride to afford the corresponding
pyrimidine-spacered iso-C-nucleosides 8a–8f (Scheme 3).
All the reactions, except for the one in which guanidinium
chloride was used, proceeded in high yields.As expected, sig-
nals for the acetylenic carbon atoms and the carbonyl group
were not observed in the 13C NMR spectra. Moreover, mass
spectra and elemental analyses were in agreement with the
proposed structures.

106
I. Otero et al.
6؅
OBn
O
O
4؅
R1NHNH2, MeOH,
room temp.
Ph
5؅
R ϭ H, R1 ϭ H 78%
5a
5b
5c
5d
O
R ϭ Ph, R1 ϭ H 90%
1؅
2؅
4a or 4b
3؅
2
N
R ϭ Ph, R1 ϭ Me 86%
R ϭ Ph, R1 ϭ CH2CH2OH 73%
3
OMe
R1N
4
1
5
R
6؅
6؅
OH
OBn
HO
HO
HO
HCOONH4/Pd(H2),
MeOH, reflux
5؅
5؅
O
O
HO
4؅
3؅
4؅
5a, AcOH/H2O, 70ºC
90%
1؅
1؅
2؅
2؅
3؅
2
2
N
90%
3
3
N
OMe
OMe
HN
1
HN
1
4
4
5
5
6
7
6؅
6؅
OBn
O
OBn
O
4؅
O
4؅
Ph
5؅
Ph
5؅
O
O
O
1؅
1؅
2؅
2؅
3؅
3؅
2
N
2
N
3
3
OMe
OMe
1؆
MeN
N
4
2؆
1
4
1
HO
5
5
5c
5d
NOESY experiments
Scheme 2. Synthesis of 3-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)-
pyrazoles 5a–5d and deprotection of 5a.
6؅
6؅
6؅
OBn
O
OBn
OH
O
4؅
HO
HO
HO
HO
R2C(NH2)ϭNHϩ2XϪ
,
Ph
R2
5؅
5؅
5؅
O
HCOONH4/Pd(H2),
MeOH, reflux
O
8b, AcOH/H2O,
O
4؅
3؅
4؅
Na2CO3, EtOAc/H2O
70ºC
1؅
1؅
1؅
2؅
2؅
2؅
3؅
3
3
3
N
3؅
4a or 4b
Ph
N
Ph
N
2
4
2
4
2
4
reflux
84%
82%
OMe
OMe
OMe
5
5
5
N
N
N
1
1
1
6
6
6
R
8a R ϭ H, R2 ϭ Me 88%
8b R ϭ H, R2 ϭ Ph 95%
8c R ϭ H, R2 ϭ SMe 83%
8d R ϭ Ph, R2 ϭ Me 91%
8e R ϭ Ph, R2 ϭ Ph 90%
8f R ϭ Ph, R2 ϭ NH2 40%
9
10
Scheme 3. Synthesis of 4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)pyrimidines 8a–8f and deprotection
of 8b.
Deprotection of compound 8b by treatment with aque-
ous acetic acid afforded 4-(methyl 2-O-benzyl-3-deoxy-α-
d-altropyranosid-3-ylmethyl)-6-phenylpyrimidine 9 in 84%
yield. Compound 9 was subsequently allowed to react with
10% palladium on carbon and ammonium formate to fur-
nish 4-(methyl 3-deoxy-α-d-altropyranosid-3-ylmethyl)-6-
confirmed with the help of NOESY spectroscopy. A correla-
tion was observed for 7a between H4 and H6, while in the
NOESY spectrum of compound 7b, cross peaks were found
between the ortho protons of the 4-phenyl ring and H3 and
H6. Moreover, the ortho hydrogen atoms displayed different
chemical shifts (δ 7.40 and 7.24); this indicates that rotation
of the phenyl ring around the bond axis is hindered. In the
1H NMR spectrum, the signal for H6 was significantly shifted
upfield in comparison to the signal for H9. This is caused by
the anisotropy effect of the phenyl ring.
All the remaining spectroscopic data, including mass
spectra, were in accordance with the proposed structures.
Reaction of compound 11a with aqueous acetic acid
afforded 2-(methyl 2-O-benzyl-3-deoxy-α-d-altropyranosid-
3-ylmethyl)benzo[4,5]imidazo[1,2-a]pyrimidine 13 in 95%
1
phenylpyrimidine 10 in 82% yield. The C4 conformation
of this compound was confirmed by NMR spectroscopy.
Compounds 4a and 4b were also allowed to react with 2-
aminobenzimidazole to afford iso-C-nucleosides with a fused
heterocyclic unit. From the proposed reaction pathway, iso-
mers 7a and 7b, as well as 8a and 8b, respectively, were
expected to be formed (Scheme 4). However, the 13C NMR
spectra of the isolated compounds only showed the pres-
ence of compounds 7a and 7b, the structures of which were

Nucleoside Analogues from Branched-Chain Pyranosides
107
6؅
6؅
OBn
OBn
HO
HO
O
4؅
5؅
5؅
Ph
O
O
11a, AcOH/H2O, 70ºC
O
4؅
3؅
1؅
1؅
2؅
2؅
1
N
1
N
3؅
95%
10
N
10
10a
10a
N
OMe
OMe
9a
7
2
9a
7
2
9
9
N
N
3
3
5
5
5a
4
5a
8
4
8
6
R
6
MeOH,
reflux
11a R ϭ H 33%
11b R ϭ Ph 40%
13
N
N
4a or 4b ϩ
NH2
6؅
OBn
O
4؅
3؅
5؅
Ph
7
O
O
1؅
2؅
6
8
5a
OMe
4
5
N
9
3
9a
N
10
10a
N
2
R
1
R1 ϭ H
R1 ϭ Ph
12a
12b
6؅
6؅
OBn
OBn
O
4؅
O
4؅
Ph
5؅
Ph
5؅
O
O
O
O
1؅
1؅
2؅
2؅
3؅
3؅
1
N
1
10
N
10
N
10a
10a
N
2
OMe
OMe
9a
7
9a
7
2
3
3
9
9
N
N
5a
5
H
4
5
5a
6
4
8
8
6
11a
11b
NOESY experiments
Scheme 4. Synthesis of 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)benzo[4,5]imidazo-
[1,2-a]pyrimidines 11a and 11b, and deprotection of 8b.
yield. Unfortunately, attempts to remove the benzyl protect-
ing group in compound 13 were unsuccessful.
on an AVANCE 500 spectrometer using a mixing time of 1 s. Mass
spectra were recorded on an AMD 402/3 spectrometer (AMD Intectra
GmbH). Merck silica gel 60 (230–400 mesh) was used for chromatogra-
phy. TLC was performed on silica gel 60 GF254 (Merck) using UV light
and charring with sulfuric acid for detection. Elemental analyses were
performed on a Leco CHNS-932 instrument. Solvents were distilled,
and if necessary, dried using standard procedures.
Conclusions
We described here the synthesis of iso-C-nucleosides based
on 1-(α-d-altropyranosid-3-yl)but-3-yn-2-ones. These com-
pounds should be suitable to test for antiviral activity in
that they are unusual nucleoside analogues of pyrazoles,
pyrimidines, and benzo[4,5]imidazo[1,2-a]pyrimidine that
are attached with a pyranosid-3-yl unit through a methylene
group spacer.
Preparation of (2R,S)-1-(Methyl 2-O-Benzyl-4,6-O-benzylidene-
3-deoxy-α-D-altropyranosid-3-yl)-but-3-yn-2-ol 3a
Ethynylmagnesium bromide (10 mL, 0.5 M solution in THF) was added
dropwise to a solution of 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-
deoxy-α-d-altropyranosid-3-yl)ethanal 2 (0.8 g, 2.0 mmol) in dry THF
(10 mL). The mixture was stirred for 4 h at room temperature, poured
into water (20 mL), and extracted with dichloromethane (3 × 20 mL).
The combined organic phases were then washed with water (2 × 20 mL),
dried (Na2SO4), and evaporated under reduced pressure. The residue
was purified by column chromatography (toluene/EtOAc, 10 : 1) to
afford 3a as a colourless syrup (0.406 g, 85%; R-to-S ratio 2 : 3), RF
0.42 (toluene/EtOAc, 10 : 1), [α]2D2 +54.8 (c 0.5 in CHCl3) (Found: C
70.7, H 6.8. C25H28O6 requires C 70.7, H 6.7%). νmax/cm−1 3454 (OH),
3257 (CH). δH (250 MHz; CDCl3) 7.47–7.26 (10H, m, Ph), 5.61 and
5.59 (1H, 2 s, CHPh), 4.66 and 4.64 (1H, 2 br s, H1ꢀ), 4.65 and 4.64
Experimental
Instrumentation
Melting points were measured with a Boëtius apparatus and are cor-
rected. Specific rotations were determined with a Polar LµP polarimeter
(IBZ Messtechnik). IR spectra were recorded with a Nicolet 205
FT-IR spectrometer. 1H NMR (500.13, 300.13, and 250.13 MHz) and
13C NMR (125.7, 75.5, and 62.9 MHz) spectra were recorded on Bruker
AVANCE 500, ARX 300, and AC 250 instruments using CDCl3 as
solvent. The spectra were calibrated to TMS (internal 1H, δ 0) and
(2H, 2 ABq, 2JA,B 12.0, CH2Ph), 4.53–4.41 (1H, m, H2), 4.29 (1H, dd,
2
J6 ax,6 eq 10.0 and 3J5 ,6 eq 5.0, H6ꢀeq), 4.21 and 4.19 (1H, 2 dd, 3J4 ,5
ꢀ
CDCl3 (
13C, δ 77.0) signals. The 13C NMR signals were assigned by
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.8 and 3J3 ,4 5.2, H4 ), 3.97 and 3.96 (1H, 2 dt, J5 ,6 ax ≈ J4 ,5 9.8 and
ꢀ
3
3
DEPT and/or two-dimensional 13C–1H correlation spectra. For exam-
ple, HMBC spectra were recorded for compounds 5b, 6f, 7a, and 7b
in order to assign the quaternary carbon signals. The two-dimensional
NOESY spectra for the structure elucidation of 5 and 7 were recorded
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
J5 ,6 5.0, H5ꢀ), 3.81 and 3.80 (1H, 2 t, 2J6 ax,6 eq 10.0 and 3J5 ,6 ax
ꢀ
ꢀ
ꢀꢀ
3
ꢀ
ꢀ
ꢀ eq
9.8, H6ꢀax), 3.72 and 3.63 (1H, 2 dd, 3J2 ,3 2.0 and J1 ,2 1.0, H2 ), 3.36
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
and 3.35 (3H, 2 s, OMe), 2.98–2.82 and 2.73–2.60 (1H, 2 m, H3ꢀ), 2.43

108
I. Otero et al.
4
and 2.42 (1H, 2 d, J2,4 2.1, H4), 2.35–2.23 and 2.10–1.96 (2H, 2 m,
H1). δC (62.9 MHz; CDCl3) 137.7, 137.7, 137.4, and 137.1 (ipso-Ph),
129.2, 129.0, 128.5, 128.4, 127.9, and 127.8 (o-, m-, and p-Ph), 102.2
and 101.9 (CHPh), 100.2 and 100.1 (C1ꢀ), 84.9 and 84.7 (C3), 78.3 and
77.5 (C2ꢀ), 76.0 (C4ꢀ), 73.1 and 72.8 (C4), 71.7 (CH2Ph), 69.4 (C6ꢀ),
61.6 and 61.4 (C2), 59.4 and 59.4 (C5ꢀ), 55.1 (OMe), 36.0 and 35.6
(C3ꢀ), 33.6 and 33.5 (C1). m/z (CI) 425 (10%, [M + H]+•).
s, H1ꢀ), 4.29 (1H, dd, 2J6 ax,6 eq 9.5 and 3J5 ,6 eq 4.5, H6ꢀeq), 4.19 (1H,
ꢀ ꢀ ꢀ ꢀ
3
3
dd, J4 ,5 9.5 and J3 ,4 5.0, H4ꢀ), 3.91 (1H, dt, J5 ,6 ax 10.0, J4 ,5
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.5, and 3J5 ,6 eq 4.5, H5ꢀ), 3.82 (1H, app. t, 3J5 ,6 ax 10.0 and 2J6 ax,6 eq
9.5, H6ꢀax), 3.64 (1H, br s, H2ꢀ), 3.36 (3H, s, OMe), 3.26–3.16 (3H,
m, H1 and H3ꢀ). δC (62.9 MHz; CDCl3) 186.6 (C2), 137.9 and 137.5
(2 ipso-Ph), 133.0, 130.6, 128.9, 128.6, 128.4, 128.2, 127.9, 127.8, and
126.1 (o-, m-, and p-Ph), 119.9 (ipso-PhC≡C), 101.8 (CHPh), 100.7
(C1ꢀ), 90.4 (C4), 88.1 (C3), 76.3 (C4ꢀ), 75.1 (C2ꢀ), 71.6 (CH2Ph), 69.4
(C6ꢀ), 59.7 (C5ꢀ), 55.2 (OMe), 40.7 (C1), 33.8 (C3ꢀ). m/z (FAB+) 521
(100%, [M + Na]+•).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(2R,S)-1-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-yl)-4-phenyl-but-3-yn-2-ol 3b
Reaction of 2 (0.8 g, 2.0 mmol) with lithium phenylacetylide (8 mL,
1.0 M solution inTHF) was carried out as described above for the prepa-
ration of 3a.The crude product was purified by column chromatography
(toluene/EtOAc, 6 : 1) to afford 3b as a white solid (0.870 g, 87%; R-to-S
ratio 2 : 3), mp 45–48◦C, RF 0.45 (toluene/EtOAc, 6 : 1), [α]2D4+40.2
(c 1 in CHCl3) (Found: C 74.4, H 6.6. C31H32O6 requires C 74.4,
H 6.4%). νmax (KBr)/cm−1 3453 (OH). δH (250 MHz; CDCl3) 7.43–
7.12 (15H, m, Ph), 5.61 and 5.60 (1H, 2 s, CHPh), 4.78–4.65 (1H, br
s, H2), 4.67 and 4.66 (1H, 2 br s, H1ꢀ), 4.64 and 4.63 (2H, 2 ABq,
3(5)-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-1H(2H)-pyrazole 5a
A mixture of 4a (0.210 g, 0.5 mmol) and hydrazine hydrate (0.035 mL,
0.75 mmol) in dry methanol (5 mL) was stirred for 1 h. The solvent
was evaporated under reduced pressure and the crude product was puri-
fied by column chromatography (toluene/EtOAc, 1 : 1) to afford 5a as a
white solid (0.170 g, 78%), mp 58–60◦C, RF 0.24 (toluene/EtOAc, 1 : 1),
[α]2D1 +21.5 (c 1 in CHCl3) (Found: C 68.7, H 6.5, N 6.0. C25H28N2O5
requires C 68.8, H 6.5, N 6.4%). δH (250 MHz; CDCl3) 7.52–7.15 (11H,
m, H5 and Ph), 6.03 (1H, br s, H4), 5.64 (1H, s, CHPh), 4.65 (1H, s,
2JA,B 12.0, CH2Ph), 4.29 (1H, dd, 2J6 ax,6 eq 10.0, 3J5 ,6 eq 5.0, H6ꢀeq),
ꢀ
ꢀ
ꢀ
ꢀ
3
3
4.22 and 4.21 (1H, 2 dd, J4 ,5 10.0, J3 ,4 5.0, H4ꢀ), 3.99 and 3.98
ꢀ
ꢀ
ꢀ
ꢀ
H1ꢀ), 4.40 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.32 (1H, dd, 2J6 ax,6 eq 10.0
(1H, 2 dt, 3J5 ,6 ax ≈ J4 ,5 10.0, 3J5 ,6 eq 5.0, H5ꢀ), 3.82 and 3.81 (1H,
3
ꢀ
ꢀ
ꢀ
ꢀ
2
ꢀ
ꢀ
ꢀ
ꢀ
and 3J5 ,6 eq 5.0, H6ꢀeq), 4.22 (1H, dd, 3J4 ,5 9.8 and 3J3 ,4 5.2, H4ꢀ),
2 t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.80 and 3.68 (1H, 2 dd, 3J2 ,3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
4.06 (1H, dt, 3J5 ,6 ax ≈ J4 ,5 9.8 and 3J5 ,6 eq 5.0, H5ꢀ), 3.83 (1H, app.
3
2.0 and 3J1 ,2 1.0, H2ꢀ), 3.36 and 3.35 (3H, 2 s, OMe), 2.99–2.88 and
2.83–2.68 (1H, 2 m, H3ꢀ), 2.42–2.30 and 2.20–2.06 (2H, 2 m, H1). δC
(62.9 MHz; CDCl3) 137.8, 137.7, 137.7, and 137.4 (ipso-Ph), 131.6,
131.6, 129.1, 129.0, 128.9, 128.4, 128.3, 128.3, 128.2, 128.2, 127.7,
127.7, 127.6, 126.1, and 125.2 (o-, m-, and p-Ph), 122.6 (ipso-PhC≡C),
102.1 and 101.9 (CHPh), 100.2 and 100.2 (C1ꢀ), 90.1 and 90.0 (C3), 85.1
and 84.7 (C4), 78.3 and 77.5 (C2ꢀ), 76.1 (C4ꢀ), 71.7 and 71.6 (CH2Ph),
69.4 (C6ꢀ), 62.2 and 62.0 (C2), 59.4 and 59.3 (C5ꢀ), 55.0 (OMe), 36.0
and 35.7 (C3ꢀ), 33.7 and 33.6 (C1). m/z (70 eV) 500 (3%, [M + H]+•).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
2
t, J5 ,6 ax 9.8 and J6 ax,6 eq 10.0, H6ꢀax), 3.44 (1H, br s, H2ꢀ), 3.41
(3H, s, OMe), 3.17–3.06 (2H, m, 3-CH2), 2.67–2.55 (1H, m, H3ꢀ). δC
(62.9 MHz;CDCl3)144.4(C5), 137.5and137.4(2ipso-Ph), 137.0(C3),
129.2, 128.4, 128.3, 127.9, 127.8, and 126.2 (o-, m-, and p-Ph), 104.3
(C4), 102.1 (CHPh), 100.5 (C1ꢀ), 76.2 (C4ꢀ), 75.6 (C2ꢀ), 71.7 (CH2Ph),
69.4 (C6ꢀ), 59.3 (C5ꢀ), 55.2 (OMe), 39.8 (C3ꢀ), 21.8 (3-CH2).
ꢀ
ꢀ
ꢀ
ꢀ
3-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-5-phenyl-1H-pyrazole 5b
1-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-yl)but-3-yn-2-one 4a
The reaction of 4b (0.250 g, 0.5 mmol) with hydrazine hydrate
(0.035 mL, 0.75 mmol) was carried out as described above for the prepa-
ration of 5a.The crude product was purified by column chromatography
(toluene/EtOAc, 1 : 1) to afford 5b as a white solid (0.230 g, 90%), mp
75–78◦C, RF 0.49 (toluene/EtOAc, 1 : 1), [α]D24 +86.2 (c 0.5 in CHCl3)
(Found: C 72.8, H 6.4, N 5.2. C31H32N2O5 requires C 72.6, H 6.3, N
5.5%). δH (250 MHz; CDCl3) 7.75–7.72 (2H, m, Ph), 7.52–7.13 (13H,
m, Ph), 6.32 (1H, s, H4), 5.64 (1H, s, CHPh), 4.66 (1H, s, H1ꢀ), 4.41 (2H,
Manganese dioxide (0.86 g, 10.0 mmol) was added to a solution of 3a
(0.640 g, 1.5 mmol) in dry dichloromethane (40 mL). The mixture was
stirred for 12 h, filtered, and the residue was washed with EtOAc. The
solvent was removed under reduced pressure and the crude product was
purified by column chromatography (toluene/EtOAc, 10 : 1) to afford
4a as white crystals (0.360 g, 57%), mp 119–121◦C (ethanol), RF 0.48
(toluene/EtOAc, 10 : 1), [α]2D3 +72.9 (c 1 in CHCl3) (Found: C 71.2,
H 6.3. C25H26O6 requires C 71.1, H 6.2%). νmax (KBr)/cm−1 3257
(CspH), 2092 (C≡C), 1687 (CO). δH (250 MHz; CDCl3) 7.47–7.28
(10H, m, Ph), 5.59 (1H, s, CHPh), 4.68 (2H, ABq, 2JA,B 12.0, CH2Ph),
4.61 (1H, s, H1ꢀ), 4.32–4.23 (1H, m, H6ꢀeq), 4.21–4.12 (1H, m, H4ꢀ),
2
2
3
ꢀ
ꢀ
ꢀ
ꢀ
ABq, JA,B 12.0, CH2Ph), 4.32 (1H, dd, J6 ax,6 eq 10.0 and J5 ,6 eq
5.0, H6ꢀeq), 4.23 (1H, dd, J4 ,5 9.8 and J3 ,4 5.2, H4ꢀ), 4.07 (1H,
3
3
ꢀ
ꢀ
ꢀ
ꢀ
app. dt, J5 ,6 ax 10.0, J4 ,5 9.8, and J5 ,6 eq 5.0, H5ꢀ), 3.85 (1H, t,
3
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.47 (1H, br s, H2ꢀ), 3.44 (3H, s,
3
2
ꢀ
ꢀ
ꢀ
ꢀ
OMe), 3.10 (2H, d, J3-CH ,3 8.6, 3-CH2), 2.63–2.55 (1H, m, H3ꢀ).
3
ꢀ
2
3.86 (1H, dt, J5 ,6 ax ≈ J4 ,5 10.0, and J5 ,6 eq 4.0, H5ꢀ), 3.79 (1H,
3
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
δC (62.9 MHz; CDCl3) 150.9 (C5), 144.4 (C3), 137.5, 137.2, and 133.0
(3 ipso-Ph), 129.2, 128.6, 128.4, 128.0, 127.9, 127.8, 127.7, 126.2, 125.5
(o-, m-, and p-Ph), 102.2 (C4), 101.7 (CHPh), 100.4 (C1ꢀ), 76.2 (C4ꢀ),
75.2 (C2ꢀ), 71.8 (CH2Ph), 69.4 (C6ꢀ), 59.3 (C5ꢀ), 55.3 (OMe), 39.8
(C3ꢀ), 21.8 (3-CH2). m/z (70 eV) 512 (5%, M+•).
t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.56 (1H, br s, H2ꢀ), 3.34 (3H, s,
OMe), 3.17 (1H, s, H4), 3.17–3.11 (3H, m, H1 and H3ꢀ). δC (62.9 MHz;
CDCl3) 186.0 (C2), 137.8 and 137.4 (2 ipso-Ph), 129.0, 128.4, 128.2,
127.9, 127.8, and 126.1 (o-, m-, and p-Ph), 101.8 (CHPh), 100.6 (C1ꢀ),
81.6 (C3), 78.3 (C4), 76.2 (C4ꢀ), 74.9 (C2ꢀ), 71.6 (CH2Ph), 69.4 (C6ꢀ),
59.7 (C5ꢀ), 55.2 (OMe), 40.8 (C2), 33.5 (C3ꢀ). m/z (FAB+) 445 (100%,
[M + Na]+•).
2
ꢀ
ꢀ
ꢀ
ꢀ
1-Methyl-3-(methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-5-phenyl-1H-pyrazole 5c
The reaction of 4b (0.250 g, 0.5 mmol) with methylhydrazine
(0.070 mL, 0.75 mmol) was carried out as described above for the prepa-
ration of 5a.The crude product was purified by column chromatography
(toluene/EtOAc, 2 : 1) to afford 5c as a colourless syrup (0.225 g, 86%),
RF 0.56 (toluene/EtOAc 2 : 1), [α]2D1 +40.1 (c 0.5 in CHCl3) (Found: C
72.7, H 6.5, N 5.0. C32H34N2O5 requires C 73.0, H 6.5, N 5.3%). δH
(250 MHz; CDCl3) 7.52–7.15 (15H, m, Ph), 6.06 (1H, s, H4), 5.65 (1H,
s, CHPh), 4.68 (1H, s, H1ꢀ), 4.53 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.32
1-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-yl)-4-phenyl-but-3-yn-2-one 4b
Pyridinium chlorochromate (0.808 g, 3.75 mmol) was added to a solu-
tion of 3b (0.750 g, 1.5 mmol) in dry dichloromethane (40 mL). The
mixture was stirred for 12 h, filtered, and the residue was washed with
EtOAc. The solvent was removed under reduced pressure and the crude
productwaspurifiedbycolumnchromatography(toluene/EtOAc, 10 : 1)
to afford 4b as white crystals (0.410 g, 55%), mp 137–140◦C (ethanol),
RF 0.54 (toluene/EtOAc, 10 : 1), [α]2D4 +133.4 (c 1 in CHCl3) (Found:
C 74.6, H 6.1. C31H30O6 requires C 74.7, H 6.1%). νmax (KBr)/cm−1
2201 (C≡C), 1669 (CO). δH (250 MHz; CDCl3) 7.55–7.28 (15H, m,
Ph), 5.62 (1H, s, CHPh), 4.71 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.64 (1H,
2
3
3
(1H, dd, J6 ax,6 eq 10.0 and J5 ,6 eq 5.0, H6ꢀeq), 4.22 (1H, dd, J4 ,5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.8 and 3J3 ,4 5.5, H4ꢀ), 4.06 (1H, dt, 3J5 ,6 ax ≈ J4 ,5 9.8 and 3J5 ,6 eq
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
5.0, H5ꢀ), 3.84 (1H, app. t, 3J5 ,6 ax 9.8 and 2J6 ax,6 eq 10.0, H6ꢀax), 3.82
ꢀ
ꢀ
ꢀ
ꢀ
(3H, s, NMe), 3.69 (1H, br s, H2ꢀ), 3.39 (3H, s, OMe), 3.11 (2H, d,
J3-CH ,3 7.3, 3-CH2), 2.90–2.76 (1H, m, H3ꢀ). δC (62.9 MHz; CDCl3)
3
ꢀ
2

Nucleoside Analogues from Branched-Chain Pyranosides
109
150.5 (C5), 143.9 (C3), 137.9, 137.8, and 130.9 (3 ipso-Ph), 128.9,
128.6, 128.5, 128.3, 128.2, 128.1, 127.9, 127.6, and 126.2 (o-, m-, and
p-Ph), 105.6 (C4), 101.7 (CHPh), 100.9 (C1ꢀ), 76.3 (C4ꢀ), 75.4 (C2ꢀ),
71.1 (CH2Ph), 69.6 (C6ꢀ), 59.3 (C5ꢀ), 55.1 (OMe), 39.4 (C3ꢀ), 37.2
(NMe), 22.9 (3-CH2). m/z (70 eV) 526 (5%, M+•).
[62.9 MHz; (CD3)2SO] 103.7 and 103.0 (C4 and C1ꢀ), 73.1 (C5ꢀ), 68.6
(C2ꢀ), 64.2 (C4ꢀ), 61.7 (C6ꢀ), 54.8 (OMe), 43.7 (C3ꢀ), 20.9 (3-CH2); C3
and C5 are not given as a result of strong signal broadening. m/z (70 eV)
259 ([M + H]+•).
2-Methyl-4-(methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)pyrimidine 8a
1-(2-Hydroxyethyl)-3-(methyl 2-O-Benzyl-4,6-O-benzylidene-
3-deoxy-α-D-altropyranosid-3-ylmethyl)-5-phenyl-1H-pyrazole 5d
Amixtureof 4a (0.210 g, 0.5 mmol), acetamidiniumchloride(0.061 mg,
0.65 mmol), Na2CO3 (0.138 g, 1.38 mmol), water (0.01 mL), and EtOAc
(5 mL) was heated at reflux until the starting material disappeared by
TLC (24 h). The solution was then filtered and the solvent was evapo-
rated under reduced pressure.The crude product was purified by column
chromatography (toluene/EtOAc, 2 : 1) to afford 8a as a colourless syrup
(0.205 g, 88%), RF 0.22 (toluene/EtOAc, 2 : 1), [α]2D2 +52.5 (c 1 in
CHCl3) (Found: C 70.2, H 6.7, N 5.9. C27H30N2O5 requires C 70.1,
The reaction of 4b (0.250 g, 0.5 mmol) with 2-hydroxyethylhydrazine
(0.050 mL, 0.75 mmol) was carried out as described above for the prepa-
ration of 5a.The crude product was purified by column chromatography
(toluene/EtOAc, 1 : 2) to afford 5d as a white solid (0.203 g, 73%), mp
50–53◦C, RF 0.42 (toluene/EtOAc, 1 : 2), [α]D24 +42.9 (c 1 in CHCl3)
(Found: C 71.4, H 6.5, N 4.9. C33H36N2O6 requires C 71.2, H 6.5, N
5.0%). νmax (KBr)/cm−1 3424 (OH). δH (500 MHz; CDCl3) 7.51–7.14
(15H, m, Ph), 6.08 (1H, s, H4), 5.64 (1H, s, CHPh), 4.68 (1H, s, H1ꢀ),
3
H 6.5, N 6.1%). δH (250 MHz; CDCl3) 8.39 (1H, d, J5,6 4.6, H6),
4.52 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.32 (1H, dd, 2J6 ax,6 eq 10.4 and
7.44–7.18 (10H, m, Ph), 6.90 (1H, d, 3J5,6 4.6, H5), 5.62 (1H, s, CHPh),
ꢀ
ꢀ
J5 ,6 eq 5.0, H6ꢀeq), 4.23 (1H, dd, 3J4 ,5 9.8 and 3J3 ,4 5.4, H4ꢀ), 4.14
3
2
4.65 (1H, s, H1ꢀ), 4.54 (2H, ABq, JA,B 12.0, CH2Ph), 4.32 (1H, dd,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
3
3
3
(2H, t, 3JCH OH,CH CN 4.6, CH2OH), 4.05 (1H, app. dt, 3J5 ,6 ax 10.0,
J6 ax,6 eq 10.0 and J5 ,6 eq 5.0, H6ꢀeq), 4.24 (1H, dd, J4 ,5 9.8 and
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
2
J4 ,5 9.8, and 3J5 ,6 eq 5.0, H5ꢀ), 3.94–3.83 (2H, m, CH2N), 3.84 (1H,
3
J3 ,4 4.3, H4 ), 4.03 (1H, app. dt, J5 ,6 ax 10.0, 3J4 ,5 9.8, and J5 ,6 eq
ꢀ
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
2
app. t, J5 ,6 ax 10.0 and J6 ax,6 eq 10.4, H6ꢀax), 3.64 (1H, br s, H2ꢀ),
3.39 (3H, s, OMe), 3.21–3.01 (2H, m, 3-CH2), 2.87–2.80 (1H, m, H3ꢀ).
δC (62.9 MHz; CDCl3) 151.1 (C5), 144.5 (C3), 137.7, 137.6, and 130.4
(3 ipso-Ph), 129.0, 128.9, 128.6, 128.5, 128.3, 128.2, 127.8, 127.6, and
126.2 (o-, m-, and p-Ph), 105.7 (C4), 101.9 (CHPh), 100.8 (C1ꢀ), 76.3
(C4ꢀ), 75.5 (C2ꢀ), 71.3 (CH2Ph), 69.6 (C6ꢀ), 62.1 (CH2OH), 59.3 (C5ꢀ),
55.1 (OMe), 50.5 (CH2N), 39.2 (C3ꢀ), 23.1 (3-CH2). m/z (70 eV) 556
(5%, M+•).
5.0, H5ꢀ), 3.84 (1H, t, J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.44 (1H, br
s, H2ꢀ), 3.39 (3H, s, OMe), 3.22–3.07 (3H, m, 4-CH2 and H3ꢀ), 2.69
(3H, s, Me). δC (62.9 MHz; CDCl3) 169.5 (C4), 167.7 (C2), 156.2 (C6),
137.6 and 137.5 (2 ipso-Ph), 128.9, 128.4, 128.1, 127.79, 127.76, 126.1
(o-, m-, and p-Ph), 118.6 (C5), 101.8 (CHPh), 100.7 (C1ꢀ), 75.9 (C4ꢀ),
75.3 (C2ꢀ), 71.4 (CH2Ph), 69.5 (C6ꢀ), 59.5 (C5ꢀ), 55.2 (OMe), 37.7
(C3ꢀ), 32.4 (Me), 26.1 (4-CH2). m/z (CI) 463 (100%, [M + H]+•).
3
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
4-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-2-phenylpyrimidine 8b
3(5)-(Methyl 2-O-Benzyl-3-deoxy-α-D-altropyranosid-3-ylmethyl)-
1(2H)-pyrazole 6
The reaction of 4a (0.210 g, 0.5 mmol) with benzamidinium chloride
(0.102 g, 0.65 mmol) was carried out as described above for the prepa-
ration of 8a (reaction time 3 h). The crude product was purified by
column chromatography (toluene/EtOAc, 10 : 1) to afford 8b as a white
solid (0.250 g, 95%), mp 45–48◦C, RF 0.43 (toluene/EtOAc, 10 : 1),
[α]2D1 +52.3 (c 0.5 in CHCl3) (Found: C 73.0, H 6.2, N 5.3. C32H32N2O5
requires C 73.3, H 6.2, N 5.3%). δH (250 MHz; CDCl3) 8.57 (1H, d, 3J5,6
5.2, H6), 8.50–8.47 (2H, m, Ph), 7.49–7.45 (5H, m, Ph), 7.37–7.31 (3H,
A solution of compound 5a (0.220 g, 0.5 mmol) in acetic acid (5 mL) and
water (0.5 mL) was heated at 70◦C for 7 h. Water (10 mL) and NaHCO3
were then added until the solution was neutralized, and the mixture was
extractedwithEtOAc(3 × 50 mL).Thecombinedorganicfractionswere
washed with water (2 × 50 mL), dried (Na2SO4), and the solvent was
evaporated under reduced pressure. The crude product was purified by
column chromatography (EtOAc/MeOH, 10 : 1) to afford 6 as a white
solid(0.160 g, 90%), mp53–55◦C, RF 0.49(EtOAc/MeOH, 10 : 1), [α]D21
+47.6 (c 0.5 in MeOH) (Found: C 61.6, H 6.9, N 7.7. C18H24N2O5
requires C 62.1, H 6.9, N 8.0%). νmax (KBr)/cm−1 3387, 3304 (OH).
δH [250 MHz; (CD3)2SO] 12.40 (1H, br s, NH), 7.44 (1H, br s, H5),
7.37–7.20 (5H, m, Ph), 5.99 (1H, br s, H4), 4.94 (1H, br s, 4ꢀ-OH),
3
m, Ph), 7.18–7.08 (5H, m, Ph), 6.98 (1H, d, J5,6 5.2, H5), 5.66 (1H,
s, CHPh), 4.66 (1H, s, H1ꢀ), 4.51 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.34
2
3
3
(1H, dd, J6 ax,6 eq 10.0 and J5 ,6 eq 5.0, H6ꢀeq), 4.28 (1H, dd, J4 ,5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.8 and 3J3 ,4 5.2, H4ꢀ), 4.08 (1H, app. dt, 3J5 ,6 ax 10.0, 3J4 ,5 9.8, and
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J5 ,6 eq 5.0, H5ꢀ), 3.87 (1H, t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.46
3
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
4.60 (1H, br s, 6ꢀ-OH), 4.56 (1H, s, H1ꢀ), 4.45 (2H, ABq, JA,B 12.0,
(1H, br s, H2ꢀ), 3.40 (3H, s, OMe), 3.35–3.23 (3H, m, 4-CH2 and H3ꢀ).
δC (62.9 MHz; CDCl3) 169.6 (C4), 164.2 (C2), 156.6 (C6), 137.9, 137.6,
and 137.5 (3 ipso-Ph), 130.5, 128.9, 128.5, 128.3, 128.2, 128.17, 127.7,
127.6, and 125.3 (o-, m-, and p-Ph), 119.6 (C5), 101.9 (CHPh), 100.7
(C1ꢀ), 75.9 (C4ꢀ), 75.3 (C2ꢀ), 71.4 (CH2Ph), 69.5 (C6ꢀ), 59.6 (C5ꢀ), 55.2
(OMe), 37.5 (C3ꢀ), 32.5 (4-CH2). m/z (CI) 525 (100%, [M + H]+•).
CH2Ph), 3.80–3.68 (1H, m, H4ꢀ), 3.67–3.28 (4H, m, H2ꢀ, H5ꢀ, and H6ꢀ),
3.31 (3H, s, OMe), 2.97–2.75 (2H, m, 3-CH2), 2.32–2.18 (1H, m, H3ꢀ).
δC [62.9 MHz; (CD3)2SO] 138.6 (ipso-Ph), 128.4 and 127.8 (o- and
m-Ph), 127.6 (p-Ph), 103.6 (C4), 101.0 (C1ꢀ), 76.6 (C2ꢀ), 72.5 (C5ꢀ),
71.1 (CH2Ph), 64.2 (C4ꢀ), 61.7 (C6ꢀ), 54.6 (OMe), 41.5 (C3ꢀ), 21.6
(3-CH2); C3 and C5 are not given as a result of strong signal broadening.
m/z (70 eV) 349 ([M + H]+•).
4-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-2-methylthiopyrimidine 8c
3(5)-(Methyl 3-Deoxy-α-D-altropyranosid-3-ylmethyl)-1H(2H)-
pyrazole 7
The reaction of 4a (0.210 g, 0.5 mmol) with S-methylisothiouronium
sulfate (0.181 g, 0.65 mmol) was carried out as described above for the
preparation of 8a (reaction time 2 h). The crude product was purified by
column chromatography (toluene/EtOAc, 10 : 1) to afford 8c as a colour-
less syrup (0.205 g, 83%), RF 0.47 (toluene/EtOAc, 10 : 1), [α]2D1 +61.1
(c 0.5 in CHCl3) (Found: C 65.7, H 6.2, N 5.2, S 6.4. C27H30N2O5S
requires C 65.6, H 6.1, N 5.6, S 6.5%). δH (250 MHz; CDCl3) 8.27 (1H,
d, 3J5,6 5.2, H6), 7.45–7.14(10H, m, Ph), 6.74(1H, d, 3J5,6 5.2, H5), 5.62
(1H, s, CHPh), 4.63 (1H, s, H1ꢀ), 4.54 (2H, ABq, 2JA,B 12.0, CH2Ph),
A mixture of 6 (0.105 g, 0.3 mmol), ammonium formate (0.1 g), and
10% palladium on carbon (0.200 g, Lancaster) in dry methanol (10 mL)
was heated at reflux for 2 h. The catalyst was then filtered off and
washed with the solvent, and the filtrate was evaporated under reduced
pressure. The crude product was purified by column chromatography
(EtOAc/MeOH, 5 : 1) to afford 7 as a white foam (0.070 g, 90%), RF
0.39 (EtOAc/MeOH, 5 : 1). [α]2D1 +89.5 (c 0.4 in MeOH) (Found: C
51.6, H 6.8, N 10.5. C11H18N2O5 requires C 51.2, H 7.0, N 10.9%). νmax
(KBr)/cm−1 3374, 3139, 3113 (OH). δH [250 MHz; (CD3)2SO] 12.40
4.31 (1H, dd, 2J6 ax,6 eq 10.0 and 3J5 ,6 eq 5.0, H6ꢀeq), 4.27–4.19 (1H, m,
ꢀ
ꢀ
ꢀ
ꢀ
H4ꢀ), 4.01 (1H, app. dt, 3J5 ,6 ax 10.0, 3J4 ,5 9.8, and 3J5 ,6 eq 5.0, H5ꢀ),
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(1H, br s, NH), 7.42 (1H, br s, H5), 6.02 (1H, d, J4,5 1.8, H4), 4.99
2
(1H, d, 3J2 ,2 -OH 4.9, 2ꢀ-OH), 4.80 (1H, d, 3J4 ,4 -OH 5.5, 4ꢀ-OH), 4.56
3.83 (1H, t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.41 (1H, br s, H2ꢀ), 3.37
(3H, s, OMe), 3.20–3.08 (3H, m, 4-CH2 and H3ꢀ), 2.55 (3H, s, SMe).
δC (62.9 MHz; CDCl3) 172.1 (C2), 169.8 (C4), 156.5 (C6), 137.6 and
137.5 (2 ipso-Ph), 128.9, 128.3, 128.1, 127.8 127.7, and 126.1 (o-, m-,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
3
(1H, t, J6 ,6 -OH 5.5, 6ꢀ-OH), 4.34 (1H, d, J1 ,2 3.0, H1ꢀ), 3.74–3.64
(1H, m, H4ꢀ), 3.64–3.40 (3H, m, H5ꢀ and H6ꢀ), 3.38 (1H, br s, H2ꢀ), 3.29
(3H, s, OMe), 2.95–2.70 (2H, m, 3-CH2), 2.05–1.92 (1H, m, H3ꢀ). δC

110
I. Otero et al.
and p-Ph), 116.8 (C5), 101.7 (CHPh), 100.6 (C1ꢀ), 75.8 (C4ꢀ), 75.2
(C2ꢀ), 71.4 (CH2Ph), 69.4 (C6ꢀ), 59.5 (C5ꢀ), 55.1 (OMe), 37.3 (C3ꢀ),
32.3 (4-CH2), 14.0 (SMe). m/z (CI) 495 (51%, [M + H]+•).
(o-, m-, and p-Ph), 108.3 (C5), 101.9 (CHPh), 100.8 (C1ꢀ), 76.0 (C4ꢀ),
75.5 (C2ꢀ), 71.4 (CH2Ph), 69.5 (C6ꢀ), 59.6 (C5ꢀ), 55.2 (OMe), 37.9
(C3ꢀ), 32.6 (4-CH2). m/z (70 eV) 539 (2%, M+•).
4-(Methyl 2-O-Benzyl-3-deoxy-α-D-altropyranosid-3-ylmethyl)-
2-phenylpyrimidine 9
2-Methyl-4-(methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-6-phenylpyrimidine 8d
The deprotection of compound 8b (0.260 g, 0.5 mmol) was carried out as
described above for the preparation of 6 (reaction time 12 h). The crude
product was purified by column chromatography (EtOAc) to afford 9
as a white foam (0.180 g, 84%), RF 0.57 (EtOAc), [α]2D1 +66.1 (c 0.5
in MeOH) (Found: C 68.4, H 6.5, N 5.9. C25H28N2O5 requires C 68.8,
H 6.5, N 6.4%). νmax (KBr)/cm−1 3426, 3363 (OH). δH [250 MHz;
(CD3)2SO] 8.68 (1H, d, 3J5,6 5.2, H6), 8.43–8.39 (2H, m, o-Ph), 7.21
The reaction of 4b (0.250 g, 0.5 mmol) with acetamidinium chloride
(0.061 mg, 0.65 mmol) was carried out as described above for the prepa-
ration of 8a (reaction time 8 h). The crude product was purified by
column chromatography (toluene/EtOAc, 10 : 1) to afford 8d as a white
solid (0.245 g, 91%), mp 43–46◦C, RF 0.55 (toluene/EtOAc, 10 : 1),
[α]2D3 +60.2 (c 0.5 in CHCl3) (Found: C 74.0, H 6.4, N 5.0. C33H34N2O5
requires C 74.0, H 6.4, N 5.2%). δH (250 MHz; CDCl3) 7.99–7.96 (2H,
m, Ph), 7.48–7.15 (14H, m, Ph and H5), 5.62 (1H, s, CHPh), 4.66 (1H,
3
(1H, d, J5,6 5.2, H5), 7.20–7.11 (3H, m, m- and p-Ph), 5.05 (1H, d,
3
3
J4 ,4 -OH 5.2, 4ꢀ-OH), 4.64–4.59 (1H, m, 6ꢀ-OH), 4.60 (1H, d, J1 ,2
br s, H1ꢀ), 4.55 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.33 (1H, dd, 2J6 ax,6 eq
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2.4, H1ꢀ), 4.47 (2H, ABq, 2JA,B 12.0, CH2Ph), 3.87–3.77 (1H, m, H4ꢀ),
3
3
3
10.0 and J5 ,6 eq 5.0, H6ꢀeq), 4.25 (1H, dd, J4 ,5 9.8 and J3 ,4 4.3,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3.72–3.44 (3H, m, H5ꢀ and H6ꢀ), 3.36–3.33 (1H, br s, H2ꢀ), 3.33 (3H, s,
H4ꢀ), 4.07 (1H, app. dt, 3J5 ,6 ax 10.0, 3J4 ,5 9.8, and 3J5 ,6 eq 5.0, H5ꢀ),
3.85 (1H, t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.53 (1H, dd, 3J2 ,3 2.0
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
OMe), 3.08 (2H, d, 3J
7.7, 4-CH2), 2.84–2.72 (1H, m, H3ꢀ). δC
ꢀ
4-CH2,3
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ
ꢀ
[62.9 MHz; (CD3)2SO] 170.4 (C4), 163.0 (C2), 157.2 (C6), 138.4 and
137.7 (2 ipso-Ph), 130.8, 128.8, 128.3, 127.9, and 127.5 (o-, m-, and p-
Ph), 120.0 (C5), 100.7 (C1ꢀ), 76.2 (C2ꢀ), 72.1 (C5ꢀ), 70.9 (CH2Ph), 64.1
(C4ꢀ), 61.7 (C6ꢀ), 54.6 (OMe), 40.3 (C3ꢀ), 32.6 (4-CH2). m/z (70 eV)
437 ([M + H]+•).
and 3J1 ,2 1.0, H2 ), 3.41 (3H, s, OMe), 3.29–3.11 (3H, m, 4-CH2, H3 ),
2.76 (3H, s, Me). δC (62.9 MHz; CDCl3) 170.0 (C4), 167.9 (C6), 163.7
(C2), 137.6, 137.4, and 137.3 (3 ipso-Ph), 130.4, 128.9, 128.8, 128.3
(2×), 128.1, 127.8, 127.2, and 126.1 (o-, m-, and p-Ph), 114.2 (C5),
101.9 (CHPh), 100.8 (C1ꢀ), 76.1 (C4ꢀ), 75.8 (C2ꢀ), 71.5 (CH2Ph), 69.5
(C6ꢀ), 59.6 (C5ꢀ), 55.2 (OMe), 37.9 (C3ꢀ), 32.9 (4-CH2), 26.3 (Me). m/z
(70 eV) 538 (5%, [M + H]+•).
ꢀ
ꢀ
4-(Methyl 3-Deoxy-α-D-altropyranosid-3-ylmethyl)-2-
phenylpyrimidine 10
The deprotection of compound 9 (0.130 g, 0.3 mmol) was carried out as
described above for the preparation of 7. The crude product was puri-
fied by column chromatography (EtOAc/MeOH, 10 : 1) to afford 10 as
a white solid (0.085 g, 82%), mp 162–164◦C, RF 0.42 (EtOAc/MeOH,
10 : 1), [α]2D1 +54.9 (c 1 in MeOH) (Found: C 62.4, H 6.5, N 7.6.
C18H22N2O5 requires C 62.4, H 6.4, N 8.1%). νmax (KBr)/cm−1 3424
(OH). δH [500 MHz; (CD3)2SO] 8.74 (1H, d, 3J5,6 5.0, H6), 8.42–8.38
(2H, m, o-Ph), 7.54–7.51 (3H, m, m- and p-Ph), 7.28 (1H, d, 3J5,6 5.0,
4-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-2,6-diphenylpyrimidine 8e
The reaction of 4b (0.250 g, 0.5 mmol) with benzamidinium hydrochlo-
ride (0.102 g, 0.65 mmol) was carried out as described above for the
preparation of 8a. The crude product was purified by column chro-
matography(toluene/EtOAc, 10 : 1)toafford 8easawhitesolid(0.270 g,
90%), mp 125–128◦C, RF 0.55 (toluene/EtOAc, 10 : 1), [α]2D4 +64.3
(c 1 in CHCl3) (Found: C 76.2, H 6.3, N 4.3. C38H36N2O5 requires
C 76.0, H 6.0, N 4.7%). δH (250 MHz; CDCl3) 8.65–8.60 (2H, m, Ph),
8.18–8.13 (2H, m, Ph), 7.55–7.43 (9H, m, Ph and H5), 7.33–7.28 (3H,
m, Ph), 7.14–7.09 (5H, m, Ph), 5.66 (1H, s, CHPh), 4.67 (1H, br s,
3
3
H5), 5.06 (1H, d, J23,2 -OH 5.2, 2ꢀ-OH), 4.90 (1H, d, J43,4 -OH 5.2,
ꢀ
ꢀ
ꢀ
ꢀ
4ꢀ-OH), 4.56 (1H, t, J6 ,6 -OH 6.0, 6ꢀ-OH), 4.39 (1H, d, J1 ,2 3.0,
ꢀ
ꢀ
ꢀ
ꢀ
H1ꢀ), 3.77 (1H, dt, J3 ,4 ≈ J4 ,4 -OH 5.2 and J4 ,5 8.0, H4ꢀ), 3.63
3
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(1H, ddd, 3J5 ,6 a 3.0, 3J6 ,6 -OH 6.0, and 2J6 a,6 b 11.0, H6ꢀa), 3.54 (1Hꢀ,
ꢀꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H1ꢀ), 4.54 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.35 (1H, dd, 2J6 ax,6 eq 10.0
ꢀ
ꢀ
ddd, 3J5 ,6 a 3.0, 2J5 ,6 b 5.5, and 3J4 ,5 8.0, H5 ), 3.51–3.43 (2H, m, H2
and H6ꢀb), 3.32 (3H, s, OMe), 3.05 (2H, m, 4-CH2), 2.46 (1H, m, H3ꢀ).
δC [62.9 MHz; (CD3)2SO] 170.9 (C4), 163.0 (C2), 157.1 (C6), 137.7
(ipso-Ph), 130.8, 128.8, and 127.9 (o-, m-, and p-Ph), 120.0 (C5), 102.9
(C1ꢀ), 73.0 (C5ꢀ), 68.7 (C2ꢀ), 64.1 (C4ꢀ), 61.7 (C6ꢀ), 54.7 (OMe), 42.7
(C3ꢀ), 33.0 (4-CH2). m/z (70 eV) 346 (M+•).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
and 3J5 ,6 eq 5.0, H6ꢀeq), 4.30 (1H, dd, 3J4 ,5 9.8 and 3J3 ,4 5.0, H4ꢀ),
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
4.12 (1H, app. dt, 3J5 ,6 ax 10.0, 3J4 ,5 9.8, and 3J5 ,6 eq 5.0, H5ꢀ), 3.88
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
(1H, t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.56 (1H, dd, 3J2 ,3 2.0 and
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
J1 ,2 1.0, H2ꢀ), 3.42 (3H, s, OMe), 3.41–3.21 (3H, m, 4-CH2 and
H3ꢀ). δC (62.9 MHz; CDCl3) 170.2 (C4), 164.1 (C6), 163.5 (C2), 138.2,
137.7, 137.5, and 137.4 (4 ipso-Ph), 130.6, 130.4, 128.9, 128.8, 128.38,
128.35, 128.3, 128.2, 127.7, 127.6, 127.2, and 126.1 (o-, m-, and p-Ph),
115.0 (C5), 101.9 (CHPh), 100.8 (C1ꢀ), 76.1 (C4ꢀ), 75.7 (C2ꢀ), 71.4
(CH2Ph), 69.6 (C6ꢀ), 59.7 (C5ꢀ), 55.2 (OMe), 37.8 (C3ꢀ), 32.9 (4-CH2).
m/z (70 eV) 600 (5%, M+•).
ꢀ
ꢀ
2-(Methyl 2-O-Benzyl-4,6-O-Benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)benzo[4,5]imidazo-
[1,2-a]pyrimidine 11a
A mixture of 4a (0.210 g, 0.5 mmol) and 2-aminobenzimidazol (0.073 g,
0.55 mmol) in ethanol (5 mL) was heated at reflux for 2 h before
being cooled to 20◦C, treated with sodium ethanolate (1.5 mmol) in
ethanol (5 mL), and stirred for 1 h. After neutralization of the mixture
with amberlite IR-120 (Fluka-Chemie), the solvent was removed under
reduced pressure and the residue was purified by column chromatog-
raphy (toluene/EtOAc, 1 : 1) to afford 11a as a yellow solid (0.201 g,
75%), mp 215–218◦C, RF 0.30 (toluene/EtOAc, 1 : 1), [α]2D1 +36.8 (c 1
in CHCl3) (Found: C 71.2, H 5.9, N 7.6. C32H31N3O5 requires C 71.5,
H 5.8, N 7.8%). δH (250 MHz; CDCl3) 8.39 (1H, d, 3J3,4 7.0, H4), 8.01
(1H, m, 4J7,9 1.0, 3J8,9 8.2, H9), 7.79 (1H, m, 4J6,8 1.2, 3J6,7 7.9, H6),
7.57 (1H, ddd, 3J8,9 8.2, 3J7,8 7.3, and 4J6,8 1.2, H8), 7.43–7.02 (11H,
m, Ph, H7), 6.70 (1H, d, 3J3,4 7.0, H3), 5.62 (1H, s, CHPh), 4.70 (2H,
2-Amino-4-(methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-6-phenylpyrimidine 8f
The reaction of 4b (0.250 g, 0.50 mmol) with guanidinium chloride
(0.138 g, 1.3 mmol) was carried out as described above for the prepa-
ration of 8a (reaction time 24 h). The crude product was purified by
column chromatography (toluene/EtOAc, 2 : 1) to afford 8f as a white
solid (0.108 g, 40%), mp 78–80◦C, RF 0.34 (toluene/EtOAc, 2 : 1), [α]D24
+56.4 (c 1 in CHCl3) (Found: C 71.4, H 6.2, N 7.6. C32H33N3O5
requires C 71.2, H 6.2, N 7.8%). νmax (KBr)/cm−1 3315, 3192 (NH2).
δH (250 MHz; CDCl3) 7.93–7.88 (2H, m, Ph), 7.47–7.18 (13H, m, Ph),
6.90 (1H, s, H5), 5.64 (1H, s, CHPh), 5.13 (2H, br s, NH2), 4.65 (1H, br s,
ABq, 2JA,B 12.0, CH2Ph), 4.66 (1H, br s, H1ꢀ), 4.34 (1H, dd, 2J6 ax,6 eq
H1ꢀ), 4.53 (2H, ABq, 2JA,B 12.0, CH2Ph), 4.32 (1H, dd, 2J6 ax,6 eq 10.0
ꢀ
ꢀ
ꢀ
ꢀ
3
3
3
10.0 and J5 ,6 eq 5.0, H6ꢀeq), 4.28 (1H, dd, J4 ,5 9.8 and J3 ,4 4.3,
and 3J5 ,6 eq 5.0, H6ꢀeq), 4.24 (1H, m, H4ꢀ), 4.04 (1H, app. dt, 3J5 ,6 ax
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H4ꢀ), 4.06 (1H, app. dt, 3J5 ,6 ax 10.0, 3J4 ,5 9.8, and 3J5 ,6 eq 5.0, H5ꢀ),
10.0, 3J4 ,5 9.8, and J5 ,6 eq 5.0, H5ꢀ), 3.84 (1H, t, 3J5 ,6 ax ≈ J6 ax,6 eq
3
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3.86 (1H, t, 3J5 ,6 ax ≈ J6 ax,6 eq 10.0, H6ꢀax), 3.66 (1H, dd, 3J2 ,3 2.0
2
10.0, H6ꢀax), 3.56 (1H, dd, J2 ,3 2.0 and J1 ,2 1.0, H2ꢀ), 3.40 (3H,
s, OMe), 3.21–2.98 (3H, m, 4-CH2 and H3ꢀ). δC (62.9 MHz; CDCl3)
171.3 (C4), 165.1 (C6), 163.3 (C2), 137.7, 137.6, and 137.6 (3 ipso-
Ph), 130.2, 128.9, 128.6, 128.4, 128.2, 127.9, 127.8, 127.2, and 126.1
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
and 3J1 ,2 1.0, H2ꢀ), 3.39 (3H, s, OMe), 3.42–3.27 (3H, m, 2-CH2 and
H3ꢀ). δC (62.9 MHz; CDCl3) 168.6 (C2), 150.8 (C10a), 144.3 (C9a),
137.7 and 137.6 (2 ipso-Ph), 131.7 (C4), 129.0, 128.8, 128.14, 128.05,
ꢀ
ꢀ

Nucleoside Analogues from Branched-Chain Pyranosides
111
127.5, 125.9 (o-, m-, and p-Ph), 126.9 (C5a), 126.1 (C8), 121.5 (C7),
120.4 (C9), 110.2 (C6), 108.6 (C3), 101.5 (CHPh), 100.9 (C1ꢀ), 75.8
(C4ꢀ), 75.2 (C2ꢀ), 71.4 (CH2Ph), 69.5 (C6ꢀ), 59.7 (C5ꢀ), 55.2 (OMe),
37.2 (C3ꢀ), 33.7 (2-CH2). m/z (70 eV) 537 (67%, M+•).
J.Q. is grateful to the Fundação de Amparo à Pesquisa
do Estado de São Paulo (FAPESP, Brasil). I.O. is grate-
ful to the Deutscher Akademischer Austauschdienst for a
scholarship.
2-(Methyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-
α-D-altropyranosid-3-ylmethyl)-4-phenyl-benzo[4,5]imidazo-
[1,2-a]pyrimidine 11b
References
[1] D. E. Levy, C. Tang, The Chemistry of C-Glycosides 1995
(Pergamon: Oxford).
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Pure Appl. Chem. 1998, 70, 435.
[3] Z. J.Yang, H.W.Yu, J. M. Min, L.T. Ma, L. H. Zhang,Tetrahedron:
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[9] M. E. Jung, C. J. Nichols, J. Org. Chem. 1998, 63, 347.
doi:10.1021/JO971890C
[10] H. Dietrich, C. Regele-Mayer, R. R. Schmidt, Carbohydr. Lett.
1994, 1, 115.
The reaction of 4b (0.250 g, 0.5 mmol) with 2-aminobenzimidazol
(0.073 g, 0.55 mmol) was carried out as described above for the prepa-
ration of 11a (reaction time 24 h). The crude product was purified by
column chromatography (toluene/EtOAc, 1 : 1) to afford 11b as a yel-
low solid (0.217 g, 65%), mp 93–95◦C, RF 0.41 (toluene/EtOAc, 1 : 1),
[α]2D1 +27.9 (c 0.5 in CHCl3) (Found: C 74.2, H 5.7, N 7.0. C38H35N3O5
requires C 74.4, H 5.8, N 6.9%). δH (500 MHz; CDCl3) 7.98 (1H, m,
3
3
3
4
4J7,9 1.0, J8,9 8.2, H9), 7.45 (1H, ddd, J8,9 8.2, J7,8 7.3, and J6,8
3
3
1.0, H8), 7.66–7.07 (15H, m, Ph), 7.01 (1H, ddd, J6,7 8.2, J7,8 7.3,
and 4J7,9 1.0, H7), 6.60 (1H, m, 4J6,8 1.0, 3J6,7 8.2, H6), 6.56 (1H, s,
H3), 5.59 (1H, s, CHPh), 4.77 (2H,ABq, 2JA,B 12.0, CH2Ph), 4.67 (1H,
s, H1ꢀ), 4.33 (1H, dd, 2J6 ax,6 eq 10.4 and 3J5 ,6 eq 5.0, H6ꢀeq), 4.28 (1H,
ꢀ
ꢀ
ꢀ
ꢀ
dd, 3J4 ,5 9.8 and J3 ,4 5.0, H4 ), 4.06 (1H, app. dt, J5 ,6 ax 10.0, 3J4 ,5
3
ꢀ
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.8, and 3J5 ,6 eq 5.0, H5ꢀ), 3.85 (1H, app. t, 3J5 ,6 ax 10.0 and 2J6 ax,6 eq
10.4, H6ꢀax), 3.75 (1H, br s, H2ꢀ), 3.54–3.30 (3H, m, H3ꢀ, 2-CH2), 3.38
(3H, s, OMe). δC (62.9 MHz; CDCl3) 168.1 (C2), 151.9 (C4), 148.0
(C10a), 144.8 (C9a), 137.9, 137.7, and 132.2 (3 ipso-Ph), 130.8, 129.2,
128.7, 128.3, 128.2, 128.1, 128.0, 125.9, and 125.6 (o-, m-, and p-Ph),
127.5 (C8), 127.4 (C5a), 120.8 (C7), 120.1 (C9), 114.4 (C6), 109.8 (C3),
101.5 (CHPh), 100.9 (C1ꢀ), 76.0 (C4ꢀ), 75.9 (C2ꢀ), 71.5 (CH2Ph), 69.5
(C6ꢀ), 59.7 (C5ꢀ), 55.2 (OMe), 37.2 (C3ꢀ), 33.7 (2-CH2). m/z (70 eV)
613 (9%, M+•).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
[11] H. Dietrich, R. R. Schmidt, Liebigs Ann. Chem. 1994, 975.
[12] T. Granier, A. Vasella, Helv. Chim. Acta 1995, 78, 1738.
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L. Chen, R. Wang, D. H. Steensma, J. Org. Chem. 1995, 60, 1492.
[14] J. Streith, A. Boiron, A. Frankowski, D. Le Nouen, H. Rudyk,
T. Tschamber, Synthesis (Mass.) 1995, 944. doi:10.1055/ S-1995-
4040
2-(Methyl 2-O-Benzyl-3-deoxy-α-D-altropyranosid-3-yl-
methyl)benzo[4,5]imidazo[1,2-a]pyrimidine 13
[15] A. Frankowski, D. Deredas, D. Le Nouen,T.Tschamber, J. Streith,
Helv. Chim. Acta 1995, 78, 1837.
[16] A. B. Hughes, R. V. Stick, D. M. G. Tilbrook, Aust. J. Chem. 1990,
43, 1681.
[17] M. H. D. Postema, J. L. Piper, L. Liu, J. Shen, M. Faust,
P. Andreana, J. Org. Chem. 2003, 68, 4748. doi:10.1021/
JO030039X
[18] A. Fürstner, J. Baumgartner, Tetrahedron 1993, 49, 8541.
doi:10.1016/S0040-4020(01)96261-1
[19] M. Nakata, K. Toshima, T. Kai, M. Kinoshita, Bull. Chem. Soc.
Jpn. 1985, 58, 3457.
[20] A. J. Wood, D. J. Holt, M.-C. Domínguez, P. R. Jenkins, J. Org.
Chem. 1998, 63, 8522. doi:10.1021/JO981225J
[21] C. M. Brennan, D. C. Johnson, P. D. McDonnell, J. Chem. Soc.,
Perkin Trans. 2 1989, 957. doi:10.1039/P29890000957
[22] S. Hoffmann, K.-J. Hartung, N.-T. Hahn, R. Mewes, W. Baluzow,
Z. Chem. 1986, 26, 105.
[23] G. T. Crisp, M. J. Millan, Tetrahedron 1998, 54, 637.
doi:10.1016/S0040-4020(97)10323-4
The deprotection of compound 11a (0.270 g, 0.5 mmol) was carried out
as described above for the preparation of 6 (reaction time: 17 h). The
crude product was purified by column chromatography (EtOAc/MeOH,
10 : 1) to afford 13 as white needles (0.210 g, 95%), mp 210◦C (dec.),
RF 0.31 (EtOAc/MeOH, 10 : 1) [α]2D2 +36.9 (c 0.5 in MeOH) (Found:
C 66.7, H, 6.1, N 9.1. C25H27N3O5 requires C 66.8, H 6.1, N 9.4%).
νmax (KBr)/cm−1 3435, 3191 (OH). δH [500 MHz; (CD3)2SO] 9.26
3
3
3
(1H, d, J3,4 6.9, H4), 8.23 (1H, d, J8,9 8.1, H9), 7.82 (1H, d, J6,7
3
3
3
3
8.1, H6), 7.52 (1H, t, J6,7 ≈ J7,8 8.1, H7), 7.39 (1H, t, J8,9 ≈ J7,8
3
8.1, H8), 7.17–6.99 (5H, m, Ph), 6.97 (1H, d, J3,4 6.9, H3), 5.06
(1H, d, J4 ,4 -OH 5.0, 4ꢀ-OH), 4.63 (1H, t, J6 ,6 -OH 6.0, 6ꢀ-OH),
3
3
ꢀ
ꢀ
ꢀ
ꢀ
4.60 (1H, d, J1 ,2 2.5, H1ꢀ), 4.50 (2H, ABq, JA,B 12.0, CH2Ph),
3
2
ꢀ
ꢀ
3.83 (1H, dt, J3 ,4 ≈ J4 ,4 -OH 5.0 and J4 ,5 8.5, H4ꢀ), 3.67 (1H,
3
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ddd, J5 ,6 a 2.5, J6 ,6 -OH 6.0, and J6 a,6 b 11.0, H6ꢀa), 3.56 (1H,
3
3
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ddd, J5 ,6 a 2.5, J5 ,6 b 6.5, and J4 ,5 8.5, H5ꢀ), 3.49 (1H, ddd,
3
3
3
ꢀ
ꢀ
ꢀ
J5 ,6 b 6.5, J6 ,6 -OH 6.0, and J6 a,6 b 11.0, H6ꢀb), 3.41 (1H, dd,
3
3
3
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J1 ,2 2.5 and 3J2 ,3 5.5, H2ꢀ), 3.34 (3H, s, OMe), 3.20–3.10 (2H, m,
ꢀ
ꢀ
2-CH2), 2.73 (1H, m, H3ꢀ). δC [62.9 MHz; (CD3)2SO] 169.6 (C2),
150.5 (C10a), 143.8 (C9a), 138.4 (ipso-Ph), 134.5 (C4), 128.1 and 127.7
(o- and m-Ph), 127.3 (p-Ph), 127.2 (C5a), 125.9 (C8), 121.1 (C7), 119.1
(C9), 112.3 (C6), 108.4 (C3), 100.9 (C1ꢀ), 76.1 (C2ꢀ), 72.3 (C5ꢀ), 70.9
(CH2Ph), 64.2 (C4ꢀ), 61.7 (C6ꢀ), 54.6 (OMe), 40.6 (C3ꢀ), 33.9 (2-CH2).
m/z (70 eV) 449 (M+•).
[24] F. C. Pigge, F. Ghasedi, Tetrahedron Lett. 2000, 41, 6545.
doi:10.1016/S0040-4039(00)01125-4
[25] B. C. Bishop, K. M. Brands, A. D. Gibb, D. J. Kennedy, Synthesis
2004, 43.
[26] T. Bieg, W. Szeja, Synthesis 1985, 76. doi:10.1055/S-1985-31113
[27] R. M. Adlington, J. E. Baldwin, D. Catterick, G. J. Pritchard,
Acknowledgments
J. Chem. Soc., Perkin Trans.
1 1999, 855. doi:10.1039/
A806741D
The authors thank the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie for financial support.