Preparation of 8-Aza-7-deazaaristeromycin and -neplanocin A and Their 5′-Homologs

Article abstract of DOI:10.1002/jhet.2137

The synthesis of new members of the aristeromycin and neplaoncin A families of carbocyclic nucleosides possessing the 1H-pyrazolo[3,4-d]pyrimidine ring is reported. For this purpose, an adapted route to 4-amino-1H-pyrazolo[3,4-d]pyrimidine is described.

Full text of DOI:10.1002/jhet.2137

Month 2014
Preparation of 8-Aza-7-deazaaristeromycin and -neplanocin A and Their
5′-Homologs
*
Haisheng Wang, Yan Zhang, Wei Ye, and Stewart W. Schneller
Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL
36849-5312, USA
*
E-mail: schnest@auburn.edu
Received July 4, 2013
DOI 10.1002/jhet.2137
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
The synthesis of new members of the aristeromycin and neplaoncin A families of carbocyclic
nucleosides possessing the 1H-pyrazolo[3,4-d]pyrimidine ring is reported. For this purpose, an adapted
route to 4-amino-1H-pyrazolo[3,4-d]pyrimidine is described.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
Thus, beginning with the conversion of commer-
cially available 4,6-dihydroxypyrimidine to 5-formyl-
4,6-dichloropyrimidine (8) followed a literature procedure
with slight modification [7]. Aminolysis of 8 with
dimethylamine afforded compound 9 [8], which was
treated with sodium hydroxide to provide the
ring-cleaved product 10 [9]. The synthesis to 7 was
completed by ring closure of 10 (to 11) followed by treat-
ment with formamide [10].
With 7 in hand, the Mitsunobu reaction with 12 [11] was
first investigated in the presence of DIAD and PPh3. How-
ever, only trace amounts of the desired coupled compound
13 were detected. Converting 12 to its triflate 14 [12] led
successfully to 13 when reacted with 7 in the presence of
sodium hydride. Oxidative cleavage of the alkenic center of
13 with osmium tetroxide/sodium periodate followed by so-
dium borohydride reduction yielded 15. Acidic deprotection
of 15 removed the isopropylidene protecting group to result
in compound 3. Regioselective hydroboration of 13 using
9-BBN, followed by oxidative hydrolysis to 16, was followed
by deprotection to smoothly provide 4 (Scheme 2).
For some time, a research focus in our laboratory has been
the synthesis and biological properties of 5′-noraristeromycin
(1) [1] and related compounds [2]. Among those studies
was an investigation into the anti-trypanosomal properties
of compounds based on 8-aza-7-deaza-5′-noraristeromycin
(2) [3]. At the time of those investigations, we did not have
available the parent carbocyclic aristeromycin analog 3
and, for comparative purposes, the corresponding
neplanocin A 5, as the 8-aza-7-deaza analog of the natu-
rally occurring neplanocin [4], and the side chain extended
5′-homo pair 4 and 6, which are related to the biologically
active 5′-homoaaristeromycin and 5′-homoneplanocin
[5,6]. With the possibility that we will return to further
work on the anti-trypanosomal properties of 8-aza-7-
deazaadenine derived carbocyclic nucleosides, a synthetic
means to 3–6 was sought (Figure 1). These results are
described here.
RESULTS AND DISCUSSION
The neplanocin A analogs 5 and 6 were synthesized by
converting cyclopentenols 17 [13] and 18 [5] to their
mesylates 19 and 20. These latter products were reacted
with 7 in the presence of sodium hydride to afford 21
and 22. The targets 5 and 6 were achieved from 21 and
22 by deprotection using 1N HCl in methanol (Scheme 3).
We first sought a cost-effective route to the requisite
1H-pyrazolo[3,4-d]-pyrimidine (7-deaza-8-azaadenine, 7) for
the subsequent coupling reactions with cyclopentyl and
cyclopentenyl co-reactants. For this purpose, adaptation/
combination of existing procedures was undertaken (Scheme 1).
© 2014 HeteroCorporation

H. Wang, Y. Zhang, W. Ye, and S. W. Schneller
Vol 000
Figure 1. Adenine-based carbocyclic nucleosides
Scheme 1. Synthesis of 1H-pyrazolo[3,4-d]pyrimidine (7). Reagents and
conditions: (a) POCl3, DMF, 63%; (b) HOAc, (CH3)2NH (aq.), 90%; (c)
NaOH, H2O, product was used directly in step d; (d) NH2NH2, EtOH,
55% from 8; (e) formamidine acetate, EtOH, 75%.
series of carbocyclic 8-aza-7-deazaadenine derivatives 3–6
based on aristeromycin and neplanocin A has been synthe-
sized via the SN2-displacement between deprotonated
8-aza-7-deazaadenine and
a
corresponding protected
cyclopentanol/cyclopentenol triflate or mesylate in the
presence of sodium hydride.
EXPERIMENTAL
Materials and methods. All melting points were recorded
on
a Meltemp II melting point apparatus (Barnstead/
Thermolene, Dubuque, IA) and are uncorrected. The 1H and
13C NMR spectra were recorded on Bruker AC 250 (Bruker,
Billerica, MA) spectrometer (operated at 250 and 62.9 MHz,
respectively) or Bruker AV 400 (Bruker, Billerica, MA)
spectrometer (operated at 400 and 100 MHz, respectively) and
referenced to internal TMS at 0.0 ppm. The reactions were
monitored by TLC using 0.25 mm Whatman Diamond silica gel
CONCLUSIONS
By adapting existing conditions for the preparation of
1H-pyrazolo[3,4-d]-pyrimidine (7-deaza-8-azaadenine, 7), a
Scheme 2. Synthesis of compounds 3 and 4. Reagents and conditions: (a) NaH, DMF then add 14, 0°C to room temperature, 88%; (b) for 15: (i) NaIO4,
MeOH/H2O, 0°C, OsO4 added; (ii) NaBH4, 48% from 13; (c) for 16: (i) 9-BBN, THF, 0°C; (ii) NaOH, H2O2, 80% from 13; (d) 1N HCl, MeOH, 95% for
both 3 and 4.
Scheme 3. Synthesis of compounds 5 and 6. Reagents and conditions: For 5 (a) MsCl, Et3N, CH2Cl2, 0°C, 83%; (b) 7, NaH, DMF, 0°C to room
temperature, 88%; (c) 1N HCl, MeOH, 95%. For 6, overall yield after steps a (using 18), b, and c is 31%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Preparation of 8-Aza-7-deazaaristeromycin and -neplanocin A and Their 5′-Homologs
60-F254 precoated plates (Whatman, Florham Park, NJ) with
visualization by irradiation with a Mineralight UVGL-25 lamp
(UVP, Upland, CA). Column chromatography was performed
on Whatman silica, 230–400 mesh, 60 Å, and elution was
carried out with the indicated solvent system. Yields refer to
chromatographically and spectroscopically (1H and 13C NMR)
homogeneous materials.
dried (Na2SO4). The solvent was removed under reduced
pressure, and the residue purified by column chromatography
(5: 1, hexanes/EtOAc) to afford 13 as a white solid (0.26 g, 88%).
1H NMR (250 MHz, CDCl3) δ 8.34 (s, 1H), 7.99 (s, 1H), 6.82
(brs, 2H), 5.88–5.97 (m, 1H), 5.28–5.33 (m, 1H), 5.16 (td, 1H,
J = 1.2Hz, J = 13.2 Hz), 5.10–5.12 (m, 2H), 4.57 (t, 1H,
J = 6.8Hz), 2.80–2.85 (m, 1H), 2.38–2.44 (m, 1H), 2.32–2.35
(m, 1H), 1.56 (s, 3H), 1.31 (s, 3H); 13C NMR (62.5 MHz, CDCl3)
δ 158.1, 155.8, 153.5, 138.0, 131.7, 115.6, 113.7, 100.9, 84.0,
83.8, 61.5, 48.2, 31.5, 27.4, 25.0. HRMS Calcd. for C15H20N5O2
[M+ H]+: 302.1617; Found: 302.1605.
1H-Pyrazolo[3,4-d]pyrimidin-4-amine (8-aza-7-deazaadenine, 7)
[10].
To a solution of POCl3 (50 mL) in anhydrous DMF
(16 mL) at 0°C under N2, 4,6-dihydroxypyrimidine (12.5 g,
112 mmol) was added portionwise, and the reaction mixture was
stirred at same temperature for 30 min. Then, the heterogeneous
mixture was refluxed for 5 h. The volatiles were removed under
reduced pressure, the residue was poured onto ice, and the mixture
neutralized by adding solid NaHCO3 followed by extraction with
diethyl ether. The organic phase was dried over Na2SO4 and
concentrated, and the residue of 4,6-dichloropyrimidine-5-
carbaldehyde (8) [7] (12.4 g, 63%) was found sufficiently pure by
mp 68–70°C (lit. [7] mp 69–70°C) for use in the next step. 1H
NMR (250 MHz, CDCl3) δ 10.49 (s, 1H), 8.93 (s, 1H); 13C NMR
(62.9 MHz, CDCl3) δ 185.65, 162.73, 159.60, 124.89.
To a stirred solution of 8 (17.7 g, 100mmol) in dioxane (200 mL)
was added HOAc (5.7 mL, 100mmol) at 0°C. To this mixture,
dimethylamine (40% aq., 11.4mL, 100mmol) was added,
dropwise. Stirring was continued at room temperature for 5 h. The
reaction mixture was concentrated under reduced pressure, and the
residue purified by recrystallization from EtOH to give 4-chloro-
6-(dimethylamino)pyrimidine-5-carbaldehyde (9) [8] (16.7 g,
90%) that was used directly in the next step. 1H NMR (250 MHz,
CDCl3) δ 10.37 (s, 1H), 8.35 (s, 1H), 3.11 (s, 6H).
To a solution of 9 (7.5g, 51mol) in H2O (5mL) was added 2N
NaOH (10 mL), together with dioxane (1–2 mL) to aid partial
dissolution. The mixture was stirred for 24h at room temperature
and then extracted with CH2Cl2 (100 mL). The extracts were com-
bined, dried (Na2SO4), and evaporated to dryness in vacuo. The
residue of (Z)-3-amino-3-(dimethylamino)-2-formylacrylonitrile
(10) [9] was used in the next step without purification.
To a solution of crude 10 (1.76g, 13mmol) in EtOH (30 mL)
was added hydrazine hydrate (0.61 mL, 14mmol), and the resultant
mixture refluxed for 12 h. The mixture was concentrated in vacuo,
and the residue purified by recrystallization from H2O to give
2-amino-1H-pyrazole-3-carbonitrile (11) [9] as pale yellow solid
(0.77 g, 55% from 8), mp 171–173°C (lit. [9] mp 173–174°C). 1H
NMR (250 MHz, CDCl3) δ 8.24 (s, 1H), 5.32 (s, 1H).
((3aR,4R,6R,6aS)-6-(4-Amino-1H-pyrazolo[3,4-d]pyrimidin-
1-yl)-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-
4-yl)methanol (15).
To a mixture of 13 (4.3 g, 14.3 mmol)
dissolved in MeOH (35mL) and H2O (18 mL) was added
NaIO4 (4.33g, 20.2 mmol). After cooling the mixture to 0°C,
OsO4 (30 mg) was added. This new reaction mixture was stirred
at the same temperature for 1 h and then at room temperature for
2 h. The resultant white solid was removed by filtration, and the
filtrate removed in vacuo at ambient temperature. Methylene
chloride (200 mL) was added to the residue, and the resultant
organic solution washed with H2O (30 mL) and brine (30 mL) and
dried (Na2SO4). The CH2Cl2 was removed under reduced
pressure at ambient temperature, and the residue dissolved in
MeOH (40mL). This new solution was cooled to 0°C, and
NaBH4 (1.2g, 30.8 mmol) added portionwise. After the reaction
was stirred at 0°C for 1 h, the solvent was removed, and CH2Cl2
(150 mL) and H2O (30 mL) were added. The organic layer was
separated and washed with brine and dried (Na2SO4). After
removing the solvent under reduced pressure, the product was
purified by chromatography with a short silica gel column (2: 1
hexanes/EtOAc to only EtOAc) to give 15 (2.09 g, 48% from 13)
1
as a white solid: H NMR (250MHz, CDCl3) δ 8.37 (s,1H), 7.92
(s,1H), 6.00(s, 2H), 5.29–5.33 (m, 1H), 4.99 (dd, 1H, J = 4.4 Hz,
J = 6.4Hz), 4.70 (dd, 1H, J = 3.6 Hz, J = 6.0 Hz), 3.80 (s, 2H),
2.59–2.62 (m, 1H), 2.52 (s, br, 1H), 1.59 (s, 3H), 1.32 (s, 3H);
13C NMR (62.5MHz, CDCl3) δ 157.8, 156.2, 153.6, 131.1,
112.9, 101.0, 85.5, 82.9, 64.4, 63.4, 46.5, 33.5, 27.6, 25.2. HRMS
Calcd. for C14H20N5O3 [M + H]+: 306.1566; Found: 306.1576.
(1R,2S,3R,5R)-3-(4-Amino-1H-pyrazolo[3,4-d]pyrimidin-1-
yl)-5-(hydroxymethyl)-cyclopentane-1,2-diol (3). A solution
of 15 (400mg, 1.31 mmol) dissolved in a mixture of 1N HCl
(10 mL) and MeOH (10mL) was stirred at room temperature for
3 h and then neutralized with basic ion-exchange resin (Amberlite
IRA-67). Filtration of this mixture and followed by evaporation of
this filtrate under reduced pressure afforded 3 as a white solid
(330 mg, 95%); 1H NMR (400 MHz, MeOD) δ 8.09 (s, 1H), 7.93
(s, 1H), 3.73–3.79 (m, 1H), 3.62 (dd, 1H, J = 4.4, 6.4 Hz), 3.80
(s, 2H), 3.30–3.32 (m, 2H), 2.18–2.22 (m, 1H), 1.70–1.71
(m, 1H); 13C NMR (100 MHz, MeOD) δ 157.4, 154.4, 153.8,
133.2, 101.3, 74.4, 72.8, 65.1, 64.2, 45.6, 26.2. HRMS Calcd. For
C11H16N5O3 [M+ H]+: 266.1253; Found: 266.1270.
To a solution of 11 (1.6 g, 15 mmol) in EtOH (20 mL) was
added formamidine acetate (3.0 g, 29 mmol). This mixture was
heated under reflux for 5 h, and the solvent then removed in
vacuum. The resulting residue was purified by recrystallization
from H2O to give 7 (1.5 g, 75%) as a pale solid, mp >300°C
1
(lit. [10] mp 353–356°C). H NMR (250 MHz, CDCl3) δ 13.34
(s, 1H), 8.15 (s, 1H), 8.08 (s, 1H), 7.59 (s, br, 2H).
1-((3aS,4R,6R,6aR)-2,2-Dimethyl-6-vinyltetrahydro-3aH-
cyclopenta[d][1,3]dioxol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-
4-amine (13). To a stirred solution of 7 (0.14 g, 1.0 mmol) in
DMF (5mL), sodium hydride (40 mg, 60% in mineral oil,
1.1 mmol ) was added at 0°C. This mixture was stirred for 30min
at 0°C before a solution of 14 [12] (0.32 g, 1.0 mmol) in CH2Cl2
was added dropwise. After stirring the reaction at room
temperature for 16h, saturated NH4Cl (10 mL) was added, and the
resultant mixture stirred for 10min. To this was added CH2Cl2
(50 mL), and the organic layer separated, washed with H2O, and
2-((3aR,4R,6R,6aS)-6-(4-Amino-1H-pyrazolo[3,4-d]pyrimidin-
1-yl)-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)
ethanol (16).
To a solution of 13 (1.0 g, 3.13 mmol) in THF
(20 mL) at 0°C under N2 was added 9-BBN (0.5M in THF,
10.0mL, 5.00 mmol), and the resultant mixture stirred at this
temperature for 3 h. To this, NaOH solution (1M, 6 mL) was
added, followed by H2O2 (50% in H2O, 3 mL), and the stirring
continued for an additional 30min. The reaction mixture was
diluted with CH2Cl2 (100 mL), and the CH2Cl2 solution washed
with saturated NaHCO3 solution (30mL). The organic layer was
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DOI 10.1002/jhet

H. Wang, Y. Zhang, W. Ye, and S. W. Schneller
Vol 000
dried (MgSO4) and filtered, and the filtrate concentrated in vacuo to
give the crude product as a colorless oil, which was purified by flash
column chromatography (EtOAc/hexanes, 4 : 1) to afford 16 as a
(1S,2R,5R)-5-(4-Amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-
3-(hydroxymethyl)-cyclopent-3-ene-1,2-diol (5). Compound
21 (400mg, 1.31 mmol) was dissolved in a mixture of 1N HCl
(10 mL) and MeOH (10 mL). This reaction mixture was stirred at
room temperature for 3 h and then neutralized with basic ion-
exchange resin (Amberlite IRA-67). Filtration and evaporation of
the filtrate under reduced pressure afforded 5 as a pale solid
1
white solid (0.84 g, 80%), mp 190–191°C. H NMR (400 MHz,
CDCl3) δ 8.39 (s, 1H), 7.93 (s, 1H), 5.51 (s, br, 2H), 5.29–5.30
(m, 1H), 5.04–5.07 (m, 1H), 4.51 (t, 1H, J = 6.8 Hz), 3.75–3.79
(m, 2H), 2.42–2.48 (m, 1H), 2.17–2.22 (m, 2H), 1.74–1.82 (m,
3H), 1.57 (s, 3H), 1.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
154.7, 156.0, 153.8, 130.7, 112.6, 100.8, 84.5, 84.3, 61.8, 61.5,
42.5, 37.7, 35.9, 27.5, 25.3. HRMS Calcd. for C15H22N5O3
[M+ H]+: 320.1723; Found: 320.1711.
Synthesis of (1R,2S,3R,5R)-3-(4-amino-1H-pyrazolo[3,4-d]
pyrimidin-1-yl)-5-(2-hydroxyethyl)-cyclopentane-1,2-diol(4).
Compound 16 (400 mg, 1.31 mmol) was dissolved in a mixture of 1N
HCl (10 mL) and MeOH (10 mL). This reaction mixture was stirred
at room temperature for 3 h and then neutralized with basic
ion-exchange resin (Amberlite IRA-67). Filtration and evaporation
of the filtrate in vacuo afforded 4 as a white solid (330 mg, 95%).
1H NMR (400 MHz, MeOD) δ 8.17 (s, 1H), 8.09 (s, 1H), 5.08
(dd, 1H, J=6.0Hz, J= 8.8 Hz), 4.34 (t, 1H, J= 6.0 Hz), 3.91 (t, 1H,
J= 6.0 Hz), 3.63–3.67 (m, 2H), 2.38–2.41 (m, 1H), 2.15–2.20
(m, 2H), 1.88–1.94 (m, 1H), 1.71–1.75 (m, 2H); 13C NMR
(100 MHz, MeOD) δ 157.4, 153.6, 151.4, 130.5, 101.2, 74.5, 74.2,
60.2, 58.8, 45.4, 38.5, 35.2. HRMS Calcd. for C12H18N5O3
[M + H]+: 280.1410; Found: 280.1407.
1
(330 mg, 95%). H NMR (400 MHz, MeOD) δ 8.25 (s, 1H), 8.01
(s, 1H), 5.56–5.59 (m, 1H), 4.54–4.56 (m, 1H), 4.19–4.23
(m, 2H), 4.09–4.11 (m, 1H), 3.72 (s, br, 1H); 13C NMR
(100 MHz, MeOD) δ 157.4, 154.5, 153.7, 146.7, 132.9, 121.7,
101.3, 78.8, 72.8, 69.6, 65.6. HRMS Calcd. for C11H14N5O3
[M+ H]+: 264.1097; Found: 264.1099.
(5R)-5-(4-Amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-(2-
hydroxyethyl)cyclopent-3-ene-1,2-diol (6).
Following a
procedure similar to that for preparing 5, 6 was prepared from 18
[5] as a white solid (31% in three steps): 1H NMR (MeOD,
400 MHz) δ 8.27 (s, 1H), 7.98 (s, 1H), 5.38–5.36 (m, 1H), 4.50–
4.56 (m, 1H), 4.07 (dd, 1H, J = 3.6 Hz, J = 6.0 Hz), 3.39–3.55
(m, 3H), 2.15–2.13 (m, 2H); 13C NMR (MeOD, 100 MHz)
δ 157.4, 154.7, 153.8, 144.9, 132.9, 121.0, 101.0, 82.8, 72.8,
69.6, 60.9, 29.8. HRMS Calcd. for C12H16N5O3 [M+ H]+:
278.1253; Found: 278.1247.
1-((3aS,4R,6aR)-6-(Trityloxymethyl)-2,2-dimethyl-4,6a-dihydro-
3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-
amine (21). To a stirred solution of 17 [13] (1.07 g, 2.5 mmol) in
CH2Cl2 (20 mL) and Et3N (15 mL) at 0°C was added, dropwise,
MsCl (428 mg, 3.75 mmol) in CH2Cl2 (5 mL). This mixture was
kept at 0°C for 30 min, and to this was added cold H2O (10mL).
The organic layer was washed with brine, dried (Na2SO4),
and evaporated under reduced pressure. The residue was purified
by column chromatography (EtOAc/hexanes, 4 : 1) to afford
(3aR,4S,6aR)-6-(trityloxymethyl)-2,2-dimethyl-4,6a-dihydro-3aH-
cyclopenta[d][1,3]dioxol-4-yl methanesulfonate (19) (1.05g, 83%)
as a white solid. This solid was used in the next step directly.
To a stirred solution of 7 (0.14 g, 1.0 mmol) in DMF (5 mL) at 0°C
was added sodium hydride (40 mg, 60% in mineral oil, 1.1 mmol).
This mixture was stirred for 30 min at 0°C before a solution of 19
(0.51 g, 1.0 mmol) in CH2Cl2 was added, dropwise. After stirring
the reaction mixture at room temperature for 16 h, saturated NH4Cl
(10 mL) was added, and the stirring continued for 10 min. To this
was added CH2Cl2 (50 mL), and the resultant organic layer separated,
washed with H2O, and dried (Na2SO4). Evaporation of the organic
solvent under reduced pressure yielded a residue that was purified
by column chromatography (EtOAc/hexanes, 4 : 1) to afford 21 as a
white solid (0.48 g, 88%). 1H NMR (400 MHz, CDCl3) δ 8.43
(s, 1H), 7.92 (s, 1H), 7.40–7.47 (m, 5H), 7.19–7.30 (m, 10H), 6.05
(d, J= 9.0 Hz, 2H), 5.68 (s, br, 2H), 5.33 (d, 1H), 4.87 (d, 1H,
J= 6.0 Hz), 3.97 (d, 1H, J= 15.0 Hz), 3.78 (d, 1H, J= 15.0 Hz),
1.45 (s, 3H), 1.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.4,
156.0, 153.6, 148.1, 143.9, 131.0, 128.6, 127.9, 127.1, 123.6,
112.3, 100.9, 87.1, 84.6, 84.2, 66.8, 61.6, 27.6, 26.3. HRMS Calcd.
for C33H32N5O3 [M + H]+: 546.2505; Found: 546.2508.
Acknowledgments. The support from the Molette Fund and
Auburn University is appreciated.
REFERENCES AND NOTES
[1] Siddiqi, S. M.; Chen, X.; Schneller, S. W.; Ikeda, S.; Snoeck, R.;
Andrei, G.; Balzarini, J.; De Clercq, E. J Med Chem 1994, 37, 551.
[2] For example, Roy, A.; Serbessa, T.; Schneller, S. W. Bioorg
Med Chem 2006, 14, 4980.
[3] Seley, K. L.; Schneller, S. W.; Rattendi, D.; Lane, S.; Bacchi,
C. J. J Med Chem 1997, 40, 625.
[4] Tosh, D. K.; Kim, H. O.; Pal, S.; Jeong, A.; Jeong, L. S.
Syntheses and biological activity of neplanocin and analogs. In Modified
Nucleosides, Herdewijn, P., Ed.; Wiley-VCH Verlag GmbH and Co.
KGaA: Weinheim, 2009, pp. 525.
[5] Yang, M.; Schneller, S. W.; Korba, B. J Med Chem 2005,
48, 5043.
[6] Yang, M.; Schneller, S. W. Bioorg Med Chem Lett 2005, 15, 149.
[7] Gomtsyan, A.; Didomenico, S.; Lee, C.-H.; Matulenko, M. A.;
Kim, K.; Kowaluk, E. A.; Wismer, C. T.; Mikusa, J.; Yu, H.; Kohlhaas, K.;
Jarvis, M. F.; Bhagwat, S. S. J Med Chem 2002, 45, 3639.
[8] Ryabova, O. B.; Evstratova, M. I.; Makarov, V. A.; Tafeenko,
V. A.; Granik, V. G. Chem Heterocycl Compd 2004, 40, 1352.
[9] Clark, J.; Parvizi, B.; Colman, R. J Chem Soc Perkin Trans 1,
1976, 1004.
[10] Zhang, H.-C.; Brakta, M.; Davies, G. D., Jr. Nucleosides
Nucleotides 1995, 14, 105.
[11] Yang, M.; Ye, W.; Schneller, S. W. J Org Chem 2004, 69, 3993.
[12] Zhang, Y.; Ye, W.; Wang, H.; Schneller, S. W. Synthesis
2012, 723.
[13] Cho, J. H.; Bernard, D. L.; Sidwell, R. W.; Kern, E. R.; Chu,
C. K. J Med Chem 2006, 49, 1140.
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