Synthesis and biological evaluation of 6-substituted purine and 9-β-D-ribofuranosyl purine analogues

Article abstract of DOI:10.1016/j.bmc.2004.01.005

6-Substituted purine and 9-β-D-ribofuranosyl purine analogues were synthesized and their biological activities were evaluated. CD Spectra and thermal melting studies showed that compounds 8, 9, 10 could interact with RNA and DNA in solution. Compound 8 and 10 may bind with RNA single strand and interfere the formation of RNA duplex. Among of these compounds, compound 8 showed middle inhibition on the growth of HeLa cells (70.21%) and HL-60 cells (70.85%) at 10 μM. Comparing to the structures of these synthetic compounds, it may indicate that the sugar moiety and the 6-amino side chain of nucleoside 8 play an important role in the biological activities.

Full text of DOI:10.1016/j.bmc.2004.01.005

Bioorganic & Medicinal Chemistry 12 (2004) 1425–1429
Synthesis and biological evaluation of 6-substituted purine and
9-ꢀ-D-ribofuranosyl purine analogues
Jun-Feng Wang, Liang-Ren Zhang, Zhen-Jun Yang and Li-He Zhang*
National Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China
Received 17 October 2003;accepted 5 January 2004
Abstract—6-Substituted purine and 9-b-d-ribofuranosyl purine analogues were synthesized and their biological activities were
evaluated. CD Spectra and thermal melting studies showed that compounds 8, 9, 10 could interact with RNA and DNA in solution.
Compound 8 and 10 may bind with RNA single strand and interfere the formation of RNA duplex. Among of these compounds,
compound 8 showed middle inhibition on the growth of HeLa cells (70.21%) and HL-60 cells (70.85%) at 10 mM. Comparing to the
structures of these synthetic compounds, it may indicate that the sugar moiety and the 6-amino side chain of nucleoside 8 play an
important role in the biological activities.
# 2004 Elsevier Ltd. All rights reserved.
1. Introduction
the modified nucleosides could be used as a site-direct-
ing moiety towards RNA. Some aminoglycosyl-nucleo-
sides and peptide-conjugated nucleosides have been
synthesized in our laboratory and showed the high affi-
nity of interaction with RNA.7ꢀ9 In our previous works,
all of the modifications focus on the sugar moiety of
nucleosides. Here, we reported the synthesis and biolo-
gical evaluation of 6-substituted purine and 9-b-d-ribo-
furanosyl purine analogues. CD Spectra and thermal
melting studies showed that compounds 8, 9, 10 could
interact with RNA and DNA in solution. Among of
these compounds, 6-(20-aminoethyl)-9-b-d-ribofur-
anosyl purine 8 showed the interesting growth inhibi-
tion to HeLa cells and HL-60 cells in vitro.
Aminoglycoside antibiotics have long been used as very
efficient drugs against Gram-positive and Gram-nega-
tive bacteria, and against mycobacterial infections.
These molecules are multiply charged compounds of
high flexibility. The positive charges are attracted to the
negatively charged RNA backbone. The flexibility of
the aminoglycosides facilitates accommodation into a
binding pocket within internal loops of RNA helices or
into ribozyme cores for making specific contacts. On the
basis of the study of RNA in the presence of aminogly-
cosides and other small molecules, the interactions of
RNA with small molecules are affected by the distribu-
tion of charged, aromatic, and H-bonding groups of a
relatively rigid scaffold.1ꢀ5 Furthermore, the structure of
RNA is dynamic, and the conformational change can be
induced by a small molecule. Nucleoside analogues play
an important role in the antiviral and anticancer
chemotherapy. Most of these nucleosides act as inhibi-
tors of varied enzymes by disrupting the synthesis of
nucleic acids.6 It would be interesting to study whether
2. Results and discussion
6-(20-Aminoethyl)-9H-purine 3 and 6-(20-butylamino-
ethyl)-9H-purine 4b were synthesized starting from
6-chloropurine.10 For the substitution at 6- position,
6-chloropurine was protected by benzyl group first, but
the reaction gave a mixture of N-7 and N-9 benzyl pro-
tected 6-chloropurine. After the further reaction, the N-
benzyl group was very difficult to remove. However, the
6-chloropurine was selectively protected by DHP, the N-9
protected 6-chloropurine was in 89% yield and the
tetrahydropyran-2-yl group can be deprotected smoothly
after reaction. Therefore, the protected 6-chloropurine 1
was vinylated via a Pd (II)-catalyzed Stille-coupling
Abbreviations: CD, circular dichroism spectrum;DNA, deoxyr-
ibonucleic acid;RNA, ribonucleic acid;DHP, 3,4-dihydro-2H-pyran;
HMPT, hexamethylphosphorous triamide;DMF, dimethylforma-
mide;NMR, nuclear magnetic resonance;DMSO, dimethyl sulfoxide;
CSA, D(+)-10-Camphorsulfonic acid;EDTA, ethylenediaminete-
traacetic acid.
* Corresponding author. E-mail: zdszlh@bjmu.edu.cn
0968-0896/$ - see front matter # 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2004.01.005

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J.-F. Wang et al. / Bioorg. Med. Chem. 12 (2004) 1425–1429
Scheme 1. Regents and conditions: (i) (PhP3)2PdCl2, tributylvinyltin,
DCE, reflux;(ii) NH 3/CH3OH or n-butylamine/DCM, rt;(iii) DCM/
CH3OH, 1M HCl, rt.
reaction and 6-vinyl-9-(tetrahydropyran-2-yl)-purine 2
was obtained in 84% yield.11 Nucleophilic addition to
the terminal olefin of 6-vinyl purine 2 with ammonia or
n-butylamine and followed deprotection gave 3 (78%)
and 4b (70%) respectively (Scheme 1). For the synthesis
of 6-substituted 9-b-d-ribofuranosyl purine analogues,
inosine was reacted with Ac2O in pyridine, then 20,30,50-
tri-O-acetyl-inosine 5 was treated with CCl4, HMPT in
CH3CN at reflux and 6-chloro-9-(20,30,50-tri-O-acetyl-b-
d-ribofuranosyl)-purine 6 was obtained in 60% yields.12
Similar reaction as described in the synthesis of com-
pound 2, 6-vinyl 9-(20,30,50-tri-O-acetyl-b-d-ribofur-
anosyl)-purine 7 was obtained from compound 6 in 85%
yield by treatment with (Ph3P)3PdCl2, tributylvinyltin in
DMF at 100 ꢁC.13 Nucleophilic addition to 6-vinylpur-
ine nucleoside 7 with ammonia or aniline or sodium
methoxide in methanol and then deprotection gave
6-(20-aminoethyl)-9-b-d-ribofuranosylpurine 8 (79%),
6-(20-anilinoethyl)-9-b-d-ribofuranosyl purine 9 (66%)
and 6-(20-methoxyethyl)-9-b-d-ribofuranosylpurine 10
(54%) respectively.14 (Scheme 2).
Figure 1. (a) and (b). Thermal melting curves of dA14/dT14 (a) and
polyA/polyU (b) in the absence or presence of synthetic 6-Substituted
9-b-D-ribofuranosyl purine analogues.
It has been demonstrated that the total number of
amino groups and aromatic substitutions in the ami-
noglycoside are correlated with the activities of RNA
binding and modify gene expression.15,16 In order to
explore the biological properties of compounds 8, 9, 10,
the interaction of 6-modified nucleoside analogues with
dA14/dT14 duplex and polyA/polyU duplex were studied
by thermal denaturation and CD spectra (Figs 1 and 2).
The stability of RNA (DNA) duplex was affected by
the integrated effects of hydrogen bonding, stacking
and electrostatic interactions between RNA (DNA) and
small molecule.17ꢀ20 It was found that compounds 8, 9,
10 effected significantly the stabilities of duplex both of
DNA and RNA. Melting curves showed that com-
pounds 8, 9, 10 resulted in an increase of melting temp-
erature of DNA duplex with an extent of 2.5 to 6.0 ꢁC, it
indicated that the binding of those compounds could
enhance the duplex stabilities (Fig. 1a, Table 1). The
decreases of hyperchromicity were also observed in all
cases. CD Spectra showed that the 6-substituted 9-b-d-
ribofuranosyl purine analogues did not make obvious
effect to the configuration of DNA duplex (Fig. 2a).
Melting curves showed that compound 9 resulted in no
change of melting temperature of RNA (Table 1). By
contrast with the results in the case of DNA, no obvious
melting behavior of RNA duplexes was observed in the
presence of compounds 8 and 10 (Fig. 1b). It implied
that the stable complex of RNA single strand with
compound 8 or 10 was formed in this condition, which
hindered the formation of stable RNA duplex. How-
ever, the melting curve and temperature of RNA in the
presence of compound 9 showed the existence of duplex
Scheme 2. Regents and conditions: (i) CCl4, HMPT, ACN, 70 ꢁC;(ii) (Ph 3P)2PdCl2, tributylvinyltin, DMF, 100 ꢁC;(iii) for compd 8, NH3/CH3OH,
rt;(iv) for compd 9, a. CSA, Aniline, DCM, rt;b. NaOCH 3/CH3OH, rt;(v) for compd 10, CSA, NaOCH3/CH3OH, rt.

J.-F. Wang et al. / Bioorg. Med. Chem. 12 (2004) 1425–1429
1427
Table 2. Inhibition on the growth of various tumor cells by com-
pound 8
Tumor cell line
HeLa(SRB)
conc (mM)
Inhibition rate
1
2
3
4
1
10
100
1
10
100
1
10
100
1
10
100
–8.76%
70.21%
83.49%
–6.91%
70.85%
79.62%
–8.94%
0.64%
HL-60 (MTT)
BGC-823 (SRB)
Bel-7420 (SRB)
35.49%
–23.79%
7.29%
59.76%
enhance the duplex stability of DNA, but compounds 8
and 10 may bind with RNA single strand and interfere
the formation of RNA duplex. Among of these com-
pounds, compound 8 showed the middle inhibition on
the growth of HeLa cells (70.21%) and HL-60 cellc
(70.85%) at 10 mM. Comparing to the structures of
these synthetic compounds, it may indicate that the
sugar moiety and the 6-amino side chain of nucleoside 8
play an important role in the biological activities.
Figure 2. (a) and (b). CD spectra of dA14/dT14 (a) and polyA/polyU
(b) in the absence or presence of synthetic 6-substituted 9-b-d-ribo-
furanosyl purine analogues.
3. Experimental
Thin-layer chromatography was performed by using
silica gel GF-254 (Qing Dao Chemical Company,
China) plates with detection by UV. NMR spectra were
recorded on Varian-300 or Varian INOVA-500 instru-
ment with TMS as an internal standard. The structural
positions of the synthetic compounds are numbered as
described in Notes.24 PE SCLEX QSTAR and Auto-
spec-Ultima ETOF spectrometers were used for mass
spectra. Melting points were determined on an XT-
4Amelting point apparatus and are uncorrected.
(Fig. 1b, Table 1). The anilino group in compound 9
may contribute the aromatic interaction with RNA
duplex. CD Spectra showed the significant changes of
intensity in all of these compounds (Fig. 2b), the rear-
rangement in the configuration of RNA duplex may
occur in the presence of compounds 8, 9, 10.21 The
synthetic compounds 3, 4b, 8, 9, 10 were screened by
culture of tumor cells (Table 2),22,23 only compound 8
exhibited inhibition effects on the growth of HeLa cells
(70.21%) and HL-60 cells (70.85%) at 10 mM. Com-
paring to the structures of compounds 3, 8 and 10, it
may indicate that the sugar moiety and the 6-amino side
chain of nucleoside 8 play an important role in the bio-
logical activity.
3.1. 6-(20-Aminoethyl)-9H-purine (3)
Compound 2 (373 mg, 1.6 mmol) was dissolved in 50
mL of saturated NH3/CH3OH solution and stirred at
room temperature for 21 h. The solvent was evaporated
and CH2Cl2/CH3OH (3 mL:30 mL) was added to the
residue. 1M HCl was added to the resulting solution
and stirring was continued overnight. A solution of 2N
NaOH/H2O was added to adjust the solution to
PH=12 and the solvent was evaporated to dryness. The
residue was dissolved with MeOH and the undissolved
salt was filtered. The filtrate was evaporated and
In summary, 6-substituted purine and 9-b-d-ribofur-
anosyl purine derivatives were synthesized and the
interaction of 6-substituted 9-b-d-ribofuranosyl purine
derivatives with polyA/polyU duplex and dA14/dT14
duplex were studied by thermal denaturation and CD
spectra. It was found that compounds 8, 9, 10 could
Table 1. Melting temperatures of polyA/polyU duplex and dA14/dT14 duplex in the absence or presence of synthetic 6-substituted 9-b-d-ribofur-
anosyl purine analogues
PolyA/polyU/compd
Tm (ꢁC)
ÁTm (xꢁC)
dA14/dT14/compd
Tm (ꢁC)
ÁTm (xꢁC)
PolyA/polyU
60.97
—
60.97
—
dA14/dT14
dA14/dT14/8
dA14/dT14/9
dA14/dT14/10
35.00
40.99
37.51
41.01
PolyA/polyU/8
PolyA/polyU/9
PolyA/polyU/10
—
0
—
5.99
2.51
6.01

1428
J.-F. Wang et al. / Bioorg. Med. Chem. 12 (2004) 1425–1429
separated with silica gel column. 215 mg (78%) of 3 was
obtained as a white solid. Mp 240 ꢁC (dec). HRMS
151.08 (C4), 151.98 (C2), 152.70 (C6), 169.31 (CO),
169.51 (CO), 170.18 (CO).
(TOF) calcd for C7H10N5 (MH+): 164.0930;found:
1
0
164.0932. H NMR(DMSO) d: 3.36 (t, 1H, H2 ), 3.46 (t,
3.4. 6-(20-Aminoethyl)-9-ꢀ-D-ribofuranosyl-purine (8)
0
0
0
1H, J1 ,2 =7.5 Hz, H1 ), 8.56 (s, 1H, H2), 8.80 (s, 1H,
13
0
0
H8) ; C NMR (DMSO) d: 30.74 (C2 ), 38.35 (C1 ),
130.73 (C5), 146.55 (C8), 153.23 (C4), 154.95 (C2),
156.50 (C6).
Compound 7 (90 mg, 0.2 mmol) was dissolved in 25 mL
of saturated NH3/CH3OH solution. After stirred at
ambient temperature in a sealed vessel for 22 h, the
mixture was evaporated and purified by a silica gel col-
umn. Compound 8 (54 mg, 79%) was obtained as a
white solid. Mp 182–184 ꢁC. HRMS (TOF) calcd for
C12H18N5O4 (MH+): 296.1353;found: 296.1368. 1H
3.2. 6-(20 -Butylaminoethyl)-9-(tetrahydro-pyran-2-yl)-
purine (4a)
0
0
Compound 2 (707 mg, 3.1 mmol) was dissolved in 30
mL of dry CH2Cl2, and n-butylamine (3.04 mL, 30.8
mmol) was added under stirring. After stirring at ambi-
ent temperature for 25 h, the solution was evaporated
and the residue was separated with a silica gel column.
Compound 4a (830 mg, 89%) was collected as a light
NMR (CDCl3) d: 3.51 (br, 4H, H1 ,2 ), 3.51 (br,
00
2H, –NH2), 3.76 (dd, 1H, H5 ), 3.90 (dd, 1H, H5 ), 4.18
00
(d, 1H, J4 , 5 =2.5 Hz, H4 ), 4.33 (dd, 1H, J3 , 4 =2.5
00
00
00
00
00
00
Hz, H3 ), 4.75 (t, 1H, J2 , 3 =5.0 Hz, H2 ), 5.96 (d, 1H,
00
00
00
00
00
J1 , 2 =6.5 Hz, H1 ), 8.19 (s, 1H, H2), 8.20 (s, 1H, H8) ;
00
13
0
0
00
C NMR(CDCl3) d: 39.02 (C2 , 1 ), 63.51 (C5 ), 72.68
1
00
00
00
00
yellow oil. EI: 303. H NMR(DMSO) d: 0.94 (t, 3H,
butyl), 1.42–1.92 (m, 4H, butyl), 1.42–1.92 (m, 6H,
(C3 ), 75.22 (C2 ), 88.12 (C4 ), 91.20 (C1 ), 121.98 (C5),
140.17 (C8), 150.65 (C4), 152.65 (C2), 156.23 (C6).
0
THP), 3.11 (t, 2H, butyl), 3.59 (t, 1H, H2 ), 3.82 (t, 1H,
0
0
0
J1 ,2 =6.6 Hz, H1 ), 4.18 (d, 2H, THP), 5.79 (d, 1H,
THP), 8.39 (s, 1H, H2), 8.84 (s, 1H, H8); 13CNMR
(DMSO) d: 13.27 (butyl), 19.72, 22.39, 24.50, 28.39,
3.5. 6-(20-Anilinoethyl)-9-ꢀ-D-ribofuranosylpurine (9)
Compound 7 (295 mg, 0.75 mmol) was dissolved in 15
mL of CH2Cl2 and CSA (173 mg, 0.75 mmol), aniline
(0.12 mL, 1.21 mmol) were added to the solution under
stirring. After stirred at room temperature for 2 h, the
solution was evaporated and the residue was dissolved
in 15 mL of CH3OH. Catalytic amount of NaOCH3/
CH3OH solution (5.4 mol/L) was added and stirring
was continued at room temperature for 3 h. The mix-
ture was evaporated and separated with a silica gel col-
umn. Compound 9 (185 mg, 66%) was obtained as a
slight yellow solid. HRMS (TOF) calcd for C18H22N5O4
(MH+): 372.1666;found: 372.1666. 1H NMR(CDCl3)
0
31.37 (butyl and THP), 45.11 (butyl), 47.50 (C2 ), 49.88
0
(C1 ), 81.91 (THP), 131.78 (C5), 142.43 (C8), 149.80 (C4),
151.85 (C2), 157.44 (C6).
3.2.1. 6-(20-Butylaminoethyl)-9H-purine (4b). Compound
3 (810 mg, 2.6 mmol) was dissolved in a solution of
CH2Cl2/CH3OH (3 mL/30 mL), and 1M HCl (7 mL)
was added. After stirred at ambient temperature for 3 h,
the solution was neutralized with saturated NaHCO3/
H2O and evaporated. The residue was purified by a
silica gel column, which gave compound 4b (426 mg,
72%) as a white solid. Mp 145–147 ꢁC. HRMS (TOF)
calcd for C11H18N5 (MH+): 220.1556;found: 220.1543.
1H NMR (DMSO) d: 0.87 (t, 3H, butyl), 1.32 (m, 2H,
butyl), 1.62 (m, 2H, butyl), 2.94 (t, 2H, butyl), 3.55 (m,
1H, H2 ), 3.70 (t, 1H, J1 ,2 =7.5 Hz, H1 ), 8.45 (s, 1H,
H2), 8.77 (s, 1H, H8), 9.33 (br, 1H, Base –NH–); 13C
NMR (DMSO) d: 13.50 (butyl), 19.34, 27.44 (butyl),
41.36 (butyl), 44.06 (C2 ), 46.43 (C1 ), 131.88 (C5),
144.18 (C8), 150.68 (C4), 151.65 (C2), 156.32 (C6).
0
0
0
0
0
d: 3.38 (t, 2H, J1 ,2 =7.2 Hz, H1 ), 3.59 (t, 2H, J1 ,2 =7.2
0
Hz, H2 ), 3.72 (dd, 1H, H5 b), 3.85 (dd, 1H, H5 a), 4.11
00
00
00
(d, 1H, H4 ), 4.32 (t, 1H, J3 ,4 =3.6 Hz, H3 ), 4.67 (t,
00 00
00
00 00
00
00 00
1H, J2 ,3 =5.1 Hz, H2 ), 6.06 (d, 1H, J1 ,2 =5.4 Hz,
00
H1 ), 8.67 (s, 1H, H2), 8.77 (s, 1H, H8); 13C NMR
0
0
0
0
0
0
00
(CDCl3) d: 32.61 (C2 ), 41.44 (C1 ), 61.37 (C5 ), 70.43
00
00
00
00
(C3 ), 73.72 (C2 ), 85.79 (C4 ), 87.68 (C1 ), 112.18 (2C,
PH), 115.91 (PH), 129.03 (2C, PH), 132.98 (C5), 144.35
(C8), 148.54 (PH), 150.40 (C4), 151.91 (C2), 159.72
(C6).
0
0
3.3. 6-Vinyl-9-(200,300,500-tri-O-acetyl-ꢀ-D-ribofuranosyl)—
purine (7)
3.6. 6-(20-Methoxyethyl)-9-ꢀ-D-ribofuranosylpurine (10)
A solution of compound 6 (0.84 g, 2.1 mmol) and
(PhP3) PdCl2 (99 mg, 0.14 mmol) in 30 mL of DMF was
treated with tributylvinyltin (1.15 mL, 3.94 mmol)
under argon, and stirring was continued for 2.5 h at
100 ꢁC. The solution was evaporated and separated with
a silica gel column. Compound 7 (700 mg, 85%) was
Compound 7 (166 mg, 0.48 mmol) was dissolved in 20
mL of CH2Cl2 and CSA (100 mg, 0.42 mmol) was
added. The solution was stirred at room temperature for
10 min and a solution of NaOCH3/CH3OH (15.4 mmol/
2.8 mL) was added. After stirred at room temperature
overnight, the mixture was evaporated and purified with
a silica gel column. Compound 10 (80 mg, 54%) was
collected. HRMS (TOF) calcd for C13H19N4O5 (MH+):
311.1349;found: 311.1346. 1H NMR (CDCl3) d: 3.31 (s,
1
collected as a light yellow oil. H NMR(CDCl3) d : 2.03
(s, 3H, –OAc), 2.08 (s, 3H, –OAc), 2.11 (s, 3H, –OAc),
00
4.36–4.51 (m, 3H, H4 , H5 ), 5.61 (t, 1H, J3 , 4 =4.8 Hz,
00
00
00
00
00
00
00
00
H3 ), 5.89 (t, 1H, J2 , 3 =5.4 Hz, H2 ), 6.05 (d, 1H, J1 ,
0
0
0
3H, ꢀOCH3), 3.33 (t, 2H, J1 , 2 =6.6 Hz, H1 ), 3.89 (t,
0
0
00
00
00
2 a=10.5 Hz, H2 a), 6.23 (d, 1H, J1 , 2 =5.4 Hz, H1 ),
0 0 00 00
2H, J1 , 2 =6.6 Hz, H2 ), 3.56 (m, 1H, H5 b), 3.68 (dd,
0
0
0
0
0 00 00 00
1H, H5 a), 4.17 (d, 1H, J4 , 5 =4.2 Hz, H4 ), 4.64 (dd,
7.14 (d, 1H, J1 , 2 b=17.4 Hz, H2 b), 7.31 (dd, 1H, H1 ),
8.28 (s, 1H, H2), 8.91 (s, 1H, H8); 13CNMR(CDCl3) d:
00
62.90 (C5 ), 70.48 (C3 ), 73.10 (C2 ), 80.48 (C4 ), 86.39
0
(C1 ), 129.65 (C2 ), 130.06 (C1 ), 131.23 (C5), 143.75 (C8),
00
1H, J3 , 4 =5.7 Hz, H3 ), 5.12 (t, 1H, J2 , 3 =5.1 Hz,
00
00
00
00
00
00
00
00
00
13
00
00
H2 ), 6.01 (d, 1H, J1 , 2 =6.0 Hz, H1 ), 8.77 (s, 1H, H2),
00
0
0
8.84 (s, 1H, H8) ; C NMR (CDCl3) d: 42.30 (C1 ),

J.-F. Wang et al. / Bioorg. Med. Chem. 12 (2004) 1425–1429
1429
00
61.40 (C5 ), 57.82 (C2 ), 69.82 (–OCH3), 70.46 (C3 ),
0
00
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00
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73.70 (C2 ), 85.82 (C4 ), 87.66 (C1 ), 133.15 (C5), 144.33
(C8), 150.37 (C4), 151.81 (C2), 159.29 (C6).
3.7. Circular dichroism and thermal melting measure-
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Growth inhibition of the synthetic compounds to various
tumor cells were determined by MTT and SRB assays.22,23
4
Briefly, tumor cells (1–2.5ꢂ10 cells mLꢀ1) were inocu-
.
lated in 96-well culture plates (180 mL/well). After 24 h
culture, 20 mL of culture medium containing synthetic
compound of various concentrations were added to the
wells, and RPMI-1640 medium in control cells, then
the cells were incubated for 48 h. The growth inhibition of
HL-60 cells were determined by MTT method, and the
other cell lines were assayed by SRB method. The absor-
bance of each well was measured using a microculture
plate reader at 570 nm (MTT) and 540 nm (SRB).
21. Ke, L.;Fernandez-Saiz, M.;Rigl, C. T.;Kumar, A.;
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Acknowledgements
This work was supported by the National Natural
Science Foundation of China (20272032 and 20132030).
24. In this paper, the structural positions of 6-substituted
purine and 9-b-d-ribofuranosyl purine analogues are
numbered as follows: for the 6-substituted purine, a single
prime numbering scheme is used for the position of 6-side
chain of purine;for the 6-substituted 9- b-d-ribofuranosyl
purine, a single prime numbering scheme is used for the
position of 6-side chain of purine and a double prime
numbering scheme is used for the position of the N-9
ribosyl moiety.
References and notes
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