Cytostatic 6-arylpurine nucleosides III. Synthesis and structure-activity relationship study in cytostatic activity of 6-aryl-, 6-hetaryl-and 6-benzylpurine ribonucleosides

Article abstract of DOI:10.1135/cccc20010483

A series of fifteen 6-aryl-, 6-hetaryl-and 6-benzylpurine ribonucleosides has been prepared by Pd-catalyzed cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-purine with arylboronic acids, hetarylzinc halides, hetarylstannanes

Full text of DOI:10.1135/cccc20010483

Cytostatic 6-Arylpurine Nucleosides
483
CYTOSTATIC 6-ARYLPURINE NUCLEOSIDES III.+ SYNTHESIS AND
STRUCTURE–ACTIVITY RELATIONSHIP STUDY IN CYTOSTATIC
ACTIVITY OF 6-ARYL-, 6-HETARYL- AND 6-BENZYLPURINE
RIBONUCLEOSIDES
a3
b
Michal HOCEKa1,*, Antonín HOLÝa2, Ivan VOTRUBA and Hana DVOŘÁKOVÁ
a
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
CZ-166 10 Prague 6, Czech Republic; e-mail: hocek@uochb.cas.cz, holy@uochb.cas.cz,
1
2
3
votruba@uochb.cas.cz
b
Laboratory of NMR Spectroscopy, Institute of Chemical Technology, Prague, CZ-166 28 Prague 6,
Czech Republic; e-mail: hana.dvorakova@vscht.cz
Received Jan uary 18, 2001
Accepted March 5, 2001
A series of fifteen 6-aryl-, 6-h etaryl- an d 6-ben zylpurin e ribon ucleosides h as been prepared
by Pd-catalyzed cross-couplin g reaction s of 6-ch loro-9-(2,3,5-tri-O-acetyl-β-D-ribofuran osyl)-
purin e with arylboron ic acids, h etarylzin c h alides, h etarylstan n an es or ben zylzin c h alides
followed by deprotection . Structure–activity relation sh ip study revealed th at besides
6-(4-substituted ph en yl)purin e n ucleosides, also som e 6-h etaryl- an d 6-ben zylpurin e
ribon ucleosides possess con siderable cytostatic activity.
Keyw ord s: Purin es; Nucleosides; Cross-couplin g reaction s; An tin eoplastic agen ts; An titum or
activity; Arylboron ic acids; Stan n an es; Organ ozin c reagen ts; Suzuki reaction .
Purin es bearin g a carbon substituen t in position 6 display diverse types of
biological activity. Th e paren t com poun d of th is group, 6-m eth ylpurin e1, is
kn own for its cytotoxicity; its liberation from th e 2′-deoxyribon ucleoside
by purin e n ucleoside ph osph orylases is used for detection of m ycoplasm a
in cell cultures2. It is h igh ly poten t an d toxic to n on -proliferatin g an d pro-
liferatin g tum or cells. Recen tly, th e form ation of cytotoxic bases liberated
by purin e n ucleoside ph osph orylases such as 6-m eth ylpurin e was proposed
as a n ovel prin ciple in th e gen e th erapy of can cer3. Very little h as been
kn own about biological activity of oth er 6-C-substituted purin es un til re-
cen t n ew fin din gs of a cytokin in activity of 6-(arylalkyn yl)-, 6-(arylalken yl)-
an d 6-(arylalkyl)purin es4, a cytostatic activity of 6-(trifluorom eth yl)purin e
+ Part II of th is Series, see ref.10
Collect. Czech. Chem. Commun. (Vol. 66) (2001)
doi: 10.1135/cccc20010483

484
Hocek, Holý, Votruba, Dvořáková:
riboside5,6, a corticotropin -releasin g h orm on e an tagon ist activity of som e
2,8,9-trisubstituted 6-arylpurin es7 an d an an tim ycobacterial activity of
6-aryl-9-ben zylpurin es8.
Recen tly we h ave discovered a n ew class of cytostatic com poun ds – sub-
stituted 6-ph en ylpurin e derivatives9. Th e SAR studies revealed a crucial in -
fluen ce of th e presen ce of th e β-D-ribofuran osyl m oiety in th e position N-9
an d substitution effect on th e biological activity. Th e 6-(substituted
ph en yl)purin e ribon ucleosides displayed sign ifican t in vitro cytostatic activ-
ity (in h ibition of th e cell growth of L1210, HeLa S3 an d CCRF-CEM cell cul-
tures, IC50 = 0.25 · 10 µm ol l–1), wh ile th e 6-ph en ylpurin e bases an d
2-am in o-6-ph en ylpurin e ribon ucleosides were en tirely in active in th ese as-
says. Sugar-m odified 6-arylpurin e n ucleosides10 (2′- or 5′-deoxyribosides
an d acyclon ucleosides) as well as 6-(h et)arylpurin e acyclic n ucleotide an a-
logues11,12 were also devoid of an y cytostatic activity. As an exten sion of
th e SAR study of th is class of com poun ds, we report h ere on th e syn th esis
an d cytostatic activity of purin e ribon ucleosides bearin g selected aryl,
h etaryl or ben zyl substituen ts in position 6.
RESULTS AND DISCUSSION
Chemistry
Sin ce in th e in itial series th e m ost active com poun ds were 6-(4-X-substi-
tuted ph en yl)purin e ribosides (wh ere X = H, h alogen or alkoxy substituen t),
th e first group of com poun ds un der study were an alogous purin e n ucleo-
sides bearin g ph en yl rin g substituted with som e oth er types of substituen ts
in position 4 (X = SCH3, N(CH3)2, CF3 an d OH) as well as 3,4-dim eth oxy-
ph en yl an d 3,4-(m eth ylen edioxy)ph en yl m oieties occurrin g in m an y
cytostatic n atural products such as alkaloids. To study steric lim itation s of
th e aryl m oiety, purin e n ucleosides bearin g 1- or 2-n aph th yl substituen ts in
position 6 were devised. Replacem en t of th e ph en yl rin g by a six- or
five-m em bered h eterocyclic m oiety was an oth er structural m odification
studied. Fin ally, 6-ben zylpurin e derivatives were selected in order to test
wh eth er a con jugation of th e aryl an d purin e m oieties is n ecessary for th e
cytostatic activity.
Th e Suzuki reaction of 6-h alopurin es with boron ic acids was reported13 to
be a facile an d efficien t m eth od for th e preparation of diverse purin es bear-
in g a carbon substituen t in position 6. A m ajor advan tage of th is m eth od
for th e preparation of com poun ds for biological activity screen in g in com -
parison with cross-couplin g reaction s with oth er types of organ om etallics
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Cytostatic 6-Arylpurine Nucleosides
485
(e.g. stan n an es, organ ozin c reagen ts, cuprates) con sists in th e fact th at n o
toxic m etal-con tain in g by-products are form ed. Sin ce th e use of th is reac-
tion un der an h ydrous con dition s in toluen e was foun d9,13 to be superior for
th e in troduction of ph en yl groups bearin g electron -rich , electron eutral or
weakly electron -with drawin g substituen ts, it was th e m eth od of ch oice for
th e in troduction of substituted ph en yl an d n aph th yl substituen ts. Th us th e
reaction of 6-ch loro-9-(2,3,5-tri-O-acetyl-β-D-ribofuran osyl)purin e (1) with a
series of com m ercially available ph en yl- or n aph th ylboron ic acids 2a–2h in
toluen e un der Pd(PPh 3)4 catalysis afforded th e protected 6-arylpurin e
ribon ucleosides 3a–3h in good yields (Sch em e 1). In con trast to th e lack of
reactivity9,13 of oth er electron -deficien t ph en ylboron ic acids (n itro-, cyan o-,
form yl-, acetyl- an d pen tafluoroph en yl) un der an h ydrous con dition s,
4-(trifluorom eth yl)ph en ylboron ic acid (2c) reacted un der th ese con dition s
relatively sm ooth ly. Th e THP-protected boron ic acid 2d was used as a
4-h ydroxyph en yl precursor an d th e THP group in com poun d 3d was quan -
titatively cleaved un der very m ild con dition s (catalytic am oun t of HCl in
m eth an ol at am bien t tem perature) prior to deacetylation (vide infra).
Th e Negish i cross-couplin g reaction s of organ ozin c reagen ts with
6-h alopurin es are th e m ost versatile m eth ods for th e in troduction of di-
verse types of carbon substituen ts11,12,14,15 (alkyl, alken yl, aryl an d h etaryl).
Th e drawback of th is approach is its lower toleran ce to th e presen ce of
som e un protected fun ction al groups an d difficult rem oval of th e residual
zin c com poun ds wh ich often m ake stron g com plexes with purin es. In our
study, th is approach was successfully used for th e in troduction of n itro-
gen -h etaryl (2-pyridyl an d 1-m eth ylpyrrol-2-yl) an d substituted ben zyl sub-
stituen ts. Th us th e protected 6-ch loropurin e n ucleoside 1 reacted sm ooth ly
with th e h etaryl- or ben zylzin c h alides 2i–2m in THF in th e presen ce of
Pd(PPh 3)4 to afford th e protected 6-h etaryl- or 6-ben zylpurin e n ucleosides
3i–3m . Th e zin c residues were rem oved by extraction with EDTA. Wh ile th e
use of com m ercially available ben zylzin c ch lorides (Rieke® organ ozin c re-
agen ts) 2k –2m well tolerated th e presen ce of th e acetyl-protected
ribofuran ose to give th e protected n ucleosides 3k–3m in good yields, th e
reaction s of h etarylzin c ch lorides 2i (com m ercial Rieke® organ ozin c re-
agen t) an d 2j [gen erated from 1-m eth ylpyrrole by th e use of BuLi in th e
presen ce of N,N,N′,N′-tetram eth yleth an e-1,2-diam in e (TMEDA) followed by
tran sm etallation with Zn Cl2] was accom pan ied by partial deacetylation
durin g th e work-up givin g th e triacetyl n ucleosides 3i an d 3j in low yields
on ly.
An oth er approach widely used for th e in troduction 11,12,14,16–18 of alkyl,
alken yl, aryl an d h etaryl substituen ts is th e Stille couplin g of organ o-
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

486
Hocek, Holý, Votruba, Dvořáková:
Scheme 1:
Cl
N
R
N
R
R-M (2a-2o)
Pd cat.
MeONa
N
N
N
N
N
N
N
N
N
N
O
AcO
AcO
HO
O
O
OAc OAc
OAc OAc
OH OH
1
3a-3o
4a-4o
Yield Yield
of 3 of 4
Yield Yield
of 3 of 4
Entry
Entry
R
M
R
M
SCH3
i
a
68% 65%
ZnCl 27% 65%
B(OH)2
N
CH3
N(CH3)2
B(OH)2
N
j
b
c
82% 63%
55% 79%
ZnCl
22% 86%
CF3
k
ZnCl 62% 66%
B(OH)2
B(OH)2
B(OH)2
CH2
CH2
CH2
F
OX
da
l
83% 60%
74% 67%
ZnCl 76% 67%
OCH3
ZnCl 60% 88%
OCH3
m
e
OCH3
O
S
n
o
f
B(OH)2 72% 71%
B(OH)2 76% 70%
SnBu3 89% 66%
O
O
g
SnBu3
85% 59%
B(OH)2 72% 78%
h
1. HCl, 2. MeONa
a
3d, X = THP
4d, X = H
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Cytostatic 6-Arylpurine Nucleosides
487
stan n an es with 6-h alopurin es. As in th e previous case, th e m ajor drawback
of th is m eth od is a difficult rem oval of h igh ly toxic organ otin reagen ts an d
side-products. In th is study, com m ercially available 2-th ien yl- an d
2-furylstan n an es 2n an d 2o reacted sm ooth ly with th e 6-ch loropurin e 1 in
DMF in th e presen ce of PdCl2(PPh 3)2 to give th e protected 6-h etarylpurin e
n ucleosides 3n an d 3o in good yields. Stan dard14 treatm en t of th e crude
products with m eth an olic KF to destroy th e stan n an es led sim ultan eously
to deacetylation . Th erefore th e organ ostan n an es were rem oved by repeated
colum n ch rom atograph y.
All th e triacetyl n ucleosides 3a–3o were quan titatively deprotected by th e
use of catalytic am oun t of MeONa in m eth an ol an d th e free n ucleosides
4a–4o were isolated in good yields (59–88%) after crystallization .
All com poun ds were ch aracterized by spectral an d an alytical m eth ods.
1
Assign m en t of th e H an d 13C NMR spectra was based on a com bin ation of
COSY, HMBC an d HMQC experim en ts in selected typical com poun ds. UV
spectra of th e series of com poun ds 4a–4o revealed a sign ifican t effect of th e
substituen t in position 6 displayin g th e m axim a between 263–265 n m for
th e 6-ben zylpurin e derivatives 4k–4m , an d between 290–375 n m for th e
6-aryl- an d 6-h etarylpurin es 4a–4j an d 4n an d 4o.
Cytostatic Activity Evaluation
Th e title 6-substituted purin e ribon ucleosides 4a–4o were tested on th eir in
vitro in h ibition of th e cell growth in th e followin g cell cultures: (i) m ouse
leukem ia L1210 cells (ATCC CCL 219); m urin e L929 cells (ATCC CCL 1);
h um an cervix carcin om a HeLa S3 cells (ATCC CCL 2.2); an d h um an T-
lym ph oblastoid CCRF-CEM cell lin e (ATCC CCL 119). Th e results (Table I)
sh ow th at, an alogously to th e results9 of th e paren t group of 6-ph en yl-
purin e ribon ucleosides, m ost of th e n ucleosides 4 possessed powerful
cytostatic poten cy again st T-lym ph oblastoids (CCRF-CEM: IC50 values from
0.5 to 15 µm ol l–1), wh ile L1210 an d HeLa S3 cells were m uch less sen sitive
an d on ly m argin al effects h ave been foun d toward L929 cell lin e (data n ot
sh own ).
Th ese results m ake an exten sion of th e structure–activity relation sh ip
study of th is group of com poun ds. In addition to th e previously reported9
h igh an tiproliferative activity of 6-ph en yl-, 6-(4-h aloph en yl)- an d
6-(4-alkoxyph en yl)purin e ribon ucleosides, com parably h igh subm icrom olar
activity was foun d in 6-[4-(m eth ylsulfan yl)ph en yl]purin e derivative 4a.
Com poun d 4d bearin g an acidic ph en ol m oiety was about on e order of
m agn itude less effective th an th e 4-alkoxyph en yl derivatives, wh ile basic
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

488
Hocek, Holý, Votruba, Dvořáková:
4-(dim eth ylam in o)ph en yl derivative 4b was m uch less active. Th e 4-(tri-
fluorom eth yl)ph en yl derivative 4c was en tirely in active. In troduction of a
secon d alkoxy group in to th e ph en yl m oiety caused a dram atic decrease of
cytostatic poten cy (com poun ds 4e an d 4f). Also attach m en t of a bulky
n aph th yl m oiety to th e purin e rin g led to less active or in active com pun ds
(4g an d 4h ). Th e best results were obtain ed with purin e n ucleosides bearin g
a six- or five-m em bered h eteroarom atic m oiety in position 6: th e
TABLE I
Cytostatic activity of 6-R-substituted purin e ribon ucleosides 4
IC50a, µm ol l–1
Com poun d
R
CCRF-CEM
L1210
HeLa S3
4a
4b
4c
4d
4e
4f
4-(CH3S)C6H4
4-[(CH3)2N]C6H4
4-CF3C6H4
0.8
20.0
NA
1.25
NA
5.0
NA
NA
NA
5.0
NA
NA
NA
NA
4.3
NA
NA
NA
NA
0.4
2.0
NA
NA
NA
32.5
NA
NA
NA
NA
9.7
4-HOC6H4
3,4-di(CH3O)C6H3
3,4-(OCH2O)C6H3
1-n aph th yl
4g
4h
4i
NA
20.0
0.9
2-n aph th yl
2-pyridyl
4j
1-m eth ylpyrrol-2-yl
ben zyl
2.0
NA
NA
NA
NA
25.0
25.0
4k
4l
8.8
4-fluoroben zyl
4-m eth oxyben zyl
2-th ien yl
7.0
4m
4n
4o
NA
0.6
2-furyl
0.6
ph en ylb
0.7
9.0
4.5
1.5
2.7
2.5
4.3
4-fluoroph en ylb
4-m eth oxyph en ylb
0.75
0.25
a
b
NA = n ot active (in h ibition of cell growth at c = 10 µm ol l–1 was lower th an 20%). Taken
from ref.9
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Cytostatic 6-Arylpurine Nucleosides
489
6-(2-pyridyl)- (4i), 6-(2-th ien yl)- (4n ) an d 6-(2-furyl)purin e (4o) derivatives
displayed subm icrom olar activity towards CCRF-CEM an d m icrom olar ac-
tivity towards L1210 an d HeLa cells. Th e 1-m eth ylpyrrol-2-yl derivative 4j
was less active, an alogously to th e previously described9 in active ortho-sub-
stituted ph en ylpurin e n ucleosides. Surprisin gly, a lower but still con sider-
able in h ibition of th e cell growth was foun d in 6-ben zylpurin es 4k an d 4l,
sh owin g th at con jugation of th e aryl an d purin e rin gs is n ot crucial for th e
cytostatic activity.
CONCLUSIONS
Cross-couplin g reaction s of 6-ch loro-9-(2,3,5-tri-O-acetyl-β-D-ribofuran osyl)-
purin e (1) with arylboron ic acids, h etaryl- or ben zylzin c ch lorides an d
h etarylstan n an es afforded effectively a series of 6-aryl-, 6-h etaryl- an d
6-ben zylpurin e ribon ucleosides. Th e cytostatic activity was stron gly de-
pen den t on th e n ature an d steric dem an ds of substituen t in position 6. Be-
sides som e 6-(4-substituted ph en yl)purin e derivatives, also 6-h etaryl
n ucleosides sh owed a sign ifican t cytostatic activity. Com poun ds bearin g
m ore bulky substituen ts were less active or in active. Con siderable cytostatic
activity was also foun d in 6-ben zylpurin e ribon ucleosides. Th ese an d previ-
ous9,10 fin din gs en able us to form ulate th e followin g structural features of
th e ph arm acoph ore for th e cytostatic activity of th is group of com poun ds:
a purin e n ucleoside bearin g a β-D-ribofuran osyl residue in position 9 an d an
aryl group in position 6 wh ich m igh t con sist in (i) ph en yl m oiety bearin g a
h alogen o, alkoxy or m eth ylsulfan yl substituen ts in para-position or in (ii)
six- or five-m em bered h eterocycle. Furth er studies will be n ecessary to in -
vestigate th e m ech an ism of action of th is group of com poun ds.
EXPERIMENTAL
Un less oth erwise stated, solven ts were evaporated at 40 °C/2kPa an d com poun ds were dried
at 60 °C/2kPa over P2O5. Meltin g poin ts were determ in ed on a Kofler block an d are un cor-
rected. Optical rotation s were m easured at 25 °C on a Perkin –Elm er 141 MC polarim eter,
[α]D values are given in 10–1 deg cm 2 g–1. NMR spectra were m easured on a Bruker AMX-3
400 (400 MHz for 1H, 100.6 MHz for 13C an d 376.5 MHz for 19F n uclei), a Bruker DRX 500
(500 MHz for 1H, 125.7 MHz for 13C an d 470.59 MHz for 19F). TMS was used as in tern al
stan dard for th e 1H an d 13C NMR spectra; CFCl3 was an in tern al stan dard for 19F spectra.
Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J) in Hz. Mass spectra were
m easured on a ZAB-EQ (VG An alytical) spectrom eter usin g FAB (ion ization by Xe, accelerat-
in g voltage 8 kV, glycerol m atrix). UV absorption spectra (λm ax, n m ; ε, l m ol–1 cm –1) were
m easured on a Sh im adzu UVm in i 1240 spectrom eter in m eth an olic solution s. Toluen e was
degassed in vacuo an d stored over m olecular sieves un der argon . DMF was distilled from
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

490
Hocek, Holý, Votruba, Dvořáková:
P2O5, degassed in vacuo an d stored over m olecular sieves un der argon . THF was refluxed
with Na an d ben zoph en on e un der argon an d fresh ly distilled prior to use. Substituted
ph en ylboron ic acids 2a–2f were purch ased from Fron tier Scien tific (U.K.), n aph th ylboron ic
acids 2g an d 2h , Rieke® organ ozin c reagen ts 2i an d 2k–2m , as well as stan n an es 2n an d 2o
were supplied by Aldrich . Cytostatic activity tests were perform ed as described in ref.9.
Cross-Couplin g Reaction s of 6-Ch loropurin e Nucleoside 1 with Arylboron ic Acids.
Gen eral Procedure
Toluen e (10 m l) was added to an argon -purged flask con tain in g th e protected 6-ch loro-
purin e n ucleoside19 1 (413 m g, 1 m m ol), K2CO3 (200 m g, 1.5 m m ol), arylboron ic acid
2a–2h (1.5 m m ol) an d Pd(PPh 3)4 (59 m g, 0.05 m m ol) an d th e m ixture was stirred un der ar-
gon at 100 °C for 8 h . After coolin g to am bien t tem perature th e m ixture was evaporated
in vacuo an d th e residue was ch rom atograph ed on a silica gel colum n (50 g, eth yl acetate–
ligh t petroleum 1 : 2 to 9 : 1). Evaporation an d dryin g of th e product con tain in g fraction s
afforded 6-arylpurin es 3a–3h as foam s or am orph ous solids.
6-[4-(Methylsulfanyl)phenyl]-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3a ). Yellowish
am orph ous solid, yield 68%. FAB MS, m/z (rel.%): 501 (44) [M + H], 243 (100). 1H NMR
(400 MHz, CDCl3): 2.09, 2.14 an d 2.17 (3 × s, 3 × 3 H, 3 × CH3CO); 2.56 (s, 3 H, SCH3);
4.36–4.48 (m , 3 H, H-4′ an d 2 × H-5′); 5.71 (dd, 1 H, J = 4.5 an d 5.4, H-3′); 6.01 (t, 1 H, J =
5.4, H-2′); 6.30 (d, 1 H, J = 5.4, H-1′); 7.40 (d, 2 H, J = 8.6, H-arom .); 8.26 (s, 1 H, H-8); 8.73
(d, 2 H, J = 8.6, H-arom .); 8.99 (s, 1 H, H-2). 13C NMR (100 MHz, CDCl3): 15.12 (SCH3);
20.41, 20.55 an d 20.78 (3 × CH3); 63.11 (CH2-5′); 70.73 (CH-3′); 73.14 (CH-2′); 80.45
(CH-4′); 86.42 (CH-1′); 125.74 (CH-arom .); 130.12 (CH-arom .); 131.39 an d 131.88 (C-5 an d
C-i-arom .); 142.24 (H-8); 143.23 (C-SMe); 152.01 (C-4); 152.71 (C-2); 154.90 (C-6); 169.38,
169.59 an d 170.32 (3 × CO). HR MS (FAB), calculated for C23H25N4O7S [M + H]: 501.1444;
foun d: 501.1455.
6-[4-(Dimethylamino)phenyl]-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3b). Yellow am or-
ph ous solid, yield 82%. FAB MS, m/z (rel.%): 498 (45) [M + H], 240 (42), 93 (100). 1H NMR
(400 MHz, CDCl3): 2.08, 2.13 an d 2.15 (3 × s, 3 × 3 H, 3 × CH3CO); 3.08 (s, 6 H, N(CH3)2);
4.36–4.47 (m , 3 H, H-4′ an d 2 × H-5′); 5.71 (dd, 1 H, J = 4.2 an d 5.4, H-3′); 6.00 (t, 1 H, J =
5.4, H-2′); 6.29 (d, 1 H, J = 5.4, H-1′); 6.83 (d, 2 H, J = 8.9, H-arom .); 8.19 (s, 1 H, H-8); 8.76
(d, 2 H, J = 8.9, H-arom .); 8.90 (s, 1 H, H-2). 13C NMR (100.6 MHz, CDCl3): 20.41, 20.57 an d
20.79 (3 × CH3); 40.13 ((CH3)2N); 63.17 (CH2-5′); 70.79 (CH-3′); 73.13 (CH-2′); 80.38
(CH-4′); 86.15 (CH-1′); 111.63 (CH-arom .); 122.95 an d 130.55 (C-5 an d C-i-arom .); 131.37
(CH-arom .); 141.15 (H-8); 151.58 (C-NMe2); 152.46 an d 155.68 (C-4 an d C-6); 152.71 (C-2);
169.38, 169.61 an d 170.36 (3 × CO). HR MS (FAB), calculated for C24H28N5O7 [M + H]:
498.1989; foun d: 498.1954.
9-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-6-[4-(trifluoromethyl)phenyl]purine (3c). Yellowish
am orph ous solid, yield 55%. FAB MS, m/z (rel.%): 523 (44) [M + H], 264 (100). 1H NMR
(400 MHz, CDCl3): 2.11, 2.14 an d 2.18 (3 × s, 3 × 3 H, 3 × CH3CO); 4.40–4.51 (m , 3 H, H-4′
an d 2 × H-5′); 5.72 (dd, 1 H, J = 4.6 an d 5.4, H-3′); 6.02 (t, 1 H, J = 5.4, H-2′); 6.31 (d, 1 H,
J = 5.2, H-1′); 7.82 (d, 2 H, J = 8.3, H-arom .); 8.32 (s, 1 H, H-8); 8.91 (d, 2 H, J = 8.2,
H-arom .); 9.07 (s, 1 H, H-2). 19F NMR (376.5 MHz, CDCl3): –63.42 (s, CF3). HR MS (FAB),
calculated for C23H22F3N4O7 [M + H]: 523.1441; foun d: 523.1430.
6-{4-[(Tetrahydropyran-2-yl)oxy]phenyl}-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3d ).
Colourless am orph ous solid, yield 83%. FAB MS, m/z (rel.%): 555 (48) [M + H], 471 (12)
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Cytostatic 6-Arylpurine Nucleosides
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[M + H – THP], 213 (100). 1H NMR (400 MHz, CDCl3): 1.62–1.74 an d 1.88–1.93 (2 × m , 6 H,
CH2, THP); 2.09, 2.14 an d 2.16 (3 × s, 3 × 3 H, 3 × CH3CO); 3.61–3.67 an d 3.87–3.95 (2 × m ,
2 × 1 H, OCH2, THP); 4.36–4.47 (m , 3 H, H-4′ an d 2 × H-5′); 5.56 (brm , 1 H, NCHO, THP);
5.71 (dd, 1 H, J = 4.1 an d 5.3, H-3′); 6.01 (t, 1 H, J = 5.3, H-2′); 6.29 (d, 1 H, J = 5.3, H-1′);
7.22 (d, 2 H, J = 8.4, H-arom .); 8.24 (s, 1 H, H-8); 8.77 (d, 2 H, J = 8.4, H-arom .); 8.97 (s,
1 H, H-2). 13C NMR (100.6 MHz, CDCl3): 18.66 (CH2, THP); 20.41, 20.57 an d 20.79 (3 ×
CH3); 25.18 an d 30.26 (CH2, THP); 62.06 an d 63.12 (CH2O, THP an d CH2-5′); 70.75 (CH-3′);
73.14 (CH-2′); 80.44 (CH-4′); 86.34 (CH-1′); 96.18 (NCHO, THP); 116.49 (CH-arom .); 128.77
an d 131.16 (C-5 an d C-i-arom .); 131.53 (CH-arom .); 142.01 (H-8); 151.91 an d 155.20 (C-4
an d C-6); 152.70 (C-2); 159.77 (C-OTHP); 169.37, 169.59 an d 170.33 (3 × CO). HR MS (FAB),
calculated for C27H31N4O9 [M + H]: 555.2091; foun d: 555.2085.
6-(3,4-Dimethoxyphenyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3e). Yellowish am or-
ph ous solid, yield 74%. FAB MS, m/z (rel.%): 515 (30) [M + H], 257 (100). 1H NMR
(400 MHz, CDCl3): 2.09, 2.14 an d 2.17 (3 × s, 3 × 3 H, 3 × CH3CO); 3.98 an d 4.04 (2 × s, 2 ×
3 H, 2 × OCH3); 4.38–4.50 (m , 3 H, H-4′ an d 2 × H-5′); 5.71 (ddt, 1 H, J = 4.4, 5.4, H-3′);
6.01 (t, 1 H, J = 5.4, H-2′); 6.30 (d, 1 H, J = 5.3, H-1′); 7.05 (d, 1 H, J = 8.6, H-arom .); 8.25 (s,
1 H, H-8); 8.41 (d, 1 H, J = 1.6, H-arom .); 8.58 (dd, 1 H, J = 1.6 an d 8.6, H-arom .); 8.97 (s,
1 H, H-2). HR MS (FAB), calculated for C24H27N4O9 [M + H]: 515.1778; foun d: 515.1761.
6-[3,4-(Methylenedioxy)phenyl]-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3f). Yellowish
am orph ous solid, yield 72%. FAB MS, m/z (rel.%): 499 (27) [M + H], 241 (100). 1H NMR
(400 MHz, CDCl3): 2.09, 2.14 an d 2.17 (3 × s, 3 × 3 H, 3 × CH3CO); 4.38–4.50 (m , 3 H, H-4′
an d 2 × H-5′); 5.71 (dd, 1 H, J = 4.6, 5.4, H-3′); 6.01 (t, 1 H, J = 5.4, H-2′); 6.07 (s, 2 H,
OCH2O); 6.29 (d, 1 H, J = 5.4, H-1′); 7.00 (d, 1 H, J = 8.3, H-arom .); 8.25 (s, 1 H, H-8); 8.33
(d, 1 H, J = 1.7, H-arom .); 8.51 (dd, 1 H, J = 1.7 an d 8.3, H-arom .); 8.96 (s, 1 H, H-2). HR MS
(FAB), calculated for C23H23N4O9 [M + H]: 499.1465; foun d: 499.1508.
6-(1-Naphthyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3g). Yellowish am orph ous solid,
yield 76%. FAB MS, m/z (rel.%): 505 (19) [M + H], 247 (100). 1H NMR (400 MHz, CDCl3):
2.13, 2.14 an d 2.18 (3 × s, 3 × 3 H, 3 × CH3CO); 4.40–4.52 (m , 3 H, H-4′ an d 2 × H-5′); 5.76
(dd, 1 H, J = 5.5 an d 4.4, H-3′); 6.09 (dd, 1 H, J = 5.1 an d 5.5, H-2′); 6.33 (d, 1 H, J = 5.1,
H-1′); 7.49–7.56 (m , 2 H, H-arom .); 7.65 (t, 1 H, J = 7.7, H-arom .); 7.92–7.95 (m , 1 H,
H-arom .); 8.03 (d, 2 H, J = 7.6, H-arom .); 8.26 (s, 1 H, H-8); 8.26–8.29 (m , 1 H, H-arom .);
9.17 (s, 1 H, H-2). HR MS (FAB), calculated for C26H25N4O7 [M + H]: 505.1723; foun d:
505.1720.
6-(2-Naphthyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3h ). Yellowish am orph ous solid,
yield 72%. FAB MS, m/z (rel.%): 505 (48) [M + H], 360 (100). 1H NMR (400 MHz, CDCl3):
2.11, 2.16 an d 2.18 (3 × s, 3 × 3 H, 3 × CH3CO); 4.40–4.51 (m , 3 H, H-4′ an d 2 × H-5′); 5.74
(dd, 1 H, J = 5.4 an d 4.4, H-3′); 6.05 (t, 1 H, J = 5.4, H-2′); 6.34 (d, 1 H, J = 5.4, H-1′);
7.52–7.59 (m , 2 H, H-arom .); 7.91 (d, 1 H, J = 7.5, H-arom .); 8.02 (d, 1 H, J = 8.7, H-arom .);
8.08 (d, 1 H, J = 7.4, H-arom .); 8.34 (s, 1 H, H-8); 8.87 (dd, 1 H, J = 8.7 an d 1.2, H-arom .);
9.09 (s, 1 H, H-2); 9.41 (s, 1 H, H-arom .). HR MS (FAB), calculated for C26H25N4O7 [M + H]:
505.1723; foun d: 505.1763.
Cross-Couplin g Reaction s of 6-Ch loropurin e Nucleoside 1 with Organ ozin c Halides.
Gen eral Procedure
THF (10 m l) was added to an argon -purged flask con tain in g th e 6-ch loropurin e 1 (413 m g,
1 m m ol) an d Pd(PPh 3)4 (59 m g, 0.05 m m ol). Th e m ixture was stirred at am bien t tem pera-
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Hocek, Holý, Votruba, Dvořáková:
ture for 10 m in an d, after dissolution of th e solids, a solution of organ ozin c h alide 2i–2m
(2i an d 2k –2m : Rieke® organ ozin c reagen ts, 0.5 M solution in THF, 3 m l, 1.5 m m ol; 2j
(2 m m ol) was gen erated accordin g to publish ed procedure) was added dropwise (with in
10 m in ) at am bien t tem perature. Th e stirrin g at am bien t tem perature was con tin ued for
15 m in followed by stirrin g at 60 °C for 8 h . Th en th e reaction m ixture was allowed to
stan d overn igh t at am bien t tem perature an d poured in to saturated aqueous NH4Cl (10 m l).
To th is m ixture, saturated aqueous Na2EDTA (10 m l) was added an d th e m ixture was stirred
for 10 m in . Th en th e reaction m ixture was extracted with eth yl acetate (3 × 20 m l) an d th e
collected organ ic layers were wash ed with saturated aqueous Na2EDTA (20 m l) an d brin e
(20 m l), dried with an h ydrous MgSO4 an d evaporated in vacuo. Colum n ch rom atograph y of
th e residue on silica gel (50 g, eth yl acetate–ligh t petroleum 1 : 2 to 9 : 1) afforded, after
evaporation an d dryin g, th e 6-h etaryl- or 6-ben zylpurin es 3i–3m as am orph ous solids.
6-(2-Pyridyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3i). Yellowish am orph ous solid,
yield 27%. FAB MS, m/z (rel.%): 456 (35) [M + H], 198 (100). 1H NMR (400 MHz, CDCl3):
2.09, 2.14 an d 2.18 (3 × s, 3 × 3 H, 3 × CH3CO); 4.39–4.50 (m , 3 H, H-4′ an d 2 × H-5′); 5.71
(dd, 1 H, J = 5.4 an d 4.3, H-3′); 6.02 (t, 1 H, J = 5.4, H-2′); 6.34 (d, 1 H, J = 5.4, H-1′); 7.46
(dd, 1 H, J = 6.6 an d 4.8, H-arom .); 7.94 (dt, 1 H, J = 1.7 an d 7.8, H-arom .); 8.38 (s, 1 H,
H-8); 8.80 (d, 1 H, J = 7.9, H-arom .); 8.97 (d, 1 H, J = 4.0, H-arom .); 9.15 (s, 1 H, H-2).
HR MS (FAB), calculated for C21H22N5O7 [M + H]: 456.1519; foun d: 456.1536.
6-(1-Methylpyrrol-2-yl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3j). Yellowish am or-
ph ous solid, yield 22%. FAB MS, m/z (rel.%): 458 (70) [M + H], 200 (100). 1H NMR
(400 MHz, CDCl3): 2.08, 2.14 an d 2.16 (3 × s, 3 × 3 H, 3 × CH3CO); 4.20 (s, 3 H, CH3N);
4.36–4.49 (m , 3 H, H-4′ an d 2 × H-5′); 5.70 (dd, 1 H, J = 5.4 an d 4.4, H-3′); 6.00 (t, 1 H, J =
5.4, H-2′); 6.26 (d, 1 H, J = 5.4, H-1′); 6.31 (dd, 1 H, J = 2.5 an d 3.9, H-arom .); 6.88 (brs, 1 H,
H-arom .); 7.83 (dd, 1 H, J = 1.6 an d 3.9, H-arom .); 8.16 (s, 1 H, H-8); 8.83 (s, 1 H, H-2).
13C NMR (100 MHz, CDCl3): 20.38, 20.53 an d 20.76 (3 × CH3CO); 38.30 (CH3N); 63.11
(CH2-5′); 70.68 (CH-3′); 73.02 (CH-2′); 80.29 (CH-4′); 86.12 (CH-1′); 109.11, 119.88 an d
129.73 (CH-arom .); 126.91 an d 129.50 (C-5 an d C-i-arom .); 141.10 (CH-8); 150.24 an d
150.74 (C-4 an d C-6); 152.05 (CH-2); 169.33, 169.57 an d 170.34 (3 × CO). HR MS (FAB),
calculated for C21H24N5O7 [M + H]: 458.1676; foun d: 458.1691.
6-Benzyl-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3k ). Colourless am orph ous solid,
yield 62%. FAB MS, m/z (rel.%): 469 (14) [M + H], 211 (100). 1H NMR (400 MHz, CDCl3):
2.07, 2.10 an d 2.15 (3 × s, 3 × 3 H, 3 × CH3CO); 4.35–4.47 (m , 3 H, H-4′ an d 2 × H-5′); 4.52
(s, 2 H, CH2Ph ); 5.68 (dd, 1 H, J = 4.3 an d 5.5, H-3′); 5.98 (dd, 1 H, J = 5.3, 5.5, H-2′); 6.23
(d, 1 H, J = 5.3, H-1′); 7.17–7.49 (m , 5 H, H-arom .); 8.20 (s, 1 H, H-8); 8.90 (s, 1 H, H-2).
13C NMR (100 MHz, CDCl3): 20.40, 20.54 an d 20.74 (3 × CH3); 39.57 (CH2Ph ); 63.08
(CH2-5′); 70.69 (CH-3′); 73.07 (CH-2′); 80.45 (CH-4′); 86.43 (CH-1′); 126.75, 128.62 an d
129.39 (CH-arom .); 133.17 an d 137.62 (C-5 an d C-i-Ph ); 142.52 (H-8); 150.80 (C-4); 152.92
(C-2); 161.34 (C-6); 169.36, 169.57 an d 170.31 (3 × CO). HR MS (FAB), calculated for
C
23H25N4O7 [M + H]: 469.1723; foun d: 469.1694.
6-(4-Fluorobenzyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3l). Colourless am orph ous
solid, yield 76%. FAB MS, m/z (rel.%): 487 (56) [M + H], 229 (100). 1H NMR (400 MHz,
CDCl3): 2.08, 2.11 an d 2.15 (3 × s, 3 × 3 H, 3 × CH3CO); 4.35–4.50 (m , 3 H, H-4′ an d 2 ×
H-5′); 4.49 (s, 2 H, CH2Ph F); 5.68 (dd, 1 H, J = 4.7 an d 5.3, H-3′); 5.97 (t, 1 H, J = 5.3, H-2′);
6.23 (d, 1 H, J = 5.3, H-1′); 6.94–6.98 an d 7.40–7.45 (2 × m , 2 × 2 H, H-arom .); 8.21 (s, 1 H,
H-8); 8.90 (s, 1 H, H-2). 13C NMR (100 MHz, CDCl3): 20.33, 20.46 an d 20.68 (3 × CH3);
38.60 (CH2Ph F); 62.98 (CH2-5′); 70.57 (CH-3′); 73.03 (CH-2′); 80.35 (CH-4′); 86.48 (CH-1′);
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Cytostatic 6-Arylpurine Nucleosides
493
2
3
115.36 (d, JC,F= 21.3, CH-arom .); 130.79 (d, JC,F = 7.9, CH-arom .); 133.85 (C-5); 133.99 (d,
4JC,F= 2.1, CH-arom .); 142.53 (H-8); 150.73 (C-4); 152.86 (C-2); 160.55 (C-6); 161.98 (d,
1JC,F= 201.5, C-F); 169.30, 169.50 an d 170.23 (3 × CO). 19F NMR (376.5 MHz, CDCl3):
–116.85 (s, FPh ). HR MS (FAB), calculated for C23H24FN4O7 [M + H]: 487.1629; foun d:
487.1655.
6-(4-Methoxybenzyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3m ). Colourless am or-
ph ous solid, yield 60%. FAB MS, m/z (rel.%): 499 (27) [M + H], 241 (100). 1H NMR
(400 MHz, CDCl3): 2.08, 2.11 an d 2.15 (3 × s, 3 × 3 H, 3 × CH3CO); 3.76 (s, 3 H, OCH3);
4.35–4.47 (m , 3 H, H-4′ an d 2 × H-5′); 4.46 (s, 2 H, CH2Ph OMe); 5.68 (brm , 1 H, H-3′); 5.98
(t, 1 H, J = 5.2, H-2′); 6.23 (d, 1 H, J = 5.2, H-1′); 6.83 (d, 2 H, J = 8.3, H-arom .); 7.39 (d, 2 H,
J = 8.3, H-arom .); 8.20 (s, 1 H, H-8); 8.90 (s, 1 H, H-2). 13C NMR (100 MHz, CDCl3): 20.34,
20.47 an d 20.68 (3 × CH3); 38.64 (CH2Ph ); 55.18 (OCH3); 63.02 (CH2-5′); 70.64 (CH-3′);
73.01 (CH-2′); 80.38 (CH-4′); 86.35 (CH-1′); 114.04 an d 130.31 (CH-arom .); 129.64 an d
132.99 (C-5 an d C-i-Ph ); 142.37 (CH-8); 152.88 (CH-2); 150.71, 158.43 an d 161.65 (C-4, C-6
an d C-OMe); 169.30, 169.51 an d 170.25 (3 × CO). HR MS (FAB), calculated for C24H27N4O8
[M + H]: 499.1829; foun d: 499.1797.
Cross-Couplin g Reaction s of 6-Ch loropurin e Nucleoside 1 with Stan n an es.
Gen eral Procedure
DMF (5 m l) was added to an argon -purged flask con tain in g th e 6-ch loropurin e 1 (413 m g,
1 m m ol), a h etaryl(tributyl)tin 2n or 2o (1.5 m m ol) an d PdCl2(PPh 3)2 (35 m g, 0.05 m m ol).
Th e m ixture was stirred at 100 °C for 12 h an d th e solven t was evaporated in vacuo. Th e resi-
due was twice ch rom atograph ed on a silica gel colum n (50 g, eth yl acetate–ligh t petroleum
1 : 3 to 9 : 1) to give th e 6-h etarylpurin e n ucleosides 3n an d 3o as am orph ous solids.
6-(2-Thienyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3n ). Colourless am orph ous solid,
yield 89%. FAB MS, m/z (rel.%): 461 (100) [M + H]. 1H NMR (400 MHz, CDCl3): 2.09, 2.14
an d 2.16 (3 × s, 3 × 3 H, 3 × CH3CO); 4.37–4.50 (m , 3 H, H-4′ an d 2 × H-5′); 5.70 (dd, 1 H,
J = 5.4 an d 4.4, H-3′); 6.00 (t, 1 H, J = 5.4, H-2′); 6.28 (d, 1 H, J = 5.4, H-1′); 7.27 (m , 1 H,
H-arom . overlapped with CHCl3); 7.63 (dd, 1 H, J = 4.9 an d 0.9, H-arom .); 8.26 (s, 1 H, H-8);
8.66 (dd, 1 H, J = 3.7 an d 0.9, H-arom .); 8.90 (s, 1 H, H-2). 13C NMR (100 MHz, CDCl3):
20.37, 20.49 an d 20.74 (3 × CH3); 63.04 (CH2-5′); 70.67 (CH-3′); 73.11 (CH-2′); 80.42
(CH-4′); 86.33 (CH-1′); 128.82 (CH-arom .); 129.44 (C-5); 131.11 an d 132.95 (CH-arom .);
139.70 (C-i-arom .); 142.47 (CH-8); 150.64 an d 151.58 (C-4 an d C-6); 152.75 (CH-2); 169.32,
169.54 an d 170.27 (3 × CO). HR MS (FAB), calculated for C20H21N4O7S [M + H]: 461.1131;
foun d: 461.1137.
6-(2-Furyl)-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3o). Colourless am orph ous solid,
yield 85%. FAB MS, m/z (rel.%): 445 (34) [M + H], 187 (100). 1H NMR (400 MHz, CDCl3):
2.09, 2.13 an d 2.16 (3 × s, 3 × 3 H, CH3CO); 4.37–4.48 (m , 3 H, H-4′ an d 2 × H-5′); 5.70 (dd,
1 H, J = 5.5 an d 4.4, H-3′); 6.00 (dd, 1 H, J = 5.3 an d 5.5, H-2′); 6.28 (d, 1 H, J = 5.3, H-1′);
6.68 (m , 1 H, H-arom .); 7.78 (m , 1 H, H-arom .); 7.87 (d, 1 H, J = 3.5, H-arom .); 8.27 (s, 1 H,
H-8); 8.96 (s, 1 H, H-2). 13C NMR (100 MHz, CDCl3): 20.32, 20.41 an d 20.69 (3 × CH3);
62.96 (CH2-5′); 70.57 (CH-3′); 73.06 (CH-2′); 80.36 (CH-4′); 86.33 (CH-1′); 112.63 an d
117.74 (CH-arom .); 128.83 (C-5); 142.72 (CH-8); 146.05 (CH-arom .); 146.36 (C-6); 149.41
(C-i-arom .); 151.53 (C-4); 152.83 (CH-2); 169.26, 169.48 an d 170.21 (3 × CO). HR MS (FAB),
calculated for C20H21N4O8 [M + H]: 445.1359; foun d: 445.1334.
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Deprotection of Nucleosides 3. Gen eral Procedure
Method A: A 1 M m eth an olic MeONa (200 µl, 0.2 m m ol) was added to a solution of a pro-
tected n ucleoside 3a–3c an d 3e–3o (0.5–0.8 m m ol) in MeOH (20 m l) an d th e m ixture was
stirred at am bien t tem perature overn igh t. Th e crystals (if form ed) were filtered off. Th en th e
solution was n eutralized by addition of Dowex 50X8 (H+) (ca 100 m g) an d filtered. Th e
ion -exch an ger was wash ed with saturated m eth an olic am m on ia (5 m l) followed by m eth a-
n ol (20 m l) an d th e com bin ed filtrates were evaporated to dryn ess. Th e collected crystals
an d th e residue were recrystallized from EtOH–toluen e to give free n ucleosides 4a–4c an d
4e–4o.
Method B: A 1
M m eth an olic HCl (100 µl, 0.1 m m ol) was added to a solution of
THP-protected n ucleoside 3d (443 m g, 0.8 m m ol) in m eth an ol (20 m l) an d th e m ixture was
stirred at am bien t tem perature overn igh t (com plete cleavage of th e THP group; TLC). Th en a
1
M m eth an olic MeONa (300 µl, 0.3 m m ol) was added an d th e solution was stirred at room
tem perature for 8 h . Th e work-up was don e in th e sam e m an n er as in m eth od A to afford
th e free n ucleoside 4d .
6-[4-(Methylsulfanyl)phenyl]-9-(β-D-ribofuranosyl)purine (4a). Yellowish crystals, yield 65%,
m .p. 186–188 °C, [α]D –61.4 (c 0.2, DMF). FAB MS, m/z (rel.%): 375 (62) [M + H], 243 (100).
1H NMR (400 MHz, DMSO-d6): 2.57 (s, 3 H, SCH3); 3.55–3.65 an d 3.68–3.78 (2 × m , 2 H, 2 ×
H-5′); 4.01 (m , 1 H, H-4′); 4.22 (m , 1 H, H-3′); 4.65 (ddd, 1 H, J = 5.0, 5.5 an d 5.9, H-2′);
5.12 (t, 1 H, J = 5.5, 5′-OH); 5.23 (d, 1 H, J = 5.0, 3′-OH); 5.54 (d, 1 H, J = 5.9, 2′-OH); 6.09
(d, 1 H, J = 5.5, H-1′); 7.47 (d, 1 H, J = 8.5, H-arom .); 8.80 (d, 1 H, J = 8.5, H-arom .); 8.90 (s,
1 H, H-8); 9.00 (s, 1 H, H-2). 13C NMR (100 MHz, DMSO-d6): 14.07 (SCH3); 61.18 (CH2-5′);
70.22 (CH-3′); 73.71 (CH-2′); 85.63 (CH-4′); 87.64 (CH-1′); 125.29 (CH-arom .); 129.63
(CH-arom .); 130.48 an d 131.41 (C-5 an d C-i-arom .); 142.73 (C-SMe); 144.62 (C-8); 151.84
(C-2); 152.05 an d 152.46 (C-4 an d C-6). UV (MeOH), λm ax (εm ax): 332 (1 700). For
C
17H18N4O4S (374.4) calculated: 54.53% C, 4.85% H, 14.96% N, 8.56% S; foun d: 54.32% C,
4.87% H, 14.57% N, 8.50% S.
6-[4-(Dimethylamino)phenyl]-9-(β-D-ribofuranosyl)purine (4b ). Yellow crystals, yield 63%,
m .p. 206–208 °C, [α]D –72.6 (c 0.2, DMF). FAB MS, m/z (rel.%): 372 (42) [M + H], 240 (35)
[M + H – Rf], 93 (100). 1H NMR (400 MHz, DMSO-d6): 2.50 (s, 6 H, N(CH3)2); 3.56–3.62 an d
3.68–3.74 (2 × m , 2 × 1 H, 2 × H-5′); 4.00 (m , 1 H, H-4′); 4.21 (m , 1 H, H-3′); 4.65 (ddd, 1 H,
J = 4.9, 5.7 an d 5.0, H-2′); 5.16 (t, 1 H, J = 5.8, 5′-OH); 5.21 (d, 1 H, J = 4.9, 3′-OH); 5.51 (d,
1 H, J = 6.0, 2′-OH); 6.05 (d, 1 H, J = 5.7, H-1′); 6.87 (d, 2 H, J = 9.0, H-arom .); 8.76, 8.78
an d 8.82 (3 × s, 4 H, H-2, H-8 an d 2 × H-arom .). 13C NMR (100 MHz, DMSO-d6): ≈39
(N(CH3)2 overlapped by DMSO); 61.25 (CH2-5′); 70.27 (CH-3′); 73.59 (CH-2′); 85.59 (CH-4′);
87.54 (CH-1′); 111.34 (CH-arom .); 122.16 an d 129.52 (C-5 an d C-i-arom .); 130.74
(CH-arom .); 143.44 (C-8); 151.68 (C-2); 151.41, 152.10 an d 153.50 (C-NMe2, C-4 an d C-6).
UV (MeOH), λm ax (εm ax): 375 (27 300), 243 (12 300). For C18H21N5O4 (371.4) calculated:
58.21% C, 5.70% H, 18.86% N; foun d: 57.90% C, 5.85% H, 18.63% N.
9-(β-D-Ribofuranosyl)-6-[4-(trifluoromethyl)phenyl]purine (4c). Colourless crystals, yield 79%,
m .p. 179–181 °C, [α]D –42.9 (c 0.2, DMF). FAB MS, m/z (rel.%): 397 (19) [M + H], 265 (100).
1H NMR (400 MHz, DMSO-d6): 3.58–3.64 an d 3.70–3.76 (2 × m , 2 H, 2 × H-5′); 4.02 (m , 1 H,
H-4′); 4.24 (m , 1 H, H-3′); 4.67 (m , 1 H, H-2′); 5.11 (t, 1 H, J = 5.3, 5′-OH); 5.24 (d, 1 H, J =
5.0, 3′-OH); 5.55 (d, 1 H, J = 5.8, 2′-OH); 6.12 (d, 1 H, J = 5.4, H-1′); 7.99 (d, 1 H, J = 8.3,
H-arom .); 9.00 (s, 1 H, H-8); 9.02 (d, 1 H, J = 8.2, H-arom .); 9.08 (s, 1 H, H-2). 13C NMR
(100 MHz, DMSO-d6): 61.11 (CH2-5′); 70.15 (CH-3′); 73.77 (CH-2′); 85.65 (CH-4′); 87.75
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Cytostatic 6-Arylpurine Nucleosides
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1
3
(CH-1′); 124.04 (q, JC,F = 272.0, CF3); 125.59 (d, JC,F = 3.6, CH-arom .); 129.95 (CH-arom .);
2
130.73 (d, JC,F = 31.7, CCF3); 131.22 (C-5); 138.99 (C-i-arom .); 145.57 (C-8); 151.07 (C-4);
151.94 (H-2); 152.50 (C-6). 19F NMR (376.5 MHz, DMSO-d6): –60.90 (s, CF3). UV (MeOH),
λm ax (εm ax): 290 (14 400), 245 (7 000). For C17H15F3N4O4 (396.3) calculated: 51.52% C,
3.81% H, 14.38% F, 14.14% N; foun d: 51.25% C, 3.73% H, 14.25% F, 13.83% N.
6-(4-Hydroxyphenyl)-9-(β-D-ribofuranosyl)purine (4d ). Meth od B; wh ite h ygroscopic crystals,
yield 60%, m .p. 172–175 °C, [α]D –51.31 (c 0.2, DMF). FAB MS, m/z (rel.%): 345 (14) [M +
H], 93 (100). 1H NMR (400 MHz, DMSO-d6): 3.60 (dd, 1 H, J = 3.7 an d 11.9, H-5′a); 3.72 (dd,
1 H, J = 3.6 an d 11.9, H-5′b); 4.00 (ddd, 1 H, J = 3.6, 3.6 an d 3.7, H-4′); 4.22 (dd, 1 H, J = 3.6
an d 4.6, H-3′); 4.65 (dd, 1 H, J = 4.6, 5.6, H-2′); 5.16 (br, 1 H, 5′-OH); 5.22 (br, 1 H, 3′-OH);
5.54 (br, 1 H, 2′-OH); 6.06 (d, 1 H, J = 5.6, H-1′); 6.97 (d, 2 H, J = 8.6, H-arom .); 8.75 (d, 2 H,
J = 8.6, H-arom .); 8.84 an d 8.90 (2 × s, 2 × 1 H, H-2 an d H-8); 10.20 (brs, 1 H, OH).
13C NMR (100 MHz, DMSO-d6): 61.24 (CH2-5′); 70.27 (CH-3′); 73.69 (CH-2′); 85.64 (CH-4′);
87.61 (CH-1′); 115.52 (CH-arom .); 126.14 an d 129.95 (C-5 an d C-i-arom .); 131.32
(CH-arom .); 144.07 (C-8); 151.74 (C-2); 153.18 an d 160.47 (C-4 an d C-6). UV (MeOH), λm ax
(εm ax): 317 (17 000). For C16H16N4O5·4/3H2O (368.3) calculated: 52.17% C, 5.11% H,
15.21% N; foun d: 52.27% C, 5.24% H, 14.91% N.
6-(3,4-Dimethoxyphenyl)-9-(β-D-ribofuranosyl)purine (4e). Yellowish crystals, yield 67%, m .p.
137–139 °C (90% aqueous EtOH), [α]D –56.7 (c 0.2, DMF). FAB MS, m/z (rel.%): 389 (46)
[M + H], 360 (100). 1H NMR (400 MHz, DMSO-d6): 3.61 (dd, 1 H, J = 3.8 an d 12.0; H-5′a);
3.73 (dd, 1 H, J = 3.8 an d 12.0; H-5′b); 3.88 an d 3.89 (2 × s, 2 × 3 H, 2 × OCH3); 4.01 (m ,
1 H, H-4′); 4.23 (m , 1 H, H-3′); 4.65 (brt, 1 H, J= 5.2, H-2′); OH sign als were exch an ged; 6.09
(d, 1 H, J = 5.5, H-1′); 7.19 (d, 1 H, J = 8.6, H-arom .); 8.47 (d, 1 H, J = 1.6, H-arom .); 8.60
(dd, 1 H, J = 1.6 an d 8.6, H-arom .); 8.88 an d 8.94 (2 × s, 2 × 1 H, H-8 an d H-2). 13C NMR
(100.6 MHz, DMSO-d6): 55.43 an d 55.54 (OCH3); 61.17 (CH2-5′); 70.20 (CH-3′); 73.71
(CH-2′); 85.59 (CH-4′); 87.61 (CH-1′); 111.50, 111.82 an d 123.47 (CH-arom .); 127.68 an d
130.23 (C-i-arom . an d C-5); 144.35 (CH-8); 151.69 (CH-2); 148.60, 151.45, 151.88 an d
152.69 (C-4, C-6 an d 2 × CO). UV (MeOH), λm ax (εm ax): 329 (17 100). For C18H20N4O6·H2O
(406.4) calculated: 53.20% C, 5.46% H, 13.79% N; foun d: 53.53% C, 5.25% H, 13.40% N.
6-[3,4-(Methylenedioxy)phenyl]-9-(β-D-ribofuranosyl)purine (4f). Yellowish crystals, yield 71%,
m .p. 130–135 °C (96% aqueous EtOH–toluen e), [α]D –53.5 (c 0.2, DMF). FAB MS, m/z (rel.%):
373 (65) [M + H], 360 (100). 1H NMR (400 MHz, DMSO-d6): 3.57–3.64 an d 3.70–3.75 (2 × m ,
2 H, 2 × H-5′); 4.00 (m , 1 H, H-4′); 4.22 (m , 1 H, H-3′); 4.65 (ddd, 1 H, J = 4.8, 5.5 an d 5.9,
H-2′); 5.11 (t, 1 H, J = 5.5, 5′-OH); 5.20 (d, 1 H, J = 5.0, 3′-OH); 5.51 (d, 1 H, J = 5.9, 2′-OH);
6.08 (d, 1 H, J = 5.5, H-1′); 6.15 (s, 2 H, OCH2O); 7.15 (d, 1 H, J = 8.3, H-arom .); 8.36 (d,
1 H, J = 1.5, H-arom .); 8.55 (dd, 1 H, J = 1.5 an d 8.3, H-arom .); 8.88 an d 8.93 (2 × s, 2 × 1 H,
H-8 an d H-2). 13C NMR (100.6 MHz, DMSO-d6): 61.18 (CH2-5′); 70.21 (CH-3′); 73.70 (CH-2′);
85.62 (CH-4′); 87.65 (CH-1′); 101.62 (OCH2O); 108.48, 108.64 an d 124.82 (CH-arom .);
129.29 an d 130.19 (C-i-arom . an d C-5); 144.46 (CH-8); 151.69 (CH-2); 147.67, 149.83,
151.97 an d 152.35 (C-4, C-6 an d 2 × CO). UV (MeOH), λm ax (εm ax): 331 (13 000), 231
(8 700). For C17H16N4O6·1/2H2O (372.3) calculated: 53.54% C, 4.49% H, 14.69% N; foun d:
53.40% C, 4.49% H, 14.35% N.
6-(1-Naphthyl)-9-(β-D-ribofuranosyl)purine (4g). Yellowish crystals, yield 70%, m .p. 133–
139 °C (slow dec., 96% aqueous EtOH–toluen e), [α]D –52.9 (c 0.2, DMF). FAB MS, m/z
(rel.%): 379 (25) [M + H], 247 (100). 1H NMR (400 MHz, DMSO-d6): 3.61 (dd, 1 H, J = 3.6
an d 11.9, H-5′a); 3.73 (dd, 1 H, J = 3.7 an d 11.9, H-5′b); 4.03 (m , 1 H, H-4′); 4.24 (m , 1 H,
H-3′); 4.70 (dd, 1 H, J = 4.8 an d 5.6, H-2′); 5.15, 5.55 an d 5.82 (3 × vbrs, 3 × OH); 6.14 (d,
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496
Hocek, Holý, Votruba, Dvořáková:
1 H, J = 5.6, H-1′); 7.49–7.72 (m , 3 H, H-arom .); 7.96–8.17 (m , 4 H, H-arom .); 8.86 (s, 1 H,
H-8); 9.12 (s, 1 H, H-2). 13C NMR (100.62 MHz, DMSO-d6): 61.27 (CH2-5′); 70.33 (CH-3′);
73.72 (CH-2′); 85.76 (CH-4′); 87.72 (CH-1′); 125.13, 125.76, 126.14, 126.60, 128.28, 129.66
an d 130.19 (7 × CH-arom .); 130.51, 132.42, 132.72 an d 133.41 (3 × C-arom . an d C-5);
145.10 (CH-8); 151.74 (CH-2); 156.68 (C-4 an d C-6). UV (MeOH), λm ax (εm ax): 311 (6 900),
260 sh (7 200), 249 (8 000). For C20H18N4O4·1/2H2O (387.4) calculated: 62.01% C, 4.94% H,
14.46% N; foun d: 62.12% C, 4.82% H, 14.11% N.
6-(2-Naphthyl)-9-(β-D-ribofuranosyl)purine (4h ). Yellowish crystals, yield 78%, m .p. 193–
195 °C (96% aqueous EtOH), [α]D –63.8 (c 0.2, DMF). FAB MS, m/z (rel.%): 379 (40) [M + H],
247 (100). 1H NMR (400 MHz, DMSO-d6): 3.62–3.68 an d 3.74–3.80 (2 × m , 2 × 1 H, 2 ×
H-5′); 4.05 (m , 1 H, H-4′); 4.27 (m , 1 H, H-3′); 4.71 (m , 1 H, H-2′); 5.17 (t, 1 H, J = 5.1,
5′-OH); 5.27 (d, 1 H, J = 4.0, 3′-OH); 5.60 (d, 1 H, J = 3.7, 2′-OH); 6.16 (d, 1 H, J = 5.3, H-1′);
7.60–7.68 (m , 2 H, H-arom .); 8.02 (d, 1 H, J = 7.4, H-arom .); 8.14–8.17 (m , 2 H, H-arom .);
8.92 (d, 1 H, J = 8.6, H-arom .); 9.00 an d 9.08 (2 × s, 2 × 1 H, H-8 an d H-2); 9.51 (s, 1 H,
H-arom .). 13C NMR (100.62 MHz, DMSO-d6): 61.21 (CH2-5′); 70.25 (CH-3′); 73.83 (CH-2′);
85.68 (CH-4′); 87.83 (CH-1′); 125.63, 126.71, 127.66, 127.79, 128.15, 129.18 an d 130.26 (7 ×
CH-arom .); 131.12, 132.67, 132.77 an d 134.15 (3 × C-arom . an d C-5); 145.02 (CH-8); 151.93
(CH-2); 152.27 an d 152.86 (C-4 an d C-6). UV (MeOH), λm ax (εm ax): 314 (22 200), 267
(23 100). For C20H18N4O4·1/2H2O (387.4) calculated: 62.01% C, 4.94% H, 14.46% N; foun d:
62.21% C, 4.76% H, 14.30% N.
6-(2-Pyridyl)-9-(β-D-ribofuranosyl)purine (4i). Yellowish crystals, yield 65%, m .p. 136–139 °C
(96% aqueous EtOH–toluen e), [α]D –51.5 (c 0.2, DMF). FAB MS, m/z (rel.%): 330 (38) [M +
H], 198 (100). 1H NMR (500 MHz, DMSO-d6): 3.58–3.62 an d 3.69–3.75 (2 × m , 2 H, 2 ×
H-5′); 4.01 (m , 1 H, H-4′); 4.22 (m , 1 H, H-3′); 4.67 (ddd, 1 H, J = 5.9, 5.5 an d 4.8, H-2′);
5.14 (t, 1 H, J = 5.5, 5′-OH); 5.27 (d, 1 H, J = 5.0, 3′-OH); 5.58 (d, 1 H, J = 5.9, 2′-OH); 6.12
(d, 1 H, J = 5.5, H-1′); 7.57 (dd, 1 H, J = 6.5 an d 4.8, H-4-Py); 8.05 (dt, 1 H, J = 1.7 an d 7.8,
H-5-Py); 8.61 (d, 1 H, J = 7.9, H-6-Py); 8.84 (d, 1 H, J = 4.0, H-arom .); 8.93 (s, 1 H, H-8); 9.07
(s, 1 H, H-2). 13C NMR (100.6 MHz, DMSO-d6): 61.14 (CH2-5′); 70.19 (CH-3′); 73.72 (CH-2′);
85.61 (CH-4′); 87.64 (CH-1′); 124.97 (CH-4-Py); 125.34 (CH-6-Py); 131.41 (C-5); 136.83
(CH-5-Py); 145.50 (C-8); 149.81 (CH-3-Py); 151.78 (C-2); 152.62, 153.08 an d 153.26 (C-4,
C-6 an d C-1-Py). HR MS (FAB), calculated for C15H16N5O4 [M + H]: 330.1202; foun d:
330.1187. UV (MeOH), λm ax (εm ax): 295 (13 000). For C15H15N5O4·H2O (347.3) calculated:
51.87% C, 4.93% H, 20.16% N; foun d: 51.82% C, 4.73% H, 20.02% N.
6-(1-Methylpyrrol-2-yl)-9-(β-D-ribofuranosyl)purine (4j). Yellowish crystals, yield 86%, m .p.
176–178 °C (EtOH–toluen e), [α]D –62.9 (c 0.2, DMF). FAB MS, m/z (rel.%): 332 (38) [M + H],
200 (100). 1H NMR (500 MHz, DMSO-d6): 3.56–3.61 an d 3.68–3.73 (2 × m , 2 H, 2 × H-5′);
3.99 (m , 1 H, H-4′); 4.15 (s, 3 H, CH3); 4.21 (m , 1 H, H-3′); 4.64 (ddd, 1 H, J = 4.9, 5.7 an d
6.0, H-2′); 5.15 (t, 1 H, J = 5.7, 5′-OH); 5.23 (d, 1 H, J = 5.0, 3′-OH); 5.53 (d, 1 H, J = 6.0,
2′-OH); 6.04 (d, 1 H, J = 5.7, H-1′); 6.25 (dd, 1 H, J = 2.5 an d 3.9, H-arom .); 7.14 (brt, 1 H,
J = 1.9, H-arom .); 7.80 (dd, 1 H, J = 1.9 an d 3.9, H-arom .); 8.75 (s, 1 H, H-8); 8.81 (s, 1 H,
H-2). 13C NMR (125.77 MHz, DMSO-d6): 38.05 (CH3); 61.32 (CH2-5′); 70.35 (CH-3′); 73.71
(CH-2′); 85.67 (CH-4′); 87.54 (CH-1′); 108.63, 119.35 an d 130.10 (CH-arom .); 126.32 an d
128.62 (C-5 an d C-i-arom .); 143.45 (CH-8); 148.91 an d 150.75 (C-6 an d C-4); 151.33 (CH-2).
UV (MeOH), λm ax (εm ax): 343 (25 500), 240 (8 600). For C15H17N5O4 (331.3) calculated:
54.38% C, 5.17% H, 21.14% N; foun d: 54.41% C, 5.27% H, 20.78% N.
6-Benzyl-9-(β-D-ribofuranosyl)purine (4k ). Colourless crystals, yield 66%, m .p. 97–100 °C
(EtOH–toluen e–h eptan e), [α]D –47.7 (c 0.2, DMF). FAB MS, m/z (rel.%): 343 (16) [M + H], 52
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Cytostatic 6-Arylpurine Nucleosides
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(32), 185 (45), 93 (100). 1H NMR (500 MHz, DMSO-d6): 3.55–3.60 an d 3.66–3.71 (2 × m ,
2 H, 2 × H-5′); 3.98 (m , 1 H, H-4′); 4.19 (m , 1 H, H-3′); 4.42 (s, 2 H, CH2Ph ); 4.65 (m , 1 H,
H-2′); 5.09 (t, 1 H, J = 5.5, 5′-OH); 5.22 (d, 1 H, J = 4.8, 3′-OH); 5.51 (d, 1 H, J = 5.9, 2′-OH);
6.02 (d, 1 H, J = 5.7, H-1′); 7.15–7.39 (m , 5 H, H-arom .); 8.81 an d 8.83 (2 × s, 2 × 1 H, H-8
an d H-2). 13C NMR (100 MHz, DMSO-d6): 38.57 (CH2Ph ); 61.23 (CH2-5′); 70.29 (CH-3′);
73.52 (CH-2′); 85.67 (CH-4′); 87.58 (CH-1′); 126.32, 128.34 an d 129.02 (CH-arom .); 132.36
an d 137.92 (C-5 an d C-i-arom .); 144.52 (C-8); 151.88 (C-2); 150.67 an d 159.75 (C-4 an d
C-6). UV (MeOH), λm ax (εm ax): 263 (5 600). For C17H18N4O4 (342.3) calculated: 59.64% C;
5.30% H, 16.37% N; foun d: 59.25% C, 5.31% H, 15.99% N.
6-(4-Fluorobenzyl)-9-(β-D-ribofuranosyl)purine (4l). Colourless crystals, yield 67%, m .p.
89–91 °C (EtOH–toluen e–h eptan e), [α]D –45.6 (c 0.2, DMF). FAB MS, m/z (rel.%): 361 (8)
[M + H], 279 (82), 93 (100). 1H NMR (500 MHz, DMSO-d6): 3.56–3.60 an d 3.66–3.71 (2 × m ,
2 H, 2 × H-5′); 3.98 (m , 1 H, H-4′); 4.19 (m , 1 H, H-3′); 4.42 (s, 2 H, CH2Ph F); 4.64 (m , 1 H,
H-2′); 5.09 (t, 1 H, J = 5.2, 5′-OH); 5.22 (d, 1 H, J = 4.5, 3′-OH); 5.51 (d, 1 H, J = 5.7, 2′-OH);
6.02 (d, 1 H, J = 5.6, H-1′); 7.07–7.11 an d 7.38–7.42 (2 × m , 2 × 2 H, H-arom .); 8.81 an d 8.83
(2 × s, 2 × 1 H, H-8 an d H-2). 13C NMR (100 MHz, DMSO-d6): 37.65 (CH2Ph ); 61.23 (CH2-5′);
70.29 (CH-3′); 73.54 (CH-2′); 85.68 (CH-4′); 87.59 (CH-1′); 115.05 (d, JF,C = 20.9, CH-arom .);
130.88 (CH-arom .); 132.29 an d 134.00 (C-5 an d C-i-arom .); 144.56 (C-8); 151.90 (C-2);
150.69 an d 159.55 (C-4 an d C-6), 160.83 (d, JF,C = 256.0, C-F). 19F NMR (376.5 MHz,
DMSO-d6): –116.19 (s, FPh ). UV (MeOH), λm ax (εm ax): 264 (7 700). For C17H17FN4O4 (360.3)
calculated: 56.66% C, 4.76% H, 15.55% N; foun d: 56.37% C, 4.67% H, 15.29% N.
6-(4-Methoxybenzyl)-9-(β-D-ribofuranosyl)purine (4m ). Colourless crystals, yield 88%, m .p.
120–123 °C (EtOH–toluen e–h eptan e), [α]D –47.4 (c 0.2, DMF). FAB MS, m/z (rel.%): 373 (8)
[M + H], 279 (100). 1H NMR (400 MHz, DMSO-d6): 3.55–3.61 an d 3.66–3.72 (2 × m , 2 H, 2 ×
H-5′); 3.70 (s, 3 H, OCH3); 3.99 (m , 1 H, H-4′); 4.21 (m , 1 H, H-3′); 4.37 (s, 2 H, CH2Ph );
4.66 (ddd, 1 H, J = 4.6, 5.7 an d 5.9, H-2′); 5.10 (t, 1 H, J = 5.5, 5′-OH); 5.23 (d, 1 H, J = 4.8,
3′-OH); 5.52 (d, 1 H, J = 5.9, 2′-OH); 6.04 (d, 1 H, J = 5.7, H-1′); 6.84 (d, 2 H, J = 8.4,
H-arom .); 7.30 (d, 2 H, J = 8.4, H-arom .); 8.81 an d 8.83 (2 × s, 2 × 1 H, H-8 an d H-2).
13C NMR (100.6 MHz, DMSO-d6): 37.79 (CH2Ph ); 54.98 (OCH3); 61.31 (CH2-5′); 70.37
(CH-3′); 73.59 (CH-2′); 85.73 (CH-4′); 87.64 (CH-1′); 113.86 an d 130.07 (CH-arom .); 129.86
an d 132.28 (C-i-arom . an d C-5); 144.48 (CH-8); 151.93 (CH-2); 150.71, 157.90 an d 160.23
(C-4, C-6 an d C-OMe). UV (MeOH), λm ax (εm ax): 265 (6 900). HR MS (FAB), calculated for
C
18H21N4O5 [M + H]: 373.1512; foun d: 373.1479. For C18H20N4O5 (372.4) calculated:
58.06% C, 5.41% H, 15.05% N; foun d: 57.92% C, 5.59% H, 14.59% N.
6-(2-Thienyl)-9-(β-D-ribofuranosyl)purine (4n ). Colourless crystals, yield 66%, m .p. 126–
129 °C (96% aqueous EtOH–toluen e), [α]D –55.3 (c 0.2, DMF). FAB MS, m/z (rel.%): 335 (19)
[M + H], 93 (100). 1H NMR (400 MHz, DMSO-d6): 3.58–3.64 an d 3.70–3.75 (2 × m , 2 H, 2 ×
H-5′); 4.01 (m , 1 H, H-4′); 4.22 (m , 1 H, H-3′); 4.65 (ddd, 1 H, J = 4.7, 5.4 an d 5.9, H-2′);
5.13 (t, 1 H, J = 5.5, 5′-OH); 5.24 (d, 1 H, J = 5.0, 3′-OH); 5.55 (d, 1 H, J = 5.9, 2′-OH); 6.07
(d, 1 H, J = 5.4, H-1′); 7.35 (dd, 1 H, J = 3.2 an d 4.9, H-arom .); 7.94 (d, 1 H, J = 4.9,
H-arom .); 8.65 (d, 1 H, J = 3.2, H-arom .); 8.87 an d 8.90 (2 × s, 2 × 1 H, H-8 an d H-2).
13C NMR (100.6 MHz, DMSO-d6): 61.23 (CH2-5′); 70.27 (CH-3′); 73.80 (CH-2′); 85.71
(CH-4′); 87.76 (CH-1′); 128.63 (C-5); 129.13, 131.87 an d 132.54 (CH-arom .); 139.59
(C-i-arom .); 145.06 (CH-8); 148.76 (C-6); 151.67 (C-4); 152.02 (CH-2). UV (MeOH), λm ax
(εm ax): 323 (23 300), 270 (6 400), 228 (8 900). For C14H16N4O5S·H2O (352.4) calculated:
47.72% C, 4.58% H, 15.90% N; foun d: 47.81% C, 4.60% H, 15.67% N.
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Hocek, Holý, Votruba, Dvořáková:
6-(2-Furyl)-9-(β-D-ribofuranosyl)purine (4o). Colourless crystals, yield 59%, m .p. 165–168 °C
(96% aqueous EtOH–toluen e), [α]D –54.1 (c 0.2, DMF). FAB MS, m/z (rel.%): 319 (15) [M +
H], 93 (100). 1H NMR (400 MHz, DMSO-d6): 3.57–3.63 an d 3.69–3.74 (2 × m , 2 H, 2 × H-5′);
3.99 (m , 1 H, H-4′); 4.21 (m , 1 H, H-3′); 4.64 (m , 1 H, H-2′); 5.13 (t, 1 H, J = 5.5, 5′-OH);
5.24 (d, 1 H, J = 4.6, 3′-OH); 5.55 (d, 1 H, J = 5.7, 2′-OH); 6.06 (d, 1 H, J = 5.4, H-1′); 6.82
(brs, 1 H, H-arom .); 7.85 (d, 1 H, J = 3.0, H-arom .); 8.08 (brs, 1 H, H-arom .); 8.87 an d 8.90
(2 × s, 2 × 1 H, H-8 an d H-2). 13C NMR (100.6 MHz, DMSO-d6): 61.22 (CH2-5′); 70.26
(CH-3′); 73.76 (CH-2′); 85.70 (CH-4′); 87.69 (CH-1′); 112.95 an d 117.56 (CH-arom .); 128.25
(C-5); 144.84 (C-6); 145.00 (CH-8); 146.61 (CH-arom .); 148.95 (C-i-arom .); 151.56 (C-4);
152.05 (CH-2). UV (MeOH), λm ax (εm ax): 325 (17 200), 315 (18 500), 227 (8 800). For
C
14H16N4O6·1/2H2O (327.3) calculated: 51.38% C, 4.62% H, 17.12% N; foun d: 51.58% C,
4.56% H, 16.88% N.
This work is a part of a research project Z4055905 and it was supported by the Grant Agency of the
Czech Republic (grants No. 203/00/0036 and No. 203/94/K001). Excellent technical assistance of Ms
K. Havlíčková is gratefully acknowledged. The authors’ thanks are also due to the staff of the mass
spectrometry and analytical departments of the Institute of Organic Chemistry and Biochemistry.
REFERENCES
1. MontgomeryJ. A., Hewson K: J. Med. Chem. 1968, 11, 48.
2. a) McGarrityG. J., Carson D. A.: Exp. Cell Res. 1982, 139, 199; b) Whitaker A. M.,
Windsor G. D., Burnett C. M., Taylor C. H.: Dev. Biol. Stand. 1987, 66, 503;
c) Ishiguro K., Taira S., Sasaki T., Nariuchi H.: J. Immunol. Methods 1988, 108, 39.
3. a) Parker W. B., King S. A., Allan P. W., Bennett L. L., Jr., Secrist J. A., III, MontgomeryJ. A.,
Gilbert K. S., Waud W. R., Wells A. H., Gillespie G. Y., Sorscher E. J.: Hum. Gene Ther.
1997, 8, 1637; b) Parker W. B., Allan P. W., Shaddix S. C., Rose L. M., Speegle H. F.,
Gillespie G. Y., Bennett L. L., Jr.: Biochem. Pharmacol. 1998, 55, 1673.
4. Brathe A., Gundersen L. L., Rise F., Eriksen A. B., Vollsnes A. V., Wang L. N.: Tetrahedron
1999, 55, 211.
5. Hocek M., Holý A.: Collect. Czech. Chem. Commun. 1999, 64, 229.
6. Hocková D., Hocek M., Dvořáková H., Votruba I.: Tetrahedron 1999, 55, 11109.
7. Cocuzza A. J., Chidester D. R., Culp S., Fitzgerald L., Gilligan P.: Bioorg. Med. Chem. Lett.
1999, 9, 1063.
8. Bakkestuen A. K., Gundersen L. L., Langli G., Liu F., Nolsøe J. M. J.: Bioorg. Med. Chem.
Lett. 2000, 10, 1207.
9. Hocek M., Holý A., Votruba I., Dvořáková H.: J. Med. Chem. 2000, 43, 1817.
10. Hocek M., Holý A., Votruba I., Dvořáková H.: Collect. Czech. Chem. Commun. 2000, 65,
1683.
11. Hocek M., Masojídková M., Holý A.: Collect. Czech. Chem. Commun. 1997, 62, 136.
12. Česnek M., Hocek M., Holý A.: Collect. Czech. Chem. Commun. 2000, 65, 1357.
13. Havelková M., Hocek M., Česnek M., Dvořák D.: Synlett 1999, 1145.
14. Gundersen L. L., Bakkestuen A. K., Aasen A. J., Øveras H., Rise F.: Tetrahedron 1994, 50,
9743.
15. Hassan A. E. A., Abou-Elkair R. A. I., MontgomeryJ. A., Secrist J. A., III: Nucleosides
Nucleotides Nucleic Acids 2000, 19, 1123.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Cytostatic 6-Arylpurine Nucleosides
499
16. Gundersen L. L.: Tetrahedron Lett. 1994, 35, 3155.
17. Hocek M., Masojídková M., Holý A.: Tetrahedron 1997, 53, 2291.
18. Van Aerschot A., Mamos P., Weyns N. J., Ikeda S., De Clercq E., Herdewijn E.: J. Med.
Chem. 1993, 36, 2938.
19. Buck I. M., Reese C. B.: J. Chem. Soc., Perkin Trans. 1 1990, 2937.
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