Covalent analogues of DNA base-pairs and triplets. Part 3: Synthesis of 1,4- and 1,3-bis(purin-6-yl)benzenes and 1-(1,3-dimethyluracil-5-yl)-3 or 4-(purin-9-yl)benzenes

Article abstract of DOI:10.1016/S0040-4020(02)00833-5

The Stille cross-coupling reactions of 1,4- and 1,3-bis(trialkylstannyl)benzenes 2 or 3 with 9-benzyl-6-chloropurine (1) led either to mono-coupled 4- or 3-[(tributylstannyl)phenyl]benzenes 5a and 5b or to bis(9-benzylpurin-6-yl)benzenes (4a or 4b) depending on the ratio of the starting compounds, nature of the stannane and conditions. Analogous reaction of 1 with benzene-1,4-diboronic acid gave selectively 4a in good yield. The reaction of stannanes 5 with 1,3-dimethyl-5-iodouracil gave 1-(9-benzylpurin-6-yl)-4- or -3-(1,3-dimethyluracil-5-yl)benzenes (10a and 10b) in low yields. Compounds 4 and 10 are novel types of covalently linked analogues of nucleobase-pairs.

Full text of DOI:10.1016/S0040-4020(02)00833-5

Tetrahedron 58 (2002) 7431–7435
Covalent analogues of DNA base-pairs and triplets. Part 3:
Synthesis of 1,4- and 1,3-bis(purin-6-yl)benzenes
and 1-(1,3-dimethyluracil-5-yl)-3 or 4-(purin-9-yl)benzenesq
a
a,*
b,*
Martina Havelkov a´ , Dalimil Dvo rˇ a´ k and Michal Hocek
a
Department of Organic Chemistry, Prague Institute of Chemical Technology, CZ-16628 Prague 6, Czech Republic
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ-16610 Prague 6, Czech Republic
b
Received 15 April 2002; revised 17 June 2002; accepted 11 July 2002
Abstract—The Stille cross-coupling reactions of 1,4- and 1,3-bis(trialkylstannyl)benzenes 2 or 3 with 9-benzyl-6-chloropurine (1) led either
to mono-coupled 4- or 3-[(tributylstannyl)phenyl]benzenes 5a and 5b or to bis(9-benzylpurin-6-yl)benzenes (4a or 4b) depending on the
ratio of the starting compounds, nature of the stannane and conditions. Analogous reaction of 1 with benzene-1,4-diboronic acid gave
selectively 4a in good yield. The reaction of stannanes 5 with 1,3-dimethyl-5-iodouracil gave 1-(9-benzylpurin-6-yl)-4- or -3-(1,3-di-
methyluracil-5-yl)benzenes (10a and 10b) in low yields. Compounds 4 and 10 are novel types of covalently linked analogues of nucleobase-
pairs. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
diverse types of biological activity (inhibition of adenosine
kinase, ribosomal peptidyltransferase, etc.).
The effect of many clinically used antitumor agents is based
1
2
11
on DNA cross-linking or on intercalation to DNA.
Numerous models and analogues of Watson–Crick base-
Very recently, we have prepared various purine dimers
0
linked through positions 6 and 6 by acetylene, diacetylene,
3
4
pairs consisting of annelated or cross-linked purine and
pyrimidine heterocycles or even more simple aromatic
vinylene and ethylene linkers. Such carbon linkers con-
nected to carbon atoms of the heterocycles were expected to
be stable towards enzymatic degradation. Significant
5
,6
rings have been prepared. Such base-pairs/triplets ana-
logues may interact with DNA (e.g. by intercalation); if
incorporated into single stranded DNA, they are comple-
mentary to the abasic site of a damaged DNA strand; or
alternatively, if incorporated to the duplex, they form
permanent cross-links.
1
1
cytostatic activity has been found in some bis(purin-6-
yl)acetylenes and diacetylenes, while the partially and fully
saturated derivatives were inactive. Also inactive were
1,3,4- and 1,3,5-tris(purin-6-yl)benzenes recently pre-
1
2
pared as analogues of Hoogsteen triplets. Taking into
account the high cytostatic activity of 6-arylpurine ribo-
1
3
A number of diverse purine–purine conjugates containing
linkage (9–9, 8–8, 9–8, 9–7, 9–6 and 6–6) of various
lengths, including double- and triple-linked purinophanes,
nucleosides, we have decided to prepare a new type of
base-pair analogue consisting of purine dimers as well as
purine–pyrimidine conjugates connected by meta- or para-
phenylene linkers. Their synthesis is the subject of this
paper.
7
have been prepared in order to study the p–p stacking
of purine bases. The purine–purine dimers with a 6,6 -pyri-
0
dine-2,6-bis(carboxamido) linker have been recently pre-
8
pared to study its H-bonding properties as potential
6
6
0
artificial receptors. Methylene N ,N -linked-adenine–ade-
nine dimers are formed by the reaction of carcinogenic
formaldehyde with DNA, which was proved by independent
2. Results and discussion
Cross-coupling reactions of 6-halopurines with aryl organo-
14
9
6
6
0
15
synthesis of the products. A variety of other N ,N -linked-
adenine–adenine dimers, trimers and tetramers with the
metallics (arylmagnesium halides, arylzinc halides,
1
5
13,16
arylstannanes or arylboronic acids
) are very efficient
1
0
linkers of various lengths were prepared and exhibited
methods for the preparation of 6-arylpurines. Therefore, the
double cross-coupling reactions of phenylenebis(metallics)
were the method of choice for the synthesis of the title
compounds. Considering the lower stability of the corre-
sponding phenylenebis(magnesium or zinc halides), we
have chosen easily available 1,4- and 1,3-bis(trialkylstannyl)-
benzenes as key starting compounds.
q
For Part 2 see Ref. 11.
Keywords: purines; nucleobases; cross-coupling; stannanes.
*
Corresponding authors. Tel.: þ420-2-20183324; fax: þ420-2-33331271;
e-mail: dvorakd@vscht.cz; hocek@uochb.cas.cz
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00833-5

7432
M. Havelkov a´ et al. / Tetrahedron 58 (2002) 7431–7435
Scheme 1.
Thus, reactions of 9-benzyl-6-chloropurine (1) with 1,4- and
ZnBr or Cu O) were less effective or ineffective. While
2 2
1
1
,3-bis(tributylstannyl)benzenes (2a and 2b) as well as with
,4- and 1,3-bis(trimethylstannyl)benzenes (3a and 3b)
the reactions of bis(tributylstannyl)benzenes 2 gave
mixtures of mono- and bis-coupled products 4 and 5, the
use of more reactive bis(trimethylstannyl)benzenes (3a and
3b) gave the bis(purinyl)benzenes 4a and 4b in higher yields
of 71 and 43%, respectively (Table 1, entries 7 and 8)
accompanied by lower amounts of 6-phenylpurine 6 (no
traces of the mono-stannanes 5 were detected). In the case
of reaction of 1 with 1,3-bis(trimethylstannyl)benzene (3b),
9-benzyl-6-methylpurine (7, apparently product of methyl
transfer from stannane) was isolated as major by-product.
Its formation might be explained by a more sterically
crowded transition state of the coupling in the case of
the 1,3-disubstituted benzene. From these findings, two
preparative methods could be formulated: (i) the reactions
of bis(trimethylstannyl)benzenes 3 with 6-chloropurine 1 in
a 1:2 ratio gives in reasonable yields and good selectivity
the bis(purin-6-yl)benzenes 4a or 4b (Table 1, entries 7 and
8); (ii) the reactions of bis(tributylstannyl)benzenes 2 with
6-chloropurine 1 in a 2:1 ratio gives the [(tributylstannyl)-
phenyl]purines 5a or 5b as major products in 65 and 69%,
respectively (Table 1, entries 3 and 6).
were studied (Scheme 1). In general, three types of products
were obtained: the desired 1,4- or 1,3-bis(9-benzylpurin-6-
yl)benzenes (4a or 4b), 6-[4- or 3-(tributylstannyl)phenyl]-
purine (5a or 5b) as products of mono-coupling and
9
-benzyl-6-phenylpurine (6) as the product of reductive
destannylation of 5. The ratio of the products strongly
depended on the ratio of starting compounds, the nature of
the stannane and the reaction conditions (Table 1). Several
catalytic systems have been tested in the model reactions of
1
presence of Pd(PPh ) Cl in DMF or NMP gave the double-
with 2a and 2b and, interestingly, only the reactions in
3
2
2
coupling products 4. Other catalysts, i.e. Pd(PPh ) ,
3
Pd (dba) /AsPPh , Pd (dba) /P(o-tolyl) , Pd(dppf)Cl , did
2
4
2
3
3
3
3
2
not work at all or gave only low yields of mono-coupled
products 5 and 6. Reactions in NMP were somewhat faster
than in DMF but due to easier and more efficient isolation of
products, the latter solvent was used in preparative
experiments. Addition of CuI accelerated the second
coupling: no mono-coupled stannanes 5 were detected but
the preparative yields of the bis(purinyl)benzenes 4 were
only slightly improved (Table 1, entries 2 and 5) and the
isolation of products was complicated by some iodine-
containing by-products. Other additives (LiCl, ZnCl2,
Another possible approach to the title bis(purin-6-yl)ben-
zenes could be the use of the Suzuki cross-coupling reaction
of benzenediboronic acids with 6-halopurines. Due to the
Table 1. Reactions of purine 1 with stannanes 2 or 3
Entry
Stannane
Ratio 2(3)/1
Reaction time
Additive
Yields of products (%)
4
5
6
1
2
3
4
5
6
7
8
2a
2a
2a
2b
2b
2b
3a
3b
1:2
1:2
2:1
1:2
1:2
2:1
1:2
1:2
19
19
16
17
17
20
9
–
CuI
–
–
CuI
–
33
35
31
29
44
30
71 (41)
43 (27)
23
0
65
34
0
25
25
Traces
34
34
Traces
25
20
69
–
a
a
–
–
b
15
–
a
In parentheses isolated yield after crystallization.
9-Benzyl-6-methylpurine (7) was isolated as major byproduct in 35% yield.
b

M. Havelkov a´ et al. / Tetrahedron 58 (2002) 7431–7435
7433
diboronic acid. The stannanes 5a and 5b could be used for
another coupling with 1,3-dimethyl-5-iodouracil leading to
the 1-(9-benzylpurin-6-yl)-4- or -3-(1,3-dimethyluracil-5-
yl)benzenes (10a and 10b) in low yields. Despite the low
yields in the preparations of 10, the homo- and hetero-
disubstituted benzenes bearing two purine (compounds 4a
and 4b) or one purine and one pyrimidine (compounds 10a
and 10b) represent a novel type of covalently linked base-
pair analogues. Preliminary cytostatic activity screening
showed that, unlike the highly active bis(purin-6-yl)acetyl-
enes and -diacetylenes, all the title phenylene linked base-
pair models 4 and 10 were inactive. As the length of para-
phenylene linker in compound 4a is in between the
acetylene and diacetylene, the absence of activity is little
surprising and it might indicate that the acetylene- and
diacetylene linkers in the original cytostatic compounds
may form some covalent adducts with the target system
Scheme 2.
strong electron-withdrawing effect of the purine moiety and
1
6a,b
our previous finding
that electron-poor arylboronic
acids react with halopurines less efficiently (especially
under anhydrous conditions), we expected that (if any) the
mono-coupled products will be formed preferentially.
However, the reaction of benzene-1,4-diboronic acid (8)
with 6-chloropurine 1 in the presence of Pd(PPh ) and
(DNA or enzyme) that are excluded for the stable benzene
derivatives. Application of the title novel methodology for
the synthesis of analogous pairs of nucleosides is clearly an
attractive new target and thus it will be the subject of our
further investigations.
3
4
K CO in DME/H O proceeded very smoothly giving the
2
3
2
1
7
,4-bis(9-benzylpurin-6-yl)benzene (4a) in a good yield of
0% (Scheme 2) accompanied by the 6-phenylpurine 6 as a
minor by-product (5%). Interestingly, of the catalysts tested,
Pd(PPh ) was the only one effective for this reaction, while,
e.g. Pd(PPh ) Cl did not give any cross-coupling. When the
3
4
3. Experimental
3
2
2
reaction of chloropurine 1 with diboronic acid 8 in ratio 1:2
was attempted in order to isolate the mono-coupled product,
an inseparable complex mixture of products has been
obtained.
Melting points were determined on a Kofler block and are
uncorrected. NMR spectra were measured on a Varian
1
13
Gemini 300 ( H, 300.07 MHz; C, 75.46 MHz), a Bruker
1
13
AMX3 400 ( H, 400.13 MHz and C, 100.62 MHz) or a
1
13
The formation of mono-coupled 4- or 3-[(tributylstannyl)-
phenyl]benzenes 5a and 5b raised a possibility to synthesize
another type of base-pair analogue: benzenes bearing two
different nucleobases. Thus the stannanes 5a and 5b have
been used for cross-coupling reactions with 1,3-dimethyl-5-
iodouracil (9) in presence of Pd(PPh ) Cl in DMF (Scheme
Bruker DRX 500 Avance ( H, 500.13 MHz and C,
125.77 MHz) spectrometer at 298 K. Unambiguous assign-
1
3
1
13
ment of the NMR signals is based on C{ H}, C APT,
1
3
COSY and C HMBC spectra. IR spectra were recorded
on Nicolet 750 FT-IR. Mass spectra were measured on
ZAB-SEQ (VG Analytical) The solvents were dried and
degassed by standard procedures, silica gel (ICN SiliTech,
32–63) was used for column chromatography. 9-Benzyl-6-
3
2
2
3
1
). The desired 1,4- and 1,3-hetero-disubstituted benzenes
0a and 10b were obtained in low yields of 20 and 19%,
1
5d
17
respectively. In both cases, the de-stannylated 6-phenyl-
purine 6 was the main product. No cross-coupling has been
observed in the reaction of stannanes 5 with unprotected
chloropurine (1), 1,4-bis(trimethylstannyl)benzene (3a),
7
1,3-bis(trimethylstannyl)benzene (3b) and 1,3-dimethyl-
1
1
8
5-iodouracil (8) were prepared by the reported procedures.
1,4-Bis(tributylstannyl)benzene (2a), 1,3-bis(tributylstan-
nyl)-benzene (2b) were prepared analogously to 3a and 3b
and benzene-1,4-diboronic acid (10) was purchased from
Lancaster. Known side-products 6 and 7 were identified
based on comparison of their NMR and IR spectra with
5
-iodouracil.
In conclusion, the methodology of Stille cross-coupling
reactions of phenylenebis(stannanes) with 9-benzyl-6-
chloropurine has been developed to prepare selectively
either monocoupled 4- or 3-[(tributylstannyl)phenyl]ben-
zenes 5a and 5b or bis(purin-6-yl)benzenes 4a and 4b.
The disubstituted product 4a could alternatively be prepared
by analogous Suzuki–Miyaura coupling of benzene-1,4-
1
5d
literature values.
3.1. Reactions of bis(trialkylstannyl)benzenes with
9-benzyl-6-chloropurine—general procedure
DMF (4 ml) was added to an argon purged flask containing
9
-benzyl-6-chloropurine (1) (1–3 mmol), bis(trialkylstannyl)-
benzene 2a, 2b, 3a or 3b (1–3 mmol), CuI (none or
.2 mmol) and Pd(PPh ) Cl (134 mg, 0.19 mmol) and the
0
3
2
2
mixture was stirred at 1008C for 9–20 h. After cooling to rt,
the mixture was filtered through Celite and the Celite was
washed with CHCl /MeOH (2:1). The collected fitrates
3
were evaporated in vacuo and the residue was chromato-
graphed on silica gel (100 g). At first the column was
washed with light-petroleum and then the use of light-
petroleum/diethyl ether/acetone (8:1:1) eluted stannanes 5.
Then the other products 4, 6 and/or 7 were eluted with
Scheme 3.

7434
M. Havelkov a´ et al. / Tetrahedron 58 (2002) 7431–7435
CHCl /MeOH (99:1). For yields of products 4–6, and/or
3
7 depending on the nature and ratio of starting compounds
and reaction times see Table 1.
3.2. Reaction of 9-benzyl-6-chloropurine (1) with
1,4-phenylenediboronic acid
Mixture of benzene-1,4-diboronic acid (8, 100 mg,
0.603 mmol), 9-benzyl-6-chloropurine (1) (310 mg,
1.27 mmol), Pd(PPh3)4 (83 mg, 0.072 mmol), K CO
(473 mg, 3.42 mmol), DME (5 ml) and water (1.7 ml) was
heated under argon to 808C. After 1 h the reaction mixture
was cooled and the separated product was filtered off,
washed with DMF and MeOH and dried in vacuum. In this
way 134 mg (45%) of pure 4a was obtained. The filtrate was
evaporated in vacuum and the chromatography on silica
3
.1.1. 1,4-Bis(9-benzylpurin-6-yl)benzene (4a). Colorless
1
crystals, mp 295–2978C (DMF). H NMR (500 MHz, 408C,
DMF-d ) d 5.87 (s, 4H, CH Ph), 7.52 (m, 2H, ArH), 7.57 (t,
2
3
7
2
J¼7.4 Hz, 4H, ArH), 7.68 (d, J¼7.5 Hz, 4H, ArH), 9.07 (s,
1
3
2
H, 8-PuH), 9.25 (s, 2H, 2-PuH), 9.35 (s, 4H, ArH).
NMR (125 MHz, 408C, DMF-d , APT) d CH: 128.5, 128.6,
C
7
1
4
1
29.4, 130.3, 147.3, 152.8 (Ph, C8-Pu and C2-Pu); C, CH2:
7.5 (CH Ph), 131.8, 137.5, 138.7, 153.0, 153.7. IR (KBr) n
2
2
1
573, 1516, 1446, 1327 cm . Anal. Calcd for C H N
3
(CHCl /MeOH (95:5)) afforded another crop of 4a (70 mg,
3
0
22
8
(
4
4
494.5): C, 72.86; H, 4.48; N, 22.66; found: C, 72.50; H,
.57; N, 22.43. HRMS (EI) calcd for C H N [M]
30 22 8
94.1967. Found: 494.1980.
25%) and 9-benzyl-6-phenylpurine (6) (0.010 g, 6%).
þ
3.2.1. 1-(9-Benzylpurin-6-yl)-4-(1,3-dimethyluracil-5-
yl)benzene (10a). To the 9-benzyl-6-[(4-tributylstannyl)-
phenyl]purine (5a) (114 mg, 0.19 mmol), 1,3-dimethyl-5-
iodouracil (8) (92 mg, 0.35 mmol) and Pd(PPh ) Cl
3
crystals, mp 196–1988C (CHCl /EtOH).
(
.1.2. 1,3-Bis(9-benzylpurin-6-yl)benzene (4b). Colorless
1
H
400 MHz, CDCl ) d 5.48 (s, 4H, CH Ph), 7.31 (m, 10H,
NMR
3
3 2
2
(36 mg, 0.05 mmol) DMF (4 ml) was added under argon
and the mixture was heated to 1008C for 3.5 h. The mixture
was then cooled, filtered through celite, the celite was
3
2
ArH), 7.76 (t, J¼7.7 Hz, 1H, ArH), 8.12 (s, 2H, 8-Pu-H),
8
(
.98 (d, J¼7.5 Hz, 2H, ArH), 9.10 (s, 2H, 2-PuH), 10.14
1
3
s, 1H, ArH); C NMR (100 MHz, CDCl , APT) d CH:
3
washed with small amount of CHCl /MeOH (2:1) and the
3
1
1
1
1
27.8, 128.6, 129.0, 129.1, 131.0, 132.3, 144.4 (C8-Pu),
52.7 (C2-Pu); C, CH : 47.2 (CH Ph), 131.0, 135.2, 136.2,
52.6, 154.7 (C4, C5, C6-Pu and C-Ph). IR (KBr) n 1580,
solvents were evaporated in vacuum. Chromatography of
the residuum on silica gel (100 g, eluted with a gradient:
light-petroleum!light-petroleum/ethyl acetate!ethyl acetate/
MeOH 19:1) afforded 10a (16 mg, 20%). 9-Benzyl-6-
phenylpurine (5) (19 mg, 35%) was obtained as a side
2
2
2
1
563, 1496, 1452, 1322, 1296, 1211, 1195 cm . Anal.
Calcd for C H N (494.5): C, 72.86; H, 4.48; N, 22.66;
3
0 22 8
found: C, 72.59; H, 4.50; N, 22.54. HRMS (EI) calcd for
þ
product. 10a: Colorless crystals, mp 193–1958C (CHCl /
3
toluene/heptane); H NMR (500 MHz, CDCl ) d 3.46 (s,
3
1
C H N [M] 494.1967. Found: 494.1963.
8
3
0
22
3H, CH ), 3.52 (s, 3H, CH ), 5.50 (s, 2H, CH Ph), 7.37 (m,
3 3 2
3
Yellowish oil. H NMR (500 MHz, CDCl ) d 0.89 (t,
.1.3. 9-Benzyl-6-[(4-tributylstannyl)phenyl]purine (5a).
1
5H, ArH), 7.43 (s, 1H, CvCH–NCH ), 7.74 (d, J¼8.3 Hz,
3
2H, ArH), 8.13 (s, 1H, 8-PuH), 8.84 (d, J¼8.3 Hz, 2H,
3
1
3
J¼7.3 Hz, 9H, CH ), 1.098 (m, 6H, CH ), 1.34 (m, 6H,
ArH), 9.07 (s, 1H, 2-PuH). C NMR (125 MHz, CDCl ,
3
3
2
CH ), 1.56 (m, 6H, CH ), 5.48 (s, 2H, CH Ph), 7.36 (m, 5H,
2
APT) d CH, CH : 28.4, 37.4, 127.8, 128.3, 128.6, 129.2,
3
2
2
CH Ph), 7.68 (d, J¼8.0 Hz, J
¼36 Hz, 2H, ArH), 8.08
129.8, 140.9, 144.2, 152.6; C, CH : 47.3, 113.7, 130.9,
2
2
Sn–H
(
s, 1H, 8-PuH), 8.68 (d, J¼7.9 Hz, 2H, ArH), 9.05 (s, 1H,
135.0, 135.1, 135.5, 151.4, 152.5, 154.2, 162.1. IR (CHCl )
3
1
3
21
2
1
3
2
1
3
1
5
-PuH). C NMR (125 MHz, CDCl , APT) d CH, CH :
3
n 3012, 1705, 1657, 1582, 1452 cm . Anal. Calcd for
C H N O (424.5): C, 67.91; H, 4.75; N, 19.80; found: C,
3
3.6 (CH ), 127.8, 128.5, 128.7, 129.1, 136.8 (JSn–C
3
0 Hz), 144.0 (C8-Pu), 152.6 (C2-Pu); C, CH : 9.6, 27.3,
2
9.1 (CH CH CH CH ), 47.2 (CH Ph), 130.9, 135.1, 135.2,
2
46.8, 152.4, 155.5 (C4, C5, C6-Pu and C-Ph). IR (CHCl ) n
3
¼
24 20 6 2
68.22; H, 4.90; N, 19.43. HRMS (EI) (m/z) calcd for
C H N O 424.1647. Found: 424.1631.
2
2
3
2
24 20 6 2
018, 2959, 2928, 2872, 2854, 1581, 1542, 1446, 1384,
1
3.2.2. 1-(9-Benzylpurin-6-yl)-3-(1,3-dimethyluracil-5-yl)-
benzene (10b). The same procedure as used for the
preparation of 10a starting from 9-benzyl-6-[(3-tributyl-
stannyl)phenyl]purine (5b) (113 mg, 0.196 mmol), 1,3-
dimethyl-5-iodouracil (9) (84 mg, 0.32 mmol) and
Pd(PPh ) Cl (20 mg, 0.03 mmol) in DMF (4 ml) furnished
327 cm2 . FAB HRMS (m/z ) calcd for C H N
118
Sn
3
0
41
4
þ
75.2347 [MþH] . Found: 575.2377.
3.1.4. 9-Benzyl-6-[(3-tributylstannyl)phenyl]purine (5b).
1
Yellowish oil. H NMR (500 MHz, CDCl ) d 0.89 (t,
3
3 2
2
J¼7.4 Hz, 9H, CH ), 1.13 (m, 6H, CH ), 1.35 (m, 6H, CH ),
after 1 h of heating and chromatography (the same
conditions as for 10a), 16 mg (19%) of desired 10b.
9-Benzyl-6-phenylpurine (6) (13 mg, 23%) was obtained
as a side product. 10b: Colorless crystals, mp 212–2148C
3
2
2
1
.59 (m, 6H, CH ), 5.47 (s, 2H, CH Ph), 7.35 (m, 5H,
2 2
CH Ph), 7.52 (t, J¼7.5 Hz, 1H, ArH), 7.62 (d, J¼7.2 Hz,
2
J
¼38 Hz, 1H, ArH), 8.07 (s, 1H, 8-PuH), 8.72 (d, J¼
Sn–H
Sn–H
1
7
1
1
3
.9 Hz, 1H, ArH), 8.88 (s, J
H, 2-PuH). C NMR (125 MHz, CDCl , APT) d CH, CH :
¼41 Hz, 1H, ArH), 9.06 (s,
(CHCl /toluene/heptane). H NMR (400 MHz, CDCl ) d
3
3
1
3
3.46 (s, 3H, CH ), 3.52 (s, 3H, CH ), 5.51 (s, 2H, CH Ph),
3 3 2
7.36 (m, 5H, ArH), 7.50 (s, 1H, CvCH–NCH ), 7.62 (t,
3
3
3
3.7 (CH ), 127.8, 127.9, 128.5, 129.1, 129.7, 137.5 (JSn–C
3
¼
4 Hz), 139.0 (JSn–C¼29 Hz), 139.2, 143.9 (C8-Pu), 152.6
J¼7.7 Hz, 1H, ArH), 7.80 (d, J¼7.7 Hz, ArH), 8.13 (s, 1H,
(
C2-Pu); C, CH : 9.7, 27.3, 29.1 (CH CH CH CH ), 47.2
2
8-PuH), 8.83 (d, J¼7.9 Hz, 1H, ArH), 8.87 (s, 1H, ArH),
2
2
2
3
1
3
(
C6-Pu a C-Ph). IR (CHCl ) n 2995, 2959, 2928, 2872, 2854,
CH Ph), 131.1, 134.9, 135.3, 142.5, 152.4, 155.6 (C4, C5,
9.08 (s, 1H, 2-PuH). C NMR (100 MHz, CDCl , APT) d
3
2
CH, CH : 28.3, 37.1, 127.8, 128.6, 128.8, 129.0, 129.2,
3
129.4, 131.2, 140.7, 144.3, 152.6; C, CH : 47.3, 114.1,
2
3
21
1578, 1558, 1498, 1456, 1325 cm . Anal. Calcd for
C H N Sn ·0.5H O (584.37): C, 61.66; H, 7.07; N, 9.59.
131.0, 133.4, 135.2, 136.0, 151.5, 152.6, 154.4, 162.3. IR
2
3
0
40
4
2
1
Found: C, 61.54; H, 7.14; N, 9.20. FAB HRMS (m/z) calcd
18
(CHCl ) n 3021, 1705, 1658, 1581, 1457, 1325 cm . Anal.
3
1
4
þ
for C H N Sn 575.2347 [MþH] . Found: 575.2341.
Calcd for C H N O (424.5): C, 67.91; H, 4.75; N, 19.80;
24 20 6 2
3
0
41

M. Havelkov a´ et al. / Tetrahedron 58 (2002) 7431–7435
7435
ˇ
10. (a) Zemli cˇ ka, J.; Owens, J. J. Org. Chem. 1977, 42, 517–523.
found: C, 67.98; H, 4.65; N, 19.46. HRMS (EI) (m/z) calcd
for C H N O 424.1647. Found: 424.1632.
ˇ
(b) Bhuta, P.; Li, C.; Zemli cˇ ka, J. Biochem. Biophys. Res.
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4 20 6 2
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Commun. 1977, 77, 1237–1244. (c) Zemli cˇ ka, J. Biochemistry
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Acknowledgments
Zemli cˇ ka, J. J. Med. Chem. 1980, 23, 781–786. (e) Zemli cˇ ka,
J. Tetrahedron Lett. 1984, 25, 5619–5622. (f) Agathocleous,
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This work is a part of research projects Z4 055 905 and
MSM 22231 00001. It was supported by the Grant Agency
of the Czech Republic (Grant No. 203/00/0036).
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