Molbank 2006, M481 |
Synthesis
of novel 2-(2-(6-chloro-9H-purin-9-yl)ethoxy)-6-isobutoxy-tetrahydro-2H-pyran-3-ol
as a potential antiviral agent
A. A. Jarrahpour*, E. Torabi
Department of Chemistry,
Phone: +98 711 2284822,
Fax: +98 711 2280926, e-mail: [email protected]
and [email protected]
*Author
to whom correspondence should be addressed
Received: 18 October 2005 / Accepted: 16 March 2006 / Published:
1June 2006
Abstract : In this paper we propose the synthesis of 2-(2-(6-chloro-9H-purin-9-yl)ethoxy)-6-isobutoxy-tetrahydro-2H-pyran-3-ol as a new potential
antiviral agent Its structure has been confirmed by IR, 1H-NMR, 13C-NMR,
UV and Mass spectroscopic data.
Keywords: nucleoside, 6-chloropurine, tetrahydropyran, bromoether.
Introduction
In Keeping with the
general antineoplastic and antileukemic
properties of purine bases and their nucleosides [1-2],
natural and synthetic nucleosides can have significant antitumor
and/or antiviral activity [3-7].Biological activity and importance of
6-substituted purine bases and nucleosides have been
reported many times [8-11].This led us to the synthesis of a new series of pyran nucleosides including the following one.
Results and Discussion
In principle, coupling
condensation of the halo ethers with 6-chloropurine give the corresponding
nucleosides as a mixture of N-7 and N-9 alkylated
products. For example, 6- chloropurine 2
reacts with compound 4 in DMF to produce the 9-alkylated product 5
and N-7 isomer 6. Heating the mixture of products results in the
complete conversion of 7-alkylated isomer into 9-alkylated one (Scheme1) [12].
Scheme 1
Experimental
General
All needed chemicals were
purchased from Merck, Fluka chemical companies. and triethylamine. IR spectra were
run on a Shimadzu FT-IR 8300 spectrophotometer. 1H-NMR and 13C-NMR
spectra were recorded in DMSO-d6 and CDCl3 using a Bruker Avance DPX instrument (1H-NMR
250 MHz, 13C-NMR 62.9 MHz). Chemical shifts were reported in ppm (¦Ä) downfield
from TMS. The mass spectra were recorded on a Shimadzu GC-MS QP 1000 EX
instrument. Thin-layer chromatography was carried out on silica gel 254
analytical sheets obtained from Fluka. Column
chromatography was carried out on silica gel 60 Merck (230-270 mesh).
Synthesis of 2-(2-(6-chloro-9H-purin-9-yl)ethoxy)-6-isobutoxy-tetrahydro-2H-pyran-3-ol
To a mixture of bromoether 5 (5.94 g, 20.00mmol) and 6-chloropurine 2
(3.09g, 20.00mmol)in DMSO (50 mL) was added potassium
carbonate (3.45g, 25.00mmol) and the mixture was stirred at room temperature
for 39 hours. The reaction mixture was filtered and the mother liquor poured
into ice water, acidified to pH 5 by acetic acid and then was extracted with
ethyl acetate (4x200 mL).The organic layer was washed
with water (800 mL) and extracted. It then was dried
(Na2SO4), filtered, and then freed from solvent under
reduced pressure. The residue was purified by column chromatography on silica
gel and gave 6 as a yellow oil product in 50% (3.85g) yield (Scheme2).
Scheme 2
Boiling point: 153 ¡ãC
Rf = 0.58
1H-NMR (CDCl3): ¦Ä= 0.8
(d, 6H, C (CH3)2), J = 5 Hz); 1.6 (s, 5H, 2CH2, CH);
2.7-4.00 (m, 7H, 2CH2O, CH2N, CH); 4.2-4.7 (m, 3H, 2CH, OH); 8.2 (s, 1H, Ar-H); 8.5 (s, 1H, Ar-H).
IR
(neat, cm-1): 3500; 3100; 2960; 2880.
UV (EtOH;
¦Ëmax nm; ¦Å dm3.mol-1.cm-1): 267 (¦Å 16692); 201 (¦Å 20500).
MS (m/e): 118 (C5H2N4);
100 (C5H8O2); 99 (C5H7O2);
83 (C5H7O); 47 (C3H7).
Acknowledgment:
Authors thank
the Shiraz University Research Council for financial support (Grant
No.84-GR-SC-23).
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