Transcript Synthesis of Drug Impurities 3 Acyclovir

Synthesis of 9,9’-[ethane-1,2-diylbis(oxymethanediyl)]bis(2amino-1,9-dihydro-6H-purin-6-one). An impurity of
Acyclovir.
R. M. Suárez, M. P. Matía, J. L. Novella, J. Alvarez-Builla*
Planta Piloto de Química Fina. Universidad de Alcalá. Ctra. Madrid-Barcelona Km. 33,600. 28871 Alcalá de
Henares. Madrid. España.
Introduction
O
Acyclovir[1], is a guanosine analogue antiviral drug, marketed under trade names such
as Zovirax and Zovir (GSK). One of the most commonly-used antiviral drugs, it is
primarily used for the treatment of herpes simplex virus infections, as well as in the
treatment of herpes zoster (shingles). Acyclovir was seen as the start of a new era in
antiviral therapy, because it is extremely selective and of low cytotoxicity.
Acyclovir
N
HN
OH
N
N
H 2N
O
In the present paper, one of the impurities of Acyclovir has been
prepared. The method is indicated in scheme 1[2],[3]. The guanine derivative
4 is an intermediate used in the synthesis of Acyclovir[4],[5],[6].
Synthesis
OH
HO
(CH2O)n
Cl
HCl (g)
1
O
O
O
NaOAc
Cl
H 3C
90%
2
58%
O
O
O
O
CH 3
O
3
O
O HN
N
N
H
N
H 3C
N
O
p-TSA
TBAB
55%
Dowterm Q
CH 3
4
O
O
O
O
NH
N
HN
H 2N
N
N
O
N
O
N
N
HO
NH 2
6
References
[1]
[2]
[3]
[4]
[5]
[6]
NH 2
USP 4 544 634
T. Shimamura, Y. Yamashita; Kogyo Kagaku Zasshi, 1957, 60, 575.
F. Walter; Plastic Products, 1933, 9, 187.
DE 2 539 963
US 4 199 574
GB 1 523 865
86%
O
H 3C
NH
N
HN
N
H
N
N
O
N
N
O
N
5
Scheme 1
N
H
O
CH 3