Ruthenium tetraoxide catalyzed oxidation of nucleosides: A facile synthesis of 5'-carboxylic acid derivatives

Article abstract of DOI:10.1016/0040-4039(93)88026-F

Purine and pyrimidine nucleosides have been oxidized to the corresponding 5'-carboxylic acids using potassium persulfate and ruthenium trichloride under basic conditions. The method provides easy access to nucleosides bearing 3'-amino and 5'-carboxylic acid functionalities from 3'-azido compounds as exemplified by oxidation of AZT followed by reduction of the acid.

Full text of DOI:10.1016/0040-4039(93)88026-F

Vol. 33. No.
Britain
pp.
in
RUTHENIUM TETRAOXIDE CATALYZED OXIDATION OF NUCLEOSIDES: A
FACILE SYNTHESIS OF
ACID DERIVATIVES
and Michael E. Hogan
Rajender S.
The Center for Biotechnology, Baylor College of Medicine,
4000 Research Forest Drive, The Woodlands, TX 77381, U. S. A.
Key Words: Ruthenium tetraoxide; Potassium persulfate; Oxidation;
Nucleosides;
Carboxylic acids
and pyrimidine nucleosides have been oxidized to the corresponding
Abstract:
acids using potassium persulfate and ruthenium trichloride under basic conditions. The
method provides easy access to nucleosides bearing
from
and
acid functionalities
compounds as exemplified by oxidation of AZT followed by reduction of the acid.
The modification of hydroxymethylene moiety at the 5’ position of nucleosides is
central to the preparation of various pharmacologically important nucleoside
derivatives including vasoactive agents.
oxidation of the
There are few methods available for the
they involve
functionality to
either the use of molecular oxygen in the presence of platinum
which gives
poor yields, or involve potassium
which is applicable only to purines.
In view of the growing application of ruthenium
reactions.8 we have used ruthenium trichloride
tetraoxide assisted oxidation
to prepare purine
with
as a co-oxidant under Sharpless conditions.10
Unfortunately, this
method has only limited application among purines as the complete loss of
chromophore occurred in case of pyrimidines, cytidine, thymidine, and
In continuation of our studies, we explored a variety of co-oxidants for the
ruthenium tetraoxide catalyzed reactions that may find application in the oxidation of
both, purine and pyrimidine nucleosides.
We wish to report that using potassium
acid derivatives are obtained in good yields
The oxidation of AZT,
is representative of the general procedure employed,
To a well-stirred solution of AZT (lmmol) in
potassium persulphate followed by ruthenium trichloride trihydrate
4mg) at room temperature. Upon completion of the reaction (3 hrs), monitored on TLC
v/v), the of the reaction mixture is adjusted to -7.0 with
and the solvent removed under reduced pressure.
purified by flash chromatography on silica gel (230-400 mesh) column to afford
potassium hydroxide
is added
dilute
The crude product is
acid)thymine,
in 80% yield;
Dedicated to Dr. G. R. (Ray) Revankar on the occasion of his 55th birthday
7719

7720
mp
(dec.); FT-IR(neat): 3440,
1744, 1712, 1697 and 1606 cm-l;
NMR
each,
1163.76, and 150.431 (base
36.5, (sugar C’s)]; and 12.12 (CH3); Anal. Calcd. for
2-H’ 2-H”),
NMR
106.50
4.45, 6.131
6172.16 (COOH),
64.45, 65.08, and
and
and 9.07 (s,
138.43
Found:
H, 3.76; N, 25.24. The reduction of
under catalytic hydrogenation
conditions
3 hrs, methanol) affords amino acid,
3, mp
2-H”).
(dec)
A n a l .
NMR
2-H’
and
Found:
Calcd. for
KOH;
(Cat)
A Z T
(78%)
(81%)
(82%)
CH
Our simple method for the synthesis of nucleoside
acids may find
newer applications in the synthesis of novel nucleosides and oligonucleotide analogues.
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(Received in USA 24 July 1992; accepted 23 September 1992)