E. Petricci et al. / Tetrahedron Letters 43 (2002) 9667–9670
9669
Scheme 3.
Acknowledgements
This original and highly efficient cleavage procedure
was also applied to the Wang resin supported pyrimidi-
nones 2 to afford compounds 5 and 6 in comparable
yields (Scheme 1, Table 1).
Italian National Research Council (CNR) ‘Progetto
Finalizzato Biotecnologie’ (CNR Target Project on
‘Biotechnology’) as well as the University of Siena
(PAR 2001) are gratefully acknowledged. M.B. wishes
to thank the Merck Research Laboratories for the 2001
Academic Development Program (ADP) Chemistry
Award.
The same procedure has been also applied to the paral-
lel synthesis of a small library of 12 uracil derivatives
using a Syncore® organic synthesizer at 200 rpm; sub-
stituted uracils (6-methyl; 6-benzyl; 6-trifluoromethyl;
6-ethyl; 6-isopropyl; 6-tert-butyl; 6-chloromethyl; 6-
adamantyl; 5-ethyl-6-methyl; 5-chloro-6-methyl; 5-
fluoro-6-methyl; ethyl 6-acetate) have been obtained in
yields ranging from 20 to 40%.
References
In order to point out its synthetic flexibility, the
Oxone® cleavage methodology was also used for the
releasing of a nucleoside analog from the solid support
(Scheme 3). Thus, in the search of an original approach
for solid-phase synthesis of nucleosides, compound 8
1. Klein, R. S.; Lenzi, M.; Lim, T. H.; Hotchkiss, K. A.;
Wilson, P.; Schwartz, E. L. Biochem. Pharmacol. 2001,
62, 1257–1263.
2. (a) Botta, M.; Corelli, F.; Maga, G.; Manetti, F.; Ren-
zulli, M.; Spadari, S. Tetrahedron 2001, 57, 8357–8367;
(b) Haslam, E. Shikimic Acid Metabolism and Metabo-
lites; Wiley & Sons: New York, 1993.
3. (a) Botta, M.; Occhionero, F.; Nicoletti, R.; Mastro-
marino, R.; Conti, C.; Magrini, M.; Saladino, R. Bioorg.
Med. Chem. 1999, 7, 1925–1931; (b) Lyle, F. R. US
Patent 5 973 257, 1985; Chem. Abstr. 1985, 65, 2870.
4. Kim, D. K.; Gam, J.; Kim, Y. W.; Lim, J.; Kim, H. T.;
Kim, K. H. J. Med. Chem. 1997, 40, 2363–2373.
5. Pontikis, R.; Benhida, R.; Aubertin, A. M.; Grierson, D.
S.; Monneret, C. J. Med. Chem. 1997, 40, 1845–1854.
6. Mager, P. P.; De Clercq, E.; Takashima, H.; Ubasawa,
M.; Sekiya, K.; Baba, M.; Walther, H. Eur. J. Med.
Chem. 1996, 31, 701–712.
was synthesized starting from resin 7 and b-D-ribofura-
nose-1-acetate-2,3,5-tribenzoate (ABR), using a one-pot
approach.24 Subsequent treatment of 8 with Oxone®
provided 9 in 40% yield. In a typical experiment, the
resin 7 was swelled for 30 min in dichloromethane, then
collidine was added and the mixture was treated with
trimethylsilyl trifluoromethanesulfonate at 0°C. After
stirring for 48 h at room temperature, ABR was added.
The mixture was cooled to 0°C, treated with
iodotrimethylsilane and then stirred for additional 48 h.
Treatment of 8 with Oxone® for 12 h afforded com-
pound 9.
In conclusion, an original, efficient and mild procedure
for the cleavage of polymer-bound pyrimidinones,
anchored to the resin through an alkyl thioether spacer,
has been developed, allowing for the very convenient
preparation of uracil compounds, never prepared
before using a solid-phase approach.
7. Baraldi, P. G.; Cacciari, B.; Romagnoli, R.; Spalluto, G.;
Garuti, L.; Roberti, M.; Pani, A.; Perra, G.; Scintu, F.;
Pinna, N.; Musiu, C.; La Colla, P. Anti-Cancer Drug Des.
1996, 11, 597–609.
8. Kundu, N. G.; Mahanty, J. S.; Spears, C. P. Bioorg.
Med. Chem. Lett. 1996, 6, 1497–1502.