Syntheses and Biological Activity of Poly(methyl 3,4-dihydro-2H-pyran-2-carboxylate-alt-maleic anhydride) Derivative

Abstract

Synthesis of the alternating copolymer poly(methyl 3,4-dihydro- 2H-pyran-2-carboxylate-alt-maleic anhydride) was obtained from equimolar ratio of maleic anhydride to methyl 3,4-dihydro-2H-pyran-2-carboxylate. The molecular weight was found to be low due to the transfer reaction of the 3,4- dihydropyran monomer. Hydrolyses of the copolymer with different conditions afforded polymers with different methyl ester content. Treatment of the polymer with methanol, ammonia, 5-fluorouracil and bis(2-chloroethyl)amine gave polymer derivatives. These polymers had different functionalities and showed in vitro biological activity comparable to the reference polymer DIVEMA. The polymer covalently bound with 5-fluorouracil was found to have a strong antitumor activity.

Get full access to this article

View all access options for this article.

References

Batz, H.-G. Advances Polym. Sci., pp. 23, 25 (1977 ).

Fiel, R.J. , Mark, E.H. and H.I. Levine , in Anionic Polymeric Drugs. R. M. Ottenbrite and O. Vogl , eds. New York:John Wiley & Sons Inc., p. 21 and p. 143.

Ottenbrite, R.M. and G.B. Butler , in Anticancer and Interferon Agents. R. M. Ottenbrite and G. B. Butler , eds. New York:Marcel Dekker Inc., p. 247 (1984).

Ottenbrite, R.M. , W. Regelson , A. Kaplan , R. Carchman , P. Moarahan and A. Muson , in Polymeric Drugs. L. G. Donaruma and O. Vogl , eds. New York:Academic Press, p. 263 (1978).

Ottenbrite, R.M. ACS Sym. Ser 186, " Biological Activities of Polymer," p. 205 (1982).

Ottenbrite, R.M. , E. Goodell , E. and A. Muson. Polymer, pp. 18, 461 (1977).

Butler, G.B. J. Macromol. Sci. Rev., Macromol. Chem. Phys. , p. C22, 89 (1982-83).

Breslow, D.S. Pure and Appl. Chem., pp. 46, 103 (1976 ).

Butler, G.B. J. Macrolol, Sci.-Chem., p. A13, 351 ( 1979).

10.

Donaruma, L.G. , in Anionic Polymeric Drugs. L. G. Donaruma , R. M. Ottenbrite and O. Vogl , eds. New York:John Wiley & Sons Inc., Vol. 1, p. 50 (1980).

11.

Tamura, S. , Y. Shiminishi and N. Murata. Kogyo Kagaku Zasshi, pp. 67, 1073 (1964).

12.

Fujimori, K. Macromol. Sci.-Chem., pp. A9, 496 ( 1975 ).

13.

Kimbrough, R. D., Jr. , W.P. Dickson and J.M. Wilkerson. Polymer Sci. Polymer Letter, pp. B2, 85 (1964).

14.

Fritz, J.S. and N.M. Lisicki. Anal. Cherm, pp. 23, 589 (1951 ).

15.

Drobnik, J. and F. Rypacek. Advances Polym. Sci., pp. 57, 1 (1984 ).

16.

Butler, G.B. and C.C. Wu . Macromolecular Syntheses. E. M. Pearce , ed. New York: John Wiley & Sons Inc., 8:89 (1982).

17.

Breslow, D.S. , E.I. Edwards and N.R. Newburg. Nature, pp. 246, 16 (1973 ).

18.

Ottenbrite, R.M. , K. Kuus and A.M. Kaplan , in Polymers in Medicine. E. Chiellini , and P. Giusti , eds. New York: Plenum Press , p. 3 (1983 ).