생물활성을 갖는 1-메타크릴로일옥시메틸-5-플루오로우라실 및 그 중합체의 합성과 가용매반응

이능주; 오상훈; 하창식; 이진국; 조원제

Journal of the Korean Industrial and Engineering Chemistry, Vol.1, No.2, 190-196, December, 1990

Export Citation

생물활성을 갖는 1-메타크릴로일옥시메틸-5-플루오로우라실 및 그 중합체의 합성과 가용매반응

Syntheses and Solvolysis of Biological Active 1-(Methacryloyloxymethyl)-5-fluorouracil and Its Polymers

이능주, 오상훈, 하창식, 이진국, 조원제

초록

생물활성을 가질 것으로 예상되는 1-(methacryloyloxymethyl)-5-fluorouracil(MAOMFU)을 2, 4-bis(trimethylsilyloxy)-5-fluoropyrimidine으로 부터 합성하고, MAOMF 와 메틸메타크릴레이트(MMA) 를 cyclohexanone 용매로 사용하여 60℃에서 라디칼 공중합을 하였다. 공중합체 내의 단량체조성은 공중합체의 UV스펙트럼으로 부터 정량분석하여 구하였다. Kelen-Tudos법에 의해 구한 각각의 단량체 반응성비의 값은 r₁(MAOMFU)=0.72, r₂(MMA)=1.24이었다. 얻어진 단량체 반응성비의 값들로부터 MAOMFU와 MMA의 공중합에서 MAOMFU의 입체장애 효과가 영향을 미치는 것을 알 수 있다. MAOMFU와 poly(MAOMFU)의 가용매분해속도상수는 각각 6.42×10^-5sec^-1와 7.40×10^-6sec^-1이 었다. 얻어진 가용매분해속도상수로부터 poly(MAOMFU)에서 5-fluorouracil의 가용매분해속도는 MAOMFU보다 약 5배 느리다는 것을 알 수 있었다.

The biological active monomer, 1-(methacryloyloxymethyl)-5-fluorouracil(MAOMFU) was synthesized from 2, 4-bis(trimethylsilyloxy)-5-fluoropyrimidine. Poly(MAOMFU) poly(1-methacryloyloxymethyl-5-f1uorouracil-co-methyl methacrylate), and poly(MAOMFU-co-MMA) were also obtained by radical polymerization at 60℃. The monomer reactivity ratios, r₁ and r₂ were determined by Kelen-Tudos method ; r₁(MAOMFU)=0.72, and r₂(MMA)=1.24. These reactivity values imply that the copolymerization was mainly affected by the steric hindrance of MAOMFU. It was found from kinetic measurements that the rate constants of solvolysis are given as 6.42×10^-5sec^-1 and 7.40×10^-6sec^-6, respectively, for MAOMFU and poly(MAOMFU).

[References]

Pato J, Azori M, Ulbrich K, Kopecek J, Makromol. Chem., 185, 231 (1984)
Ouchi T, Sakamoto Y, Jokei S, Chikashita H, Makromol. Chem., 185, 255 (1984)
Matsuzaki K, Yamamoto I, Sato T, Oshima R, Makromol. Chem., 186, 449 (1984)
Hung RY, Kopeck J, Andrade JD, Makromol. Chem., 190, 69 (1987)
Breslow DS, Pure Appl. Chem., 46, 103 (1976)
Bounous G, Pageau R, Regoli D, J. Chem. Pharmacol. Biopharm., 16, 519 (1978)
Bosch L, Harbers E, Heidelberger C, Cancer Rev., 18, 335 (1958)
Umrigar PP, Ohashi S, Butler GB, J. Polym. Sci. A: Polym. Chem., 17, 351 (1979)
Gebelein CG, Morgan RM, Polym. Prepr., 18(1), 811 (1977)
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Akashi M, Tanaka Y, Miyazaki T, Miyauchi N, J. Bioactive Compatitle Polym., 2, 120 (1987)
Kelen T, Tudos F, J. Macromol. Sci.-Chem., A9, 1 (1975)
Ozaki S, Watanabe Y, Hoshiko T, Mizuno H, Ishikawa K, Mori H, Chem. Pharm. Bull., 32(2), 733 (1984)
Duschinsky R, Gabriel TF, U.S. Patent, 3,354,160 (1967)
Ueda M, Iri K, Imari Y, Pittmann CU, Macromolecules, 14, 1046 (1981)
Guggenheim EA, Phil. Mag., 2, 538 (1926)
Buur A, Bundgaard H, Falch E, Acta Pharm. Suec., 23, 205 (1986)

[Referenced By]

[1] Pato J, Azori M, Ulbrich K, Kopecek J, Makromol. Chem., 185, 231 (1984)

[2] Ouchi T, Sakamoto Y, Jokei S, Chikashita H, Makromol. Chem., 185, 255 (1984)

[3] Matsuzaki K, Yamamoto I, Sato T, Oshima R, Makromol. Chem., 186, 449 (1984)

[4] Hung RY, Kopeck J, Andrade JD, Makromol. Chem., 190, 69 (1987)

[5] Breslow DS, Pure Appl. Chem., 46, 103 (1976)

[6] Bounous G, Pageau R, Regoli D, J. Chem. Pharmacol. Biopharm., 16, 519 (1978)

[7] Bosch L, Harbers E, Heidelberger C, Cancer Rev., 18, 335 (1958)

[8] Umrigar PP, Ohashi S, Butler GB, J. Polym. Sci. A: Polym. Chem., 17, 351 (1979)

[9] Gebelein CG, Morgan RM, Polym. Prepr., 18(1), 811 (1977)

[10] Akashi M, Beppu K, Kikuchi I, Miyauchi N, J. Macromol. Sci.-Chem., A23, 1233 (1986)

[11] Akashi M, Tanaka Y, Miyazaki T, Miyauchi N, J. Bioactive Compatitle Polym., 2, 120 (1987)

[12] Kelen T, Tudos F, J. Macromol. Sci.-Chem., A9, 1 (1975)

[13] Ozaki S, Watanabe Y, Hoshiko T, Mizuno H, Ishikawa K, Mori H, Chem. Pharm. Bull., 32(2), 733 (1984)

[14] Duschinsky R, Gabriel TF, U.S. Patent, 3,354,160 (1967)

[15] Ueda M, Iri K, Imari Y, Pittmann CU, Macromolecules, 14, 1046 (1981)

[16] Guggenheim EA, Phil. Mag., 2, 538 (1926)

[17] Buur A, Bundgaard H, Falch E, Acta Pharm. Suec., 23, 205 (1986)