Synthesis of tyrosine derived polyarylates
A method for preparing tyrosine derived polyarylates includes combining a desaminotyrosyl-tyrosine ethyl ester, a desaminotyrosyl-tyrosine benzylester, succinic acid and a catalyst in a flask to produce a first mixture. Methylene chloride is added to the first mixture to produce a first suspension. Diisopropylcarbodiimide (DIPC) is added to the first mixture to produce a first solution. The first solution is added to a non-solvent to produce a precipitate. The precipitate is dissolved in methylene chloride to form a polymer solution. The polymer solution is blended with a slurry to produce polymer shreds. The polymer shreds are blended with a second slurry to produce a tyrosine derived polyarylate.
1. A method for preparing a polyarylate having the formula:
the method comprising:
combining a desaminotyrosyl-tyrosine ethyl ester having the formula:
a desaminotyrosyl-tyrosine benzylester having the formula:
succinic acid and a catalyst in a flask to produce a first mixture;
adding methylene chloride to the first mixture to produce a first suspension;
adding diisopropylcarbodiimide (DIPC) to the first mixture to produce a first solution;
adding the first solution to a non-solvent to polymerize the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine ethyl ester and produce a precipitate;
dissolving the precipitate in methylene chloride to form a polymer solution;
blending the polymer solution with a slurry of 2-propanol and dry ice to produce polymer shreds; and
blending the polymer shreds with a second slurry of 2-propanol and dry ice to produce the polyarylate.
2. A method as recited in claim 1 , wherein the first mixture comprises a stoichiometric ratio of 1 mole of the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester to 1 mole of the succinic acid.
3. A method as recited in claim 1 , wherein the first mixture comprises an excess of the succinic acid relative to the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester.
4. A method as recited in claim 1 , wherein the first mixture comprises a 1-5% excess of the succinic acid relative to the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester.
5. A method as recited in claim 1 , wherein the first mixture comprises a 2% excess of the succinic acid relative to the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester.
6. A method as recited in claim 1 , wherein about 308.6 g of the desaminotyrosyl-tyrosine ester, about 40.3 g of the desaminotyrosyl-tyrosine benzylester and about 113.4 g of succinic acid are added to the flask to produce the first mixture.
7. A method as recited in claim 1 , wherein desaminotyrosyl-tyrosine ester, desaminotyrosyl-tyrosine benzylester and succinic acid are added in the mole ratio 0.864:0.086:0.96 to the flask to produce the first mixture.
8. A method as recited in claim 1 , further comprising:
titrating the first mixture to obtain COOH and OH equivalent numbers; and
adjusting the ratio of the succinic acid relative to the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester to maintain a constant COOH and OH ratio.
9. A method as recited in claim 1 , wherein:
the first mixture comprises about a 5% excess of the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester relative to the succinic acid; and
the ratio of the succinic acid relative to the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester is adjusted until a 1:1.02 ratio of the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester is achieved.
10. A method as recited in claim 1 , wherein:
the first mixture comprises about a 1% to about a 5% excess of the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester relative to the succinic acid; and
the ratio of the succinic acid relative to the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester is adjusted until a 1:1.02 ratio of the desaminotyrosyl-tyrosine ethyl ester and the desaminotyrosyl-tyrosine benzylester is achieved.
11. A method as recited in claim 1 , wherein the catalyst is dimethyllaminopyridine and P-toluenesulfonic acid (DPTS).
12. A method as recited in claim 11 , wherein the catalyst comprises about 696.5 g of DPTS.
13. A method as recited in claim 1 , further comprising adding at least one acid to the first solution.
14. A method as recited in claim 13 , wherein the at least one acid comprises at least one of succinic acid, adipic acid and glutaric acid.
15. A method as recited in claim 13 , further comprising cooling the first solution to room temperature and stirring the first solution.
16. A method as recited in claim 15 , wherein the first solution is stirred overnight.
17. A method as recited in claim 1 , further comprising collecting the polyarylate from the blended polymer shreds and second slurry and drying overnight under a stream of air.
18. A method as recited in claim 17 , further comprising dissolving the polyarylate in methylene chloride to produce a second solution.
19. A method as recited in claim 18 , further comprising adding an acid to the second solution to produce a third solution.
20. A method as recited in claim 1 , wherein the method does not use NaCl.