Synthesis of tyrosine derived polyarylates

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 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 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 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 for preparing a polyarylate having the formula:

the method comprising:

dissolving a second polyarylate having the formula:

with DMF to produce a first solution;

starting a flow of nitrogen;

adding a catalyst to the first solution to produce a polymer solution;

starting a flow of hydrogen;

filtering the polymer solution to produce a filtrate; and

adding the filtrate to water and stirring to precipitate the polyarylate,

wherein a first amount of the catalyst is added to the first solution after the flow of nitrogen is started to produce a first catalyst suspension,

wherein a second amount of the catalyst is added to the first catalyst suspension to produce a second catalyst suspension,

wherein a third amount of the catalyst is added to the second catalyst suspension to produce a third catalyst suspension, and

wherein the first amount is greater than the second amount and the second amount is greater than the third amount.

12. A method as recited in claim 11 , wherein:

the first catalyst suspension is stirred for about 5.5 hours before adding the second amount of the catalyst to the first catalyst suspension;

the second catalyst suspension is stirred overnight before adding the third amount of the catalyst to the second catalyst suspension; and

the third catalyst solution is in suspension for about 1.75 hours.

13. A method as recited in claim 11 , further comprising drying the polyarylate having the formula:

under a stream of air for about 24 hours and then under vacuum.

14. A method as recited in claim 11 , wherein the first solution includes DMF and a solvent.

15. A method as recited in claim 14 , wherein the solvent comprises methanol or acetic acid.

16. A method as recited in claim 14 , wherein the solvent comprises 20% of the first solution by volume.

17. A method as recited in claim 11 , further adding a scavenger to remove leached catalyst before filtering the polymer solution.

18. A method as recited in claim 17 , wherein the scavenger comprises a metal scavenger.

19. A method for preparing a polyarylate having the formula:

the method comprising:

dissolving a second polyarylate having the formula:

with DMF to produce a first solution;

starting a flow of nitrogen;

adding a catalyst to the first solution to produce a polymer solution;

starting a flow of hydrogen;

filtering the polymer solution to produce a filtrate; and

adding the filtrate to water and stirring to precipitate the polyarylate,

wherein a first amount of the catalyst is added to the first solution after the flow of nitrogen is started to produce a first catalyst suspension,

wherein a second amount of the catalyst is added to the first catalyst suspension to produce a second catalyst suspension, and

wherein a third amount of the catalyst is added to the second catalyst suspension to produce a third catalyst suspension.