Branched polyamines and formulations thereof for use in medical devices
View Patent ↗The present disclosure provides for the synthesis of branched polyamines. In embodiments, branched polyamines may be formed by reacting a branched polyol with a nitroaryl carboxylic acid to form a nitrobenzoyl ester which, in turn, may then be subjected to a hydrogenating step to form the branched polyamine. The resulting branched polyamine may then be reacted with another hydrogel precursor to form a hydrogel.
1. A process comprising:
reacting a branched polyol with a nitroaryl carboxylic acid to form a nitrobenzoyl ester;
hydrogenating the nitrobenzoyl ester to form a branched polyamine, and
reacting the branched polyamine with a N-protected amino acid to form a protected polyamine, wherein the N-protected amino acid is selected from the group consisting of:
and combinations thereof wherein R 1 is selected from the group consisting of alkyl, aryl, heteroaryl, and cycloalkyl, R 2 is selected from the group consisting of CH 2 , alkyl, alkoxy, and combinations thereof, and Z is selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and fluorenylmethyoxycarbonyl.
2. The process as in claim 1 , wherein at least one of the branches of the branched polyol includes an alkoxy group.
3. The process as in claim 1 , wherein the branched polyol is a branched pentaerythritol.
4. The process as in claim 1 , wherein the branched polyol is selected from the group consisting of pentaerythntol ethoxylate, pentaerythritol propoxylate, trimethylolpropane, dipentaerythritol, tripentaerythritol, and combinations thereof.
5. The process as in claim 1 , wherein the nitroaryl-carboxylic acid is selected from the group consisting of 3-nitrobenzoic acid, p-nitrophenoxyacetic acid, m-nitrophenoxyacetic acid, o-phenyl acetic acid, m-phenyl acetic acid, p-phenyl acetic acid, m,p-nitrocinnamyl acid, benzoic acid, 4-nitrobenzoic acid, and combinations thereof.
6. The process as in claim 1 , wherein the hydrogenating step includes mixing the nitrobenzoyl ester with a platinum group catalyst.
7. The process as in claim 6 , wherein the platinum group catalyst includes a metal selected from the group consisting of platinum, palladium, rhodium and ruthenium.
8. The process as in claim 1 , further comprising contacting the protected polyamine with an acid selected from the group consisting of trifluoroacetic acid (TFA), HCl in dioxane, and combinations thereof.
9. A process comprising:
reacting a branched polyol with a nitroaryl carboxylic acid to form a nitrobenzoyl ester;
reducing the nitrobenzoyl ester with a catalyst to form a branched polyamine, and
reacting the branched polyamine with an N-protected amino acid to form a protected polyamine, wherein the N-protected amino acid is selected from the group consisting of:
and combinations thereof wherein R 1 is selected from the group consisting of alkyl, aryl, heteroaryl, and cycloalkyl, R 2 is selected from the group consisting of CH 2 , alkyl, alkoxy, and combinations thereof, and Z is selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and fluorenylmethyoxycarbonyl.
10. The process as in claim 9 , wherein at least one of the branches of the branched polyol includes a hydroxyester group.
11. The process as in claim 9 , wherein the branched pentaerythritol is selected from the group consisting of pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol butoxylate, and pentaerythritol pentoxylate.
12. The process as in claim 9 , wherein the nitroaryl carboxylic acid is p-nitrophenoxyacetic acid.
13. The process as in claim 9 , wherein the catalyst is a platinum group catalyst including a metal selected from the group consisting of platinum, palladium, rhodium and ruthenium.
14. The process as in claim 9 , further comprising contacting the protected polyamine with an acid selected from the group consisting of trifluoroacetic acid (TFA), HCl in dioxane, and combinations thereof.
15. A process comprising:
reacting a branched polyol with a nitroaryl carboxylic acid to form a nitrobenzoyl ester;
hydrogenating the nitrobenzoyl ester to form a branched polyamine;
reacting the branched polyamine with an N-protected amino acid to form a protected polyamine, wherein the N-protected amino acid is selected from the group consisting of:
and combinations thereof wherein R 1 is selected from the group consisting of alkyl, aryl, heteroaryl, and cycloalkyl, R 2 is selected from the group consisting of CH 2 , alkyl, alkoxy, and combinations thereof, and Z is selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and fluorenylmethyoxycarbonyl,
deprotecting the protected polyamine with an acid selected from the group consisting of trifluoroacetic acid (TFA), HCl in dioxane, and combinations thereof; and
reacting the deprotected branched polyamine with a hydrogel precursor.
16. The process as in claim 15 , wherein the hydrogel precursor includes at least one electrophilic functional group.
17. The process as in claim 15 , wherein at least one of the branches of the branched polyol includes an alkoxy group.
18. The process as in claim 15 , wherein the branched polyol comprises a branched pentaerythritol.
19. The process as in claim 15 , wherein the branched pentaerythritol is selected from the group consisting of pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol butoxylate, and pentaerythritol pentoxylate.
20. The process as in claim 15 , wherein the nitroaryl carboxylic acid comprises p-nitrophenoxyacetic acid.
21. The process as in claim 15 , wherein the hydrogenating step includes contacting the nitrobenzoyl ester with a platinum group catalyst.
22. The process as in claim 15 , wherein the catalyst is a platinum group catalyst including a metal selected from the group consisting of platinum, palladium, rhodium and ruthenium.