Racemic drug resolution using polymer supported chiral selector

Patent metadata

Field	Value
Publication number	US-9809706-B2
Application number	US-201414915326-A
Country	US
Kind code	B2
Filing date	Sep 1, 2014
Priority date	Aug 30, 2013
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

The present invention relates to a process for the separation of enantiomers or resolution of racemic mixtures using high surface area core-shell polymer beads. The present invention further relates to a core-shell functionalized polymer comprising a core which comprises copolymer made from monomers selected from non-aromatic acrylate, ethylene dimethacrylate and divinyl-benzene, a shell which comprises monomers selected from glycidyl ethers of methacrylate and a chiral selector selected from tartaric acid derivatives and amino acids.

First claim

We claim:

1. A core-shell functionalized polymer comprising:
i. a core comprising a crosslinked copolymer made from monomers, said monomers selected from vinyl cyanide, vinylidene cyanide, non-aromatic acrylate, ethylene dimethacrylate and divinylbenzene;
ii. a shell, comprising a polymer made from monomers selected from glycidyl ethers of methacrylate; and
iii. a chiral selector selected from tartaric acid derivatives and amino acids.

2. The core-shell functionalized polymer as claimed in claim 1 , wherein the proportion of shell polymer is 5 to 90% by weight based on the total amount of the monomers of the core copolymer.

3. The core-shell functionalized polymer as claimed in claim 1 , wherein the core comprises crosslinked copolymers selected from poly(MMA-co-DVB) and poly(MMA-co-EDMA).

4. The core-shell functionalized polymer as claimed in claim 1 , wherein glycidyl ethers of methacrylate is glycidyl methacrylate.

5. The core-shell functionalized polymer as claimed in claim 1 , wherein the core-shell functionalized polymer is in the form of beads.

6. The core-shell functionalized polymer as claimed in claim 1 , wherein chiral selectors are selected D-(−)-ditoluoyl tartaric acid and D-(−)-dibenzoyl tartaric acid and amino acid is L-proline.

7. The core-shell functionalized polymer as claimed in claim 1 , wherein said polymer is useful for the separation or resolution of enantiomers of racemic mixtures by using high performance liquid chromatography.

8. The core-shell functionalized polymer as claimed in claim 7 , wherein the racemic mixture is a drug racemic mixture selected from β2-adrenergic receptor agonist drugs.

9. The core-shell functionalized polymer of claim 8 , wherein the β2-adrenergic receptor agonist drugs are selected from (±)-terbutaline and (±)-salbutamol.

10. The core-shell functionalized polymer as claimed in claim 1 , wherein efficiency of chiral selectors is in the range of 20 to 70% in the period of 2 to 50 h.

11. The core-shell functionalized polymer of claim 1 , wherein the non-aromatic acrylate is selected from ethyl acrylate, propyl acrylate, butyl acrylate, cyclohexyl acrylate, 2-ethyl hexyl acrylate, methyl acrylate, methyl methacrylate, and butyl methacrylate.

12. The core-shell functionalized polymer of claim 1 , wherein vinyl cyanide or vinylidene cyanide is selected from acrylonitrile and methacrylonitrile.

13. A process for the preparation of core-shell functionalized polymer as claimed in claim 1 , comprising the steps of:
a) providing porous crosslinked copolymer, wherein the crosslinked copolymer is made from monomers selected from vinyl cyanide, vinylidene cyanide, non-aromatic acrylate, ethylene dimethacrylate and divinylbenzene;
b) providing linear polymer containing oxiranyl groups, wherein the linear polymer is made from monomers selected from glycidyl ethers of methacrylate;
c) adding the crosslinked copolymer of step a) with the linear polymer of step b) in a ratio ranging between 0.3 to 0.7 wt % at a temperature in the range of 20 to 40° C. for a period in the range of 10 to 20 min followed by drying at a temperature in the range of 50 to 80° C. for a period in the range of 6 to 10 h to obtain epoxy coated polymer;
d) crosslinking partially the oxiranyl groups present on the epoxy coated polymer of step c) with amine groups by adding crosslinker 1,6-hexamethylene diamine with the linear polymer containing oxiranyl groups in a ratio range of 3 to 7 mol % at a temperature in the range of 20 to 40° C. for a period in the range of 10 to 20 min followed by drying at a temperature in the range of 40 to 80° C. for a period in the range of 6 to 10 hours to obtain core-shell polymer; and
e) modifying epoxy groups of the polymer product of step d) with 1 to 2 mmol/g chiral tartaric acid derivatives or L-proline derivatives to obtain core-shell functionalized polymer.

14. The process of claim 13 , wherein the non-aromatic acrylate is selected from ethyl acrylate, propyl acrylate, butyl acrylate, cyclohexyl acrylate, 2-ethyl hexyl acrylate, methyl acrylate, methyl methacrylate, and butyl methacrylate.

15. The process of claim 13 , wherein vinyl cyanide or vinylidene cyanide is selected from acrylonitrile and methacrylonitrile.

Assignees

• Council Scient Ind Res

Inventors

• Mane Sachin Tanaji
• Daniels Siona Virgil
• Deokar Sarika Babasaheb
• Mule Smita Atmaram
• Ponrathnam Surendra
• Chavan Nayaku Nivrati

Classifications

• C08F212/36

  Divinylbenzene · CPC title

• B01J20/22 Primary

  comprising organic material · CPC title

• C08F2/18

  Suspension polymerisation · CPC title

• C08F220/14

  Methyl esters {, e.g. methyl (meth)acrylate} · CPC title

• C08F226/10

  N-Vinyl-pyrrolidone · CPC title