A New And Greener Method To
Manufacture Copolymer-1
Author(s)
E. Ponnusamy
Abstract
Polyamino acid random copolymers have a wide variety of properties that mimic
proteins, which make these random copolymers suitable for the treatment of
certain diseases. For example, polyamino acid random copolymers comprising
alanine, glutamic acid, lysine, and tyrosine (copolymer-1) have been used in the
treatment of multiple sclerosis. Synthesis of this copolymer requires protecting
groups for the side chains of the glutamic acid and lysine residues. The
manufacture of copolymer-1 is typically achieved by protecting lysine with Nε-
trifluoroacetyl (TFA) and glutamic acid with -benzyl protecting groups
respectively. Deprotecting TFA and benzyl protecting groups require two
separate steps. Removal of the benzyl-protecting group from glutamic acid
requires using hazardous chemicals (HBr/acetic acid) and highly flammable
solvents and also generates a by-product, benzyl bromide a very strong
lachrymator. Removal of the TFA group from lysine, the product needs to be
further treated with flammable piperidine. These deprotection methods require
long reaction times and handling, which in-turn reduces yield. Therefore, a need
exists for an efficient, greener and less toxic process to manufacture copolymer-
1. A new greener method for the synthesis of Copolymer-1 has been developed.
The method is greener, efficient, and uses less toxic reagents than literature
methods. The present invention provides a method for the synthesis of
copolymer-1 by polymerizing a mixture of N-carboxyanhydrides of alanine,
tyrosine, -ethyl-protected-glutamic acid, and Nε-TFA-protected-lysine in the
presence of a polymerization initiator to form a protected polyamino acid
random copolymer. Then adding a base to the protected polyamino acid random
copolymer to cleave both the ethyl group from the glutamic acid and the TFA
group from the lysine in a single deprotection step and also eliminated a large
volume of hazardous chemical usage and waste generation. The new method
Keywords
polyamino acid copolymers, protecting group, deprotection, dialysis, lyophilisation
Related Book
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