Degradable polycations derived from amino acid vinyl esters

Patent metadata

Field	Value
Publication number	US-9688789-B2
Application number	US-201414305039-A
Country	US
Kind code	B2
Filing date	Jun 16, 2014
Priority date	Jan 18, 2012
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

Described herein are the synthesis and polymerization of a series of N-Boc-protected amino acid vinyl ester (BAAVE) monomers. Homopolymers and heteropolymers containing the monomers are described, particularly heteropolymers with vinyl ester monomers such as vinyl acetate. Deprotection can be used to produce hydrophilic and hydrophobic polymers that are particular useful in biological applications such as cellular delivery of biological materials.

First claim

The invention claimed is:

1. A copolymer consisting of units of the formula

and salts thereof, wherein
R t is H, halo, or methyl,
Q is cyano, halo, nitro, OH, —CR a ═CR b R c , —C(O)NR d R e , carbonyl(C 1 -C 12 )alkyl, substituted or unsubstituted C 6 -C 12 aryl, N-caprolactam, or a combination comprising at least one of the foregoing groups, wherein each R a , R b , and R c are independently H or C 1 -C 18 alkyl, and wherein each R d and R e are independently H or C 1 -C 18 alkyl,
x+y is an integer greater than two,
R is H, a substituted or unsubstituted C 1 -C 18 alkyl, a substituted or unsubstituted C 2 -C 18 alkenyl, a substituted or unsubstituted C 2 -C 18 alkynyl, a substituted or unsubstituted C 3 -C 18 cycloalkyl, a substituted or unsubstituted C 1 -C 18 haloalkyl, a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, a substituted or unsubstituted C 6 -C 18 aryl, a substituted or unsubstituted C 7 -C 18 arylalkylene, or a substituted or unsubstituted C 3 -C 18 heteroaryl;
R′ is a substituted or unsubstituted C 1 -C 18 alkyl, a substituted or unsubstituted C 2 -C 18 alkenyl, a substituted or unsubstituted C 2 -C 18 alkynyl, a substituted or unsubstituted C 3 -C 18 cycloalkyl, a substituted or unsubstituted C 1 -C 18 haloalkyl, a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, a substituted or unsubstituted C 6 -C 18 aryl, a substituted or unsubstituted C 7 -C 18 arylalkylene, or a substituted or unsubstituted C 3 -C 18 heteroaryl, wherein substituted for R′ comprises replacement of one or more hydrogen atoms of a group with a substituent selected from a C 1 to C 6 alkyl group; a C 1 to C 6 hydroxyalkyl group; a C 2 to C 6 alkenyl group; a C 2 to C 30 alkynyl group; a C 6 to C 30 aryl group; a C 1 to C 6 heteroalkyl group; a C 3 to C 30 cycloalkyl group; a C 3 to C 15 cycloalkenyl group; a C 6 to C 30 cycloalkynyl group; a C 2 to C 30 heterocycloalkyl group; halogen; a haloalkyl group; an alkoxy group; —NO 2 ; —CN; —NR′″ 2 wherein each R″′ is independently a hydrogen or a C 1 to C 6 alkyl group, a C 2 to C 6 alkynyl group, or a C 6 to C 30 aryl group; a carbamyl group; —C(═O)OR″ wherein R″ is a C 1 to C 6 alkyl group or a C 6 to C 10 aryl group; or —C(═O)OH; and
G is a group of the formula

 wherein
one of *′ and *″ indicates a point of attachment to the carbonyl and the other indicates a point of attachment to N, and *′″ indicates a point of attachment to R,
z is 0, 1, or 2, and
R w , R x and R y are each independently H, a substituted or unsubstituted C 1 -C 18 alkyl, a substituted or unsubstituted C 2 -C 18 alkenyl, a substituted or unsubstituted C 2 -C 18 alkynyl, a substituted or unsubstituted C 3 to C 18 cycloalkyl, a substituted or unsubstituted C 1 -C 18 haloalkyl, a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, a substituted or unsubstituted C 6 to C 18 aryl, a substituted or unsubstituted C 7 to C 18 arylalkylene, or a substituted or unsubstituted C 4 -C 18 heteroaryl, or any two of R, R′, R w , R x , and R y together form a substituted or unsubstituted C 5 -C 18 cycloalkyl, substituted or unsubstituted C 2 -C 18 heterocycloalkyl, or substituted or unsubstituted C 2 -C 18 heteroaryl group, each having 5 to 8 ring members.

2. A copolymer consisting of units of the formula

and salts thereof, wherein
R t is H, halo, or methyl,
Q is cyano, halo, nitro, OH, —CR a ═CR b R c , —C(O)NR d R e , carbonyl(C 1 -C 12 )alkyl, carbonyloxy(C 1 -C 12 )alkyl, substituted or unsubstituted C 6 -C 12 aryl, N-caprolactam, or a combination comprising at least one of the foregoing groups, wherein each R a , R b , and R c are independently H or C 1 -C 18 alkyl, and wherein each R d and R e are independently H or C 2 -C 18 alkyl, carbonyl(C 1 -C 12 )alkyl,
x+y is an integer greater than two,
z is 0, 1, or 2, and
R′ together with R forms a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, or substituted or unsubstituted C 2 -C 18 heteroaryl group, each having 5 to 8 ring members.

3. The copolymer of claim 2 , wherein R and R′ together form propylene to provide a monomer having a 5-membered ring.

4. The copolymer of claim 2 , wherein Q is carbonyl(C 1 -C 12 )alkyl, carbonyloxy(C 1 -C 12 )alkyl, substituted or unsubstituted C 6 -C 12 aryl, N-caprolactam, or a combination comprising at least one of the foregoing groups.

5. A copolymer consisting of units of the formula

and salts thereof, wherein
R t is halo,
Q is cyano, halo, nitro, OH, —CR a ═CR b R c , —C(O)NR d R e , carbonyl(C 1 -C 12 )alkyl, carbonyloxy(C 1 -C 12 )alkyl-substituted or unsubstituted C 6 -C 12 aryl, N-caprolactam, or a combination comprising at least one of the foregoing groups, wherein each R a , R b , and R c are independently H or C 1 -C 18 alkyl, and wherein each R d and R e are independently H or C 1 -C 18 alkyl,
x+y is an integer greater than two,
R is H, a substituted or unsubstituted C 1 -C 18 alkyl, a substituted or unsubstituted C 2 -C 18 alkenyl, a substituted or unsubstituted C 2 -C 18 alkynyl, a substituted or unsubstituted C 3 -C 18 cycloalkyl, a substituted or unsubstituted C 1 -C 18 haloalkyl, a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, a substituted or unsubstituted C 6 -C 18 aryl, a substituted or unsubstituted C 7 -C 18 arylalkylene, or a substituted or unsubstituted C 3 -C 18 heteroaryl;
R′ is H, a substituted or unsubstituted C 1 -C 18 alkyl, a substituted or unsubstituted C 2 -C 18 alkenyl, a substituted or unsubstituted C 2 -C 18 alkynyl, a substituted or unsubstituted C 3 -C 18 cycloalkyl, a substituted or unsubstituted C 1 -C 18 haloalkyl, a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, a substituted or unsubstituted C 6 -C 18 aryl, a substituted or unsubstituted C 7 -C 18 arylalkylene, or a substituted or unsubstituted C 3 -C 18 heteroaryl, wherein substituted for R′ comprises replacement of one or more hydrogen atoms of a group with a substituent selected from a C 1 to C 6 alkyl group; a C 1 to C 6 hydroxyalkyl group; a C 2 to C 6 alkenyl group; a C 2 to C 30 alkynyl group; a C 6 to C 30 aryl group; a C 1 to C 6 heteroalkyl group; a C 3 to C 30 cycloalkyl group; a C 3 to C 15 cycloalkenyl group; a C 6 to C 30 cycloalkynyl group; a C 2 to C 30 heterocycloalkyl group; halogen; a haloalkyl group; an alkoxy group; —NO 2 ; —CN; —NR′″ 2 wherein each R′″ is independently a hydrogen or a C 1 to C 6 alkyl group, a C 2 to C 6 alkynyl group, or a C 6 to C 30 aryl group; a carbamyl group; —C(═O)OR″ wherein R″ is a C 1 to C 6 alkyl group or a C 6 to C 10 aryl group; or —C(═O)OH; and
G is a group of the formula

 wherein
one of *′ and *″ indicates a point of attachment to the carbonyl and the other indicates a point of attachment to N, and *′″ indicates a point of attachment to R,
z is 0, 1, or 2, and
R w R x and R y are each independently H, a substituted or unsubstituted C 1 -C 18 alkyl, a substituted or unsubstituted C 2 -C 18 alkenyl, a substituted or unsubstituted C 2 -C 18 alkynyl, a substituted or unsubstituted C 3 to C 18 cycloalkyl, a substituted or unsubstituted C 1 -C 18 haloalkyl, a substituted or unsubstituted C 2 -C 18 heterocycloalkyl, a substituted or unsubstituted C 6 to

Assignees

• Wisconsin Alumni Res Found
• Nat Science Found

Inventors

• Mahanthappa Mahesh Kalyana
• Thomas Glen Bradley
• Lipscomb Corinne Elizabeth

Classifications

• C08F218/08

  Vinyl acetate · CPC title

• C08F218/04

  Vinyl esters · CPC title

• C08F18/22

  Esters containing nitrogen · CPC title

• C08F18/04

  Vinyl esters · CPC title

• C08F216/1458 Primary

  Monomers containing nitrogen · CPC title