Antimicrobial cationic peptoid and n-subtituted peptidic copolymers, preparation and uses thereof

Process for the preparation of cationic peptoid/N-substituted peptidic copolymers comprising-:

• A) at least one step of reacting in a polar solvent:
• (i) at least a first N-carboxyanhydride monomer having the structure (I):
• wherein
• R1 independently represents a cyclic or acyclic, substituted or unsubstituted, linear or branched C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl or C2-12heteroalkynyl group;
• each of the foregoing alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl group, optionally bearing one or more substituents selected from F;
• Cl;
• Br;
• I;
• —NO2;
• —CN;
• —CF3;
• —CH2CF3;
• CHCl2;
• or -GRA1 wherein G is —O—, —S—, —NRB1—, —C(═O)—, —S(═O)—, —SO2—, —C(═O)O—, —C(═O)NRB1—, —OC(═O)—, —NRB1C(═O)—, wherein each occurrence of RA1 and RB1 independently represents hydrogen, or a C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12haloalkyl, C2-12haloalkenyl, C2-12haloalkynyl, C1-12heteroalkyl, C2-12heteroalkenyl or C2-12heteroalkynyl group;
• and
• R2 independently represents H, a cyclic or acyclic, substituted or unsubstituted, linear or branched C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, substituted or unsubstituted C6-10aryl or C4-10heteroaryl group;
• —ORA2;
• —C(═O)RA2;
• or —SRA2;
• wherein each occurrence of RA2 independently represents hydrogen or a cyclic or acyclic, substituted or unsubstituted, linear or branched C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, C6-10aryl or C4-10heteroaryl group;
• wherein each of the foregoing alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl or heteroaryl group may optionally bear one or more substitutents selected from F;
• Cl;
• Br;
• I;
• —NO2;
• —CN;
• —CF3;
• —CH2CF3;
• CHCl2;
• or -GRB2 wherein G is —O—, —S—, —NRC2—, —C(═O)—, —S(═O)—, —SO2—, —C(═O)O—, —C(═O)NRC2—, —OC(═O), —NRC2C(═O)—, wherein each occurrence of RB2 and RC2 independently represents independently represents hydrogen, or a C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12haloalkyl, C2-12haloalkenyl, C2-12haloalkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, C6-10aryl or C4-10heteroaryl group;
• wherein at least one of R1 or R2 bears at least one cationic moiety or protected form thereof;
• (i) at least a second N-carboxyanhydride monomer having the structure (II):
• wherein
• R3 independently represents a cyclic or acyclic, substituted or unsubstituted, linear or branched C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, or C2-12heteroalkynyl;
• each of the foregoing alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl or heteroalkynyl group optionally bearing one or more substituents selected from C1-12alkyl;
• C2-12alkenyl;
• C2-12alkynyl;
• C1-12heteroalkyl;
• C2-12heteroalkenyl;
• C2-12heteroalkynyl;
• C6-10aryl;
• C6-10heteroaryl;
• F;
• Cl;
• Br;
• I;
• —NO2;
• —CN;
• —CF3;
• —CH2CF3;
• CHCl2;
• or -GRA3 wherein G is —O—, —S—, —NRB3—, —(═O)—, —S(═O)—, —SO2—, —C(═O)O—, —C(═O)NRB3—, —OC(═O)—, —NRB3C(═O)—, wherein each occurrence of RA3 and RB3 independently represents hydrogen, or a C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12haloalkyl, C2-12haloalkenyl, C2-12haloalkynyl, C1-12heteroalkyl, C2-12heteroalkenyl or C2-12heteroalkynyl;
• and
• R4 independently represents H, a cyclic or acyclic, substituted or unsubstituted, linear or branched C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, substituted or unsubstituted C6-10aryl or C4-10heteroaryl group;
• —ORA4;
• —C(═O)RA4;
• or —SRA4;
• wherein each occurrence of RA4 independently represents hydrogen or a cyclic or acyclic, substituted or unsubstituted, linear or branched C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, C6-10aryl or C4-10heteroaryl group;
• wherein each of the foregoing alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl or heteroaryl, group may optionally bear one or more substitutents selected from C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, C6-10aryl, C4-10heteroaryl, F;
• Cl;
• Br;
• I;
• —NO2;
• —CN;
• —CF3;
• —CH2CF3;
• CHCl2;
• or -GRB4 wherein G is —O—, —S—, —NRC4—, —(═O)—, —S(═O)—, —SO2—, —C(═O)O—, —C(═O)NRC4—, —OC(═O)—, —NRC4C(═O)—, wherein each occurrence of RB4 and RC4 independently represents independently represents hydrogen, or a C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12haloalkyl, C2-12haloalkenyl, C2-12haloalkynyl, C1-12heteroalkyl, C2-12heteroalkenyl, C2-12heteroalkynyl, C6-10aryl or C4-10heteroaryl group;
• (ii) in the presence of at least one nucleophilic compound initiator and/or at least one base;
• wherein the base and the nucleophilic compound initiator may be different compounds or one and the same compound;
• and
• B) when R1 or R2 bears a protected form of at least one cationic moiety, the process further comprises at least one deprotection step of the protected form of the at least one cationic moiety to yield cationic peptoid/N-substituted peptidic copolymers;
• such as acidic or basic treatment.