Accelerants for the modification of non-natural amino acids and non-natural amino acid polypeptides

A reaction mixture comprising a compound having the structure of Formula (I):

• wherein:
• A is optional, and when present is lower alkylene, substituted lower alkylene, lower cycloalkylene, substituted lower cycloalkylene, lower alkenylene, substituted lower alkenylene, alkynylene, lower heteroalkylene, substituted heteroalkylene, lower heterocycloalkylene, substituted lower heterocycloalkylene, arylene, substituted arylene, heteroarylene, substituted heteroarylene, alkarylene, substituted alkarylene, aralkylene, or substituted aralkylene;
• B is optional, and when present is a linker selected from the group consisting of lower alkylene, substituted lower alkylene, lower alkenylene, substituted lower alkenylene, lower heteroalkylene, substituted lower heteroalkylene, —O—, —O-(alkylene or substituted alkylene)-, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —N(R′)-, —NR'-(alkylene or substituted alkylene)-, —C(O)N(R′)—, —CON(R′)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R′)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(S)N(R′)—, —N(R′)S(O)kN(R′)—, —C(R′)═N—, —C(R′)═N—N(R′)—, —C(R′)═N—N═, —C(R′)2—N═N—, and —C(R′)2—N(R′)—N(R′)—, where each R′ is independently H, alkyl, or substituted alkyl;
• J is
• R is H, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl;
• each R″ is independently H, alkyl, substituted alkyl, or a protecting group, or when more than one R″ group is present, two R″ optionally form a heterocycloalkyl;
• R1 is optional, and when present, is H, an amino protecting group, resin polypeptide, or polynucleotide;
• and
• R2 is optional, and when present, is OH, an ester protecting group, resin, polypeptide, or polynucleotide;
• each of R3 and R4 is independently H, halogen, lower alkyl, or substituted lower alkyl, or R3 and
• R4 or two R3 groups optionally form a cycloalkyl or a heterocycloalkyl;
• or the -A-B-J-R groups together form a bicyclic or tricyclic cycloalkyl or heterocycloalkyl comprising at least one carbonyl group, including a dicarbonyl group, protected carbonyl group, including a protected dicarbonyl group, or masked carbonyl group, including a masked dicarbonyl group;
• or the -J-R group together forms a monocyclic or bicyclic cycloalkyl or heterocycloalkyl comprising at least one carbonyl group, including a dicarbonyl group, protected carbonyl group, including a protected dicarbonyl group, or masked carbonyl group, including a masked dicarbonyl group;
• a compound comprising a hydroxylamine moiety, and an accelerant selecting from the group consisting of bifunctional aromatic amines, oxoamine derivatives, and compounds having the following structures:
• wherein Rx, Ry and Rz are selected from the group consisting of:
• Lx-H, Lx-alkyl, Lx-aryl, Lx-heteroaryl, Lx-alkenyl, Lx-alkynyl, Lx-alkoxy, and Lx-alkylamine, where Lx is a bond, C(═O), C(═NH), C(═NH)—NH, SO, and SO2.