The present invention relates to a photochemical process for the manufacturing of a C-terminal -amide, which are a class of compounds that represent up to half of all biologically relevant peptide hormones. The invention provides mild, broad in scope, economically efficient process, which is suitable for large scale manufacturing.

Provided herein are polymeric -hydroxy aldehyde or -hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the -carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Provided herein are polymeric -hydroxy aldehyde or -hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the -carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

The present disclosure provides a method for synthesizing an amide and/or a polypeptide using an unprotected amino acid as an ammonia component. In the method for preparing the polypeptide, an amino acid or peptide fragment with amino and carboxyl groups both unprotected is used as an ammonia component for the synthesis of a polypeptide, and after an -acyloxyenamide derivative of a carboxylic acid forms an amide bond or peptide bond with the amino group of the unprotected amino acid or peptide fragment, the next peptide bond construction cycle can be carried out without removing the carboxyl protecting group.