4‐Methylbenzhydryl Bromine Resin: Bridging the Gap between 2‐Chlorotrityl Chloride and Wang‐Type Resins for the Solid‐Phase Synthesis of C‐Terminal Acid Peptides

Over the last year, peptides have been consolidated as an important class of biomolecules, receiving increased attention from the pharmaceutical, cosmetic, and food industries. Most peptides currently used in both industrial and research modes are prepared by means of solid‐phase peptide synthesis, which is based on the use of a solid polymeric support. The preparation of C‐terminal amide peptides is easier than for their acid counterparts, and there are several resins available for this purpose. In contrast, the synthesis of peptides bearing a C‐terminal acid is more challenging because ester formation is more difficult than amide formation, and esters show increased lability. The two main resins employed in peptide synthesis are Wang resin, which is used for the preparation of unprotected peptides, and 2‐chlorotrityl chloride (CTC) resin, which can also be used to obtain side‐chain protected peptides. Herein, a new solid support, 4‐Methylbenzhydryl bromine resin, isdiscussed, which, although slightly more stable than CTC resin, allows the preparation of protected peptides, renders less diketopiperazine (DKP) formation than Wang resin, and does not degrade during the final global cleavage and deprotection, and is therefore exempt of back alkylation.