Direct palladium-mediated on-resin disulfide formation from Allocam protected peptides.
The synthesis of disulfide-containing polypeptides represents a long-standing challenge in peptide chemistry, and broadly applicable methods for the construction of disulfides are in constant demand. Few strategies exist for on-resin formation of disulfides directly from their protected counterparts. We present herein a novel strategy for the on-resin construction of disulfides directly from Allocam-protected cysteines. Our palladium-mediated approach is mild and uses readily available reagents, requiring no special equipment. No reduced peptide intermediates or S-allylated products are observed, and no residual palladium can be detected in the final products. The utility of this method is demonstrated through the synthesis of the C-carboxy analog of oxytocin.
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. stockdill@wayne.edu.
Thilini D
TD
Kondasinghe
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. stockdill@wayne.edu.
Hasina Y
HY
Saraha
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. stockdill@wayne.edu.
Samantha B
SB
Odeesho
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. stockdill@wayne.edu.
Jennifer L
http://orcid.org/0000-0003-4238-6530
JL
Stockdill
D004220:Disulfides / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D012117:Resins, Synthetic / Q000737:chemistry*
D004220:Disulfides; D010455:Peptides; D012117:Resins, Synthetic; D010165:Palladium