New synthetic methodology for chiral amines and peptides via gap technology

The recent push in modern medicine to utilize biopolymeric structures as therapeutics has driven research in a number of different areas. Peptides and proteins have been the most prominent biopolymer in biomedical sciences, due to their ease of synthesis and manipulation compared to their oligosaccharide and oligonucleotide counterparts. Therefore, research concerning synthetic methodology of peptides and their various chiral amine building blocks is of high importance. Reducing peptide production costs is vital to expanding the peptide market. The candidate has developed important and practical methodologies for chiral, α-amino amide synthesis via carbamoyl anion additions to chiral, N-phosphonyl imines. The process is greener and more effective than previous counterparts, by avoiding the use of column chromatography and other traditional purification techniques using GAP chemistry. Most substrates can be obtained as single isomers after simple ether washing, which is also a significant benefit of GAP chemistry. The candidate has also developed a novel method of peptide synthesis (PS) via GAP chemistry, which can overcome nearly every disadvantage of SPPS while maintaining facile purification. GAP-PS avoids wasteful polymer resins and linkers while also avoiding column chromatography. GAP-PS is also observed to have highly efficient coupling reactions, which greatly reduces amino acid and coupling reagent waste, while avoiding deletion sequences and providing crude peptides of high purity. Protected peptides are consistently and selectively precipitated as white solids, making them easy to handle for large scale synthesis while also making GAP-PS amenable to Fmoc chemistry. These surprising properties lead us to propose Group-Assisted Synthesis (GASyn) as an appendage to GAP chemistry, wherein we hypothesize that GAP groups can actually help increase synthetic efficiencies, such as chemical yields, diastereo- and enantioselectivities, etc., in general.