Synthesis of libraries of peptide tertiary amides

A process for preparing a peptide tertiary amide of formula (I) or its enantiomer with the opposite stereochemistry at Cα:

• wherein
• R1 is selected from optionally substituted C1-C10 alkyl, optionally substituted aryl, optionally substituted alkaryl, optionally substituted alkoxyl, optionally substituted heteroaryl, arylalkoxyl, optionally substituted acyl, OH, OR′, NH2, NHR′, NR′2, SH, SR′, C(O)R′, and an amino acid side chain;
• R2 is selected from optionally substituted C2-C10 alkyl, optionally substituted aryl, optionally substituted alkaryl, optionally substituted alkoxyl, optionally substituted heteroaryl, arylalkoxyl, optionally substituted acyl, OH, OR′, NH2, NHR′, NR′2, SH, SR′, C(O)R′, and an amino acid side chain;
• wherein
• R′ is selected from optionally substituted C1-C10 alkyl, optionally substituted C1-C10 alkenyl, optionally substituted C1-C10 alkynyl, optionally substituted aryl, optionally substituted alkaryl, and optionally substituted acyl;
• comprising:
• oxidizing a primary amine of an amino acid of formula (II)
• with an oxidizing agent followed by treatment with a nucleophilic bromide source to give an optically pure 2-bromo acid of formula (III):
• wherein the synthesis further comprises a solid or semi-solid phase synthetic step
• wherein the solid or semi-solid phase synthetic step comprises bonding the 2-bromo acid of formula (III)
• to the solid-phase bead using a coupling agent in a solvent to give a compound of formula (V)
• wherein the compound of formula (V) is reacted with an amine of formula (IV)
• H2N—R2 (IV)
• to give a compound of formula (VI):
• and wherein the compound of formula (VI) is further reacted with additional 2-bromo acid of formula (III) followed by an amine of formula (IV) to obtain oligomers of the compound of formula (VI).