Amino acids and peptides. Part 38. Development of a new amino-protecting group, 2-adamantyloxycarbonyl, and its application to peptide synthesis

Abstract

A new &-amino protecting group, 2-adamantyloxycarbonyl (2-Adoc), was developed, and its application to the solid-phase synthesis of protected peptides was demonstrated in combination with N "f I uoren -9-ylmet hoxycarbonyl ( Fmoc) protection and trif luoroacetic acid (TFA) -cleavable resin support. The 2-Adoc group was applied successfully also to the solution-phase peptide synthesis depending on tertbutoxycarbonyl (Boc) -chemistry.Paper 4/03202K

Solution‐Phase Peptide Synthesis

“…2-Adoc Group Lys(2-Adoc) 37 ( Figure 6.9) was developed by Nishiyama and Okada [116], and it was prepared using Lys 2 /Cu 2þ complex and 2-adamantyl chloroformate in the usual manner [117]. The 2-Adoc group was stable to 7.6 M HCl in dioxane, TFA, 25% HBr in acetic acid and 1 M trimethylsilylbromide (TMSBr)-thioanisole-TFA for up to 24 h. It could be removed by 1 M trifluoromethanesulfonic acid (TFMSA)-thioanisole-TFA or anhydrous HF in a few minutes at 0 C, but was cleaved very slowly by methanesulfonic acid (MSA).…”

Chapter 9. Synthetic methods

“…Other protecting groups for amines include the 2,5-dimethylpyrrole group;268 the 2-adamantyl carbamate group for the protection of &-amino groups in peptide synthesis. 269 Amide chemistry has seen much study this year. 2-Pentafluorothiophenyl esters have been shown to be useful acyl donors for amide bond formation.270 Amides are chemoselectively hydrolysed in the presence of esters by copper(~~)/glyoxal.~~ The N-(2-hydroxybenzyl) protecting group has been used for protection of the amide bond in solid-phase peptide synthesis overcoming problems with chain aggregation.272 Nitriles may be converted into amides by treatment with manganese dioxide on silica gel.273 N,N-Dialkyl carbamatesgenerated from the amine and carbon dioxideare converted into the corresponding carbamoyl chloride with thionyl the carbon dioxide is effectively a phosgene replacement.…”