Utilization of the p-nitrobenzyloxycarbonyl (pNZ) amine protecting group and pentafluorophenyl (Pfp) esters for the solid phase synthesis of spiroligomers

作者：Pfeiffer Conrad T; Northrup Justin D; Cheong Jae Eun; Pham Melody A; Parker Matthew F L; Schafmeister Christian E^*

来源：Tetrahedron Letters, 2018, 59(30): 2884-2888.

DOI：10.1016/j.tetlet.2018.05.041

• Spiroligomer
• Bis-amino acid
• Peptidomimetic
• Solid phase synthesis
• P-Nitrobenzyl carbamate
• Pentafluorophenyl ester

Spiroligomers are a class of peptidomimetics that connect interchangeable, stereochemically pure, cyclic monomers through pairs of amide bonds to form diketopiperazines between the monomers. This enables them to adopt predictable and programmable structure due to the rigidity of the final molecule. We present a new method for the solid phase synthesis of highly functionalized spiroligomers that incorporates the use of the p-nitrobenzyloxycarbonyl (pNZ) as a temporary amine protecting group and the pentafluorophenyl ester for monomer activation. This new method allows for the synthesis of spiroligomers with higher purity and increased yields when compared to previous methods. This improved method of synthesis of functionalized spiroligomers will facilitate the development of applications as catalysts, therapeutics and membrane channels.