A Post‐Modification Strategy for the Synthesis of Uniform, Hydrophilic/Hydrophobic Patterned α‐Hydroxy Acid Oligomers

Abstract

AbstractHydrophilic/hydrophobic patterning is a well‐established design strategy to guide secondary structure formation of both natural as well as non‐natural oligomers and polymers. This contribution explores the feasibility of a new approach for the synthesis of uniform, sequence‐defined, hydrophilic/hydrophobic patterned oligo(α‐hydroxy acid)s. The proposed strategy is based on post‐modification of a reactive oligoester scaffold composed of an alternating sequence of hydrophobic [(2S)‐2‐hydroxy‐4‐methylpentanoic acid] and masked hydrophilic [(2S)‐2‐hydroxypent‐4‐enoic acid] α‐hydroxy acids. The use of (2S)‐2‐hydroxypent‐4‐enoic acid instead of a complex side‐chain‐protected hydrophilic building block obviates the need for additional protective group chemistry during chain extension. In a subsequent post‐modification step, the allyl side chains can be quantitatively modified via free‐radical addition of different ω‐functional thiols to afford hydrophilic/hydrophobic patterned oligoesters. The proposed synthetic strategy provides an interesting alternative to rapidly generate libraries of foldamers with identical chain length and monomer sequence but different side‐chain functionalities.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)