Absolute control over polymer stereo- and sequence structure is highly challenging in polymer chemistry. Here, an acid-orthogonal deprotection strategy is proposed for the iterative synthesis of a family of unimolecular polymers starting with enantiopure serines, featuring precise sequence, stereoconfiguration and side-chain functionalities that cannot be achieved using traditional polymerization techniques. Acid-orthogonal deprotections proceed independently of one another by the selection of protecting groups that feature the respective acid-lability. Under p-toluenesulfonic acid, acidolysis of tert-butyloxycarbonyl can proceed exclusively, while low-dosage trifluoroacetic acid and low temperature only trigger the selective and quantitative cleavage of trityl. The pioneering use of this acid-orthogonal deprotection chemistry increases the compatibility with otherwise sensitive groups and opens up pathways to facilely introduce structural and functional diversity into stereo- and sequence-defined polymers, thus imparting their unique properties beyond natural biopolymers.
Keywords: Acid-Orthogonal; Iterative; Sequence-Defined; Stereochemistry; Thioetheramide.
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