A Scalable and High‐Yield Strategy for the Synthesis of Sequence‐Defined Macromolecules

Abstract

The efficient synthesis of a sequence-defined decamer, its characterization, and its straightforward dimerization through self-metathesis are described. For this purpose, a monoprotected AB monomer was designed and used to synthesize a decamer bearing ten different and selectable side chains by iterative Passerini three-component reaction (P-3CR) and subsequent deprotection. The highly efficient procedure provided excellent yields and allows for the multigram-scale synthesis of such perfectly defined macromolecules. An olefin was introduced at the end of the synthesis, allowing the self-metathesis reaction of the resulting decamer to provide a sequence-defined 20-mer with a molecular weight of 7046.40 g mol(-1). The obtained oligomers were carefully characterized by NMR and IR spectroscopy, GPC and GPC coupled to ESI-MS, and mass spectrometry (FAB and orbitrap ESI-MS).

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

“…In parallel, strategies involving the consecutive insertion of single monomer units (vinyl or acrylate) based on radical processes started to emerge for the synthesis of sequence-defined polymers3738. Further, notable synthetic strategies towards sequence-defined polymers conducted in bulk include the use of thiolactones394041 and multi-component reactions424344. Concomitant to the development of new synthetic approaches to sequence-defined polymers, selected applications of such molecules are emerging, for example, bio-inspired structures for which high sequence definition is essential4546.…”

1H PFG‐NMR Diffusion Study on a Sequence‐Defined Macromolecule: Confirming Monodispersity

“…The 1D 1 H‐NMR spectrum of the decamer (Figure ) shows the characteristic peaks, here labeled with numbers, as reported previously . The lines in the spectrum correspond to various chemical groups of the studied decamer.…”

“…The relative deviation between diffusion coefficients obtained by PFG‐STE and β‐PFG‐SE is about 9%, which is within a reasonable range. Finally, the molecular weight of the sequence‐defined decamer was determined from 1 H PFG‐NMR diffusion experiments and agrees well with expectations from the chemical structure and the value obtained by electrospray ionization mass spectrometry . It should be pointed out that the diffusion properties of macromolecules depend on the molecular architecture and the solvent type.…”

“…To achieve ten different and selectable side chains, a sequence‐defined decamer was synthesized via iterative Passerini three‐component reaction (P‐3CR) and subsequent deprotection . Both the stimulated echo (PFG‐STE) and a fast spin‐echo pulse sequence (β‐PFG‐SE) were applied to explore the diffusion properties of decamer solutions at different concentrations and confirm the monodispersity.…”

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

“…All compounds of this investigation were carefully characterized via NMR (1D and 2D), IR and HRMS. The herein presented strategy is currently under investigation for the preparation of sequence-defined macromolecules [39–40]. Furthermore, the obtained compounds present a rigid, geometrically fixed and highly functionalized DHMP moiety, which could potentially be utilized for covalent organic frameworks and porous materials [41–42].…”