Synthesis of Monodisperse Sequence‐Defined Polymers Using Protecting‐Group‐Free Iterative Strategies

Abstract

The synthesis of “precision” polymers with finely controlled molecular structures is an important new development in synthetic polymer chemistry. This trend is the logical outcome of the continuing evolution of the field of polymer synthesis. Indeed, during the last few decades, synthetic tools, such as living ionic polymerizations, controlled radical polymerizations, and click chemistry, have revolutionized the synthesis of polymers with controlled architectures such as block, graft, star, brush, hyperbranched or cyclic polymers. These aspects being solved, it is now time for polymer chemists to address more challenging questions such as the design of monodisperse polymers and the control of primary (i.e., comonomer sequences), secondary (i.e., single‐chain folding), and tertiary (i.e., single‐chain compartmentalization) structures. Here, new synthetic tools have to be developed or imported from other disciplines such as organic chemistry and biochemistry. For instance, solid‐phase iterative chemistry, which was initially introduced for the synthesis of oligopeptides and oligonucleotides, is an interesting methodology for preparing monodisperse sequence‐defined polymers. However, such approaches are usually time‐consuming and request demanding coupling/capping/deprotection steps. Yet, interesting protecting‐group‐free methodologies have been described in recent years for simplifying and accelerating these processes. These promising new approaches are briefly listed and explained in this article.

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

“…Although solid-state peptide synthesis was introduced by Merrifield6—the first example of a true synthetic sequence-defined peptide—macromolecular chemists have initially focused on and developed a diverse number of solution-based polymerization strategies for imparting a certain level of control over statistical polymerization processes and exploited these for controlling the order of the building blocks (sequence-controlled polymers)7891011121314151617181920. In addition, the advent of modular synthetic strategies21222324 has contributed significantly towards achieving a high level of control over macromolecular formation processes.…”

Tandem mass spectrometry sequencing in the negative ion mode to read binary information encoded in sequence‐defined poly(alkoxyamine amide)s

“…In the latter case, the molecular structure of the studied poly(alkoxyamine amide)s contained two coded amide synthons, –NH–(CO)–CH(CH) 3 – (71.0 Da) and –NH–(CO)–C((CH) 3 ) 2 – (85.1 Da), respectively defined as the 0‐ and 1‐bit, spaced by a TEMPO (T) alkoxyamine moiety (Scheme ). These sequence‐defined terpolymers were synthesized using iterative solid‐phase methodologies based on either a monomer‐by‐monomer construction of the chains or a convergent approach involving pre‐prepared X ‐T‐ X dyads (with X = 0 or 1 ) to shorten the preparation time of long chains …”

Enzymatic Continuous Flow Synthesis of Thiol‐Terminated Poly(δ‐Valerolactone) and Block Copolymers

“…Chemoselective polymerization with multifunctional initiator/monomer is one of the most challenging topics in polymer chemistry . Due to the chemical activities of thiol, a protecting group was generally employed in mercapto‐alcohol initiated ROP .…”