Synthesis of Enantiomeric ω-Substituted Hydroxy Acids from Terminal Epoxides and Alkenes: Functional Building Blocks for Discrete and Sequence-Defined Polyesters

Abstract

Polyesters exhibiting a protein-like absolute atomic precision have unlimited potential for application as biomaterials and polymeric materials. Herein, we report the synthesis of enantiomeric ω-hydroxy acids (OHAs) from terminal epoxides and alkenes as starting materials. Our synthetic strategy allows the synthesis of a library of OHAs with a well-defined atomic composition (carbon number), stereochemical configuration, and substituent chemistry. These monomers can serve as building blocks for the preparation of discrete and sequence-defined polyesters, wherein various functional groups can be introduced at specific locations via the cross-convergent method. We demonstrated that the specific locations of the reactive functional groups of the sequence-defined polyester could be utilized to form a concentrically cyclic polymer upon cyclization. Our results provide a facile platform for engineering polyesters with the structural sophistication exhibited only by biopolymers, such as proteins and nucleic acids.

Shotgun sequencing of 512-mer copolyester allows random access to stored information

“…3b). 41 The MALDI-TOF mass spectrometry analysis of this solution con rmed that the PcL chain was fragmented into oPcLs with distinguished molecular weights ranging from 891.2 to 8162.9 Da (Fig. 3c).…”

Modular Preparation of Discrete Polyesters through Iterative Growth

“…14,22−31 Nevertheless, the wide application of this approach is hindered by a limited number and structure diversity of monomers that can be orthogonally protected/ deprotected and efficiently coupled. 32,33 In this work, we reported a robust platform for designing and synthesizing orthogonally protected monomers bearing desirable substituents that can be used for convergent syntheses of sequence-defined polyesters. Hydrophobic, hydrophilic, and omniphobic building blocks were prepared based on the malic acid derivatives, affording a diverse monomer library for modular preparation of discrete polymers.…”

“… , Chain length increases exponentially with each cycle, and a high degree of polymerization can be achieved in relatively fewer steps. This approach has been applied in syntheses of discrete polymers with exact chemical structure, uniform chain length, and programmable monomer sequence, especially those to be scaled up for further applications. ,− Nevertheless, the wide application of this approach is hindered by a limited number and structure diversity of monomers that can be orthogonally protected/deprotected and efficiently coupled. , …”

Structural Homogeneity of Macromolecular Networks by End-to-End Click Chemistry between Discrete Tetrahedral Star Macromolecules

“…27,32−36 Therefore, we synthesized a cleavable dTSM having sequence-defined PLA arms with mandelic acid (MA) as a cleavable unit at the penultimate position from the COOH terminus of PLA (COOH-LA•MA• LA 32 -OH). 47 The sequence-defined dTSM was converted to dTS-[LA• MA•LA 32 -DBCO], which was subsequently reacted with dTS-[LA 32 -N 3 ] to form SPAAC-N-dTS-[LA•MA•LA 64 ] by 4 × 4 click reaction in CH 2 Cl 2 (10 w/v %) (Figure 4a). The degree of swelling of the resulting network in CH 2 Cl 2 (1790 w/w %) coincided with that of SPAAC-N-dTS-[LA 64 ] (1800 w/w % in CH 2 Cl 2 ) (Figure S13 and Table S6).…”

“…To identify the presence of defects in N -dTSMs, we carried out the mass spectrometry analysis of the fragments resulting from the disassembly of N -dTSM. We anticipated that the network disassembly spectrometry (NDS) could provide quantitative information on the homogeneity of N -dTSMs by site-specific chain scission of the sequence-defined PLA chain between cross-links. ,− Therefore, we synthesized a cleavable dTSM having sequence-defined PLA arms with mandelic acid (MA) as a cleavable unit at the penultimate position from the COOH terminus of PLA (COOH-LA·MA·LA 32 -OH) …”