Stereodivergent transformation of a natural polyester to enantiopure PHAs

• 成果类型: Article
• 署名作者: Tian, Jun-Jie; Li, Ruirui; Quinn, Ethan C.; Nam, Jiyun; Chokkapu, Eswara Rao; Zhang, Zhen; Zhou, Li; Gowda, Ravikumar R.; Chen, Eugene Y. -X.
• 署名单位: Colorado State University System; Colorado State University Fort Collins
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1323
• DOI: 10.1038/s41586-025-09220-7
• 发表日期: 2025-07-24
• 关键词: ring-opening polymerization; active beta-butyrolactone; anionic-polymerization; catalysts; poly(3-hydroxybutyrate); polyhydroxyalkanoates; semicrystalline; polymers; lactones

摘要

Natural chiral polymers, such as DNA, proteins, cellulose and poly[(R)-3-hydroxybutyrate] ((R)-P3HB), are prevalent in their enantiopure forms1,2. Existing methods to synthesize enantiopure polymers focus on enantiospecific polymerization, in which only one specific enantiomer is obtained from the corresponding chiral monomer3, 4, 5-6. Here we introduce a catalytic stereodivergent synthetic strategy to access all enantiopure di-isotactic poly(3-hydroxyalkanoate) (PHA) diastereomers from bacterial (R)-P3HB as the single chiral source. A series of enantiopure (R,R)-alpha-alkylated-beta-butyrolactones are obtained from (R)-P3HB and then subjected to the catalyst-controlled diastereodivergent ring-opening polymerization (ROP) to enantiopure di-isotactic alpha-alkylated PHAs. Metal-catalysed coordination-insertion ROP results in threo-(R,R)-di-isotactic PHAs with chiral retention, whereas anionic ROP catalysed by an organic superbase produces erythro-(R,S)-di-isotactic PHAs with chiral inversion, achieving precision di-isotactic PHAs with exclusive regio- and stereoregularity. This strategy has also enabled the stereodivergent synthesis of all four [(R,R), (S,S), (R,S) and (S,R)] stereoisomers of alpha,alpha-dialkylated PHAs from (R)-P3HB, which can be depolymerized to chiral alpha,alpha-dialkylated-beta-butyrolactones with high stereoselectivity. Overall, this catalyst-controlled regio- and stereoselective, stereodivergent synthetic methodology provides access to 16 enantiopure stereoisomers of alpha(alpha)-(di)substituted PHAs and enables the stereochemistry-defined structure-property relationship study of the di-isotactic PHAs, providing insights into the effects of main-chain stereoconfigurations and alkyl side chains on their thermal properties, melt processability, mechanical performance and supramolecular stereocomplexation.