美国科罗拉多州立大学Chen, Eugene Y.-X.团队近日研究了天然聚酯向对映纯相芳烃的立体发散转化。相关论文于2025年7月2日发表在《自然》杂志上。

天然手性聚合物，如DNA、蛋白质、纤维素和聚[（R）-3-羟基丁酸酯]（（R）-P3HB），以对映体形式普遍存在。现有的合成对映体纯聚合物的方法主要集中在对映体特异性聚合上，其中从相应的手性单体中只获得一种特定的对映体。研究组介绍了一种催化立体发散合成策略，以从细菌（R）-P3HB中获得所有对映体纯二等规聚（3-羟基链烷酸酯）（PHA）非对映体作为单一手性来源。由（R）-P3HB得到一系列对映体纯（R，R）-α-烷基化-β-丁内酯，然后进行催化剂控制的非对映体开环聚合（ROP），得到对映体全同立构α-烷基化PHA。 

金属催化的配位-插入ROP导致具有手性保留的苏-（R，R）-二等规PHA，而由有机超级酶催化的阴离子ROP产生具有手性反转的排他的区域性和立体性。该策略还实现了从（R）-P3HB中立体发散合成α，α-二烷基化PHA的所有四种[（R，R），（S，S），（R，S）和（S，R）]立体异构体，这些异构体可以解聚成具有高立体选择性的手性α，α二烷基化β-丁内酯。总的来说，这种催化剂控制的区域和立体选择性、立体发散合成方法提供了获得α（α）-（二）取代PHA的16种对映体纯立体异构体的途径，并使二元等规PHA的立体化学定义的结构-性质关系研究成为可能，从而深入了解主链立体构型和烷基侧链对其热性能、熔体加工性、机械性能和超分子立体络合的影响。

附：英文原文

Title: Stereodivergent transformation of a natural polyester to enantiopure PHAs

Author: Tian, Jun-Jie, Li, Ruirui, Quinn, Ethan C., Nam, Jiyun, Chokkapu, Eswara Rao, Zhang, Zhen, Zhou, Li, Gowda, Ravikumar R., Chen, Eugene Y.-X.

Issue&Volume: 2025-07-02

Abstract: 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)-α-alkylated-β-butyrolactones are obtained from (R)-P3HB and then subjected to the catalyst-controlled diastereodivergent ring-opening polymerization (ROP) to enantiopure di-isotactic α-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 α,α-dialkylated PHAs from (R)-P3HB, which can be depolymerized to chiral α,α-dialkylated-β-butyrolactones with high stereoselectivity. Overall, this catalyst-controlled regio- and stereoselective, stereodivergent synthetic methodology provides access to 16 enantiopure stereoisomers of α(α)-(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.

DOI: 10.1038/s41586-025-09220-7

Source: https://www.nature.com/articles/s41586-025-09220-7