基于Passerini反应构筑吗啉-2,5-二酮类单体及其可控开环聚合研究

Polydepsipeptides (PDPs) composed of alternatively arranged alpha-hydroxy acid unit and alpha-amino acid unit represent an important branch of various aliphatic poly(ester amide)s. PDPs are biodegradable and possess good biocompatibility due to the native degradation products. The major approach toward PDPs is the melt ring-opening polymerization (ROP) of morpholine-2,5-diones (cyclic depsipeptides, CDPs) under catalysis of Sn(Oct)2 or lipase. Though there are many publications on the ROP studies of CDPs, poor control of the ROP process and difficulty in CDP synthesis limit the development of PDPs as promising biomaterials. Herein, we will develop a new synthetic method for the highly efficient preparation of various CDP monomers based on the boric acid-assisted Passerini-type reaction. Then，organic bases such as TBD and DBU that are powerful as organocatalysts for well controlled ROP of various lactones, lactide or cyclic carbonates, will be used to catalyze the ROP of CDPs with the assistance of thiourea co-catalyst. Hopefully, we can find the appropriate catalytic systems and conditions for well controlling the ROP of CDPs, which is important for synthesizing various versatile PDPs with well-defined structures. During this process, we will investigate the chiral effect of the 3-/6-alkyl groups on the ROP of CDPs. On the whole, this project focuses on the improvements in synthesis of CDP monomers and controlling of the ROP process.

Polydepsipeptide (PDP) 是氨基酸和羟基酸的交替共聚物，生物相容性优异，可降解，在药物传递、组织工程领域有较大应用价值。PDPs主要通过吗啉-2,5-二酮类单体（CDP）在辛酸亚锡或脂肪酶催化下的开环聚合制备，该方法存在单体合成效率低、聚合过程不易调控、聚合物结构精准度差等问题。发展高效合成CDP的新方法，实现其温和条件下的可控聚合，对于拓展PDP的种类及应用有重要意义。本项目拟利用硼酸介导的Passerini-type反应发展合成CDP的新方法，以实现高效制备结构多样CDP的目标；将有机碱-硫脲体系用于催化CDP开环聚合，旨在温和条件下精密调控聚合过程，制备结构精确的PDPs；探索CDP的手性结构对有机碱催化聚合的影响，揭示PDP的立构规整度与其性质之间的关系规律。此外，还拟探讨CDP环的酰胺键对聚合过程的影响，这有助于丰富有机碱催化体系在环状单体开环聚合方面的知识。

脂肪族聚酯酰胺（PEA）结合了常规脂肪族聚酯和脂肪族聚酰胺的优点，但有关分子量可控、分布窄、组成结构易调的PEAs的合成仍不易实现。本项目结合Passerini-type 反应和后续的酸催化环化反应，建立了一种高效合成 吗啉-2,5-二酮（CDP） 环状酯酰胺单体的新方法，制备了一系列6-位取代基不同的CDPs；以有机强碱-硫脲为催化体系，实现了温和条件下CDP的可控开环聚合，制得一系列分子量不同、端基结构明确的窄分布均聚物（PDP）及嵌段共聚物。提出了可能的聚合机理，阐明了酰胺基团上氢对CDP开环聚合过程的影响；探究了有机强碱催化手征性CDP聚合过程中手性中心的消旋化，证实了PDPs是一类可循环利用的高分子材料。该项目还系统研究了6-位烷基取代基结构对CDPs单体的开环聚合、所得聚合物的热学及力学性质的影响。此外，以商业易得的邻苯二甲酸酐与β-氨基醇为原料，采用组合-环化策略发展了半芳香族八元环酯酰胺单体的合成方法