The enantioselective synthesis of chiral cis-3-hydroxyazetidin-2-ones mediated by Porcine Pancreatic Lipase (PPL) via hydrolysis of cis-3-(chloro acetoxy) azetidin-2-ones in the presence of a phosphate buffer (0.1M, pH = 7.2) in acetonitrile at a temperature range of 25-35 °C was optimized. Under the optimized reaction conditions, the influence of various electron withdrawing/donating/neutral groups on ester functionality of cis-3-(substituted acetoxy)azetidin-2- ones towards hydrolysis was extensively studied, and the bromoacetoxy, propanyloxy, and formyloxy groups provided moderate to good yields of 90%, 91%, and 81%, respectively. Moreover, the chiral cis-3-hydroxyazetidin-2-ones underwent acetylation, and their enantiomeric excess was assessed using the 1H NMR technique, employing chiral shift reagents. To gain insights into the active sites of the biocatalyst, molecular docking studies of compounds 5(a-i) with pancreatic lipase (PDB ID: 1LBS) were carried out. Additionally, the proposed interaction of substituents with the biocatalyst established the absolute stereochemistry of the target chiral cis-3-hydroxyazetidin-2-ones using Seebach's model in comparison to Jone's models.

中文翻译：

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取代基的优化和对3-(取代乙酰氧基)氮杂环丁烷-2-酮转化为手性3-羟基氮杂环丁烷-2-酮的影响、分子对接和对映体过量测定

在磷酸盐缓冲液（0.1M，pH）存在下，通过顺式-3-（氯乙酰氧基）氮杂环丁酮的水解，由猪胰脂肪酶（PPL）介导手性顺-3-羟基氮杂环丁酮-2-酮的对映选择性合成= 7.2) 在乙腈中在 25-35 °C 的温度范围内进行了优化。在优化的反应条件下，广泛研究了各种吸电子/供电子/中性基团对cis-3-(取代乙酰氧基)氮杂环丁烷-2-酯水解的酯官能团的影响，并提供了溴乙酰氧基、丙酰氧基和甲酰氧基。中等至良好的收益率分别为 90%、91% 和 81%。此外，手性顺式-3-羟基氮杂环丁烷-2-酮进行乙酰化，并使用手性位移试剂通过 1H NMR 技术评估其对映体过量。为了深入了解生物催化剂的活性位点，对化合物 5(ai) 与胰腺脂肪酶 (PDB ID: 1LBS) 进行了分子对接研究。此外，与 Jone 模型相比，取代基与生物催化剂的相互作用建立了目标手性顺-3-羟基氮杂环丁烷-2-酮的绝对立体化学，使用 Seebach 模型。