Data for: The first target specific, highly diastereoselective synthesis, design and characterization of pyranoquinolinyl acrylic acid diasteromers as potential α-glucosidase inhibitors.

In the present investigation we report the first target specific, highly diastereoselective synthesis of new class of pyranoquinolinyl/furoquinolinyl-acrylic acid diastereomers and evaluation of their in vitro α-glucosidase inhibitory activity. All the products were thoroughly characterized by 1H-NMR, 13C-NMR, FT-IR, Mass spectral and CHN analysis. A highly diastereoselective target specific route of synthesis for the biologically active diastereomers were developed by using chiral catalyst Europium tris[3-heptafluoropropylhydroxyl methylene]-(-)-camporate (A) or Europium tris[3-(trifluoromethyl)hydroxylmethylene]-(+)-camporate (B). It was found that among a set of 4 diastereomeric products obtained, exo diasteromers of pyranoquinolinyl acrylic acid adducts exhibited relatively high α-glucosidase inhibitory activity. The newly synthesized compounds exhibited IC50 values in the range of (0.40 ± 0.02 - 30.3 ± 0.84μM) as compared to standard acarbose (IC50=0.65± 0.02μM). It was found that compounds 11a, 11c, 11d and 12d were found to be more active than standard acarbose. It was also found that unsubstituted compound (11a) or compounds with chlorine or methoxy substituent (11c, 11d, 12d) showed potential α-glucosidase inhibitory activity. However a reversal in activity was observed with Nitro substituent (11b, 13b) wherein the endo diastereomers were found to be more active than exo diastereomers. Molecular docking studies were used for design of the compound and understand the mode of binding between the compound and target enzyme. A plausible mechanism for the diastereoselective synthesis was also proposed.

在本项研究中，我们首次报道了一种新型吡喃喹啉基/呋喃喹啉基丙烯酸异构体的目标特异性、高度对映选择性合成，并对其体外α-葡萄糖苷酶抑制活性进行了评估。所有产物均经过1H-NMR、13C-NMR、FT-IR、质谱和CHN分析进行了全面表征。通过使用手性催化剂铕三[3-七氟丙基羟甲基]-(-)-庚酸酯（A）或铕三[3-(三氟甲基)羟甲基]-(+)-庚酸酯（B），开发了一种合成具有生物活性的异构体的高度对映选择性目标特异性合成路线。研究发现，在获得的四种对映体产物中，吡喃喹啉基丙烯酸加成物的外消旋异构体表现出相对较高的α-葡萄糖苷酶抑制活性。新合成的化合物与标准阿卡波糖（IC50=0.65±0.02μM）相比，其IC50值范围为（0.40±0.02 - 30.3±0.84μM）。发现化合物11a、11c、11d和12d的活性高于标准阿卡波糖。此外，未取代化合物（11a）或氯或甲氧基取代的化合物（11c、11d、12d）显示出潜在的α-葡萄糖苷酶抑制活性。然而，硝基取代物（11b、13b）活性出现了逆转，其中内消旋异构体比外消旋异构体活性更高。利用分子对接研究对化合物进行设计，并理解化合物与靶标酶之间的结合模式。还提出了一种对映选择性合成的合理机制。