Atmaca_2019_Bioorg.Chem_88_102980

Enantioselective synthesis of functionalized cyclic allylic alcohols via kinetic resolution in transesterifcation with different lipase enzymes has been developed. The influence of the enzymes and temperature activity was studied. By determination of ideal reaction conditions, byproduct formation is minimized; this made it possible to prepare enantiomerically enriched allylic alcohols in high ee's and good yields. Enantiomerically enriched allylic alcohols were used for enantiomerically enriched oxazolidinone synthesis. Using benzoate as a leaving group means that 1mol % of potassium osmate is necessary and can be obtained high yields 98%. Inhibitory activities of enantiomerically enriched oxazolidinones (8, 10 and 12) were tested against human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and alpha-glycosidase (alpha-Gly) enzymes. These enantiomerically enriched oxazolidinones derivatives had Ki values in the range of 11.6+/-2.1-66.4+/-22.7nM for hCA I, 34.1+/-6.7-45.2+/-12.9nM for hCA II, 16.5+/-2.9 to 35.6+/-13.9 for AChE, and 22.3+/-6.0-70.9+/-9.9nM for alpha-glycosidase enzyme. Moreover, they had high binding affinity with -5.767, -6.568, -9.014, and -8.563kcal/mol for hCA I, hCA II, AChE and alpha-glycosidase enzyme, respectively. These results strongly supported the promising nature of the enantiomerically enriched oxazolidinones as selective hCA, AChE, and alpha-glycosidase inhibitors. Overall, due to these derivatives' inhibitory potential on the tested enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, leukemia, epilepsy; Alzheimer's disease; type-2 diabetes mellitus that are associated with high enzymatic activity of CA, AChE, and alpha-glycosidase.