Diversity-Orientied Synthesis And α-Glucosidase Inhibition Of Phloroglucin Meroterpene Like Products

The importance of the chemical space represented by natural products（NPs）for drug discovery is now being recognized.However,the current collection of NPs can not fully response to the demands of high throughput screening（HTS）.On the other hand,many abundant NPs have not been used for further development.Recently,diversity-oriented synthesis（DOS）starting from NPs has emerged as an efficient methodology to access chemically diverse libraries with NP or NP-like scaffolds.Those NP-like libraries can meet the progress of HTS and server as convenient source for lead compounds discovery.However,the key challenge in DOS strategy has become how to design and synthesize chemical libraries with emerging biological functions as well as maximized molecular scaffold diversity.In this thesis,phloroglucinol meroterpenes were selected as template compounds andɑ-glucosidase inhibition as the guidance.There has been a diversified construction of natural-like products group by simplifying the redundant fragments and introducing privileged structures.During the DOS,the natural building blocks,monoteroenes,sesquiterpenes（β-caryophyllene,henotannic acid,ɑ-pinene,β-pinene,citronellal,comphene,etc）,phloroglucinols（2,4,6-trihydroxybenzaldehyde,2,6-dimethylbenzene,Syncarpic acid）and 2-hydroxy-1,4-naphoquinones,were selected as starting materials.In total,23 natural-like products were constructed via[4+2]cycloaddition and Knoevenagel condensation reaction.On theɑ-glucosidase inhibitory bioassay,seven compounds（7、8、14、15、16、19 and 26）showed potentialɑ-glucosidase inhibitory activity with IC₅₀ 1.70⁶.90μM,obviousely surpassing the positive controls acarbose and genistein.