Synthesis Of Multifunctional Triazole-Linked Glycosyl Amino Acids And Bis-Amino Acids; Study Of Resveratrol-Based Aβ42Fluorescent Probes

This paper is devided into two parts:Synthesis of Multifunctional Triazole-Linked Gly-cosyl Amino Acids and Bis-Amino Acids and Study of Resveratrol-Based A(342Fluorescent ProbesPart Ⅰ:Synthesis of Multifunctional Triazole-Linked Glycosyl Amino Acids and Bis-Amino AcidsCopper (I) catalyzed click reaction as a powerful synthetic tool is widely used in organic and medicinal chemistry, chemical biology, polymer and materials science. It displays salient feature such as mild condition, high yield, good chemoselectivity, modularity and biocompat-ibility. In this work, a series of glycosyl amino acids and bis-amino acids were designed and synthesized by click reaction. Furthermore, their biological activity and corrosion inhibitive activity for mild steel in HCl were also tested.Firstly, glycosyl amino acids27-34were efficiently synthesized by click reaction be-tween6-and1-azido glycosides (5,10,15,20) and serine and threonine containing a terminal alkyne. Then triazolyl glycosyl amino acid derivatives35-42and43-50were obtained by a subsequent deprotection procedure.Secondly,1,2,3-triazolyl bis-amino acid compounds89-100were synthesized by click reaction between nine azido amino acid building blocks and three terminal alkynes. Then tri-azolyl bis-amino acid derivatives101-112and113-120were obtained by removing the Boc group and Bn group, respectively.Finally, the screen of biological activity on multi-enzyme targets showed that these two compound series, glycosyl amino acids and bis-amino acids, both have good inhibitory ac-tivities against PTP-1B. Compound49displayed micromolar inhibitory activity on PTP-1B (IC50=2.2μM) as well as modest inhibitory activity on SHP-1(IC50=13.5μM) and SHP-2(IC50=10.9μM). Enzyme kinetics study and docking simulation showed that compound49was a competitive inhibitor against PTP-1B.These results provide us useful clues for further structral modification. Meanwhile, in vitro biological activity assay showed that the bis-amino acids have an IC50of30μM against PTP-1B, which facilitates our further structural modifica-tion on these compounds. Moreover, the electrochemistry impedance and polarization curve and scanning electron microscopy of compounds35-42and compounds101-112with mild steel in1M HC1were carried out. The results indicated that these two compound series showed better corrosion inhibitive performance compared to their unmodified sugar and/or natural amino acid counterparts, therefore indicating their role as a new class of green organic corrosion inhibitors.Part Ⅱ:Amino Acids and Study of Resveratrol-Based A(342Fluorescent ProbesAlzheimer’s disease is one of the major diseases in human beings, which is caused by the Amyloid β42(Aβ42) aggregations in brain cells that lead the formation of senile plaques. It was showen that resveratrol has a good neuroprotective effect on Alzheimer’s disease. We employed graphene oxide as to aggregate resveratrol by non-covalent stacking, producing a resveratrol-based fluorescent probe for exploring a potential optical sensor for Aβ42. Mean-while, several resveratrol derivatives were also designed and synthesized as potential fluores-cent or electrochemical Aβ42probes.Firstly, non-covalent modification was conducted on graphene oxide by self-assembly of resveratrol, and we found that the fluorescence of the compound was quenched followed by concentration-dependent recovery via addition of increasing Aβ42. This indicates that there exists strong and specific binding between trans-resveratrol and Aβ42. The interaction be-tween cis-resveratrol and AP42was studied in parallel and the binding was much weaker compared with the trans-counterpart. In addition, upon UV light irradiation (365nm), the flu-orescence recovered of trans-resveratrol-Aβ42complex further quenched due to a photoin-duced isomerization, revealing the possibility of developing a new class of light-tunable fluo-rescent probes for detection of AP42.Secondly,2,5-methoxy substituted resveratrol derivatives were synthesized by methylat-ing, Arbuzov rearrangement and Wittig-Hornorreaction from2,5-dihydroxybenzoic acid. In addition,2,5-methoxy-substiluted azo-analogues of resveratrol were designed and synthe-sized as potential fluorescent and electrochemical probes for developing new Aβ42probes.