Combinatorial Synthesis And Immunocompetence Study Of A Series Of Small-Molecular Compounds Related To Proglumide

Combinatorial chemistry is a new strategy for discovery and optimization of lead compounds in drug design in the early 1990s. It makes a big difference from traditional method with which pure compounds are synthesized, purified and screened one by one. Combinatorial chemistry is a type of synthetic and screening strategy which leads to large chemical libraries and extremely accelerates the rate of finding and optimizing new lead compounds. Solid-phase parallel approach is the main method in the study of combinatorial chemistry for its advantage of easy separating and purifying compounds; Proglumide is a gastrin receptor antagonist synthesized in the middle of 1960s which can be used in the treatment of peptic ulcer. Proglumide isolated from Chinese traditional medicine Acanthopanax setchuenensis is proved that it has high immunocompetence in the past experiments. In this project, we want to make proglumide as lead compound, construct the small-molecular library related to proglumide adopting solid-phase parallel approach, and expect to find some compounds which show higher immunocompetence than proglumide for further research. Conclusion:1 .established a novel synthesis method of D> L-Fmoc-Glu-OAllyland D^ L-Fmoc-Asp-OAllyl; 2.established the solid-phase synthesis method of proglumide andits analogues; 3.constructed the small-molecular library including 384 compoundsrelated to natural proglumide, and separated some by-products; 4.found 9 compounds which show higher immunocompetence thanproglumide in this small-molecule library.