Synthesis And Antitumor Evaluation Of The Allenamides

Allenes are a kind of unsaturated compounds containing high cumulative double bonds.They are becoming one of important organic synthetic intermediates because of their highintrinsic reactivity. Since the last century, chemists have isolated various natural products withallene units, this kind of natural products exhibit their unique pharmacological activity andbiological activity.With the continual research of allene, it is introduced into other pharmaceutically activemolecules to improve the pharmacological activity as a functional group. But allenic compoundshave a low count in nature, and are difficult in extraction and separation. Apart from extractingallenic compounds directly from the nature, it is essential to develop the organic synthesismethod for allenic compounds, this research is also a very challenging field. However, thereported methods of allenic compounds have some disadvantages such as complex components,complicated operations and high cost. It is urged to set up a simple, efficient and cheap synthesisfor allenic compounds.Taking allenamide compounds as the target product, we designed a synthetic route withdirect cross-coupling propargyl alcohol and isocyanide. Propargyl alcohols are a kind offunctionalized alkynes with high reactivity. Hydroxyl group is directly connected withcarbon-carbon triple bond in their compounds, which makes the big difference betweenpropargyl alcohols and isolated alkynes. The structures of isocyanides are similar to carbonmonoxide with cabbeen properties, and isocyanine is a kind of important organic synthons. Thisnew reaction is both atom and step efficient, allowing the synthesis of a range of stabile andvaluable allenamides. In addition, we also had a test for antitumor activities of our products, andwould provide the reference and help for the study of biological activity in allenic compounds.My thesis is divided into five chapters1. Preparate a variety of propargyl alcohol compounds.2. Synthesize a variety of isocyanides.3. Optimization of the reaction conditions.Product was obtained in highest yield when1,4-dioxane was employed as the solvent in thepresence of Ag2CO3at room temperature.4. The synthesis of many allenamides compounds. We obtained a variety of different functionalized groups of allenamides, and laid the foundationfor the research of biological activities for this kind of compounds.5. Study on antitumor activity of some allenamide products.Some alleneamides compounds were a good inhibition for prostate cancer cells (PC3, DU145)in vitro growth, and found the antitumor activity of a molecular potential3y; in addition, wealso find that some alleneamide compounds show different inhibition selectivity on tumor cellgrowth in vitro.