Natural Amino Acid Catalyzed Knoevenagel Condensation And Research On Synthesis The Analog Of Conidiogenone

This thesis consists of two parts:part I includ chapter 1-4, which is mainly about the studies on natural amino acid catalyzed Knoevenagel condensation. The Knoevenagel condensation is one of the most useful carbon-carbon bond forming reactions in organic synthesis. The Knoevenagel condensation of aldehydes with active methylene compounds had been commonly employed in the synthesis of numerous chemicals and chemical intermediates. Amino acid-catalyzed Knoevenagel condensations were relatively few, and among them secondary amino acid L-proline was most used. There is a large number of primay amino acids unexplored, and the catalytic mechanisms of primary and secondary amino acid are different. Therefore, the study of primary amino acids as catalysts in Knoevenagel condensation is useful in both methodology and practicality.The Knoevenagel condensations between a,β-unsaturated aldehydes and 1,3-dicarbonyl compounds generated useful a,β,γ,δ-unsaturated dicarbonyl compounds which were versatile synthons and significant substrates for Diels-Alder reactions and 1,4-additions.However, there were only few examples of Knoevenagel condensations involving a,β-unsaturated aldehydes, and most of them either gave low yields or required drastic conditions of temperature.Furthermore, the Knoevenagel condensations involving 1,3-dicarbonyl compounds often had the drawbacks of long reaction times or low yields than other active methylene compounds. It was because that 1,3-dicarbonyl compounds have an inherent tendency to form stable cyclic enols. Therefore, it is still a desirable and challenging goal to develop the mild and high-yielding Knoevenagel condensation of a,β-unsaturated aldehydes with 1,3-dicarbonyl compounds. In chapter 2, we have successfully explored L-lysine, a primary natural amino acid, as a catalyst in Knoevenagel condensations between various a,β-unsaturated aldehydes and a wide range of 1,3-dicarbonyl compounds.The catalysts of Knoevenagel condensations were generally base, zeolites, clays, layered double hydroxides (LDHs), hydrotalcites, ionic liquids, and Lewis acids such as TiCl4,ZnCl2,CeCl3.7H2O/NaI,and HC104-SiO2. Although almost all catalysts had good results in condensations of aromatic aldehydes, most catalysts were difficult to achieve in condensations of aliphatic aldehydes or a,β-unsaturated aldehydes. In our present method in chapter 3,L-tryptophan efficiently catlalyzed Knoevenagel condensation of aromatic aldehydes, aliphatic aldehydes, hetero-aromatic aldehydes, and a,β-unsaturated aldehydes with less reactive 1,3-dicarbonyl compounds.From environmental concerns, it is still desirable to develop green and facile methods for this widely used Knoevenagel condensation. On the other hand, ionic liquids had been widely used nowadays as environmentally benign reaction media because of their many fascinating and intriguing properties, such as negligible vapor pressure, excellent thermal stability, high ability to dissolve a wide range of organic and inorganic compounds, and non-flammable nature. In addition, amino acids as cheap and environmentally benign catalysts have been used as powerful catalysts in organic synthesis in the past years.Besides, if reactions can be efficiently mediated by homogeneous catalysts in ionic liquid that can be reused, the result will be nearly ideal. We reported L-arginine catalyzed Knoevenagel condensations in ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate at room temperature in chapter 4. a,β-Unsaturated nitriles and ketones were easily prepared by the reactions of aromatic, hetero-aromatic and a,β-unsaturated aldehydes with malononitrile and acetylacetone. The L-arginine/ionic liquid was successfully recycled for five runs without significant loss of activity.The structure of a new product was further confirmed by single crystal X-ray diffraction analysis. We provided a mechanism which explains the configuration of the product. Some procucts were detected by the activity of cdc25B(cell devision cycle B) inhibitor.Part II mainly studies the synthesis of the analog of the Conidiogenone. Conidiogenone was isolated from fermentation broth of penicillium cyclopium, which could induce the conidiation, thus it made the penicillium cyclopium ferment time shorter and reduced the cost of production. Meantime, the discovery of Conidiogenone could explain the mechanism of the conidiation of penicillium cyclopiu. We designed the method to synthesize the analog of the Conidiogenone 3 and expected to attain a better activity compound. Herein, we pay our attention to synthesize an important synthone 9. We tried different methods to add functional groups to the ortho position of the carbonyl of cyclopentanone and compound 18.These researches are the useful basis of the synthesis the analog of the Conidiogenone 3.