Synthetic Studies On The Syntheses Of Quinolines And Proanthocyanidin Natural Products

This thesis is mainly focused on two parts, one is the synthesis of quinoline derivatives and the other is the synthetic studies on proanthocyanidin nature products.Quinolines represent an important class of N-based heterocyclic compounds due to their wide spectrum of activities, such as antimalarials, antibacterial, antifungal agent and anticancer, which appeal to increasing synthetic organic chemists. Friedl?nder quinoline synthesis is one of the simplest and most straightforward methods among various synthetic strategies. While 2-aminobenzaldehydes, the starting materials for traditional Friedl?nder annulation, can readily undergo self-condensation reactions, which may limit the scope and generality of this quinoline synthesis. In some modified strategies, the reduction of 2-nitrobenzaldehydes or the oxidation of the 2-aminobenzyl are followed by Friedl?nder annulation. These methods always have some drawbacks, such as requirement of an external reductant or oxidant, which are not attractive from a redox-economy point of view.To overcome this problem, a modified Friedlander quinoline synthesis has been developed using 2-nitrobenzaldehydes and phenethyl alcohols as the reactants, which is concurrently converted to 2-aminobenzaldehydes and aldehydes/ketones respectively via a ruthenium(II)-catalyzed hydrogen transfer reaction. The resulted 2-aminobenz- aldehydes and aldehydes/ketones are in situ converted to quinolines by Friedlander annulation. The reaction conditions are optimized and summarized as follows: Ru(PPh3)3Cl2 is the best catalyst, Ph Cl is the the best solvent, K2CO3(1.0 equiv.) is the best additive, 150 °C is the best temperature and 24 hours is the best reaction time. And the scope of the reaction is subsequently investigated, as a range of 2-nitrobenzaldehydes and aromatic or aliphatic alcohols bearing different electron-withdrawing/donating groups are found to be suiltable reactants. Moreover, a preliminary plausible mechanism for this reaction is described and discussed, in which Ruthenium is considered as the hydrogen transfer and activated agents.Proanthocyanidins have a wide spectrum of physiological activities including antioxidant, antimicrobial, antimutagenesis, antihypertension, antidiabetic, etc. As reported in literature, proanthocyanidins are potential marine antifouling compounds. A possible synthetic route has been desighed for the synthesis of proanthocyanidin natural products according to the related literatures as well as our previous studies. Catechin and economic quercetin are used as the starting substrates, which are converted to the desired intermidiates by benzyl protection of phenolic and alcoholic hydroxyl groups, bromination, and so on.By the way, a novel synthetic for acridine synthesis is discovered during the work mentioned above. And most of the products in this thesis are characterized by NMR spectroscopy(1H NMR and 13 C NMR), MS and FTIR.