The Synthesis Of1,7-Dimethoxy-2-Hydroxy-Xanthone, Organocatalytic Asymmetric Michael Conjugation And ABT-751Analogues Research

This dissertation consists of three parts. The first part gives the synthesis of1,7-dimethoxy-2-hydroxy-xanthone, which has the potential capability of the treatment for the erectile dysfunction (ED). In the second part, cinchona alkaloid derived primary amine as an organocatalyst promotes asymmetric Michael conjugation with good yields and high enantioselectivities. The last part reports the design and synthesis of the ABT-751derivatives and their biological activities as cancer agents.ED is one of the common ailments in middle-aged men. Sildenafil has been currently the best investigated phospodiesterase5inhibitor with higher efficacy and less side-effects since1998. People also find some nature compounds have potential activities of ED treatment, such as Papaverine, Yohimbine and so on.1,7-dimethoxy-2-hydroxy-xanthone(2-18) was isolated from the Securidaca longependunculate. This compound showed a significant relaxation activity on rabbit corpus cavemosum in vitro. It was considered to be a potential compound of the treatment for erectile dysfunction (ED). We designed and synthesized the target compound(2-18) in9steps through Reimer-Tiemann reaction, Ullmann reaction and so on. The starting materials are commercial available and the conditions are simple. This method can solve the problem of the extract from the natural compound and it also supplied a new route of the synthesis of the xanthone analogues.Recently, people have paid more attention on the small molecular organocatalyts using in the asymmetric reaction. This report revealed cinchona alkaloid derived primary amine (3-3h) could catalyze a highly enantioselective Michael conjugation of nitroalkanes to enones. After screening several reaction conditions, we found the optimal condition (THF, no additives, room temperature). This Method gave a wide scope of enones and nitroalkanes (23chiral adducts) and excellent enantioselectivities (91-99%) were achieved.The vascular disrupting agents (VDAs) have been presented as a new class of anti-cancer drugs in recent years. ABT-751was the first orally bioavailable sulfonamide compound in VDAs. It inhibits microtubule polymerization by binding to the colchicine binding site on β-tubulin and induces the cancer cell apoptosis. We designed and synthesized26derivatives of ABT-751. We screened their inhibitory activities of A549cancer cell lines in vitro. The structure-activity relationship was studied:It was unfavorable when we introduced too many functional groups on A ring. The same group introduced on different site of B ring made variant inhibitory activities. We synthesized two compounds4-24a and4-25a based on above SARs, which showed better anti-cancer activities than ABT-751.We dealed with several datas technically based on the security agreement.