Study On Synthesis Of Yuehchukene & Murrapanine Analogues And Their Biological Activities

Indole and its derivatives broadly exist in the nature. Indole alkaloids are themaximum alkaloids which have been found. Indole derivatives are attentive because oftheir many biological activities, and the indolyl group is included in many clinicalpharmaceuticals. On the other hand, Non-steroidale anti-inflammatory drugs (NSAIDs)are widely used in the people's daily life for the treatment of fever, pain, andinflammation associated with arthritis and rheumatism. However the traditionalNSAIDs usually have serious side-effects in gastrointestinal tract and renal toxicityprimarily. So it is important to develop new NSAIDs with strong activity but low sideeffects. From the above mentioned, we have tried to design and synthesize some novelindole alkaloids in order to investigate their biological activities. In the literature review, the thesis discusses the research on the pharmacologicalactivities and the synthesis strategy of indole derivatives briefly, introduces mechanismsof action and the frontier of NSAIDs in recent progress of the research, and describesthe characteristics of some typical NSAIDs. Subsequently, the intention and goal of ourwork is reported briefly based on some field listed above. The synthesis of Yuehchukene and Murrapanine Analogues .We have synthesizedindole-3-aldehyde 2 by indole with DMF and POCL3, 2 was tosylated to yield1-tosyl-indole-3-aldehyde 4, then condensed with acetone to give 1-Tosyl-3-(1-methylvinyl ketone-3) indole 5[or 2 condensed with acetone to give 3-(1-methyl vinylketone-3) indole 3, 3 was tosylated to yield 5]. The key intermedidte1-Tosyl-3-(1-methyl-1,3-vinylallyl)indole 6 was obtained by Wittig reaction ofα,β-unsaturated ketone 5 with ethyltriphenylphosphonium bromide.cyclization of 6 withmonoene via a Diels-Alder [4+2] reaction by conventional heating or microwaveirradiation afforded some new Yuehchukene and Murrapanine(the alkaloids isolatedfrom Murraya species) analogues 7-10. The structure of compounds has beencharacterized by H NMR 和 MS. The principle and some relative matter have been 1mentioned too. Study on biological activities. Compounds 7-10 were submitted to the effect ofTNF-α release from rat peritoneal macrophage test. The results of the tested compoundsshowed that the TNF-α production was suppressed. The suppressive effect of TNF-α ofcompounds 7 and 10 were stronger than other compounds of the same type. Comparedwith the stimulated group, compounds 7 and 10 have significant difference. So they areworth further studying. In this thesis, ten compounds have been synthesized. Four of them haven't beenreported elsewhere.