Marine Alkaloids--Synthesis Of The Simplified Analogues Of Lamellarins

A series of the marine pyrrole alkaloids-simplified analogue of the lamellarins were synthesised by an optimized and efficient synthetic approach using the common chemicals (aldehydes, ketones, and a-amino acids etc.) as the starting material in multi-steps. All the compounds were purified by recrystallization and characterized by TLC, IR,1 HNMR and melting point meter. The results showed that the intermediates and simplified analogues of lamellarins can be efficiently synthesized by means of the improved synthetic method, which can help to Scale-up synthesis and to product industrialization. The significance of this work is to probe an effective method of synthesis for pyrrole alkaloids and to afford new chemical entities for drug screen. This paper was summarized as follows:The first chapter described the biological activity of the marine pyrrole alkaloids, the development situation of the marine pyrrole alkaloids, and the synthesis development, as reported in the literature. Furthermore, we proposed the scientific basis and purpose of the study and designed a series of routes to get to our target product.The second chapter, according to the route, designed a simple continuous-flow capillary microreactor. Twelve chalcones have been synthesized by the continuous-flow microreactor, and the yields of chalcones are up to 80～90% under the role of ultrasonic irradiation at 40KHz and 26-38℃in this continuous-flow microreactor. Compared with the 1-6 hours’reaction time of traditional synthesis in flasks, the reaction reduced to lOmin. Experiments indicated that this synthetic approach not only carry out the high yields within shorter time but also can synthesize chalcones continuously and on a large scale.The third chapter, simplified analogues of lamellarins were synthesizted by a,β-unsaturated ketone (chalcone) and tosyl-methyl iso-cyanide (TosMIC).Fristly, we used the traditional van leusen method.The traditional Van Leusen method used NaH as catalyst and carried out in ether. Generally, NaH must be used in anhydrous oxygen-free solvents, coupled with ether’s high price, low flash point.So it is difficult to Scale-up synthesis in industrial scale. Therefore, we studied and improved the traditional method of Van Leusen,using NaCH2SOCH3 alkali as the catalyst instead of NaH. So that we could make Na and the solvent DMSO react to obtain the alkali, the solvent DMSO is required in experiments.moreover, DMSO as solvent, a,β-unsaturated ketone compounds as raw materials, can be very convenient to synthesize simplified analogues of lamellarins. Studies showed that the method is simple, high yield, with low price catalyst.It is reasonable for industrial production.The fourth chapter N-carboxy-class pyrrole lamellarin simplified things was synthesized by a-amino acid and diethyl succinate Diacetyl which use Knorr-paal synthesis reaction. At the same time,Study its synthesis mechanism. The results showed that using ultrasonic and microwave can yield up to 64～91% within 3h. Its time is short and high yields, compared to the traditional reflux reaction.