Research On The Synthesis Of Bioactive Lamellarins From Marine Mollusc

Lamellarins are a group of polycyclic pyrrole alkaloids that were isolated from the marine mollusc. Some lamellarins exhibit a wide array of interesting and significant biological activities, which include cell division inhibition, cytotoxicity, HIV-1 integrasa inhibition and immuno modulation. We are interested in the synthesis of Lamellarins and financed by NSFC. There have been three synthetic approaches to the lamellarin skeleton in this paper. The first synthetic route uses 1,2,4-trimethoxybenzene and chloroacetonitrile in forming 2,4,5-trimethoxy-a-chlor-acetophenone under the anhydrous condition, then the intermediate condensates with papaverine forming the core pyrro[2,l-a]isoquinoline, followed by formation and lactonization to form the lactone ring. The second synthetic route uses prepared aldehyde with prepared ethyl nitroacetate by Knoevenagel condensation to obtain 2-Nitro-3-(2,4,5-tris-methoxy-phenyl)-acrylic acid ethyl ester and 2-Nitro-3-(2,4,5-tris-benzyloxy -phenyl)-acrylic acid ethyl ester etal intermediates. The lamellarin skeleton could arise from condensation of the papaverine and these intermediates by Michael reaction, the ester group is provided for subsequent lactonization. The third synthetic route uses coumarin or indan-l,3-dione derivatives and papaverine to form lamellarin under basic conditions. Some important derivatives have been synthesised in this paper. The optimized conditions have been studied by a lot of experiment, the experience is important for farther synthesis of lamellarins.