The Synthesis Of Several Intermediates Of Natural Product Lamellarin I

The lamellarins are a group of naturally polyaromatic pyrrole alkaloids,which are isolated from marine mollusc and show strongly biological activity.Lamellarin A～D were first isolated by Faulkner and co-worker in 1985.As a member of lamellarins,which was first collected from the dark purple ascidians by Bowden and co-workers in 1993,lamellarin I had showed unexpected chemical sensitivity during the research on the multiple resistance(MDR),and because of its predominant capability on anti-tumour activity(in particular,against human lung cancer),anti-HIV(the activities of inhibiting the integrase terminal split and the chain transfer),inhibition of topoisomerase,interaction with DNA and cleavage metal-dependent,many research groups had put emphasis on this new kind of natural products.The tiny amount and inconvenient collection pushed researchers to find an artificial route to synthesize lamellarins.In this paper,a route to synthesize lamellarin I based on the compound 3,4-bis(trimethylsilyl) -1H-pyrrole(5) as the starting material was designed.Six main intermediates of synthesizing lamellarin I had been prepared after seven steps based on using N,N-dimethyl sulfonamide as the protecting group,using n-BuLi to introduce methoxycarbonyl at theα-position of pyrrole.Because of the trimethylsilyl substituted group at the 3,4-position of pyrrole,iodination can occour step-by-step.Then based on the mechanism of suzuki cross-coupling reaction,aromatic ring was introduced to the pyrrole.By using TBAF as the deprotected reagent,compound 16 was finally got,which was the intermediate of lamellarin I.All of the six intermediates were unreported and characterized by NMR and MS.