Synthetic Studies Of Nakadomarin A, Cycloclavine,Nicotine Analogues And Rearrangement Of α,β-Epoxy-N-Aziridinylimines

This dissertation mainly focuses on synthetic studies of nakadomarin A, cycloclavine,(-)-pyrido[3,4-b]homotropane (PHT), and rearrangement of a,(3-epoxy-N-aziridinylimines.(1) Nakadomarin A, first isolated from sea sponge Amphimedon sp.(SS-264) by Kobayashi and co-workers in1997, represents a novel member of manzamine-related marine alkaloids, possessing an unprecedented full-carbon hexacyclic system embedded with a furan ring. We finished a new route to access the ABCD tetracyclic core of (-)-nakadomarin A. The route features a dipolar cycloaddition of an azomethine ylide and α,β-unsaturated carbonyl compounds to assemble the carbon framework, a Pd-catalyzed intramolecular reaction to assemble the tetracyclic ring system and xanthate formation followed by Barton-McCombie deoxygenation to reduce the C=C which generated an additional stereogenic center at C-8(a fused point between A and B rings).(2) Cycloclavine was first isolated in1969from the seeds of the African morning glory by Hoffman and co-workers. We used a dipolar cycloaddition of an azomethine ylide to construct the skeleton of cycloclavine.(3) Nicotine, an alkaloid has various biological activities. PHT was designed by Kanne and co-workers in1986. We finished the synthesis of (-)-pyrido[3,4-b]homotropane (PHT) by intramolecular hetero-Diels-Alder reaction.(4) Aziridinylimines have emerged as a class of attractive and versatile chemical entities in modern organic synthesis. For instance, these compounds have been employed as the precursors of many reactive intermediates such as diazoalkanes, carbenes, and carbocations. We have developed a novel and efficient one-step method for the construction of tetrahydro[1,2]diazepinones, featuring an base-promoted rearrangement of α,β-epoxy-N-aziridinylimines. The seven-member heterocyclic products thus generated may have potential pharmaceutical applications.