Polycyclic nitrogen containing heterocycles form the basic skeleton of numerous alkaloids and physiologically active drugs. Alloyohimbane was obtained from 3,4-dihydro-â-carboline using an iron-mediated [2+2+1] cycloaddition as the key-step. The bis-TMS-diyne was conveniently obtained by the C-alkylation of 3,4-dihydro-â-carboline followed by N-alkylation. Demetalation of the iron-complex followed by hydrogenation, E-ring expansion, and reduction provided alloyohimbane, a structurally and biologically interesting substance, via a linear eight-step sequence in 7% overall yield based on 3,4-dihydro-â-carboline. Another sequence provided (±)-alloyohimbane and (±)-3-epi-alloyohimbane in nine steps. The pyrrole unit occurs in a variety of naturally occurring compounds, pharmaceutical products and polymers. A novel two-step procedure for the synthesis of pyrroles by addition of a propargyl Grignard reagent to a Schiff base and subsequent silver(I)-promoted oxidative cyclization of the resulting homopropargylamine has been developed. The generality of this reaction was proven by the synthesis of a broad variety of substituted pyrroles using silver(I)-promoted cyclization. A three-step synthesis of (±)-harmicine, a natural product isolated from the Malaysian plant Kopsia griffithii having strong anti-leishmania activity, from 3,4-dihydro-â-carboline is achieved by addition of 3-trimethylsilylpropargyl Grignard reagent, Ag(I)-promoted oxidative cyclization to a pyrrole, and chemoselective hydrogenation of pyrrole ring. Total synthesis of anti-tumor active crispine A and biologically active 1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline have been achieved in three steps using silver(I)-promoted oxidative cyclization as key step.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:24519 |
| Date | 02 June 2005 |
| Creators | Agarwal, Sameer |
| Contributors | Knölker, Hans-Joachim, Schinzer, Dieter, Metz, Peter |
| Publisher | Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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