Total synthesis of amaminols

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dc.contributor Aalto-yliopisto fi
dc.contributor Aalto University en
dc.contributor.advisor Koskinen, Ari, Prof. Kumpulainen, Esa 2012-08-24T07:58:24Z 2012-08-24T07:58:24Z 2010
dc.identifier.isbn 978-952-60-3093-7 (electronic)
dc.identifier.isbn 978-952-60-3092-0 (printed) #8195;
dc.identifier.issn 1795-4584
dc.description.abstract Amaminols A and B are cytotoxic bicyclic aminoalcohols isolated in 1999 from an unidentified tunicate of the family Polyclinidae, with an IC50 value of 2.1 µg/mL against P388 murine leukaemia cells. These cytotoxic properties could have potential importance in the development of new therapeutical agents for cancer treatment. Since the source of amaminols is practically unknown, the development of a practical synthesis route is probably the only way to obtain material for further evaluation of biological activities of these compounds. This thesis describes the total synthesis of amaminol A using an enantioselective organocalalytic intramolecular Diels-Alder reaction as one of the key steps. The full carbon skeleton of amaminol A is constructed using the Horner-Wadsworth-Emmons reaction of a phosphonate derived from natural amino acid L-alanine. Strategic reduction with copper hydride proved to be highly important and led to further development of this technology. Final reduction followed by removal of protections gave synthetic amaminol A, which was found to be identical with the isolated natural product. Our synthetic amaminol A was tested against various cancer cell lines at the National Cancer Institute. The second part of this thesis focuses on copper hydrides. The literature part presents an extensive review of achiral phosphine stabilized copper hydrides used in conjugate reductions of various α,β-unsaturated systems. Further development by us led to a highly selective method for reduction of α-chiral enones. This was also the first phosphite stabilized copper hydride methodology used in synthesis. Applicability of this new method was demonstrated in the synthesis of amaminol A. The third part of the thesis describes mechanistic studies of aerobic oxidations of alcohols catalyzed by copper-TEMPO system. Detailed evaluation of different catalyst components revealed second order kinetic correlation for copper and first order correlation for TEMPO. This information was used to generate a new mechanistic proposal which was in agreement with the obtained kinetic data. Oxidation of allylic primary alcohols with CuBr2-TEMPO system was found to be highly efficient. Oxidation of aliphatic alcohols proved to be more challenging and required the use of copper triflate. en
dc.format.extent Verkkokirja (2911 KB, 149 s.)
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Aalto-yliopiston teknillinen korkeakoulu en
dc.relation.ispartofseries TKK dissertations, 219 en
dc.subject.other Biotechnology
dc.subject.other Chemistry
dc.title Total synthesis of amaminols en
dc.type G4 Monografiaväitöskirja fi Aalto-yliopiston teknillinen korkeakoulu fi
dc.contributor.department Kemian laitos fi
dc.contributor.department Department of Chemistry en
dc.subject.keyword amaminol en
dc.subject.keyword total synthesis en
dc.subject.keyword biological activity en
dc.subject.keyword copper hydride en
dc.subject.keyword oxidation en
dc.identifier.urn URN:ISBN:978-952-60-3093-7
dc.type.dcmitype text en
dc.type.ontasot Väitöskirja (monografia) fi
dc.type.ontasot Doctoral dissertation (monograph) en
dc.contributor.supervisor Koskinen, Ari, Prof.

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