Synthesis and Chromatography of [RuCp]+-labelled Diaryl Ether Peptoids as Precursors of the Bastadins from the Marine Sponge Ianthella basta

The bastadins are bromo tyrosine-derived tetrapeptides linked via two diaryl ether and two amide bonds. The synthesis of the ruthenium-labelled peptoids in this thesis uses the nucleophilic attack of phenolates on [RuCp]+-complexed chloroarenes to form diaryl ethers in the preparation of metal-labelled bastadin model compounds. The purification and characterisation of [RuCp]+-labelled peptoids has not, until now, been systematically studied. Despite the attractive properties of ruthenium radioisotopes for diagnostic medicine, uses of the air and water-stable [RuCp]+-labelled amino acids and peptides are very limited. For the first time, aminopropyl silica was employed as stationary phase for the purification and separation of [RuCp]+-complexes, using gradients of iPrOH-CH3CN as mobile phase. This new separation protocol solved also earlier problems including the use of [18]crown-6 with KOtBu as a base and monitoring of the reactions with TLC. Purification of the OH-free dipeptide (northern hemisphere of the bastarane skeleton) on aminopropyl silica showed that this phase is also appropriate for structures bearing an acidic moiety. A critical question concerned the behaviour of ambident nucleophiles simultaneously possessing free amine and free phenol functionalities in the ruthenium-mediated synthesis of diaryl ethers. The results revealed the preference for the phenol as nucleophile, and encouraged the synthesis of the tripeptides. The open-chain bis-[RuCp]+-complexed ABB'A' system is the largest peptoid labelled with two ruthenium moieties. This thesis brought important progress to ruthenium arene chemistry, mainly through: I) use of a base which promotes complete diaryl ether formation; II) monitoring of the reactions with TLC; III) use of the [RuCp]+-complexes in more than one reaction step and IV) preparation and purification of [RuCp]+-complexes as metal-labelled peptoids.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Universität Heidelberg

Year

2001

Author dc:creator

• Leone-Stumpf, Danielle

Contributors dc:contributor

• Lindel, Thomas

Repository record source_url

http://www.ub.uni-heidelberg.de/archiv/1842

OAI identifier oai:identifier

oai:archiv.ub.uni-heidelberg.de:1842