Zur asymmetrischen Synthese von Beta-Thio-Alpha-Aminosäuren

This thesis investigates in the asymmetric synthesis of beta-Thio-alpha-Aminoacids who are containing chiral centers in alpha- und beta-position. There are different approaches towards the diastereo- und enantioselektive synthesis of these amino acids described using chiral Amines or the SAMP-/RAMP-hydrazone methodology. Nearly all retrosynthetic approaches are starting with Bromacetaldehyde-Diethylacetale, which is nucleophil substituted with thiolates. After acidic hydrolyses of the acetals the correspending sulphur-substituted aldehydes are obtained. In the first approach the aldehyde is transformed into the chiral Imine and subsequently alpha-alkylated. Because of the low diastereoselectivities this approach was stopped. In the second approach the aldehydes are now transformed into the SAMP-hydrazone and then alpha-alkylated (de = 93 - =<96%). Attempts to quarternise the alpha-stereogenic center yielded only moderate diastereoselectivities (de = 43 - 61%). In a diastereoselctive Strecker-like reaktion the SAMP-hydrazones are transformed with TMSCN into the hydrazino nitriles (de = 90 - =<96%). Protection with Benzoylchloride and epimerisation free N,N-bound cleavage with SmI2 resulted the protected aminonitriles. Unhappily, no method could be found to transform the nitriles into the correspondending amino acids neither under acidic nor under basic conditions. Only decomposition can be observed. Nevertheless, the sulfidic group of the alpha-sulfanylated aminonitriles can be oxidized to the sulfones or the amino group can be protected a second time with Boc, without decomposition. As an alternative to the Strecker-like reaction with TMSCN the addition of metallated Dithian to the C,N-doublebond of the SAMP-hydrazone has been tested. In this reaction only moderate diastereomeric accesses (de = 59%) could be achieved, although the reacti conditions have to be optimized. The third approach started with Brompyruvicacid-Ethylester. The ketoester is transformed into the SAMP-hydrazone and then alpha-alkylated with high diastereomeric selectivity (de = 90 - =<96%). The following hydrogenation of the C,N-doublebound could only achieved with Sodiumcyanoborohydride, but the diastereomeric access is low (de = 28%).

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2004

Author dc:creator

• Gaube, Gero

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Aminosäurederivate
• Thiolgruppe
• Asymmetrische Synthese
• Chemie
• Aminosäuren
• Aminonitrile
• Strecker Synthese
• 1,2-Addition

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121137%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:59340