Asymmetrische Synthese von Gamma-Hydroxy-Alpha-Aminosäuren, 1,3-Aminoalkoholen und 2-Amino-3-Phosphonopropionsäure

In this thesis we optimised a procedure to synthesize 1,3-amino alcohols and applied it to a wide range of substituted substrates. Starting from aldehyde SAMP-hydrazones we obtained beta-hydroxy SAMP-hydrazones in a titanium-mediated aza-analogous aldol reaction. After protection, 1,2-addition and cleavage of the chiral auxiliary the products could be isolated over five steps in 30 to 54% overall yield and diastereomeric excesses of 78 to 84% and enantiomeric excesses over 96%. Furthermore we developed a hydrazone Strecker-method for the asymmetric synthesis of alpha-amino acids. The method was tested by the synthesis of six examples, including 2-amino-3-phosphonopropionic acid. The first step was the addition of TMSCN to SAMP-hydrazones to obtain hydrazino nitriles. After protection with Moc-Cl and N-N-bound cleavage with MMPP the resulting protected amino nitriles were easily converted into alpha-amino acids by acidic hydrolysis of the nitrile group under concurrent deprotection. The alpha-amino acids were synthesized in four steps in 10 to 50% overall yield. The enantiomeric excesses of 94 to 97% were determined on the diasteriomeric excesses of the Mosher-amides. We established the absolute configuration by comparison of the NMR-spektra of the Mosher-amides with the spectra of the Mosher-amide of a 1 : 2 induced sample of the purchasable alpha-amino butanoic acid. The combination of several known methods and their optimisation gave us the possibility to synthesize gamma-hydroxy alpha-amino acids in a highly diastereo- und enantioselective manner. This pathway has only slight differences to that used for the synthesis of 1,3-amino alcolhols. In the 1,2-addition we added ceriumfuryl to the C=N-double bound of the hydrazones. After cleavage of the chiral auxiliary the following ozonolysis resulted in gamma-hydroxy alpha-amino acids after six steps in 21 to 27% overall yield. The diastereo- und enantiomeric exesses were higher 96%. 1,3-Amino alcohols and gamma-hydroxy alpha-amino acids are important building blocks in the synthesis of natural products with biological activity.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2004

Author dc:creator

• Moser, Michael

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Alkanolamine
• Asymmetrische Synthese
• Hydroxyaminosäuren
• Alaninderivate
• Phosphonogruppe
• Chemie

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121213%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:59426