Zur asymmetrischen Synthese von Myriocin- und Mycestericin-Analoga

Myriocin and mycestericins were first isolated from the fermentation broths of different fungal sources in 1972 and 1992, respectively. These substances are structurally related to the class of sphingoids, which are present in mammalian tissues. Owing to the structural similarity myriocin and mycestericins can act as enzyme inhibitors (e.g. SPT) in the biosynthesis and metabolism of sphingolipids, and therefore strongly influence a large amount of biological processes. Myriocin and mycestericins are of special interest due to their antifungal, antiviral, antitumour, immunosuppressive and cytotoxic properties. On the basis of this activity, these substances have been examined as potential agents in the treatment of arteriosclerosis, colon cancer and infectious diseases. The aim of this research project was to develop a new asymmetric pathway for the synthesis of Myriocin-related substances using a Prolin-catalyzed Aldol reaction.as key step to build up the 3,4-diol-moiety of the natural products. Furthermore different methodologies for the preparation of the alpha,alpha-disubstituted amino acid starting from a ketone were investigated. The direct transformation via Strecker reaction has proven not to be successful. A six-step synthesis including Wittig-olefination, Vanadyl acetylacetonate-catalyzed epoxidation and intramolecular epoxid opening by a nitrogen nucleophile furnished an alpha,alpha-bis-hydroxymethylamine as precursor for the synthesis of both amino acid diastereomeres. A variety of C-C-coupling reactions at carbonyl compounds have been employed for the synthesis of the side chain segments. Unpolar product fragments for the application in cross coupling reactions or olefinations have been synthesized via Weinreb amides or substitution reactions via 1,3-dithianes.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Baron, Julia

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Organokatalyse
• Naturstoff
• Organische Synthese
• Asymmetrische Synthese
• Chemie
• organocatalysis
• natural products
• organic synthesis
• asymmetric synthesis

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113186%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50650