TY  - THES
A1  - Ries, Stefan
T1  - Versuche zur Totalsynthese von Pseudodistomin C und E - Ein neuer Syntheseweg
T1  - An Approach to the Total Synthesis of Pseudodistomine C and E - A New Synthetic Pathway
N2  - Die Pseudodistomine gehören zu den ersten Piperidinalkaloiden marinen Ursprungs, die 1987 von Ishibashi et al. aus der Tunikate (Ascidie) Pseudodistoma kanoko isoliert wurden. Aus der gleichen Tunikate wurde 1995 das Pseudodistomin C isoliert. Die amphiphilen Piperidinalkaloide zeigen eine Antitumor-Aktivität gegen bestimmte Mäuseleukämiezellen, wobei Pseudodistomin C auch eine Cytotoxizität gegen menschliche HeLa-abgeleitete Krebszellen KB aufweist. In der Einleitung wird ausführlich auf Vorkommen, Struktur, Biogenese, pharmakologische Perspektiven und literaturbekannten Synthesen dieser amphiphilen Piperidin-Alkaloide eingegangen. Im Hauptteil wird zunächst eine gescheiterte Synthese ausgehend von D-Ribose über das Konzept einer Tandem Wittig-[3+2]-Cycloaddition beschrieben. Daraufhin wird ein völlig neuer Syntheseweg vorgestellt, welcher den formalen Aufbau des Pseudodistomin C über einen bekannten Piperidin-Grundkörper ermöglich. Des weiteren konnte das vollständig geschützte Pseudodistomin E synthetisiert werden.
N2  - Pseudodistomines belong to the first known piperidine alkaloids of marine origin, isolated by Ishibashi et al. from the tunicate (ascidie) pseudodistoma kanoko in 1987. From the same tunicate Pseudodistomin C was isolated in 1995. The amphiphilic piperidin alkaloids show an antitumor activity against certain leukemic cells derived from mice, whereas Pseudodistomin C also exhibits an antitumor activity against human HeLa-derived cancer cells KB. The introduction goes into details about occurrence, structure, biogenesis, pharmacological perspectives and literature known synthesis of these amphiphilic piperidine alkaloids. The main part starts with a failed synthesis based on D-ribose by the concept of a tandem wittig-[3+2]-cycloaddition. Consequently an entirely new synthesis pathway is presented, which enables the formal buildup of Pseudodistomin C by a known piperidine compound. Furthermore I was able to synthesize the fully protected Pseudodistomin E.
KW  - Piperidin
KW  - Piperidinderivate
KW  - Totalsynthese
KW  - Dissertation
KW  - Sphingosin
KW  - Lactone
KW  - Asymmetrische Synthese
KW  - Piperidinalkaloide
KW  - Manteltiere
KW  - Cytotoxizität
KW  - Pseudodistomine
KW  - Stereoselektive Synthese
KW  - Tandem-Reaktion
KW  - Wittig-Reaktion
KW  - Cycload
KW  - Pseudodistomin C
KW  - Pseudodistomin E
KW  - 2-(Phenylsulfonylmethyl)-piperidin
KW  - Tandem Wittig-[3+2]-Cycloaddition
KW  - stereoselektive Synthese
KW  - pseudodistomine C
KW  - pseudodistomine E
KW  - 2-(Phenylsulfonylmethyl)-piperidine
KW  - tandem Wittig-[3+2]-cycloaddition reaction
KW  - stereoselective synthesis
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-39931
ER  - 
TY  - JOUR
A1  - Wünsch, Anna Chiara
A1  - Ries, Elena
A1  - Heinzelmann, Sina
A1  - Frabschka, Andrea
A1  - Wagner, Peter Christoph
A1  - Rauch, Theresa
A1  - Koderer, Corinna
A1  - El-Mesery, Mohamed
A1  - Volland, Julian Manuel
A1  - Kübler, Alexander Christian
A1  - Hartmann, Stefan
A1  - Seher, Axel
T1  - Metabolic silencing via methionine-based amino acid restriction in head and neck cancer
JF  - Current Issues in Molecular Biology
N2  - In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies not only reprogram metabolism to low-energy metabolism (LEM), which is disadvantageous for neoplastic cells, but also significantly inhibit proliferation. Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumour types, with over 600,000 new cases diagnosed annually worldwide. With a 5-year survival rate of approximately 55%, the poor prognosis has not improved despite extensive research and new adjuvant therapies. Therefore, for the first time, we analysed the potential of methionine restriction (MetR) in selected HNSCC cell lines. We investigated the influence of MetR on cell proliferation and vitality, the compensation for MetR by homocysteine, the gene regulation of different amino acid transporters, and the influence of cisplatin on cell proliferation in different HNSCC cell lines.
KW  - amino acid restriction
KW  - caloric restriction
KW  - methionine
KW  - HNSCC
KW  - SCCHN
KW  - cisplatin
KW  - amino acid transporter
KW  - SLC-family
KW  - cell vitality
KW  - low energy metabolism
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319257
SN  - 1467-3045
VL  - 45
IS  - 6
SP  - 4557
EP  - 4573
ER  -