Part A: The stereoselective total synthesis of Catenioblin –B and Musacin –F; Part B: Synthesis, study of biological properties of diverse Polyphenol Triazines.

Theegala, S 2016, Part A: The stereoselective total synthesis of Catenioblin –B and Musacin –F; Part B: Synthesis, study of biological properties of diverse Polyphenol Triazines., Doctor of Philosophy (PhD), Science, RMIT University.


Document type: Thesis
Collection: Theses

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Title Part A: The stereoselective total synthesis of Catenioblin –B and Musacin –F; Part B: Synthesis, study of biological properties of diverse Polyphenol Triazines.
Author(s) Theegala, S
Year 2016
Abstract In recent years polyol containing chiral γ-butyro and δ-valerolactones have attracted much attention due to their importance as building blocks in natural product synthesis and their various biological activity profiles. Thus, employing these lactone moieties in the design and construction of newly isolated natural products significantly contributes to the enrichment of the existing pool of known biologically active substances. Most of these five- and six-membered ring lactones are formed relatively easily from the respective hydroxy acids. We describe an efficient and highly flexible stereoselective total synthesis of the respective chiral γ- and δ-lactones musacin F and catenioblin B (14.0% and 7.7% overall yield). This work presents the first total synthesis of catenioblin B via a titanium(IV) mediated regioselective epoxide ring-opening of the epoxy alcohol and includes named reactions such as Grignard and Luche reduction reactions to give a hydroxy acid intermediate that, then undergoes a TEMPO/BAIB mediated intramolecular cyclization as the key steps in good yields. Similarly the structurally related musacin F was also synthesized utilising a Sharpless asymmetric dihydroxylation, Grignard, Luche reduction and acid catalyzed intramolecular cyclization reactions.

Besides the synthesis of catenioblin B and musacin F, it was of interest to prepare and investigate the medicinal applications of various 2,4,6-trisubstited polyphenol-1,3,5-triazine as inhibitors of Aβ-aggregation in Alzheimer’s disease (AD). AD is a neurodegenerative disorder characterized by progressive and irreversible impairment of memory and other cognitive functions. Previous reports suggested that pathological deterioration of AD patients has been associated with extra cellular cerebral accumulation of insoluble aggregates of amyloid-β peptides (Aβ) and intracellular hyperphosphorylated and tangled tau protein. Although the Aβ-modulating agents are in development, however there is no cure for AD and many drugs have failed in recent clinical trials. In order to tackle the problem, effective therapeutic and preventive interventions should be developed urgently. Therefore, treatment for AD research emphasize on development of drugs that can simultaneously perform multiple tasks such as reducing inflammation, preventing of Aβ and tau aggregation.

Polyphenols 1,3,5-triazines exhibit an extensive range of pharmacological activities including potent anticancer properties. Based on literature reports we also investigated their cytotoxicity and antioxidant properties. Chapter IV describes the preparation of some 2,4,6-trisubstited polyphenol s-triazine hybrid derivatives, their cell viability against Aβ toxicity monitored by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays, and their cytotoxic activity evaluation in three human cancer cell lines including antioxidant properties. Among the tested, compounds, s-triazines with pendent aromatic hydroxy groups exhibited potent biological activities. Their simple synthetic preparation and biological properties make these 2,4,6-trisubstited polyphenol s-triazine scaffolds promising new entities for the development of new drugs with diverse therapeutic applications.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Science
Subjects Natural Products Chemistry
Biologically Active Molecules
Organic Chemical Synthesis
Keyword(s) Biologically active natural products
Stereoselective total synthesis of the respective chiral γ- and δ-lactones musacin F and catenioblin B
TEMPO/BAIB mediated intramolecular cyclization
Synthesis of various polyphenol-1,3,5-triazines by using different methods
2,4,6-trisubstited polyphenol s-triazine hybrid derivatives, used to activity against Aβ toxicity monitored by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays
Cytotoxic activity evaluation in three human cancer cell lines including antioxidant properties
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