Studies on the Catalytic Asymmetric Fischer Indolization

This work describes further developments and applications of the catalytic asymmetric Fischer indolization. In the first part of this thesis, the development of an organocatalytic asymmetric synthesis of helicenes via a Fischer indolization is discussed. The application of a novel SPINOL-derived phosphoric acid, featuring extended π-surfaces as 3,3‘-substituents which can potentially participate in π-interactions with the polyaromatic intermediate, afforded the corresponding products in high yields and enantioselectivities. The second part of this work describes the development of a catalytic asymmetric dearomatizing synthesis of 1,4-diketones via an interrupted Fischer indolization. Employing aryl hydrazines with α-substituents next to the hydrazine group prevents the rearomatization which takes place in common Fischer indole syntheses, thus enabling the hydrolysis of the generated diimine species. In the presence of STRIP as catalyst, a variety of different 1,4-diketones could be obtained in generally high yields, diastereo- and enantioselectivities. The last part of this thesis deals with the development of an organocatalytic asymmetric stereodivergent synthesis of novel 3H- and 2H-pyrroles, applying an interrupted Fischer indolization and for the 2H-pyrroles a subsequent stereospecific [1,5]-alkyl shift. Employing STRIP as catalyst afforded the corresponding products in good to excellent yields and enantioselectivities. Preliminary biological investigations of these novel structure motifs in cell-based assays, monitoring biological signal transduction pathways showed an inhibition of the Hedgehog signaling pathway in a μM range.

Asymmetric polygons with maximum area

We say that a polygon inscribed in the circle is asymmetric if it contains no two antipodal points being the endpoints of a diameter. Given n diameters of a circle and a positive integer k < n, this paper addresses the problem of computing a maximum area asymmetric k-gon having as vertices k < n endpoints of the given diameters. The study of this type of polygons is motivated by ethnomusiciological applications.

Rhodium-catalysed enantioselective C-H functionalization in asymmetric synthesis

CHARACTERIZATION OF TOBACCO MOSAIC VIRUS DIRECTED REPROGRAMMING OF PHLOEM GENE EXPRESSION TO PROMOTE VIRAL PHLOEM LOADING AND SYSTMEIC MOVEMENT

Vascular phloem loading has long been recognized as an essential step in the establishment of a systemic virus infection. Yet little is known about this process and the mechanisms that control it. In this study, an interaction between the replication protein of Tobacco mosaic virus (TMV) and phloem specific auxin/indole acetic acid (Aux/IAA) transcriptional regulators was found to modulate virus phloem loading. Promoter expression studies show TMV 126/183 kDa interacting Aux/IAAs predominantly express and accumulate within the nuclei of phloem companion cells (CC). Furthermore, CC Aux/IAA nuclear localization is disrupted upon infection with an interacting virus but not during infection with a non-interacting virus. In situ analysis of virus spread shows the inability of TMV variants to disrupt Aux/IAA CC nuclear localization correlates with a reduced ability to load into the vascular tissue. Subsequent systemic movement assays also demonstrate that a virus capable of disrupting Aux/IAA localization is significantly more competitive at systemic movement than a non-interacting virus. Similarly, CC expression and over-accumulation of a degradation-resistant-interacting Aux/IAA protein was found to selectively inhibit TMV accumulation and phloem loading. Transcriptional expression studies demonstrate a role for interacting Aux/IAA proteins in the regulation of salicylic acid and jasmonic acid dependent host defense responses as well as virus specific movement factors including pectin methylesterase that are involved in regulating plasmodesmata size exclusion limits and promoting virus cell-to-cell movement. Further characterization of the phloem environment was done using two phloem specific promoters (pSUC2 and pSULTR2;2) to generate epitope-tagged polysomal-RNA complexes. Immuno-purification using the epitope tag allowed us to obtain mRNAs bound to polysomes (the translatome) specifically in phloem tissue. We found the phloem translatome is uniquely altered during TMV infection with 90% and 88% of genes down regulated in the pSUC2 and pSULTR2;2 phloem translatomes, compared to 31% of genes down regulated in the whole plant p35S translatome. Transcripts down regulated in phloem include genes involved in callose deposition at plasmodesmata, host defense responses, and RNA silencing. Combined, these findings indicate TMV reprograms gene expression within the vascular phloem as a means to enhance phloem loading and systemic spread.