Synthesis of biologically active polycyclic natural products and multifunctional imaging probes

Natural products with their ever-growing potential applications in the drug discovery process have influenced many researchers to devise flexible and concise synthetic strategies towards these biologically active substances. As more complex and structurally unique natural products are isolated from plants or microorganisms, developing innovative synthetic tools become highly desirable to obtain them in sufficient quantities. Synthetic organic chemistry allows a thorough investigation of their biological properties and the endeavor enhances the dynamic evolution process of the field. With this in mind, we have developed new synthetic methodologies to synthesize meroterpenoid paracaseolide A and an important class of 3-methylcarbazole alkaloids. In addition, the same approach enabled a direct synthesis of fluorescent rosamine probes with practical applications. The first chapter of the dissertation describes the total synthesis of potential anti-cancer agent (±)-paracaseolide A, which possesses a unique tetracyclic framework with concave and convex faces. The facile synthesis of the natural product was accomplished in 8 steps in 6.6% overall yield, utilizing multiple sulfoxide eliminations and a key tandem 1,4-conjugate addition/aldol reaction to introduce the necessary functional groups onto the tetracyclic bis-lactone scaffold. The synthetic strategy allows diverse analogue development through a common advanced intermediate. The second chapter reveals a novel inverse electron-demand Diels-Alder (IEDDA) methodology to access biologically active and naturally-occurring 3-methylcarbazoles as well as synthetic derivatives using 3-chloroindoles and the 2-pyrone methyl coumalate. The transformation constitutes the first successful example of its kind; consequently extending the scope of indole dienophiles in the IEDDA reactions. The application of the single-pot Diels-Alder/decarboxylation/elimination domino sequence resulted in the metal-free generation of carbazole alkaloids with exclusive regioselectivity in up to 90% yield. The last chapter focuses on the synthesis of rosamine probes to capitalize on a new strategy of an organolithium addition to a benzophenone imine-substituted xanthone. Subsequent acid-catalyzed deprotection and dehydration resulted in an efficient four-step synthesis from 3,6-dihydroxyxanthone. The condensed synthetic approach provides rapid access to desirable primary amine-functionalized multifunctional rosamine analogues in good yields for applications in live-cell imaging

Efficient synthesis of fluorescent rosamines: multifunctional platforms for cellular imaging

Substituted rosamines are efficiently prepared through a new organometallic addition to an imine-substituted xanthone as a novel primary amine equivalent. The synthesis reduces the number of synthetic steps to the targeted rosamines, for convenient and facile access to potential libraries of rosamine dyes. The prepared rosamine derivatives represent unique multifunctional platforms that possess radiolabeling capability and fluorescence. Rosamines have (i) useful non-specific binding properties in mammalian cells and plant root hair, and (ii) positive uptake or binding properties in microbial systems

Heterocycles from wine: synthesis and biological evaluation of salidrosides

Wine is composed of a variety of tannins, of which a sub-class includes salidrosides, which are largely uninvestigated compounds. The first syntheses of galloylated salidrosides are reported in 7 steps from commercially available starting materials through a platform approach. The antimicrobial activity of the salidrosides against Escherichia coli strains is described

Total Synthesis of Paracaseolide A

The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification

Synthesis of biologically active polycyclic natural products and multifunctional imaging probes

Natural products with their ever-growing potential applications in the drug discovery process have influenced many researchers to devise flexible and concise synthetic strategies towards these biologically active substances. As more complex and structurally unique natural products are isolated from plants or microorganisms, developing innovative synthetic tools become highly desirable to obtain them in sufficient quantities. Synthetic organic chemistry allows a thorough investigation of their biological properties and the endeavor enhances the dynamic evolution process of the field. With this in mind, we have developed new synthetic methodologies to synthesize meroterpenoid paracaseolide A and an important class of 3-methylcarbazole alkaloids. In addition, the same approach enabled a direct synthesis of fluorescent rosamine probes with practical applications. The first chapter of the dissertation describes the total synthesis of potential anti-cancer agent (±)-paracaseolide A, which possesses a unique tetracyclic framework with concave and convex faces. The facile synthesis of the natural product was accomplished in 8 steps in 6.6% overall yield, utilizing multiple sulfoxide eliminations and a key tandem 1,4-conjugate addition/aldol reaction to introduce the necessary functional groups onto the tetracyclic bis-lactone scaffold. The synthetic strategy allows diverse analogue development through a common advanced intermediate. The second chapter reveals a novel inverse electron-demand Diels-Alder (IEDDA) methodology to access biologically active and naturally-occurring 3-methylcarbazoles as well as synthetic derivatives using 3-chloroindoles and the 2-pyrone methyl coumalate. The transformation constitutes the first successful example of its kind; consequently extending the scope of indole dienophiles in the IEDDA reactions. The application of the single-pot Diels-Alder/decarboxylation/elimination domino sequence resulted in the metal-free generation of carbazole alkaloids with exclusive regioselectivity in up to 90% yield. The last chapter focuses on the synthesis of rosamine probes to capitalize on a new strategy of an organolithium addition to a benzophenone imine-substituted xanthone. Subsequent acid-catalyzed deprotection and dehydration resulted in an efficient four-step synthesis from 3,6-dihydroxyxanthone. The condensed synthetic approach provides rapid access to desirable primary amine-functionalized multifunctional rosamine analogues in good yields for applications in live-cell imaging.</p

Being Able to Exist in the City In Defiance of Planning: An Examination on a Woman-Friendly City in Izmir - Konak

Today, the world is discussing gender mainstreaming. Solutions to ensure women's equality are being sought to address male social, economic, cultural, and spatial sovereignty. However, although primary texts including treatises and legislation advocating the equal rights and freedoms of men and women have recently been composed by experts around in the world in fields such as criminal and civil law and occupational safety, or something to this effect (e.g., the European Convention on Human Rights and the United Nations Convention on the Elimination of all Forms of Discrimination Against Women), sufficient provision for gender mainstreaming in the context of transformations arising from socio-cultural structure have not yet been made. This is also the situation in Turkey, where women cannot experience gender mainstreaming due to social gender roles. However, since urban planning literally builds the future drawing upon social values, it has been unable to modify cities according to women's needs and priorities. Accordingly, this paper discusses how urban planning ignores women and explains how this issue can be addressed utilizing the Women-friendly Cities Program, which is a type of objection to this patriarchal structure. This paper then analyzes whether Konak, the central town in Izmir (known to be a "women-friendly" city), is truly women-friendly by performing a field study in one of Konak's most-used areas. In other words, this paper reveals the fact that urban spaces ignore women while explaining the spatial provisions of the "women-friendly" city as well as ways in which urban planning negatively affects women

Total Synthesis of Paracaseolide A

The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification.Reprinted (adapted) with permission from Organic Letters, 15(3); Doi: 10.1021/ol303447r. Copyright 2013 American Chemical Society.</p

Total Synthesis of Paracaseolide A

The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification

Selective pyrone functionalization: reductive alkylation of triacetic acid lactone

The one-pot reaction of aldehydes, triacetic acid lactone, and Hantzsch 1,4-dihydropyridine affords 3-alkyl pyrones via a reductive alkylation strategy.This is a manuscript of an article published as Kraus, George A., Kevin Basemann, and Tezcan Guney. "Selective pyrone functionalization: reductive alkylation of triacetic acid lactone." Tetrahedron Letters 56, no. 23 (2015): 3494-3496. 10.1016/j.tetlet.2015.01.141. Posted with permission.</p