NEW STRATEGY FOR THE SYNTHESIS OF CHIRAL N-SUBSTITUTED-3,4-DIALKOXYPYRROLE FROM 2,5-DIHYDRO-2,5-DIMETHOXYFURAN KAPAKLI, FADiLE M.S., Department of Chemistry Supervisor : Prof. Dr. Cihangir Tanyeli July 2006, 80 pages Pyrroles are very valuable class of substances which have wide usage area in organic synthesis. In this study, chiral 3,4-dialkoxy-N-substituted pyrrole derivatives were synthesized. These compounds are widely used as building blocks for the synthesis of natural compounds that have focused on heterocyclic rings in their structures. In addition, chiral pyrrole derivatives can be used as monomers for the synthesis of chiral conducting polymers which have received great interest due to their potential applications as electrodes for electrochemical asymmetric synthesis, stereoselecive analyses and in many areas, such as electronics, electrochromic devices, polymeric batteries, antielectronic coatings and functional membranes. 3,4-dialkoxy-N-substituted chiral pyrrole derivatives were synthesized starting from 2,5-dimethoxy-2,5-dihydrofuran which is a commercially available, inexpensive material. After oxidation, the resultant diol were protected with alkoxy goups and then correponding 3,4-dialkoxy-N-substituted chiral pyrrole derivatives were afforded via pyrrolization reaction by using several chiral amines or aminoalcohols.

Optically active polychlorinated bicyclic systems are important starting materials for the synthesis of complex target molecules. In the first part of the study, the syntheses of several racemic and meso hexachloronorbornene derivatives were executed successfully, starting from hexachlorocyclopentadiene. The enantio-enriched acetoxymethyl derivative (-)-2 and the hemiester (-)-6 were synthesized in high e.e. values by using several hydrolase type enzymes. The absolute configuration of (-)-2 was determined by transforming it to the corresponding norbornene derivative (-)-7 with known absolute configuration. In the second part of the study, C2 symmetric chiral ligand (-)-11 and C3 symmetric chiral triamide derivative (-)-12 were synthesized in high chemical yields starting from L-proline. In connection to these studies, the syntheses of the monoamide derivative (-)-14 and the C2 symmetric diamide derivative (-)-15 were achieved by using appropriate amounts of L-proline.

An antenna for light harvesting is an organized multicomponent system in which several chromophoric molecular species absorb the incident light and channel the excitation energy to a common acceptor component. In this study, Click chemistry has been successfully applied in the synthesis of a bay region tetraboron dipyrrin (BODIPY) appended perylenediimide (PDI). This light-harvesting molecule presents a large cross section for the absorption of light in the visible region. Excitation energy is efficiently channeled to the perylenediimide core. This novel antenna system is the first demonstration of the efficiency of energy transfer in a BODIPY- PDI bichromophoric system and appears to be highly promising for the design and synthesis of similar dendritic structures.

Photodynamic therapy (PDT) is a noninvasive method of treating malignant tumors and age-related macular degeneration. Current practice of PDT is limited to a few functionalized porphyrins, however these compounds are not considered to be ideal drugs for use in PDT. Among the limitations, the most prominent is the low extinction coefficient of porphyrins in the body&amp / #8217 / s therapeutic window. Therefore, there is a significant impetus to develop novel and better efficiency sensitizers for use in PDT. Boradiazaindacenes (BODIPY dyes or difluoroboradipyrrines) are well known fluorescent dyes. We discovered novel distyryl-derivatized boradiazaindacene dyes. These dyes have strong absorptions beyond 650nm. In order to transform these novel dyes into potential PDT reagents, bromine substituents were placed and then heavy atom effect was showed. We also demonstrated that on red-light excitation, singlet oxygen trap 1,3-diphenyl-iso-benzofuran is rapidly degraded.

Self-assembly has big importance in synthesizing supramolecular structures. Highly fluorescent molecular squares with boradiazaindacene (BODIPY) building blocks were obtained via usage of metal driven self-asembly. The boradiazaindacene units were connected with the Pd(II) complex unit enforcing a near-90 degree angle between the building blocks. Thus, we believe we have the first example of BODIPY carrying fluorescent squares. With collective experience in BODIPY chemistry in our group, we may have the first example of functionalizable molecular square. Self-assembled light harvesting systems will be ultimate biomimetic example of photosynthetic reaction center.

Conduritols have attracted a great deal of attention in recent years owing to biological activities exhibited by them and also their usefulness in the synthesis of other natural products and pharmaceuticals. Conduritols show interesting inhibitor activity for some glycosidases and serve as important intermediates in the synthesis of inositols. In this study, novel synthetic strategies leading to highly functionalized cyclohexene derivative containing an aromatic ring, namely phenyl-substituted conduritol was achieved successfully for the first time. As the starting material, substituted benzoquinone derivative, biphenyl-2-ol was used. Bromination of one double bond followed by the reduction of the carbonyl groups served the desired skeleton. Further substitution of the bromine atoms and functionalization of the remaining double bond opened up an entry for the synthesis of substituted conduritol and inositol derivatives. Moreover, by the use of hydroquinone as a starting material we developed new synthetic methodologies for the synthesis of another conduritol derivative, bromo-substituted conduritol for the first time. Oxidation of hydroquinone to the corresponding quinone followed by the bromination of one double bond gave the desired product. After the reduction of the carbonyl groups and protection of the hydroxyl groups, the key compound for the synthesis of bromo-substituted conduritol was obtained. As a result, we enabled to synthesize new conduritol derivatives and we had considerable advance for the synthesis of other conduritol derivatives, inositols and quercitols.

Photodynamic therapy (PDT) is an emerging treatment modality for a range of disease classes, both cancerous and noncancerous. This has brought about an active pursiut of new PDT agents that can be optimized for the unique set of photophysical characteristics that are required for a succesful clinical agent. There are many reported or commercially available photosensitizers, but most have limitations, such as low photostability, or a limited usable range of solvent conditions. In this study, we introduced a novel class of extended conjugation water soluble boradiazaindacene dyes which are efficient singlet oxygen generators. These sensitizers have strong absorptions in the therapeutic window and have spectacular photoinduced cytotoxicity. In addition, they display no dark toxicity at the active concentrations. With these remarkable properties, they are likely to find applications as promising new reagents for photodynamic therapy.

Many heterocyclic compounds containing nitrogen, oxygen and sulfur show wide range of physiological activities and their synthesis has always been attracted the interest of chemists. The aim of this research is to develop new synthetic methodologies leading to the synthesis of new derivatives of isocoumarines, indoles, isoquinolines, benzodiazepinones and quinazolines, which have been found to show important biological activities. Starting from homophthalic acid and bishomophthalic acid the corresponding acyl azides were proposed to be synthesized, which then would be used for the synthesis of various heterocycles. The proposed diazide from homophthalic was not formed due to the tendency of the ortho-positioned acid to undergo cyclization. Instead, new unusual benzochromen and isocoumarin derivatives have been synthesized in a single step, for which reasonable mechanisms have been proposed. The half ester produced from homophthalic acid was an important key compound for the synthesis of new highly substituted indole derivatives, which are expected to be biologically active. The diisocyanate derived from was synthesized directly from ortho-bromo xylene was treated with alcohols and hydrazine to produce seven membered rings. Instead of the intramolecular cyclization reaction, they underwent polymerization to form new polymers. Furthermore, new synthetic method for the synthesis of pyrazoles has been developed.

This thesis presents synthesis and different reactions of alpha-keto-beta-hydroxyphosphonates. Toward this aim, the hydroxyl functionality of alpha-hydroxycarboxylic acids were protected with alkyl or acyl groups and then formation of acid chloride followed by the reaction with trialkylphosphite furnished protected alpha-keto-beta-hydroxyphosponates. Nucleophilic addition reactions were applied to these compounds to obtain quaternary alcohols with phosphonate functionality. The addition reactions were tried with organocatalysts for the enantioselective formation of desired products.

Chiral polyfunctionalized 1,5-dicarbonyl compounds are important synthetic intermediates and starting materials for many biologically active compounds so their synthesis has a great importance in the literature. In the first step, 1,3-cyclohexandione and other b-diketone derivatives are protected under acid catalyzation and their corresponding b-keto enol ether derivatives are obtained. These b-keto enol ethers are then converted to a-acetoxy enones in racemic form by Mn(OAc)3 mediated oxidation. Enzymatic kinetic resolution is applied to the racemic acetoxy enones by using different lipases and enantiomerically pure a-acetoxy and hydroxy enones are obtained. Then, dicarbonyl derivatives are obtained by hydrolizing racemic a-acetoxy enones. Oxidative cleavage of racemic a-acetoxy diketones in the presence of oxone gives corresponding racemic 1,5-dimethyl ester derivatives. By using this reaction as a reference, same reactions are applied to the chiral a-acetoxy and hydroxy diketones in order to synthesize chiral a-acetoxy and hydroxy 1,5-diester derivatives.