Benzoin is an important a-hydroxy ketone which can be used as chiral intermediate for the synthesis of several drugs. In this study, it was aimed to synthesize this compound by high stereoslectivity and yield by the use of fungal bioconversions. For this purpose, whole cells of four different Fusarium spp. (F. anguoides, F. roseum, F. solanii, F.bulbigenum) were used for reduction of readily available achiral compound benzil. The reaction conditions were optimized as glucose peptone broth consisting of 30g/L glucose and 10 g/L peptone, inoculum size as 20 mg/L and substrate concentration as 200 mg/L. A complete set of derivatives substituted with electron donating and electron withdrawing groups of the benzils were also reduced to the corresponding benzoin derivatives with the same optimized condition with up to 98% ee.

The objective of the study presented here was to develop either enzymatic or whole cell mediated green procedures for the syntheses of a-hydroxy ketones. Production of optically active synthons is crucial for the preparation of fine chemicals. Enzymes and whole-cell biocatalysts have proven to be excellent vehicles with their chiral nature for the biotransformations. Under the light of this discussion, firstly benzaldehyde lyase [BAL, (EC 4.1.2.38)] was used in novel C-C bond formation reactions to obtain interesting and biologically important precursors / 2-Hydroxy-1-arylethan-1-ones and functionalized aliphatic acyloin derivatives. All the compounds were obtained with high yields and in the case of aliphatic acyloin derivatives with high enantiomeric excesses (ee&rsquo / s). Another strategy was to use whole cell biocatalysis. A.flavus 200120 was found to be a promising biocatalyst with the ability to catalyze a broad range of reactions / reduction, hydrolysis and deracemization, while another fungus / A. oryzae 5048 was utilized in bioreduction reactions of benzil and its derivatives. Each reaction was investigated, optimized and thus enhanced via medium design. Products were obtained with high yields and ee&rsquo / s. To sum up, in this study novel efficient green procedures were developed to synthesize various ahydroxy ketones with high yield and stereoselectivity. These newly established methods present promising alternatives to classical chemical methodologies.

Abstract The synthesis of α-hydroxy aldehydes and hydroxymethyl ketones as well as their interconversion to each other are discussed in this thesis. The literature survey of the monograph reviews the synthetic methods for the preparation of 1,2-bifunctionalized hydroxy aldehydes and ketones. The keto-aldehyde isomerisation reaction catalyzed by Triosephosphate isomerase enzyme (TIM) and organic compounds that interact with the TIM are also introduced. In addition, the microwave heating techniques in organic syntheses are reviewed. The practical work consists of two entities: The synthesis of new substrate candidates and transition state analogues for a mutated monomeric TIM. These compounds are model compounds for the catalytic activity and the structural studies of the mutated monomeric TIM. The synthesis of the sulphonyl α-hydroxy ketone-based substrate candidates consists of four successive syntheses. The microwave-activation was utilized in the preparation of a carbon-sulphur bond and the synthesis of hydroxymethyl ketones. The improved synthesis of the terminal α-hydroxy ketone functionality with microwave activation is presented. The formation of charged compounds was utilized to improve the absorption of microwave energy of reaction mixtures. The design and the synthetic work were carried out in accordance to principles of green chemistry. The second part of the practical work is the development of an organocatalytic α-oxybenzoylation reaction of aldehydes with high enantiomeric selectivity. This novel method generated enantiomerically pure α-hydroxy aldehydes in the stable benzoate-protected form from achiral starting materials under mild conditions at the presence of air and moisture.

A novel method for asymmetric synthesis of α-hydroxy ketone with excellent regio- and stereoselectivity has been established by the systematic investigation of asymmetric dihydroxylation of allenes. The efficiency of kinetic resolution of racemic allenes was also investigated by using the AD reaction on both 1,3-disubstituted and trisubstituted allenes. Steric effects, electronic effects and allene substitution are also discussed. Aziridines were formed by copper-catalyzed intramolecular nitrene addition to alkenes. The carbamate group was used as the tether between the alkene and the nitrene. Subsequent nucleophilic attack of the aziridine was accomplished using RSH, R2NH, N3-,or ROH as the nucleophile. This addition was found to be regio- and stereoselective. This methodology has provided a new strategy for the stereoselective construction of three adjacent functional groups, in particular the 1,2 diamino-3-hydroxy unit. The rhodium-catalyzed intramolecular aziridination of allenic N-sulfonyloxy carbamates has been established. Efficient ring opening of these bicyclic compounds may provide synthetic utility in organic chemistry. The intramolecular aziridination of allenic sulfamate esters was tested on a single example to afford in situ a ring opened product.

The objective of this presented study was to synthesize optically active compounds considered to be key intermediates in the synthesis of Oseltamivir (Tamiflu) by performing chemical and biotechnological methods. Thereof, the carboethoxy cyclohexenone skeleton first was synthesized utilizing easily available substances. The synthesis of alpha-hydroxy ketones in enantiomerically pure form offers a great importance in the synthesis of biologically active compounds. Toward this fact, the enantioselective synthesis of alpha-hydroxy carboethoxy cyclohexenone scaffold has been accomplished by following the routes which were manganese(III) acetate-mediated chemical oxidation followed by enzyme-mediated hydrolysis and additionally microbial direct biooxidation by whole cells of fungi expressly A. oryzae and A. flavus. A very satisfying results have been obtained by both of the methods.