Asymmetric (enantioselective) synthesis is one of many approaches by which chiral molecules are obtained. The concept relies on the employment of predictable, stereospecific conversions of optically impure/unspecified starting materials to chirally defined structures. The selectivity of such reactions is often enabled by the usage of chiral catalysts that interact with the prochiral substrate (i.e. its targeted functionality) in a spatially specific manner and produce a specific stereoisomer.
For the preparation of 1,2-ethylenediamine building blocks with two specified chiral centers, further used for the synthesis of new catalysts or ligands thereof, we employed the approach of asymmetric transfer hydrogenation of 5H-1,2,3-oxathiazole- 2,2-dioxides, and subsequent ring opening via azide nucleophilic attack. From these we successfully synthesized 4 novel ruthenium based Noyori-Ikariya-type catalysts for asymmetric transfer hydrogenation and 3 novel Dixon-type bifunctional iminophosphorane catalysts. In addition, we managed to, in part, develop an efficient synthetic method of potential benzotetramisole analogues harbouring a CF3- moiety. The compound structures were determined by nuclear magnetic resonance and mass spectrometry. The enantiomeric purities of the products of key stereoselective reaction steps were analysed via chiral chromatography methods (chiral high-performance liquid chromatography). Finally, the performance of novel Noyori-Ikariya-type catalysts was evaluated on a model reduction reaction of a simple aryl ketone (acetophenone reduction). The enantiomeric excess of the products was further determined by chiral gas chromatography analysis. Compound 10 was found to be most efficient, generating (R)-1-phenylethane-1-ol with more than 94 % enantiomeric excess, which is in the range of the benchmark catalyst [RuCl(p-cymene)(Ts-DPEN)].
The synthesized catalysts are applicable in the development of synthetic methodologies for novel active pharmaceutical ingredients, offering a strategy for more efficient and patent-independent synthesis of existing registered pharmaceuticals.
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