Universität zu Köln

Seelig, Bianca (2009). Contributions to the Asymmetric Catalysis of C-C Couplings, and to the Chemical Induction of Cardiomyogenesis from Embryonic Stem Cells. PhD thesis, Universität zu Köln.

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Abstract

In this work, new substances for the chemical induction of cardiomyogenesis from embryonic stem (ES) cells have been developed and contributions to asymmetric C-C couplings were made. A transgenic murine ES cell lines was used to investigate the effects of (thio)urea and cinchona-alkaloid derivatives on cardiomyogenesis. Various compound screenings yielded substances which led to a 50 % to 80 % increased cardiomyogenesis compared to untreated cells. In the test system investigated, time dependent screening approaches appeared to be of limited suitability for the identification of potential cellular targets. A facile two-step procedure for the preparation of Takemoto�s catalyst was developed. The thiourea moiety was obtained by condensation of 3,5-bis(trifluoromethyl)aniline with phenylchlorothioformate and direct reaction with trans-1,2-diaminocyclohexane. Subsequent reductive dimethylation using formaldehyde / zinc afforded Takemoto�s catalyst in an overall yield of 36 %. For the first time, an enantioselective aza-Baylis-Hillman reaction was catalysed by a chiral Lewis acidic metal complex. N-dpp-a-methylene-b-amino acid esters were obtained in up to 68 % yield and up to 90 % ee, using a La-linked-(R,R)-BINOL complex as catalyst and N-dpp-protected imines as substrates. The subsequent hydrolytic C,N-terminal deprotection provided direct access to enantio-enriched a-methylene-b-amino acids in up to 75 % yield.