Professor,
Graduate School of Pharmaceutical Sciences,
Kyoto University

Development of stereoselective asymmetric synthesis of biological information amines


     The dynamic interaction of molecules results in an information function, and the rationalized accumulation of molecular network guarantees the generation, differentiation, and homeostasis of life. In our research, based on the concept that the initial process of the chemical reaction is assumed to be the recognition process of a molecule with a molecule, development of chiral molecules operative in activation and control of the reactive chemical species is the challenge. Asymmetric reaction and selective bond formation through dynamic molecular recognition is the practical target of our study. Highly efficient total synthesis focuses on nitrogen containing biological information molecules.


1. Asymmetric synthesis of Β-amino acids by conjugate addition of a lithium amide
The ideal synthetic way to Β-amino acids relies on the asymmetric addition of an amine. The lithium amide generated from trimethylsilylbenzylamine was convertible to a chiral amine nucleophile through complexation with a chiral ligand, and was enable the asymmetric conjugate addition to unsaturated carbonyl compounds with high selectivity.



2. Asymmetric synthesis of nitrogen containing compounds by conjugate addition to nitroolefins
The nitrogen containing aromatics represented by dihydroxidine are the chemical family endowed with a full agonist activity to dopamine D1 receptor. Asymmetric conjugate addition of aryllithiums to nitroolefins was mediated by a chiral ligand to give a product with nearly complete enantiofacial selectivity 97% ee, which opened new efficient way to nitrogen containing heterocyclic compounds.



3. Asymmetric synthesis of amines by asymmetric alkylation of imines
The reaction of arylboronic acids with imines were catalyzed by chiral phosphane-Rh(I) comolex to afford the arylated amines with 94% ee.



     Promising asymmetric synthetic ways to a variety of amines were developed.


Publication
(1) H. Doi, T. Sakai, et al. J. Am. Chem. Soc. 2003, 125, 2886.
(2) M. Yamashita, K. Yamada, et al. J. Am. Chem. Soc.2004, 126, 1954.
(3) M. Kuriyama, T. Soeta, et al. J. Am. Chem. Soc. 2004, 126, 8128.