noyori lecture讲座.pdfVIP

ASYMMETRIC CATALYSIS: SCIENCE AND OPPORTUNITIES Nobel Lecture, December 8, 2001 by RYOJI NOYORI Department of Chemistry, Graduate School of Science, and Research Center of Materials Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. PROLOGUE Chirality (handedness; left or right) is an intrinsic universal feature of various levels of matter[1]. Molecular chirality plays a key role in science and tech- nology. In particular, life depends on molecular chirality, in that many biolo- gical functions are inherently dissymmetric. Most physiological phenomena arise from highly precise molecular interactions in which chiral host mo- lecules recognize two enantiomeric guest molecules in different ways. There are numerous examples of enantiomer effects which are frequently dramatic. Enantiomers often smell and taste differently. The structural difference between enanatiomers can be serious with respect to the actions of synthetic drugs. Chiral receptor sites in the human body interact only with drug mo- lecules having the proper absolute configuration, resulting in marked diffe- rences in the pharmacological activities of enantiomers. A compelling ex- ample of the relationship between pharmacological activity and molecular chirality was provided by the tragic administration of thalidomide to pregnant women in the 1960s. (R)-Thalidomide has desirable sedative properties, while its S enantiomer is teratogenic and induces fetal malformations[2,3]. Such problems arising from inappropriate molecular recognition should be avoided at all costs. Nevertheless, even in the early 1990s, about 90 % of syn- thetic chiral drugs were still racemic – that is, equimolar mixtures of both enantiomers, reflecting the difficulty in the practical synthesis of single enan- tiomeric compounds[4]. In 1992, the Food and Drug Administration in the US introduced a guideline regarding “racemic swit