Chirality link with biological activity

Chiral 3-substituted phthalides are central structures in a number of biologically active compounds. The synthesis of chiral phthalides has been achieved by Witulski and Zimmerman, starting with enantiopure substituted propargylic alcohols 409 (Scheme 2-38). The chiral ester-linked diyne 410 was cyclotrimerized with acetylene by using RhCl(PPh3)3 as the catalyst to afford enantiopure phthalides 411 in good yields. 

Asymmetric synthesis has emerged as a major preparative method, widely used in organic chemistry and in the total synthesis of natural products, and which is also of interest for industrial chemistry. The importance of enantiomerically pure compounds is connected with the applications in pharmaceutical industries, since very often the biological activity is strongly linked to the absolute configuration. In this article the historical developments of asymmetric synthesis will be briefly presented, as well as the main methods to prepare enantiomerically enriched compounds. Then recent asymmetric synthesis of two classes of compounds will be discussed i) Sulfoxides, chiral at sulfur ii) Ferrocenes with planar chirality. The last part of the article will be devoted to asymmetric catalysis with transition-metal complexes. The cases of asymmetric oxidation of sulfides to sulfoxides and nonlinear effects in asymmetric catalysis will be mainly considered. 

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