Asymmetric enantiopure drugs

Senanayake, C. H., Jacobsen, E. N. Chiral (Salen)Mn(III) Complexes in Asymmetric Epoxidations Practical Synthesis of Ci s - Am i n o i n d ano 1 and Its Application to Enantiopure Drug Synthesis, Process Chemistry in the Pharmaceutical Industry, Gadamasetti, K. G. Marcel Dekker New York, 1999, Chapter 18, 327. 

The synthesis of enantiopure drugs has taken advantage of the development of biocatalyzed reactions [161], especially of asymmetric hydrolase-catalyzed processes [41,162]. In this context, many different biocatalysts have been used to achieve... 

Although very efficient, the broad application of the direct preparation is restricted due to the limited number of pure starting enantiomers. The design of a multistep process that includes asymmetric synthesis is cumbersome and the development costs may be quite high. This approach is likely best suited for the multi-ton scale production of commodity enantiomers such as the drugs ibuprofen, naproxen, atenolol, and albuterol. However, even the best asymmetric syntheses do not lead to products in an enantiomerically pure state (100 % enantiomeric excess). Typically, the product is enriched to a certain degree with one enantiomer. Therefore, an additional purification step may be needed to achieve the required enantiopurity. 

Chiral aldehydes with high enantiopurity obtained through asymmetric hy-droformylation serve as useful intermediates for pharmaceutical drugs.For example, (5 )-2-arylpropanals (86) can be oxidized to the corresponding (5)-2-arylpropanoic acids 94, which are anti-inflammatory drugs such as (5)-ibuprofen (94a Ar = 4-isobutylphenyl), (S)-naproxen (94b Ar = 6-methoxynaphthyl), and (5)-suprofen (94c Ar = 4-(2-thienylcarbonyl)phenyl) (Eq. 45)."° ... 

Styrene epoxide is a valuable building block and is used in the production of the antihelmintic drug Levamisole. The styrene epoxide for the synthesis of drugs must be enantiopure. There are some chemical asymmetric synthetic routes but the yields are only in the range 45-50%. 

This chapter is not devoted to the development of a specific NDE or marketed drug, but to a synthetic process, exemplified by its application to the synthesis of a potential NDE class. It is inspired by the achievement of asymmetric organocata-lysis, a catalytic variant of a multi-component reaction (MCR). The resulting methodology was utilized in the synthetic pathway to enantiopure 1,2-dihydroqui-nolines with the general formulae I. 

---