Drugs unichiral

Most of the reactions applied to amines can also be transferred to alcohols (Eig. 7-5). One large group of chiral alcohols are the (i-adrenoreceptor blockers, for which a variety of derivatization agents was developed. One highly versatile reagent for the separation of (i-blockers is A-[(2-isothiocyanato)cyclohexyl]3,5-dinitrobenzoyl-amide (DDITC) [11]. Alternatively, unichiral drugs such as (3-blockers or (S)-naproxen [12] may be used in a reciprocal approach to derivatize racemic amine compounds. 

There is however a great and obvious need for a convenient term to refer to chiral substances fhat are composed of only one of the two enantiomers. Numerous terms for this purpose have been introduced over many years, but the issue remains complex and largely unresolved. The present author recently discussed this issue in detail and introduced a new term for the purpose unichiral [5]. In the present chapter unichiral will be used to specify fhe stereochemical composition of a chiral drug, substance, compound, sample, etc, as stereochemically homogeneous, i. e., consisting of a single-enantiomer (in the context where fhe term is used and wifhin the limits of measurement) [5]. 

In a book about herbs, the Chinese scholar-emperor Shen Nung described in 2735 BC the beneficial effects of Ch ang Shan in the treatment of fevers [8]. This preparation is the powdered root of a plant, Dichroafehrifitga Lour. Modern medicinal chemistry has identified several alkaloids with antimalarial properties in the plant, and it is therefore clear that the ancient use of Ch ang Shan in fevers was not entirely without basis. One of the antimalarial compounds from Ch ang Shan is fihrugine (/J-dichroine), a relatively simple unichiral compound 1. Modem attempts to develop these agents as antimalarial drugs failed, due to significant toxicity [8]. 

The vast majority of chiral drugs present in the old remedies were unichiral Mother Nature is not even-handed. All in all, chiral drugs have been of great importance in the development of pharmacotherapy, from the earliest plant remedies of miUeimia ago to the modern age. Many of these ancient chiral drugs are still in use today, and many new and important drugs have been developed by modifying the molecules of natural products identified in old remedies. 

It should be noted, however, that despite the general preference for the marketing of synthetic chiral therapeutic agents in racemic form, a few synthetic chiral drugs were introduced in a unichiral form. Such exceptions included the above-mentioned levodopa and also n-penicillamine 31 [78], (-)-timolol 32 [87], methyl-dopa 33 [88], etc, and it is clear that in most such cases the choice of developing a unichiral form was dictated by overt serious toxicity present predominantly in the ofher enantiomer. 

---