Aspects of Chirality in Natural Products Drug Discovery

Aspects of Chirality in Natural Products Drug Discovery 

Philipp Krastel, Frank Petersen, Silvio Roggo, Esther Schmitt, 

Natural products are isolated mainly from plants, fungi, bacteria, and marine macro-organisms. They are also called secondary metabolites, as they are not essential for fhe life cycle of fheir producers. In general, fhey are synthesized at the end of the microbial growth phase. In fhe case of plant derived products, fheir production is often coupled to differentiation and seasonal changes influencing fhe life cycle of a plant [1-3]. 

The therapeutic use of natural products, mainly administered as herbal preparations, has long been known in human history. It is therefore not astonishing that approximately 80 % of fhe world s population is using plant derived medicines for basic healthcare [4]. The analysis of Farnsworth and Morris of the National Prescription Audit data from 1976 showed fhat approximately 40% of fhe US prescriptions in 1973 contained natural products derived from plants and microorganisms [5]. 

Drug substances from pure natural products together wifh fheir derivatives, and synthetic compounds deduced from a natural product precursor represent a major part of today s pharmaceutical market [6, 7]. Although natural products represent less than 1% of all published chemical compounds, they accounted for 35% or 230 billion of the total pharmaceutical sales in 1996 [8]. Between 1990 and 2000, 41 drugs derived from natural products were introduced to the market [9]. Nearly, all of them are chiral with an average of eight chiral centers. Table 3.1 lists some recently launched drugs derived from natural products and Fig. 3.1 shows the structures of the active compounds [10]. 

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