Combinatorial modification of natural products: Preparation of unencoded and encoded libraries of Rauwolfia alkaloids

The potential of alkaloids in drug discovery

“…In the case of alkaloids, there is one study which reported on the combinatorial synthesis of yohimbine and rauwolscine derivatives (Atuegbu et al, 1996), one which produced a very limited number of taxol (paclitaxel) derivatives (Bhat et al, 1998), and another which yielded 400 taxoid derivatives (Xiao et al, 1997). Several of the major alkaloid classes would appear to be prime candidates for such studies, including the tropane (e.g.…”

The search for orally active medications through combinatorial chemistry

“…This library is illustrated in Figure 23. 67 A purely synthetic indole centroid library is available for comparison as seen in Figure 24. 68 The side-chains are clustered on adjacent centroid atoms limiting the space swept by them and the holdfast point is retained in the form of a carboxamide function further limiting the molecular variety arising from this chemistry.…”

Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold

“…The concept of isolating a natural product scaffold for lead optimisation studies or screening library generation has previously been reported in the literature, although relatively few examples exist. 28 The purification and subsequent use of tambjamine, 22 teicoplanin, 29 yohimbine, 30 fredericamycin A 21 and muurolane 8 scaffolds in the synthesis of biodiscovery and lead optimisation libraries all exemplify this approach. This strategy is dependent on: 1) access to adequate biota supplies for the large-scale isolation of the desired scaffold; 2) the abundance or high-yielding nature of the compound of interest from the biota source; and 3) the presence of chemical handles (e.g.…”