Structure diversity-oriented

The term diversity-oriented synthesis (DOS) is relatively new and, as mentioned above, is usually defined as the synthesis of complex, natural product-like molecules using a combinatorial approach and employing the full palette of modern organic reactions. It may be a subject of discussion what exactly qualifies a molecule as being natural product-like [4], and in most cases the similarity to an actual natural product seems reciprocal to the number of synthesized compounds. However, even in less complex cases, the products may be highly substituted polycyclic structures with defined stereochemistry, reminiscent of natural products [19, 20]. In these cases, a moderately complex backbone structure is subsequently modified with a well-established set of selective reactions to introduce diversity. 

Structural type. Diversity-oriented synthesis is a new strategy for constructing libraries with both skeletal and functional group diversity. 

Fig. 11. Structure diversity in apolipoproteins. Despite being of homologous origin and sharing an underlying 22-residue sequence periodicity, different apolipoproteins show fundamental differences in oligomerization state, subunit orientation, and supercoil angle.

Key Words Chemical diversity compound design diversity-oriented synthesis druglike compounds molecular properties natural products rule of five structure-activity relationship target-focused compound libraries. 

Despite this proven record of biological significance there had been some doubts if natural products are suitable and accessible lead structures for combinatorial libraries by solid-phase synthesis. In contrast to the diversity-oriented approach of library design, which is driven by the underlying chemistry of reliable reactions with broad substrate scope [4], natural product... 

Because of their large amount of chemically different functionalization, trans-CHD are promising precursors especially for the synthesis of, e.g., carbasugars and their analogs with potential biological activity. The simple, but highly functionalized structure of trans-CHD also has a high potential for diversity-oriented syntheses that could lead to a vast variety of different structures in short chemical reaction sequences. 

The structural diversity of metabolites belonging to the different flavonoid classes, including their oxygenation patterns, glycosylation, sulfation, acylation, methylation, and/or prenylation are best illustrated in a recent text,9 as well as in several earlier monographs.10 14 These different substitution reactions, which are catalyzed by substrate-specific and position-oriented enzymes, contribute to the enormous diversity of flavonoid compounds that amount to >5000 chemical structures in Nature and hence, to the wide spectrum of functional roles they play in... 

Metathesis is inherently flexible. As a result, this transformation allows, inter alia, for a rapid chemistry-driven evaluation of structure/activity profiles and qualifies for applications in combinatorial and diversity oriented synthesis this is particularly true when combined with suitable post-metathesis transformations exploiting diverse alkene reactivity. 

However, the latter type of metal-catalyzed cascade reactions turns out to be even more challenging since issues of selectivity and efficiency are crucially dependent on the particular catalyst structure. This type can either be performed in a parallel or sequential fashion [16,21], Whereas parallel catalysis is significantly more difficult to develop, sequential catalysis offers the possibility of altering reaction conditions and additives from step to step in the sense of bi- or multicatalytic one-pot processes, assisted tandem catalysis, or auto tandem catalysis [1]. Therefore, a demanding goal is the development of one-catalyst multireaction sequences that set the stage for new reactions in diversity-oriented syntheses of complex molecular structures (for reviews on diversity-oriented syntheses see [27-33]). 

---