Scaffold reagent-based

Finally, scaffold diversity (Fig. 2c), probably the most important element of diversity, is the generation of a collection of products with different molecular skeletons (scaffolds). This can, for example, be realized by changing the reagents added to a common substrate (reagent-based approach) or by transforming a collection of substrates having suitable preencoded skeletal information with similar reaction conditions (substrate-based approach) [2, 10]. 

Remarkably, Schreiber was able to use every single functionality of 46. Seven different highly selective pairing reactions were performed, to obtain seven different scaffolds (A-G), which is quite remarkable since they are all obtained from one single substrate. To come back to a term earlier introduced, this is an example of a reagent-based approach since a single substrate is converted by different reaction conditions, producing a diversity of scaffolds [42]. 

The reagent-based approach or branching pathways in diversity synthesis exploits different functional or reactive sites of a common substrate to yield diverse scaffold... 

Reagent-based and substrate-based approaches can also be combined in a single two-directional synthesis in which different symmetrical substrates can be used under different reaction conditions to achieve predictable scaffold diversity [23]. In an example by Spring et al, two domino reactions were used to synthesize polycyclic alkaloids from a common substrate 147. A Boc-removal/bicyclization process using AlClj as Lewis acid from 147 was used to produce 5-5, 5-6, and 6-6 bicyclic compounds (148-153), and a domino Michael addition/Dieckmann process/Michael addition reaction yielded 6-6-6, 6-6-5 tricyclic compounds (154-156). The 6-5-5 tricyclic scaffold 156 could not be synthesized by means of the same domino... 

Broadly speaking, there are three approaches to reagent selection. In reagent-based selection, a subset is chosen to maximize the diversity of the reagents at each position without considering the reagents at the other positions, or the scaffold. A good example of such a method is that reported by the... 

Traceless linker 60 based on a benzotriazole scaffold was reacted with amines and aldehydes to produce Mannich-type amine products [69]. Final product release was achieved by treatment with Grignard reagents (Scheme 29). 

Additionally, the environmental issue of utilizing waste cellulosic material and waste biomass products should be considered as an alternative green chemistry application to the production of many value added products. The combinatorial utilization of carbohydrate scaffolds based on chiral building block functionalization will also constitute attractive and relatively cheap starting materials. This rich selection of potential approaches, combined with further developments of new procedures and modem reagents, creates an enormous opportunity for the field to be at the frontier for many years to come. 

A structure-based example is to explore a given subsite in a protein active site. The special feature is positioned as a site point where the molecules to dock will be anchored this could be done using the position of the atom of the docked scaffold which is used to link the reagents or the derivative... 

Examples of library selections based on virtual products, rather than monomers, have been reported, especially when the computational burden is reduced by fixing the scaffold orientation and optimizing only the randomization points (33). From now on we will not mention specifically if selections are performed on virtual sets of reagents or products, providing that the reader remembers throughout the rest of this section the relevance of this issue and its dependence on project-related factors (number, availability of hardware/software, and so on), rather than on dogmatic assumptions. 

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