Synthetic strategies scaffold diversity

In most recent developments, it has been possible to devise synthetic strategies whereby a variety of chemical scaffolds can be obtained in one scheme (39). Whereas in former examples of combinatorial synthesis a large number of compounds were synthesized that all shared the same chemical backbone, this new technology is opening new ways toward a diversity that can be used for chemical genomics in a designed strategy (40). 

Figure 6.28 Some different scaffolds prepared through diversity oriented synthesis (DOS). (Taylor, S. J. et al. Synthetic strategy toward skeletal diversity via solid-supported, otherwise unstable reactive intermediates. Angew. Chem. Int. Ed. Engl. 2004, 43, 1681-1685.) ...

Schreiber and coworkers recently described a synthetic strategy using o elements, functionality that encodes skeletal information that can be transformed into products with different skeletons. The diversity-oriented synthetic approach, aimed at understanding the function of proteins has taken root in a number of laboratories around the world. DOS develops on what combinatorial chemistry initially sought to achieve. As previously indicated, DOS as a combinatorial approach to parallel synthesis expands the array diversity by increasing the number of stereoisomers per array and varying the number of core scaffolds per array. 

We next explored the applications of liquid-phase synthesis of benzofused heterocycles from a common building block PEG-bound nitro-activated aryl fluoride (Fig. 8). In these synthetic strategies, we created multiple accesses to the structurally diverse core molecules based on a fundamental scaffold 10. We focused on the construction of a variety of benzimidazole libraries starting from a versatile synthon 4-fluoro-3-nitrobenzoic acid via liquid-phase nucleo-... 

This review will compare the strategies taken by synthetic chemists to produce natural products with the strategies utilized by nature. What types of molecular scaffolds are made in each case in the process of assembling a natural product Rarely will the paths be identical, but are there features that reveal a more universal logic in the construction of these molecules Or, by contrast, are there fundamental distinctions between organic synthesis and biosynthesis To answer these questions we have chosen - from a biosynthetic point of view - a diverse selection of secondary metabolites, ranging from relatively simple terpenes and shikimate-derived... 

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