Diversity-oriented synthesis planning

Scheme 4.14 Schreiber diversity-oriented synthesis plan (2000). (a) MeOH/THF, heat (57%) (b) 2KN(SiMe3)2, 2 CH2=CH2 Br (89%) (c) Grubbs catalyst (59%) (d) HF, pyridine (95%).

Burke MD, Schreiber SL. (2004) A planning strategy for diversity-oriented synthesis. Angew. Chem. Int. Ed. Engl. 43 46-58. 

Garber K. Big plans for small molecules NIH launches chemical genomics initiative. J. Natl. Cancer Inst. 2003 95 1740-1741. Tan DS. Diversity-oriented synthesis exploring the intersections between chemistry and biology. Nat. Chem. Biol. 2005 1 74-84. Ede NJ, Wu Z. Beyond Rf tagging. Curr. Opin. Chem. Biol. 2003 7 374-379. 

DOS—Diversity-oriented synthesis Synthesis planning from a common set of starting materials to mnltiple target products linked to construction of compound libraries in a combinatorial sense. 

Diversity-oriented synthesis (DOS) was defined by Schreiber in 2000 [34]. He referred to synthetic processes that contain only a few steps ( 3-5) and are planned with a forward... 

Scheme 5.6 Planning target-oriented synthesis and diversity-oriented synthesis [68].

Figure 4.1. Planning strategies and end goals involved in target-oriented synthesis, focused library synthesis (combinatorial synthesis), and diversity-oriented synthesis. The first two approaches use retrosynthetic analysis to design the synthesis of target compounds. Diversity-oriented synthesis uses forward synthetic analysis to produce libraries that occupy diffuse regions of chemical space.

From a synthetic point of view, when planning a diversity-oriented synthesis, four potential types of molecular diversity to be incorporated are consistently highlighted in the literature ... 

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