Diversity-oriented synthesis development

Diversity-Oriented Synthesis Developing New Chemical Tools to Probe and Modulate Biological Systems... 

Currently, these reactions are typically conducted with Rh(l) or Ir catalysts. The Pauson-Khand-type reaction of allenynes has also witnessed important developments, especially in its applications to natural products synthesis.388 Brummond s group has been very productive in both areas. Duality in the reaction of allenynes is shown below. In the context of diversity-oriented synthesis, simply changing the reaction conditions gives versatile heterocycles in high yields (Scheme 116).389... 

When compounds such as pyrazoles are being made to develop new drugs, a number of related compounds can be prepared at once by diversity-oriented synthesis, that is, methods designed to be general for a wide range of compounds. An example where both components are aliphatic 13 and a tri-substituted example 15 make the point. In this work, the synthesis of 25 different di-or tri-substituted pyrazoles was attempted by the same method only one example failed. 

A similar kind of strategy, as developed by Kita, has also been successfully applied in a diversity-oriented synthesis of galanthamine-like molecules (Scheme 14) [51]. The... 

Here, we cover several examples that included stereoselective diversity-oriented synthesis approaches. The examples covered in this section are indicative of the growing interest in this area and of the need for developing novel approaches leading to fast access to obtaining natural product-like compounds to be used as small-molecule probes. 

Abstract In the past decade, it has been extensively demonstrated that multicomponent chemistry is an ideal tool to create molecular complexity. Furthermore, combination of these complexity-generating reactions with follow-up cyclization reactions led to scaffold diversity, which is one of the most important features of diversity oriented synthesis. Scaffold diversity has also been created by the development of novel multicomponent strategies. Four different approaches will be discussed [single reactant replacement, modular reaction sequences, condition based divergence, and union of multicomponent reactions (MCRs)], which all led to the development of new MCRs and higher order MCRs, thereby addressing both molecular diversity and complexity. 

Diversity-oriented synthesis of small molecules is a great challenge for synthetic organic chemists. DOS requires the development of new methodologies that generate scaffold diversity in addition to appendage and stereochemical diversity. 

Schreiber apphed (4a)-catalyzed RCM in the development of some of the facets of diversity-oriented synthesis toward the stereochemical control of macrocycle skeletal diversity. In this work, he showed that a chiral element such as an amino alcohol, even many bonds from the ring closnre, can influence the stereochemical outcome of RCM of otherwise identical complex substrates like a chiral auxiliary via diastereomeric transition states. Depending on which isomer is used, a completely different reaction pathway is observed. ... 

Angular epoxyquinol library A -Pyrazoline Diversity oriented synthesis (DOS). 244 80 Chemical Methodology and Library Development (CMLD) initiative to develop novel libraries. 18, 19... 

In many cases, small molecules are found for a TF of interest through assays developed with known protein partners. Structures of the interacting protein domains also have been invaluable for drug discovery. For several important TFs, however, the specific cellular partners with which they interact are unknown. In this case, using small molecule screens on solid supports is an extremely useful tool for dmg discovery. In one such screen, diversity-oriented synthesis (DOS (129) was used to identify a small molecule binder of Hap3p, a yeast protein... 

Kubota, H., Lim, J., Depew, K. M., Schreiber, S. L. Pathway development and pilot library realization in diversity-oriented synthesis. Exploring Perrier and Pauson-Khand reactions on a glycal template. Chem. Biol. 2002, 9, 265-276. 

Biology Oriented Synthesis and Diversity Oriented Synthesis in Compound Collection Development... 

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