Appendage diversity

Ikoma M, Oikawa M, Sasaki M (2009) Chemospecific allylation and domino metathesis of 7-oxanorbomenes for skeletal and appendage diversity. Eur J Org Chem 72-84... 

Molecular complexity (generally found in natural products) seems to be extremely important to obtain an optimal perturbation function and specificity of action of the chemical modulators on their protein targets [2, 9]. The goal of achieving molecular diversity can be divided in three different diversity elements (a) appendage diversity (combinatorial chemistry), (b) stereochemical diversity, and most importantly (c) scaffold diversity (Fig. 2) [2]. 

Appendage diversity b Stereochemicai diversity C Scaffoid diversity... 

MCRs are ideal to achieve appendage diversity, because all individual components can be varied to create a large library of products that have the same skeleton but differ in the substiments around it. If, for example, a 4-component reaction (4CR) is considered and 40 inputs of aU four components are combined, this will result in 40" = 2,560,000 reaction products [32],... 

The combination of MCRs in one pot is not new. It was first introduced by Domling and Ugi who developed a 7-component reaction (7CR), that was basically a one-pot combination of a modified Asinger 4CR and U CR (Scheme 15) [100, 101]. In this 7CR, an a- or (3-bromo/chloro aldehyde 158, NaSH/NaOH, NH3, another aldehyde 161, an isocyanide 166, CO2, and a primary alcohol (solvent) are combined to afford 167 efficiently. However, NaSH/NaOH, NH3 and CO2 are invariable components in this reaction which limits the substitutional diversity (appendage diversity) and thereby the scope of the MCR. 

Royer D, Wong Y-S et al (2008) Diastereodivergence and appendage diversity in the multicomponent s5mthesis of aryl-pyrrolo-tetrahydrocarbazoles. Tetrahedron 64 9607-9618... 

Appendage diversity - variation in structural moieties around a common scaffold... 

Plants have served as a food source for fish. Insects, and mammals since early biotic times. In response plants have developed intricate physical as well as chemical protective mechanisms. The two defensive structures that are the primary subject of this chapter are trichomes and glands. Trichomes are epidermal appendages of diverse form and structure, such as protective and glandular hairs and scales or peltate hair. 

Arthropoda Insects, spiders, trilobites. ticks, scorpions, centipedes, crustaceans, eurypterids Jointed appendages, hard exoskeleton largest and most diverse group freshwater, marine and terrestrial... 

As already became clear from the previous examples, MCRs are ideal to obtain complex products in an easy way. However, DOS also requires molecular diversity (appendage, stereochemical and scaffold diversity), which can also be accomplished using MCRs. 

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. 

FIGURE 17.9 Similar substrates with different appendages (u-elements) 6-8 produces a diversity of skeletons 9—11 with a unique set of reagent. ... 

A library of resin bound furans 294-296 with diverse appendages were prepared and oxidized. Those furans with appended diols gave bicyclic acetals 297, those with a single alcohols the hydropyrones 298 that underwent dehydration and those without a hydroxyl gave the open-chain compounds, thus generating three structural types from a common intermediate. This last diversity-oreiented example nicely illustrates the synthetic flexibility and power offered by the use of furans. It is certain that the role of furan in complex-molecule synthesis will continue to expand in many new directions. 

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