Undesirable functional group

Chemists and biologists have long known that certain chemical moieties are likely to produce false positives in biochemical assays because of their chemical reactivity [86]. Software filters are now routinely used at Vertex [24, 87] and other companies to flag compounds containing functional groups known empirically to contribute to reactivity, insolubility, toxicity, or poor ADME. Table 18.4 lists examples of such undesirable functional groups. 

Hit follow-up consideration was accounted for via two filters to remove undesirable functional groups and to include molecules with a desirable functional group that would act as chemistry handles to enhance compound elaboration. These filters were derived from extended discussion with medicinal chemists. A total of 12 undesirable functional group sets were created and collectively used as a negative filter ... 

Although spectroscopic analysis of resins does not lead to a quantitative determination of the loading, spectroscopic techniques can be very useful for the characterization of resins, as well as for the identification of possible undesired functional groups arising from incomplete reactions. 

Often hit compounds from an HTS screen are laden with undesirable functional groups that need to be removed or replaced with suitable bioisosteres. It can be... 

Both radiation and chemical crosslinking can produce amorphous, mechanically stable networks. Radiation crosslinking has a practical advantage in that polymer electrolyte films can be fashioned to the desired thickness or shape, and even incorporated into a device before crosslinking. Chemical crosslinking often introduces undesirable functional groups which may offer few advantages from a practical viewpoint, but this route can be very useful in the simple preparation of networks for fundamental studies [33, 49-51). 

Advantages of the Stille reaction include neutral conditions under which the reaction takes place, often with full retention of stereochemistry, and compatibility with nearly all functional groups thus eliminating additional steps required for protection and deprotection. Conversely, a highly undesirable drawback is the use of toxic tin compounds and the ensuing difficult removal of these from the reaction mixture. 

Radicals can be classified according to their tendency to give aromatic substitution, abstraction, double bond addition, or (3-scission and further classified in terms of the specificity of these reactions (see 3.4). With this knowledge, it should be possible to choose an initiator according to its suitability for use with a given monomer or monomer system so as to avoid the formation of undesirable end groups or, alternatively, to achieve a desired functionality. 

Step-growth polymerization processes must be carefully designed in order to avoid reaction conditions that promote deleterious side reactions that may result in the loss of monomer functionality or the volatilization of monomers. For example, initial transesterification between DMT and EG is conducted in the presence of Lewis acid catalysts at temperatures (200°C) that do not result in the premature volatilization of EG (neat EG boiling point 197°C). In addition, polyurethane formation requires the absence of protic impurities such as water to avoid the premature formation of carbamic acids followed by decarboxylation and formation of the reactive amine.50 Thus, reaction conditions must be carefully chosen to avoid undesirable consumption of the functional groups, and 1 1 stoichiometry must be maintained throughout the polymerization process. 

The complete elimination of functional groups is often an undesirable side reaction in organic synthesis, but on the other hand it is a possibility for the recycling of environmentally harmful compounds, for example phenols and haloarenes such as polychlorinated dibenzodioxins (PCDDs or dioxins ). For example, aryl chlorides can be effectively dechlorinated with Pd(0) NPs in tetra-butylammonium salts with almost quantitative conversions also after 19 runs (entry H, Table 1.4) [96]. On the other hand, a C-0 bond cleavage reaction also seems suitable for the fragmentation of sugar-based biomass such as cellulose or cello-biose in that way, sugar monomers and bioalcohol can be derived from renewable resources (entry F, Table 1.4) [164]. 

Tab. 18.4 Functional groups used to filter out undesirable compounds [24, 78, 86, 87, 155]...

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