Biomedical Engineering Reference
In-Depth Information
studies and the discovery of potential therapeutic leads. The development of efficient
methods for the construction of libraries featuring structural diversity that encom-
passes the maximum amount of chemical space is a particularly challenging task for
organic chemists. DOS entails the development of pathways leading to the efficient
syntheses of collections of small molecules exhibiting rich skeletal and stereochem-
ical diversity. Here, the combination of annulations of electron-deficient allenes and
alkynes under phosphine catalysis with a combinatorial scaffolding strategy provided
a branching DOS pathway that yielded up to 4600 discrete compounds, comprising
55 distinct cyclic scaffolds. The reactions summarized herein meet the high standards
of DOS in terms of their efficiency and selectivity. Furthermore, we have identified
several biologically active compounds from our DOS library based on phosphine
organocatalysis. These outcomes demonstrate the powerful premise behind DOS:
The greater the structural diversity in the screening collection, the higher the prob-
ability of discovering small-molecule biomodulators. Indeed, the implementation of
nucleophilic phosphine catalysis resulted in a compound library featuring rich struc-
tural diversity, making it well suited to probe critical biological questions and for
creative new applications. The basic transformations described herein will undoubt-
edly instigate further expansions of the scope and utility of nucleophilic phosphine
catalysis in DOS.
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