&lt;!--StartFragment--&gt;<br/>Spirocyclic framework is considered as a “privileged structural motif” since derivatization of this orthogonal ring systems has led to the discovery of novel therapeutic drugs that interacts with cancer cells. Examples include the MDM2 inhibitor, enzyme inhibition, antibiotic activity, fluorescent tagging, enantioselective binding for DNA probes, and RNA targets. Current synthetic approaches involve using isatin and isatin derivatives, unusual intramolecular rearrangements, and Lewis acid catalysis. The aforementioned procedures are linear, yield unwanted stereochemical products, have minimal functionality, and are limited by commercially available reagents. A new, convenient synthetic pathway is desired to eliminate unwanted side products, leaving stereochemically pure, highly functionalized, spirocyclic compounds. Bond severing in a tricyclic system was explored as a non-linear route to access spiro molecules. The proposed pathway involves solid phase synthesis, using the regenerating Michael linker (REM) strategy, and intramolecular silyl nitronate-olefin cycloaddition (ISOC). REM linkers are known to provide a convenient method for the synthesis of tertiary amines on the solid support. The ease of purification via simple filtration of reagents from the polymer support and the recyclability of the REM linker makes this solid phase process ideal. Synthesis of pyrrolidine oximes via ISOC can be modified to form a functionalized tricyclic scaffold, which is an ideal precursor to spirocyclic systems. Due to the rigidity of their structure, tricyclic scaffolds provide high diastereoselectivity in the synthesis of spirocyclic compounds. Current research efforts focus on streamlining the synthesis as well as assessing the biological activities of these molecules on mammalian cells.

Functionalized spirocyclic heterocycle synthesis and biological evaluations

2019 Fall National Meeting

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