Synthesis of 4H-seleno[3,2-b]pyrrole Towards the Synthesis of [4,5]Selena-L-Tryptophan ([4,5]SeTrp)
Protein structure determination provides a critical basis for drug design and information that is imperative to determining the etiology of diseases related to protein structure. X-ray crystallography is the primary experimental technique used to identify protein structure but can experience a phase problem that makes it difficult to read the electron density map produced. Multiwavelength anomalous diffraction (MAD) can improve resolution by utilizing heavy metal atoms such as selenium and tellurium in proteins to enrich x-ray diffraction data. To produce these proteins, amino acid analogues containing a heavy metal atom are synthesized. The Boles/Silks method was utilized to conduct improved synthesis of 4H-seleno[3,2-b]pyrrole, which can be used to synthesize a selenium-containing tryptophan analogue ([4,5]SeTrp). A TIPS pyrrole was brominated and then reacted with t-butyllithium to produce a transmetalated product, which was then reacted with selenium. This was followed by an alkylation step and a final annulation with a Lewis acid catalyst. Future work on this subject includes continuing to scale up the synthesis and refining methods, testing the use of different Lewis acids in the annulation step, and investigating catalytic activities of SeTrp-containing proteins.
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