Studies Toward the Total Synthesis of Ritterazine B: The Investigation of Alkynylation Reactions for Use in the Synthesis of the Western Fragment

Citation

Campbell, Taryn Langley (2014) Studies Toward the Total Synthesis of Ritterazine B: The Investigation of Alkynylation Reactions for Use in the Synthesis of the Western Fragment. Master's thesis, California Institute of Technology. doi:10.7907/Z9P848WN. https://resolver.caltech.edu/CaltechTHESIS:05282014-120132545

Abstract

The ritterazine and cephalostatin natural products have biological activities and structures that are interesting to synthetic organic chemists. These products have been found to exhibit significant cytotoxicity against P388 murine leukemia cells, and therefore have the potential to be used as anticancer drugs. The ritterazines and cephalostatins are steroidal dimers joined by a central pyrazine ring. Given that the steroid halves are unsymmetrical and highly oxygenated, there are several challenges in synthesizing these compounds in an organic laboratory.

Ritterazine B is the most potent derivative in the ritterazine family. Its biological activity is comparable to drugs that are being used to treat cancer today. For this reason, and the fact that there are no reported syntheses of ritterazine B to date, our lab set out to synthesize this natural product.

Herein, efforts toward the synthesis of the western fragment of ritterazine B are described. Two different routes are explored to access a common intermediate. An alkyne conjugate addition reaction was initially investigated due to the success of this key reaction in the synthesis of the eastern fragment. However, it has been found that a propargylation reaction has greater reactivity and yields, and has the potential to reduce the step count of the synthesis of the western fragment of ritterazine B.

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