Synthetic Studies on Kapakahine C

Undergraduate #156
Discipline: Chemistry and Chemical Sciences
Subcategory: Chemistry (not Biochemistry)

Katelyn Leets - Penn State Berks
Co-Author(s): Arijit A. Adhikari and John D. Chisholm, Syracuse University, Syracuse, NY

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Kapakahines are cyclic peptides that are isolated from the marine sponge Cribrochalina olemda. They are a set of pyrroloindoline based cyclic peptides ranging from A through G. Of the Kapakahine family members, only A, B, C, and E have shown toxicity against P388 murine leukemia cells with an IC50 = 5.0 μg/mL. The limited availability and their complex structural motifs have attracted chemists to synthesize these molecules. Initial studies on the synthesis of Kapakahine C has not been reported. The molecule was broken into three different parts – the pentamer peptide, the pyrroloindoline trichloroacetimidate motif and pyrroloindoline alcohol motif. Peptide synthesis, using three amino acids; valine, isoleucine, and proline, was used to synthesis the pentapeptide. Key steps of coupling of two amino acids using HATU and then deprotection of the protected amine using piperidine were also used. Conditions for the synthesis of the pentapeptide have been standardized and half a gram of the peptide was synthesized with a 64% yield. Throughout nine steps, an overall yield of 3.8% was reported. Initial attempts on synthesizing the alcohol were also made which provided the alcohol with a 28% yield. More optimization and wide screening of conditions have to be carried out to provide the alcohol in higher yields. The imidate portion is in the process of being synthesized. Once the imidate is synthesized, the imidate and alcohol will be connected using previously established chemistry using trichloroacetimidates to create the C-N bond. The pentapeptide will be then coupled on to the pyrroloindoline system using peptide coupling to produce Kapakahine C.

Funder Acknowledgement(s): NSF-iREU Program, Syracuse University

Faculty Advisor: John Chisholm,