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Issue 18, 2016
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The total synthesis and functional evaluation of fourteen stereoisomers of yaku'amide B. The importance of stereochemistry for hydrophobicity and cytotoxicity

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Abstract

Yaku'amide B is a highly unsaturated linear tridecapeptide and an extremely potent cytotoxin. Herein, we describe the synthesis of fourteen new stereoisomers of yaku'amide B using a unified assembly strategy. The hydrophobicities and cytotoxicities of these analogues were analyzed, along with those of four previously prepared isomers. Although all of the analogues share a common planar structure, their log D values varied significantly (3.39–5.32), presumably reflecting their distinct three-dimensional shapes. Subnanomolar-level cytotoxicity was observed for the natural yaku'amide B and its epimer of the N-terminal acyl group, whereas the other sixteen isomers exhibited 13- to 1200-fold weaker activities than that of the natural isomer. These data indicated the importance of the overall stereostructure of the 13-mer sequence of yaku'amide B for exerting its potent toxicity.

Graphical abstract: The total synthesis and functional evaluation of fourteen stereoisomers of yaku'amide B. The importance of stereochemistry for hydrophobicity and cytotoxicity

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Publication details

The article was received on 25 Mar 2016, accepted on 15 Apr 2016 and first published on 15 Apr 2016


Article type: Communication
DOI: 10.1039/C6OB00640J
Org. Biomol. Chem., 2016,14, 4199-4204
  • Open access: Creative Commons BY-NC license
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    The total synthesis and functional evaluation of fourteen stereoisomers of yaku'amide B. The importance of stereochemistry for hydrophobicity and cytotoxicity

    H. Mutoh, Y. Sesoko, T. Kuranaga, H. Itoh and M. Inoue, Org. Biomol. Chem., 2016, 14, 4199
    DOI: 10.1039/C6OB00640J

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