Total synthesis and stereochemistry revision of mannopeptimycin aglycone

Shinichiro Fuse, Hirotsugu Koinuma, Atsushi Kimbara, Miho Izumikawa, Yuto Mifune, Haiyin He, Kazuo Shin-Ya, Takashi Takahashi, Takayuki Doi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Development of efficient methods for preparation of bioactive nonribosomal peptides, containing densely functionalized nonproteinogenic amino acids, is an important task in organic synthesis. We have employed a concise synthesis for such amino acids by asymmetric aldol addition coupled with an isomeric resolution via diastereoselective cyclization. This approach is successfully applied to the first total synthesis of the cyclic hexapeptide aglycone of the mannopeptimycins, a group of glycopeptides known for potent activity against drug-resistant bacteria. The facile preparation of the key amino acids and the synthesis of the aglycone pave the way for further studies on this class of antibiotics and the development of new lead compounds with therapeutic potential. In addition, our studies have led to the revision of the stereochemistry of the β-methylphenylalanine residue in the mannopeptimycin aglycone.

Original languageEnglish
Pages (from-to)12011-12017
Number of pages7
JournalJournal of the American Chemical Society
Volume136
Issue number34
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Fuse, S., Koinuma, H., Kimbara, A., Izumikawa, M., Mifune, Y., He, H., Shin-Ya, K., Takahashi, T., & Doi, T. (2014). Total synthesis and stereochemistry revision of mannopeptimycin aglycone. Journal of the American Chemical Society, 136(34), 12011-12017. https://doi.org/10.1021/ja505105t