Communication

Combined Chemical-Enzymatic Assembly of Aminoglycoside Derivatives with N-1-AHB Side Chain

  1. Igor Nudelman1,†,
  2. Lilach Chen1,†,
  3. Nicholas M. Llewellyn2,
  4. El-Habib Sahraoui2,
  5. Marina Cherniavsky1,
  6. Jonathan B. Spencer2,‡,
  7. Timor Baasov1

Article first published online: 20 JUN 2008

DOI: 10.1002/adsc.200800229

Issue

Advanced Synthesis & Catalysis

Advanced Synthesis & Catalysis

Volume 350, Issue 11-12, pages 1682–1688, August 4, 2008

Additional Information

How to Cite

Nudelman, I., Chen, L., Llewellyn, Nicholas M., Sahraoui, E.-H., Cherniavsky, M., Spencer, Jonathan B. and Baasov, T. (2008), Combined Chemical-Enzymatic Assembly of Aminoglycoside Derivatives with N-1-AHB Side Chain. Adv. Synth. Catal., 350: 1682–1688. doi: 10.1002/adsc.200800229

Author Information

  1. 1

    The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel, Fax: (+972)4-829-5703; phone: (+972)-4-829-2590

  2. 2

    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom

  1. †

    Equal contributions

  2. ‡

    Dr. J. B. Spencer died on April 6, 2008; any correspondence to Cambridge may be directed to Dr. Finian J. Leeper

Publication History

  1. Issue published online: 31 JUL 2008
  2. Article first published online: 20 JUN 2008
  3. Manuscript Received: 15 APR 2008

Funded by

  • Marshall Aid Commemoration Commission
  • National Science Foundation Graduate Research Fellowship Program
  • Israel Science Foundation
  • Israel Academy of Sciences and Humanities. Grant Number: 515/07
  • US-Israel Binational Science Foundation. Grant Number: 2006/301
  • Biotechnology and Biological Sciences Research Council

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Keywords:

  • aminoglycosides;
  • aminoglycosides toxicity;
  • biosynthesis of butirosin;
  • chemoenzymatic synthesis;
  • resistance to aminoglycosides;
  • stop codon readthrough

Abstract

A series of unprotected pseudo-disaccharides and pseudo-trisaccharides of 2-deoxystreptamine-containing aminoglycosides have been selectively acylated at the N-1 position with the valuable (S)-4-amino-2-hydroxybutanoyl (AHB) pharmacophore by using the recombinant BtrH and BtrG enzymes from butirosin biosynthesis in combination with a synthetic acyl donor. The process was optimized by performing two enzymatic steps in a sequential manner without purification of the intermediate product.

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