2D NMR Studies of Aminoglycoside Antibiotics: Use of Relayed Coherence Transfer for1H Resonance Assignment and in Situ Structure Elucidation of Amikacin Derivatives in Reaction Mixtures

Niels H. Andersen, Hugh L. Eaton, Khe T. Nguyen, Cynthia Hartzell, R. John Nelson, John H. Priest

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Phase-sensitive 2D 11-1/1H COSY spectra can be used to identify the structures of individual pure specimens of the aminoglycoside antibiotic amikacin and its N-hemisuccinyl derivatives. However, even at 500 MHz the 2D chemical shift dispersion does not allow for unambiguous assignment of all cross-peaks. By use of 2D relayed coherence transfer experiments (RELAY) optimized to detect two-step 1H/1H scalar interactions in which one of the J-values is small, sufficient additional correlations can be obtained from the frequency-isolated resonances to allow facile tracing of all scalar connectivities. Complete assignments of the 1H NMR spectra of amikacin, its 6'-N-hemisuccinamide and a novel bis(acylate) [ϒ-N-(p-vinylbenzoyl)amikacin 6'-N-hemisuccinamide] were obtained for aqueous media. The NMR spectrum of amikacin free base was also assigned in dimethyl sulfoxide solution. The RELAY experiment can be extended to the analysis of reaction mixtures, wϒhich allows for the identification and resonance assignment of regioisomeric amikacin haptens in the mixture state. All of the N-monohemisuccinyl isomers of amikacin have been identified in reaction mixtures through the RELAY experiment. The relative reactivities of the amino functions of amikacin toward acylating agents were found to be 6'-N > 3-N ≳3”-N ≳ϒ-N. However, this reactivity order is altered after the initial acylation event.

Original languageEnglish (US)
Pages (from-to)2782-2790
Number of pages9
JournalBiochemistry
Volume27
Issue number8
DOIs
StatePublished - Apr 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of '2D NMR Studies of Aminoglycoside Antibiotics: Use of Relayed Coherence Transfer for<sup>1</sup>H Resonance Assignment and in Situ Structure Elucidation of Amikacin Derivatives in Reaction Mixtures'. Together they form a unique fingerprint.

  • Cite this