Article

Synthesis and structure/activity relationships of new guanidino derivatives of aminoglycoside antibiotics

Authors:
  • Apeiron Biologics
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Abstract

Of all known aminoglycoside antibiotics (AAs), only streptomycin and related compounds contain guanidino-groups in the streptamine part of the molecule. The authors were interested in guanidino derivatives of 2-deoxystreptamine-containing AAs. Guanylation of suitable, protected gentamicin C and kanamycin A derivatives, followed by deprotection, gave a series of highly active new compounds with N-guanyl substituents at N-1, N-3, N-2', N-6'. 2'-N-guanyl-gentamicin C 1 (86-451) was selected for further studies.

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... This less hindered aminomethyl function enables chemical distinction from the other amino functions with mildly activated acylating agents. N- benzyloxycarbonyloxy-5-norbornene-2,3-dicarboximide was hence used to selectively monoprotect paromomycin on position 6′′′ [40]. As previously described, for each of these intermediates, the other amino functions were next protected with the Teoc group. ...
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