Synthesis and activity of butirosin derivatives with 5''-amidino and 5''-guanidino substituents.
The preparation and antibacterial activity of the 5''-guanidino (6) and 5''-amidino (7) derivatives of 4'-deoxybutirosin A (1) as well as the 5''-guanidino derivative (8) of butirosin A are described. The key intermediates, tetra-N-benzyloxycarbonyl-5''-azido derivatives were selectively reduced with NiCl2-NaBH4 to give the corresponding 5'-amino derivatives. Subsequent guanidination or amidination followed by deblocking afforded the final compounds 6, 7 and 8. The 5''-guanidino derivatives (6 and 8) were more active against Gram-positive and Gram-negative bacteria than the corresponding 5''-hydroxy derivatives (1 and butirosin A). Compound 6 was also active against a variety of methicillin-resistant Staphylococcus aureus (MRSA).
Narita
Y
Y
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Masuyoshi
S
S
Yamasaki
T
T
Naito
T
T
Kawaguchi
H
H
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy*; D002076:Butirosin Sulfate / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D016106:Methicillin Resistance; D051379:Mice; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects*
D002076:Butirosin Sulfate