Synthesis of Aminoglycosides

Modification at the 2′-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity

“…1–6 In this regard the aminoglycosides (AGAs), 7–11 are strong candidates for further development because of their widespread availability, innate potency, and the extensive knowledge base covering their mechanism of action 10,12,13 and chemistry. 7,14–16 Together with the deep understanding of the mechanism of resistance, this knowledge base has long informed the structure-based design of new generations of AGAs, 17–24 as exemplified by the recent introduction of the semi-synthetic AGA plazomicin 1 into clinical practice. 25,26 In addition to the many aminoglycoside modifying enzymes (AMEs), 27–30 a second important and growing mechanism of AGA resistance is the modification of G1405 in the drug binding pocket in the decoding A site of the bacterial ribosome by the ribosomal methyl transferases (RMTs).…”

Selective Protection of Secondary Amines as the N-Phenyltriazenes. Application to Aminoglycoside Antibiotics

“…1 In particular we were struck by the need for selective protection of disymmetric secondary amines 2 without complications of the NMR spectra by the presence of slowly interconverting conformers. The use of carbamates and amides affords rotamers and thus hinders routine spectral interpretation, 3 while sulphonamides require less than ideal conditions for eventual deprotection.…”

Highly selective acylation of polyamines and aminoglycosides by 5-acyl-5-phenyl-1,5-dihydro-4H-pyrazol-4-ones

“… 28 Previous methods for the preparation of monoacyl derivatives have required either protecting groups or the acidification of the amino group(s) in aminoglycosides. 28 , 29 Moreover, those methods afforded pure products in only 20–40% isolated yields. Although modern methods for acylation of 6′-position of kanamycin, tobramycin and amikacin as sulfate salts using N -hydroxysuccinymyl (NHS) esters have been reported 30 with yields up to 91%, the scope of this methodology is limited to substituted acetyl derivatives.…”