Novel azalides derived from 16-membered macrolides. Part II: Isolation of the linear 9-formylcarboxylic acid and its sequential macrocyclization with an amino alcohol or an azidoamine

Synthesis and antibacterial activity of novel 15-membered macrolide derivatives: 4″-Carbamate, 11,12-cyclic carbonate-4″-carbamate and 11,4″-di-O-arylcarbamoyl analogs of azithromycin

“…They share a similar mechanism of action: selective binding to the 50S subunit of bacterial ribosome resulting in inhibition of protein synthesis. It seems that azithromycin modifications have not been systemically investigated since it was clinically used [17,18].…”

Structure elucidation, complete NMR assignment and PM5 theoretical studies of new hydroxy‐aminoalkyl‐α,β‐unsaturated derivatives of the macrolide antibiotic josamycin

“…These structural changes within 16-membered macrolides involving e.g. insertion of heteroatoms like nitrogen in the macrocyclic aglycone part, [10,11] replacement of diene moiety with amine or carbamate moieties, [12] removal of one of the sugars attached to aglycone, [13] inversion of configuration at carbon atoms of aglycones [14] or redistribution of diene fragments by the scission of carbon atoms [15] have been realised on the way of various chemical reactions yielding new 14-, 15-and 16-membered macrolide analogues like azalides or ketolides of important biological properties and increased biological stability. Recently, also 16-membered macrolides like leucomycin A 7 have been modified at C-3 position by means of the Heck reaction yielding compounds of improved antibacterial activity against important pathogens including erythromycinresistant Strep.…”

Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm

“…However, spiramycins, in contrast to leucomycins, additionally possess forosamine at C(9) position. The spectrum of spiramycins’ biological properties comprises mainly bacteriostatic activity against most of Gram-(+) cocci and rods, mycoplasmas, and Toxoplasma gondii. , Comparison of spiramycins’ activity against different Gram-(+) bacteria strains in vitro with that determined for 14-membered lactone macrolides such as erythromycins indicates that it is at least twice lower . However, the advantage of spiramycins over erythromycins is their good gastrointestinal tolerance, higher affinity to tissues, and a fewer adverse effects. , To the best of our knowledge, the activity of spiramycins in cancer cells has never been studied up to now, although literature provides some examples of other-group macrolides showing properties of this type, e.g., maytansine (ansamacrolide) or marine 22-membered lactone macrolide (−)-dictyostatin. − The target site of spiramycins’ action is well recognized from X-ray studies as the exit of the ribosomal tunnel near the peptidyl transferase loop and the loop of domain II of 23S rRNA, belonging to the large subunit 50S. − Spiramycin and related 16-membered lactone macrolides have a common mechanism of activity which involves binding to the 50S subunit and steric blocking of the peptide exit tunnel, which contributes to inhibiting peptide synthesis at different stages.…”

“…1,2 Spiramycin I, having hydroxyl substituent at C(3) atom, is dominant (∼80%) in the mixture produced by the bacteria. 3 Spiramycins are structurally similar to leucomycins in the presence of a common 16-membered lactone aglycone and mycaminosyl-mycarose moiety attached at C (5). However, spiramycins, in contrast to leucomycins, additionally possess forosamine at C(9) position.…”

“…The spectrum of spiramycins' biological properties comprises mainly bacteriostatic activity against most of Gram-(+) cocci and rods, mycoplasmas, and Toxoplasma gondii. 4,5 Comparison of spiramycins' activity against different Gram-(+) bacteria strains in vitro with that determined for 14-membered lactone macrolides such as erythromycins indicates that it is at least twice lower. 6 However, the advantage of spiramycins over erythromycins is their good gastrointestinal tolerance, higher affinity to tissues, and a fewer adverse effects.…”