Preparation and Antibacterial Activity of Some Spiramycin Derivatives

Relation of structures and microbiological activities of the 16-membered macrolides

“…One other important group for antibiotic activity already reported is the dimethylamino group of the mycaminose moiety of leucomycinf and spiramycin. 22 In the case of the chalcomycin, a methoxyl has replaced the dimethylamino group of mycaminose without impairing microbial activity.…”

Carbohydrate-Based Macrolides Prepared via a Convergent Ring Closing Metathesis Approach: In Search for Novel Antibiotics

“…A straightforward and intrinsically simple approach is based on chemical modification of natural macrolides that are accessible in large quantities from fermentation by microorganisms. Modifications include acylation of hydroxy groups, deacylation, aldehyde or ketone reduction, double bond reduction, and N-demethylation . More fundamental structural changes require synthesis of macrolide analogues from simple building blocks, and over the past few years four general approaches have been developed to control the critical stereochemistry: (i) ring-cleavage, where the appropriate stereorelationship of the asymmetric centers is first secured by using the conformational bias of a small or medium sized ring, which is then opened to give an acyclic fragment with the stereocenters correctly related, (ii) exploitation of the existing asymmetric centers and functionalities of a carbohydrate precursor, (iii) stereoselective introduction of new asymmetric centers on an acyclic precursor, and (iv) stereoselective introduction of new asymmetric centers onto an intact macrocyclic precursor, using the conformational bias of the macrocycle .…”

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

“…Up to now, many modifications, both within spiramycin and leucomycin groups, have been proposed and tested to obtain comparably or more active alternative agents able to fight the growing bacterial resistance. Most of the modifications were related to transformation of the aldehyde via reduction, nucleophilic addition, − hydroxyl groups within the aglycone and saccharides parts via etherification, acylation, or sulphonylation, , diene moiety via epoxidation, reduction, Diels–Alder reaction, or metathesis with contraction of the lactone ring, − forosamine and/or mycaminose N -oxidation or N -substitution, , and incorporation of the nitrogen into the lactone macrocyclic ring. − An interesting platform to synthesis and drug discovery among the group of macrolide lactone antibiotics has been recently proposed by Seiple et al Convenient synthetic strategy leading to obtaining of new chemical entities characterized by attractive biological properties is the use of click chemistry reactions. − An interesting approach to modification of these structurally complexed macrolides, in view of their known mechanism of action, has been described by Omura and Sharpless et al They proposed the functionalization of terminal hydroxyls of mycarose saccharide with alkyne followed by conversion into respective triazole moieties via Fokin–Huisgen cycloadditions. However, as a result of this transformation, the obtained derivatives were significantly less active than the parent leucomycin due to the presence of a too long arm at C(5) of the aglycone.…”

“…20 Up to now, many modifications, both within spiramycin and leucomycin groups, have been proposed and tested to obtain comparably or more active alternative agents able to fight the growing bacterial resistance. Most of the modifications were related to transformation of the aldehyde via reduction, nucleophilic addition, 21−23 hydroxyl groups within the aglycone and saccharides parts via etherification, acylation, or sulphonylation, 24,25 diene moiety via epoxidation, reduction, Diels−Alder reaction, or metathesis with contraction of the lactone ring, 26−29 forosamine and/or mycaminose N-oxidation or Nsubstitution, 30,31 and incorporation of the nitrogen into the lactone macrocyclic ring. 32−34 An interesting platform to synthesis and drug discovery among the group of macrolide lactone antibiotics has been recently proposed by Seiple et al 35 Convenient synthetic strategy leading to obtaining of new chemical entities characterized by attractive biological properties is the use of click chemistry reactions.…”