Macrocyclic lactone ring

The term macroHde was introduced to denote the class of substances produced by Streptomjces species containing a macrocyclic lactone ring (27). 

They contain 12-, 14-, or 16-membered macrocyclic lactone rings attached to amino acids and/or a neutral sugar moiety attached via glycoside bonds. Beyond this, their individual chemical structures and sizes as reflected by molecular weight are dramatically different. Thus, despite exerting similar mechanisms on bacteria, they are very chemically different from each other. 

Macrolides, as their name indicates are characterized by a large or macrocyclic lactone ring with attached sugar residue(s). They are classified as in table 9.5.1... 

The macrolides are a group of closely related compounds characterized by a macrocyclic lactone ring (usually containing 14 or 16 atoms) to which deoxy sugars are attached. The prototype drug, erythromycin, which consists of two sugar moieties attached to a 14-atom lactone ring, was obtained in 1952 from Streptomyces erythreus. Clarithromycin and azithromycin are semisynthetic derivatives of erythromycin. 

Macrolides are a group of compounds containing a macrocyclic lactone ring and up to 9 conjugated tram double bands. In recent years, new macrolides have been isolated from marine organisms, some of them reported as promising candidates for future drugs. 

The macrolide antibiotics provide us with excellent examples of natural products conforming to the acetate pathway, but composed principally of propionate units, or mixtures of propionate and acetate units. The macrolides are a large family of compounds, many with antibiotic activity, characterized by a macrocyclic lactone ring, typically 12, 14, or 16 membered, reflecting the number of units utilized. Zear-alenone (Figure 3.59), a toxin produced by the... 

Natamycin belongs to the large group of polyene antifungal antibiotics. Characteristic for this group is a macrocyclic lactone-ring with a number of conjugated carbon-carbon double bonds. 

The absolute configurations at C-7, C-8, and C-10 were elucidated to be S, S, and 5, respectively, by comparison of the NMR data of C-l-C-12 segments with those of synthetic model compounds for the tetrahydrofuran portion. The structure of amphidinolide T1 (19a) has been confirmed by a single crystal X-ray analysis.Amphidinolide T1 (19a) possesses an odd-numbered macrocyclic lactone ring but has no vicinally located one-carhon branches. 

The macrolide lactone antibiotics are isolated primarily from the genus Streptomyces. Their antibacterial activity is mostly in the Gm+ spectrum. They are classified on the basis of the size of the macrocyclic lactone rings, the aglycone component of the compound. These are 12-, 14-, or 16-membered rings, glycosidically linked to one or more amino sugars, thus making these polyfunctional compounds basic (Fig. 6-25). 

Macrolidine (70), from the heartwood of Adina rubescens, is a new glycosidic indole alkaloid in which the terminal primary alcohol function in a 5-carboxy-isovincoside derivative has formed a novel macrocyclic lactone ring with the retained tryptophan carboxy-group. The structure was deduced from the spectra of macrolidine and its tetra-acyl derivatives and confirmed by reaction of macrolidine tetra-acetate with methanolic sodium methoxide followed by re-acetylation, which gave the known methyl 3a,5a-tetrahydrodesoxycordifoline penta-acetate (71). 

EM s chemical structure consists of a 14-membered macrocyclic lactone ring (erythronolide) connected to a deoxyamino sugar (desosamine) and a deoxy sugar (cladinose) as shown in Fig. 5. We synthesized about 250 EM derivatives and examined their GMS and antibacterial activities [19, 20]. GMS activity was tested by intravenous injection of the test compounds to fasted conscious dogs with permanently implanted force transducers in the stomach, and antibacterial activity was estimated as minimum inhibitory concentration (MIC) by agar dilution method. The EM derivatives shown in Fig. 5 exhibited higher GMS activities with less antibacterial activities compared with those of EM (Table I). 

The constrained nature of the macrocyclic lactone ring, the extensive unsaturation of the chromophore, and the variety of functional groups in the polyene molecule confers sensitivity to physical and chemical attack. Unfortunately, the resulting products are usually biologically inactive. Saturation of the chromophore or breaking the lactone ring by saponiflcation reduced the affinity for sterol, the antifungal properties and the haemolytic activity [197]. 

Macrolides are bacteriostatic antibiotics composed of a macrocyclic lactone ring with one or more deoxy sugars attached to it (Fig. 4). The main representative of the... 

A branched pentasaccharide containing a macrocyclic lactone ring related to that in compounds (15) and (16) is mentioned in Chapter 7. 

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