Fourteen-Membered Macrolides

This sponge, found in the Red Sea, produces a number of toxins, three of which have been isolated and identified as possessing a thiazolidinone ring that is connected to a fourteen-membered macrolide ring.47 Latrunculins A and B have been assigned structures (42) and (43), and latrunculin C is a stereoisomer of (42). 

A. Chemical Modification of Fourteen-Membered Macrolides before 1984... 

Fourteen-membered ring macrolides can inhibit Cl secretion across the airway epithelial Cl channel. Although the subcellular mechanism of this action warrants further studies, the inhibition of Cl secretion may lead to the reduction of liquid secretion across the airway mucosa toward the lumen. It is thus likely that the favorable effects of 14-membered macrolides on chronic airway hypersecretion might be related, at least in part, to the action on airway epithelial Cl channel. 

Fourteen-Membered-Ring Macrolide Antibiotics Suppress Gene Expression of Inflammatory Cytokines in Human Bronchial Epithelial Cells We evaluated the effects of macrolides on steady-state levels of IL-6 and IL-8 mRNA by Northern blot analysis [17, 60]. As shown in Fig. 13, bronchial epithelial cells expressed constitutive IL-8 mRNA, which was significantly upregulated by the cytokines such as IL-la, IL-1[3, and TNF-a. We reported that EM, CAM, and RXM inhibited steady-state levels of IL-6 and IL-8 expression in normal and immortalized bronchial epithelial cells [60, 62, 63]. This action appeared to be unique, because other antibiotics including a 16-membered ring macrolide JM... 

Fourteen-Membered Ring Macrolide Antibiotics Suppress Activation of Transcription Factors of Inflammatory Cytokines in Human Bronchial Epithelial Cells... 

Kohyama, T., Takizawa, H., Kawasaki, S., Akiyama, N., Sato, M., and Ito, K. (1999). Fourteen-membered ring macrolides inhibit lL-8 release by human eosinophils from atopic donors. Anti-microb. Agents Chemother. 43,907-911. 

Azuma, A., Li,Y. J.,Usuki,J.,Aoyama, A., Enomoto, T., and Kudoh, S. (2001). Fourteen membered-ring macrolides inhibit the VCAM-1 mRNA induction preventing neutrophil induced lung injury and fibrosis in bleomycin challenged mice. Chest 120S, 20-22. 

Macrocyclic Olefinic Microbial Metabolites Conformational studies based on n.m.r. and c.d. measurements of fourteen-membered ring macrolides have been discussed using diamond lattice conformational models A review on stereocontrol in synthesis of acyclic systems includes the... 

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