Antifungals polyene macrolides

Pimaricin, produced by S. natalensis, is also a 26-membered antifungal polyene macrolide antibiotic. The formation of pimaricin backbone requires 12 condensation cycles in which five polyketide synthases are involved. The domain composition in the loading module of the pimaricin polyketide synthase is different from other polyketide synthases. The formation of pimaricin is predicted to start on PIMSO, a single module polyketide synthase with an N-terminal ATP-dependent carboxylic acid CoA ligase domain (CoL), and continue to the next polyketide synthase with the formation of aglycon. 

Addition of Grignard reagents to (dienone)iron complexes has been reported as part of the synthesis of an advanced intermediate of the antifungal polyene macrolide antibiotic amphotericin B. The (Ti -dienone)iron complex adopts an s-cis conformation. Clean addition of the nucleophile from the less hindered face opposite to the metal is achieved (Scheme 4-143). ... 

Many more patents and publications describe the use of TBA for dissolving liposomes. Geo-Centers, Inc., has patented a process for fabricating hpid microstructures using TBA where the dissolved lipid grows into tubular microstructures. Mehta et al. reported using TBA to lyophilize antifungal polyene macrolide-containing liposomes. 

The use of directed reductions has proven to be a versatile and reliable tool in complex molecule synthesis, in particular in the synthesis of macrolide natural products. An example that highlights this strategy is the synthesis of the antifungal polyene macrolide roxaticin (137), which incorporates both 1,3-syn and 1,3-anti dioxygenated structural motifs (Scheme 2.16). In their impressive total syntheses, Mori [83] and Evans [84] took advantage of both syn- and anti-selective reductions. In all cases, these proceeded in excellent yield and diastereoselectivity. 

The complex polyene macrolide antibiotics are clinically effective as antifungal agents. Scott Rychnovsky of the University of California at Irvine has reported (Angew. Chem. hit. Ed. 2004,43, 2822) the first synthesis of rimocidinolide methyl ester 4, the aglycone of rimocidin 1. The key step in the synthesis is the condensation of the aldehyde 2 with the phosphonate 3, leading to 4. 

Macrolides. Antibiotics in the macrolide group are macrocyclic lactones that can be further classified into two main subgroups (I) polyene macrolides that are antifungal agents and include compounds like nystatin and amphotericin B and (2) antibacterial antibiotics represented by erythromycin and tylosin. A number of other subfamilies of antibacterial and antifungal antibiotics fall into the broad category of macrolides,... 

Even larger macrolides are encountered in the polyene macrolides, most of which have antifungal properties, but not antibacterial activity. The macrolide ring size ranges from 26 to 38 atoms, and this also accommodates a conjugated polyene of up to seven E double bonds. Relatively... 

Polyene macrolides consist of a macrocyclic lactone, a polyene chromophore, and a polyhy-droxylated chain which often bears glycosidic residues. These antibiotics, e. g., amphotericin B (49) and nystatin Ai (50) (O Scheme 20), are used as potent antifungal antibiotics although they cause side effects such as nephrotoxicity, hemolytic anemia and electrolyte abnormalities [70]. 

Most polyene macrolides show antifungal activity, and they are produced by actinomycetes. Polyene macrolides are precisely described in Chapters 9 and 12 of the first edition of this book [1]. Though a few octaene macrolides have been reported, their structures have not been elucidated. 

Amphotericin Fungizone Amfostet Polyene macrolide Amphozone antifungal agent... 

In 1950, Hazen and Brown published a report [1] on a new antifungal substance called nystatin produced by Streptomyces noursei, representing the first example of a polyene macrolide. Thereafter a great number of natural substances with a similar structure [2-5] were discovered, mostly produced by soil Actinomycetes belonging to the genus Streptomyces [5]. The primary interest in these anti-... 

The antifungal polyene antibiotics levorin Aj and candicidin D, which contain mycosamine, are identical. The unusual deoxysugar L-digitoxose (2,6-dideoxy-L-ribohexose) has been isolated from the acid hydrolysis products of the macrolide antibiotics nystatin A3, candidinin, and polyfungin B. ... 

Cybulska B, Mazeiski J, Borowski E, Gaty-Bobo CM. Haemolytic activity of aromatic heptaenes. A group of polyene macrolide antifungal antibiotics. Biochem Pharmacol 1984 1 4 M6. 

Polyenes - The occurrence, production, and sources of polyene macrolide antibiotics have been summarizedThe discovery that the antifungal action of polyenes is associated with... 

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