Antifungal polyenes

Amphotericin B Cholesteryl (Amphotec) [Antifungal/Polyene Mocrollde] Uses AspCTgillosis if intolCTant/refractory to conventional amphotericin B, systemic candidiasis Action Binds ceU membrane sterols, alters permeability Dose Adults Peds. Test dose 1.6—8.3 mg, over 15-20 min, then 3-4 mg/kg/d 1 mg/kg/h inf w/ renal insuff Caution [B, ] Disp Inj SE Anaphylaxis fever, chills, HA, nephrotox, -1- BP, anemia Notes Do not use in-line filter Interactions See Amphotericin B EMS See AmphotCTicin B OD May cause cardiac arrest s ptomatic and supportive... 

Antifungal polyene antibiotic obtained from a strain of Streptomyces nodosus... 

There are relatively few chemotherapeutic drugs which cause permeability increases in membranes such as the antifungal polyenes and the antibacterial circular oligopeptides of the tyrocidin, gramicidin and polymyxin families. Most of these are too toxic for systemic use but polymyxins have been given systemically in severe Pseudomonas infections with an attending risk of renal toxicity. 

A mixture of antifungal polyenes produced by the growth of certain strains of Streptomvces nodosus or by any other means. 

Amphotericin B - Observations on the immunostimulant properties of the clinically used antifungal polyene antibiotic amphotericin B (AmB) and its methylester (AME) were extended. In mice, the drugs augmented antibody formation to TNP-HSA with pronounced enhancement of secondary IgG responses,... 

Antifungal Agents. The chemistry, mechanism of action, and clinical utility of the antifungal polyene antibiotics was discussed in Chapter 2. 

Schlegel, R., and Thrum, H. (1968). Flavomycoine, a new antifungal polyene antibiotic. Experi-entia 24, 11-12. 

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. 

Antifungal polyene drug of choice for some systemic mycoses binds to er-gosterol to disrupt fungal cell membrane permeability. Tox chills and fever, hypotension, nephrotoxicity (dose-limiting less with liposomal forms). 

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. ... 

This antifungal polyene, with the molecular formula C34H49O14N, has been... 

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. 

---