Antifungal macrolide

Hepatic metabolism of citalopram and escitalopram occurs primarily through cytochrome P450 3A4 and 2C19 isoenzymes. Inhibitors of 3A4 (eg, azole antifungals, macrolide antibiotics) and 2C19 (eg, omeprazole) would be expected to increase plasma citalopram levels. Inducters of 3A4 (eg, carbamazepine) would be expected to decrease citalopram and escitalopram levels. 

Adverse effects include abdominal cramps, diarrhoea, headache, convulsions and extrapyramidal effects. When used with imidazole antifungals/macrolide antibiotics, it may lead to Q-T prolongation and ventricular arrhythmias. 

The antifungal macrolide halichondramide (3), isolated from the Kwajalein sponge of the genus Halichondria, showed significant insecticidal activity at 3 ppm, especially against tobacco budworm. We isolated swinholides A (4) and B (5), from the Red Sea sponge The-onella swinhoei. 

Amphotericin B (15) is an antifungal macrolide antibiotic produced by Streptomyces nodosus that has been used as an alternative, albeit more toxic, drug to the antimonials- It acts as a leishmanicide against the visceral and mucocutaneous forms of the disease. To overcome its potentially severe nephrotoxicity, the drug must be administered over an extended period of time. 

Cisapride 10 mg po tid 20 mg qid 5% 100% 100% 50-75% Avoid with Azole Antifungal, Macrolide antibiotics and other P450 IIIA-4 inhibitors... 

Macrolides possessing more than 20-membered rings usually have long side chains or spiroacetals at the adjacent position of ring lactone oxygen. An antifungal macrolide venturicidin A (Fig. 7, 29) has a 20-membered ring lactone [41],... 

Bedorf, N., Schomburg, D., Gerth, K., Reichenbach, H., and Hoefle, G. (1993). Antibiotics from gliding bacteria. LIV. Isolation and structure elucidation of soraphen A[ , a novel antifungal macrolide from Sorangium ce/l /ox m. Z,/>fcigs Ann. Chem. 1017-1021. 

Achenbach, H. Muhlenfeld, A. Fauth, U. Zahner, H. "The Galbonolides Novel, Powerful Antifungal Macrolides from Streptomyces galbus ssp. eurythermus", In Antifungal Drugs, St. Georgiev, Ed., New York Academy of Sciences New York, 1988, 128-140. 

The utility of this cyclization mode is illustrated in the recent synthesis of the antifungal macrolide pamamycin 607 whose structure contains three nonactic acid-like tetrahydrofuran residues. Selenocyciization of the (2)-homoallylic alcohol derivative 157 was highly selective in favour of the 5-endo mode, despite the potential for a competing 6-exo cyclization, to give 50-60% isolated yields of the 2,5-crs-seleno-tetrahydrofuran 158 when PhSeQ or N-PSP was used as the source of selenium in the presence of 20 mol % tin(lV) chloride <01TL4969>. 

The antifungal macrolide halichondramide (3), isolated by Kernan et al. from the Kwa-jalein sponge of the genus Halichondria, showed the most significant in vitro activity of the compounds tested. With 50% inhibitory concentration (IC50) values approaching those for compounds used clinically, this marine natural product is a potential lead for the development of alternative chemotherapy for the treatment of malaria. 

Soraphens. A family of 18-membered, antifungal macrolides from Sorangium cellulosum (Myxobacteria). The main and concomitantly the most active component S. A is obtained from the cell extract by crystallization (C29H44O8, Mr 520.66, [a] -124°... 

The utility of the Al-acyl oxazolidinone alkylation has been demonstrated in the context of numerous total syntheses. For instance, in 2003, Evans and Connell used this method in the asymmetric total synthesis of the antifungal macrolide (-l-)-roxaticin 221. (+)-Roxaticin 221 is a pen-taene macrolide isolated from an unidentihed streptomycete similar to Strepfomyces ruber. Like similar compounds, it shows antifungal but not antibacterial activity. In the alkylation step (Scheme 7.32), 202 was treated with TiCLj and EtsN to provide the required Z-(0)-enolate, which was then treated with BOMCl to afford 209 in 99% yield and >200 1 diastereoselectivity. Removal of the auxiliary was... 

Kernan, M.R. and Faulkner, D.J. (1987) Halichondramide, an antifungal macrolide from the sponge Halichondria sp. Tetrahedron Lett., 28, 2809-2812. 

Matsunaga, S Fusetani, N Hashimoto, K., Koseki, K, and Noma, M. (1986a) Kabiramide C antifungal macrolide from nudibranch egg masses./. Am, Chem, Soc 108,847-849. 

The Zn-mediated alkyne addition was shown to proceed with excellent reagent control, as showcased by Carreira for the two advanced polyketide intermediates 314 and 315 (Scheme 2.40) [191]. Adduct 315 was further elaborated into the 35-deoxy aglycon 316 of the methyl ester derivative of the antifungal macrolide amphotericin B (317). 

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