Polyenic antibiotics

A second aid to the chemical classification of polyenes is the presence in the antibiotic of either a hexosamine sugar or an aromatic moiety. The presence of sugars is a characteristic of macrolide antibiotics. Polyene hexosamines are similar to the sugars present in the non-polyene macrolides [27]. The structure of polyene hexosamines has been determined and with one exception, the carbohydrate is mycosamine [28—30], the structure of which has been unequivocally established by chemical synthesis [31] as 3-amino-3,6-dideoxy-D-mannopyranose (1). The sugar perosamine, 4-amino4,6-dideoxy-D-mannose (2), an isomer of mycosamine, has been isolated from perimycin [31,32]. 

Nystatin. This compound (1) belongs to the group of polyene antimycotic antibiotics (Table 1). Siace the early 1960s, approximately 200 polyenes have been isolated from different Streptomjces strains. 

Amphotericin B. Amphotericin B (3), an important polyene antibiotic, is administered almost exclusively via the intravenous route and is therefore discussed in more detail under the systemic antimycotics. The vaginal tablets contain 50 mg amphotericin B, and 100 mg tetracycline base per tablet (see also Antibiotics, tetracyclines). The tablets for oral use contain 50 mg amphotericin B, 250 mg tetracycline base, and 125 mg sodium hexametaphosphate. A combination ointment contains 1 mg fludrocortisone acetate, 2.5 mg neomycin, 0.25 mg gramicidin, and 1 g plastibase in addition to 30 mg amphotericin B (see also Antibiotics, peptides). 

Configurational assignment of polyene macrolide antibiotics using the [ C]ace-tonide analysis 98ACR9. 

The body of chemistry described above for amphotericin B (1) allowed, for the first time, the preparation of a series of novel derivatives of this polyene macrolide antibiotic and set the stage for a total synthesis of this target molecule. Below we unfold the adventure that led to the accomplishment of this goal.910... 

Amphotericin B, is a polyene antibiotic, used in the therapy of systemic fungal infections. Its mode of action exploits differences in membrane composition between the pathogen and the human host. Ergosterol, the predominant sterol of fungi, plants, and some protozoan parasites, interacts with Amphotericin B, resulting in an increased ion permeability of the membrane. Humans contain cholesterol, which has a low affinity for amphotericin B. 

AOIABI6 DOIAAO6 G01AA09 polyene antibiotic (for treatment of candidal and trichomonal gynaecological infections, treatment of benign prostatic hypertrophy)... 

Cass A., Finklestein A. Krespi V. (1970) The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. J Gen Physiol, 56, 100-124. 

Norman A.W, Demel R.A., DeKmyff B., Geiuts Van Kessel W.S.M. Van Deenen L.L.M. (1972) Studies on the biological properties of polyene antibiotics comparison of the other polyenes widi filipin in their ability to interact specifically with sterol. Biochim BiophysActa, 290, 1-14. 

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