Polyene macrolide antibiotics are important antifungal agents. The y form ion channels in membranes containing sterols, and these ion channels are responsible for the antibiotics' activity. What interactions between polyene macrolide antibiotics and sterols lead to ion channel formation? A better understanding of these interactions will guide the development of more effective antifungal agents, and she light on the self-assembly of complex membrane structures. Comparing the membrane conductance and ion channel behavior of an antifungal antibiotic and its enantiomer will determine the nature of the sterol-antibiotic interaction. Enantiomers always have identical properties in an archiral environment, and so the two enantiomeric ion channels will have identical properties if interactions with the chiral sterol are weak and nonspecific. The two enantiomeric ion channels will have very different properties if the interactions with the chiral sterol are strong and specific. Sterol affinity is believed to determine antifungal selectivity in this class of antibiotics. Enantiodifferentiation would unambiguously demonstrate that specific sterol-antibiotic interactions control ion channel assembly. (-)-Roflamycoin is an appropriate polyene macrolide with which to determine the nature of the antibiotic-sterol interaction, and so its enantiomer, (+)-roflamycoin will be synthesized. Polyene macrolide antibiotics contain alternating polyol chains are currently synthesized with inefficient, labor intensive methods. A general, convergent synthesis of alternation polyol chains is described which will dramatically reduce the labor required to prepare a new polyene macrolide antibiotic. This new method will produce either stereoisomer at the coupling center. Our general, convergent strategy will greatly simplify the structure determination and synthesis of (+)-roflamycoin, and facilitate future studies in this area.
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