Antifungal agents echinocandin

An innovative application of these concepts is to be found in Evans synthesis of the potent antifungal agent echinocandin D (68, Scheme 7.11) [27]. When 65 is treated with dicyclohexylborane, diastereoselective hydroboration is followed by reaction of the azide with the organoborane intermediate, resulting in a ring-contraction and the formation of 67 as the sole diastereomer. 

Enzymatic Deacylation of Echinocandins and Related Antifungal Agents... 

WW Turner, WL Current. Echinocandin antifungal agents. In WR Strohl, ed. Biotechnology of Antibiotics. New York Marcel Dekker, 1997, pp 315-334. 

M Debono, BJ Abbott, DS Fukuda, M Barnhart, KE Willard, RM Molloy, KM Michel, JR Turner, TF Butler, AH Hunt. Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide synthesis of the antifungal agent cilofungin (LY121019). J Antibiot 42 389-397, 1988. 

Resistance to other antifungal agents such as amphotericin B has been observed less frequently in clinical fungal isolates however, the molecular basis of this resistance is not currently well understood. To solve the problems associated with antifungal resistance a number of novel azole drugs (e.g. voriconazole) and novel classes of drug (e.g echinocandins) have been developed (see Chapter 12). 

Caspofungin is an echinocandins/antifungal agent that inhibits synthesis of p-(l,3)-D-glucan, an integral component of fungal cell wall. 

The newest antifungals, the echinocandins, are macromolecular structures with high molecular weights (>1,000 dalton), which a student can easily visualize by looking at the chemical structure. Their relatively low volume of distribution in the body can be partially explained by their size. Clinically, these agents have not achieved high concentrations in the central nervous system and the vitreous chamber of the eye, two compartments that are subject to fungal invasion. 

Raasch RH. Anidulafungin review of a new echinocandin antifungal agent. Expert Rev Anti-Infect Ther 2004 2 499-508. 

Figure I Representatives of the six naturally occurring families of echinocandin lipopeptide antifungal agents.

Antifungal agents of the echinocandin class (both natural products and seroisynthetic analogs) chat have been studied to dace are inhibitors of fungal wall biosynthesis. They... 

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