Total Synthesis of Antifungal Natural Products

There is great concern amongst the medical profession regarding fungal disease, with dermatophyte infections such as tinea pedis and candidiasis, although usually not fatal, being prevalent throughout the world (Kwon-Chung and Bennett 1992). Pathogens such as Candida albicans, Cryptococcus neoformans, Pneumocystis carinii and Aspergillus fumi-gatus have a far more gruesome reputation and are the cause of considerable mortality in immunocompromised patients. Populations at risk from these opportunistic fungal infections include AIDS patients, recipients of cancer chemotherapy and persons with genetically impaired or drug-suppressed immune function. Fungal pneumonia, induced by Pneumocystis carinii, is the cause of death in the majority of AIDS patients. Invasive pulmonary aspergillosis is the scourge of patients subject to cancer chemotherapeutic regimes. Current treatments for serious systemic fungal infection are deficient, and the gold standard amphotericin is acutely toxic (Kwon-Chung and Bennett 1992). There are now resistance problems with azole fungistatic agents such as fluconazole. Novel therapies are therefore needed for serious fungal disease and for the management of the multitude of topical fungal infections. In consequence, several pharmaceutical companies worldwide are seeking to develop superior fungicidal agents. Due to evolutionary pressures of microbial antagonism, fermentation broths are rich sources of novel anti-infective agents.