Progress towards the synthesis of Plakinamine B

Once considered a nuisance, fungi are becoming a serious public health hazard, particularly for the growing population of immunocompromised patients in hospitals. Recent studies have shown that some 40% of all deaths from hospital acquired infections were due to fungi and, in most cases, the fungus was Candida} Fungal infections not only originate from hospitals but from nature as well. In 1994, tremors from the Northridge, California earthquake stirred fiingi from the soil, releasing infectious spores which caused more than 170 reported cases of disease. As the number of patients with impaired immtme systems due to AIDS, chemotherapy, aging, or drugs designed to prevent rejection of transplanted organs grows, instances of serious fimgal infections wiU continue to grow.

The rising incidence of fungal infections concerns public health officials and health care providers for several reasons.^ First is the growing list of fungal pathogens. Species of fungi that once posed no threat to humans are now being detected as a cause of disease in immune-deficient people. Even lowvirulence baker's yeast, found in the human mouth, are known to cause infections in susceptible burn patients. Second is an increasing resistance to existing antifungal drugs. Long-term treatment of oral candidiasis in AIDS patients has begim to breed resistant species, and other species of fungi have also begun to exhibit resistance. Third is the problem of lagging research. Because pathogenic fimgi are difficult to culture, and because many of them do not reproduce sexually, microbiological and genetic research into the disease causing organisms is falling far behind research into other organisms. Stemming from this lack of research is a lack of drugs. Only a few existing drugs are used for the treatment of fungal infections and these exhibit severe side effects.

There is a substantial need for the discovery and development of totally new, prototype antibiotics that do not share the same toxicities and resistance of the existing agents. In the past, natiwal products provided such trial bioactive compounds, and they are a continuing source of promising new agents. These natural products are extracted from plants, microorganisms, or marine organisms. Once an active compound has been found and the structiure determined, it becomes the job of the synthetic organic chemist to compose a synthetic strategy that will lead to quantities of the desired product sufficient for biological testing and drug development.