Fungal natural products

Davis RA, Kotiw M (2005) Synthesis of the Fungal Natural Product (-)-Xylariamide A. Tetrahedron Lett 46 5199... 

Phosphatidyl-inositol-3-OH kinase (PI(3)kinase) plays an important role in the fusion of endosomes. Phosphatidyl-inositol-3-phosphate (PI(3)P), a product of this enzyme, is enriched in early endosomes, and blocking PI(3)kinase activity with the small molecule wortmannin prevents endosome fusion. This fungal natural product has been shown to inhibit the endocytosis of transferrin, horseradish peroxidase, and albumin (44, 45). 

Figure 11 Identification of new fungal natural products through DANS (schematic).67...

BIOACHVE FUNGAL NATURAL PRODUCTS THROUGH CLASSIC AND BIOCOMBINATORIAL APPROACHES... 

ABSTRACT The kingdom of fungi is an important source of bioactive natural products, which have been a driving force in the development of modem pharmaceutical industry. Fungal natural products have provided revolutionary pharmaceuticals against various diseases, and have provided unique and inspirational chemicals for innovative drugs. 

During the past decade, the most important development in the field of fungal natural products may have been the discovery and successful commercialization of HMG-CoA reductase (3-hydroxy-3-methylglutaryl CoA reductase) inhibitors. Their huge success in the pharmaceutical market reflects the fact that coronary heart disease has become one of the top killers in the industrialized nations (in the U.S. alone, more than 600,000 people die of heart disease each year) [25]. Hypercholesterolemia has been identified as an important cause for this disease. In the cholesterol biosynthetic pathway, HMG-CoA reductase is a rate-limiting... 

Scheme 58 Synthesis of the fungal natural product okaramine J (309) by aza-Claisen rearrangement by Ganesan and co-workers [52]...

No designed ring transformation approaches to the 1,5-dioxocin ring system appear to have been reported. However, purpactin A (111 R = H, R = Ac) is apparently formed nonenzymatically from a related fungal natural product, purpactin B (123), via hydrolysis of the spirodione of the latter followed by spontaneous lactonization (Scheme 35) <91JAN144,92JOCi27l>. 

Thus far, only the dibenz[c/][l,5]oxathiocins have received attention as potential biologically active agents those compounds reported <92EUP490219> were clearly designed to mimic the structural features of purpactin A, the dioxocinone fungal natural product (111) discussed in Section 9.24.6. 

Millions of people in the world suffer from cardiovascular disease, and it is a leading cause of death in both men and women. Elevation in plasma low-density lipoprotein (LDL) cholesterol levels is a major risk factor for myocardial infarction (heart attack) in these patients. Drugs to reduce dyslipidemia have included niacin and the fibrate class, but each of these has clinical limitations, such as low efficacy or toxic side effects. The development of HMG-CoA reductase inhibitors, or statins, has had an enormous clinical impact on the treatment of heart disease and prevention of heart attack, and these are taken by tens of millions of patients worldwide [1]. One of the first such drugs, lovastatin, was discovered in the 1970s as a fungal natural product [2] and lowered lipid levels in animals and healthy volunteers. Problems with the development of another early statin, compactin, halted advancement of lovastatin to regular clinical use until the late 1980s. Since then. 

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