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The pentalenolactones are a growing family of acidic lipophilic sesquiterpenes with a highly compacted carbon skeleton. They present an angularly fussed tricyclo pentanoid lactone with different states of oxidation in each of the three rings. These natural products have been isolated from a variety of Streptomyces species and have shown antibiotic, antiviral and antitumoral properties. Special efforts have been devoted to study the inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone in Trypanosome brucei. These important biological effects have promoted considerable synthetic research in this area.