Enantiospecific approach toward pentalenolactone

TESTERO, S. A.; SPANEVELLO, R. A.

Canela

Simposio; 11th Brazilian Meeting on Organic Synthtesis; 2005

Sociedad Brasilera de Química

The pentalenolactones are natural products that were 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 (GAPDH) by pentalenolactone in Trypanosome brucei. This inhibitory effect provokes the disappearance of the parasite from the host´s bloodstream. These metabolites present an angularly fused tricyclo pentanoid lactone with different states of oxidation in each of the three rings. (Figure 1). Surprisingly, despite the sustained interest in the chemistry of these natural products due to their biological activities, only two research groups have addressed the issue of optical purity in the synthesis of (-) pentalenolactone E methyl ester by an enzymatic resolution of an advanced synthetic intermediate. However, to the best of our knowledge, no general enantiospecific approach toward the synthesis of these intricate quaternary carbon centered polycyclic structure has yet been recorded. In light of these considerations we were prompted to devise a simple means for building the pentalenolactone quinane skeleton in an enantiospecific form. The construction of the core bicycle [3.3.0] octane framework was achieved in 17 steps and 16 % overall yield. The final product  bears all the functionality necessary to synthesize the different members of this family of natural products.