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Concluded Synthesis

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(-)-Pironetin

Pironetin or PA-48153C is an unsaturated d-lactone derivative, which was isolated independently by two research groups from Streptomyces sp. NK10958 and from the fermentation broths of Streptomyces prunicolor PA-48153, respectively. This very interesting compound possess plant growth regulatory and imunossupressive activities and recently, was reported the biological effects of pironetin and its derivatives on cell cycle progression and antitumor activities. More importantly, the mode of action of pironetin is different from those estabilished for the imunossupressants cyclosporin A (CsA) and FK506 that inhibit T cell activation. Pironetin showed suppresive effects on the responses of T and B lymphocytes to mitogens.

The structure of pironetin has been suggested mainly by spectral methods, the relative stereochemistry has been determined by X-ray analysis, and the absolute configuration has been confirmed by total synthesis. In a recent paper, Osada et al showed that the a,b-unsaturated lactone, the chirality at the C7 - position bearing a hydroxyl group and the terminal portion of the alkyl chain are important for microtubule inhibitory activity of pironetins. To provide material for more extensive biological evaluation, and to propose a synthetic strategy useful for the preparation of promising new derivatives of pironetin, we have undertaken its total synthesis.

  1. "Total Synthesis of (-)-Pironetin". Dias, L.C.; de Oliveira, L.G.; Sousa, M.A. Organic Letters 2003, 5, 265-268.

  2. "Total synthesis of the potent immunosuppressant (-)-pironetin”. Dias, L.C.; de Oliveira, L.G.; de Sousa, M.A.; Ellensohn, R.M. ARKIVOC: Archives of Organic Chemistry 2005, 6, 62-87 (www.arkat-usa.org ).


 

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