Immunosuppressive agent pironetin

ABSTRACT Discodermolide and pironetin are two immunosuppressive agents with antitumor activity. The isolation, structure elucidation, biological activity are reported as well as the synthetic routes to these two compounds. Five syntheses of discodermolide and seven syntheses of pironetin are described. 

Recently, it has been noticed that natural products with polyketide units can be potent immunosuppressive agents as well as antitumor agents. Two structurally different polyketide lactones, discodermolide and pironetin belong to this group of compounds (Fig. 1). Due to the potential therapeutic applications and the extreme scarcity of discodermolide and pironetin, interest in the chemical synthesis of these two natural products and in their analogues continues unabated. 

Compound (80), a structural isomer of umuravarumbolide (55), is a minor constituent of Cryptocarya latifolia 89). The immunosuppressive agent, (—)-PA-48153 (81), has been isolated from Streptomyces prunicolor sp. PA 48153 (90). The same compound, obtained from Streptomyces sp. NK10958 and shown to be a plant growth regulator, has been named pironetin, and the structure based on spectral data, confirmed by X-ray analysis 91, 92) and synthesis 93). 

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