Immunosuppressive agent discodermolide

Nerenberg, I.B., Hung, D.T., Somers, P.K., Scheiber, S.L. (1993) Total Synthesis ofthe Immunosuppressive Agent (—)-Discodermolide. Journal of the American Chemical Society, 115, 12621-12622. 

Paterson et al. achieved the convergent synthesis of the immunosuppressive agent discodermolide 205 by using a lithium-mediated aldol reaction with a chiral aldehyde (Scheme 8.31). The 2,6-dimethylphenyl ester 200 was derived to -enolate 201 by employing lithium 2,2,6,6-... 

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. 

Discodermolide (3) is a polypropionate-based unique compound isolated from the Caribbean deep-sea sponge Discodermia dissoluta. It is immunosuppressive as well as highly cytotoxic. More significantly, it stabilizes microtubules more potently than taxol. " Attempts at large-scale synthesis were carried out for clinical trials as an anticancer agent but the clinical trials were discontinued in 2005 due to its toxicity. ... 

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