Polypropionate discodermolide synthesis

In 1998, Marshall and co-workers demonstrated the utility of allenyl metal addition methodology for the synthesis of the polypropionate subunits contained in discodermolide [53,54], As outlined in Scheme 18, Marshall divided the carbon backbone... 

Panek and co-workers reported their synthesis of discodermolide in 2005 [62, 63], relying on the application of their crotylsilane methodology for the synthesis of polypropionate motifs [155,156] (see [157] forareview) [158,159,182], Their strategy involved key bond disconnections at C6-C7 and C14-05, based on an aldol coupling and the established Suzuki cross-coupling respectively, employing the key subunits 137 (C1-C6), 138 (C7-C14) and 81 (C15-C24) (Scheme 29). 

We have already collected some powerful tools for use in stereocontrolled aldol reactions, but we have not finished. We shall see now in Paterson s synthesis of (+)-discodermolide, how reagent control is used not to enhance the intrinsic substrate selectivity, but to overturn it. The aldol reaction is undoubtedly one of the most powerful ways of making carbon-carbon bonds and nature thinks so too. There are numerous natural products that are replete with 1,3 related oxygen functionality. Many of these are acetate or propionate-derived in nature. The methods detailed above developed from studies into the syntheses of these natural products. The manipulations of chiral ethyl ketones of this kind are of particular interest when it comes to natural products that are polypropionate-derived. 

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. ... 

Showcase of Polypropionate Chemistry in R D Total Synthesis of (+)-discodermolide by Novartis... 

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