spongistatin 1
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2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Linda M. Suen ◽  
Makeda A. Tekle-Smith ◽  
Kevin S. Williamson ◽  
Joshua R. Infantine ◽  
Samuel K. Reznik ◽  
...  
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2018 ◽  
Author(s):  
James Leighton ◽  
Linda M. Suen ◽  
Makeda A. Tekle-Smith ◽  
Kevin S. Williamson ◽  
Joshua R. Infantine ◽  
...  

With an average GI50 value against the NCI panel of 60 human cancer cell lines of 0.12 nM, spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. It is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive, however, and its development requires more efficient and step-economical synthetic access. Using novel and uniquely enabling direct complex fragment coupling alkallyl- and crotylsilylation reactions, we have developed a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is equipotent with the natural product, and have used that synthesis to establish that the C(15) acetate may be replaced with a linker functional group-bearing ester with only minimal reductions in potency.<br><div><br></div>


2018 ◽  
Author(s):  
James Leighton ◽  
Linda M. Suen ◽  
Makeda A. Tekle-Smith ◽  
Kevin S. Williamson ◽  
Joshua R. Infantine ◽  
...  

With an average GI50 value against the NCI panel of 60 human cancer cell lines of 0.12 nM, spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. It is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive, however, and its development requires more efficient and step-economical synthetic access. Using novel and uniquely enabling direct complex fragment coupling alkallyl- and crotylsilylation reactions, we have developed a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is equipotent with the natural product, and have used that synthesis to establish that the C(15) acetate may be replaced with a linker functional group-bearing ester with only minimal reductions in potency.<br><div><br></div>


2011 ◽  
Vol 133 (35) ◽  
pp. 14042-14053 ◽  
Author(s):  
Amos B. Smith ◽  
Christina A. Risatti ◽  
Onur Atasoylu ◽  
Clay S. Bennett ◽  
Junke Liu ◽  
...  

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