ORGN 381 |
Spongistatin synthetic studies: An efficient second-generation construction of an advanced ABCD intermediate, fragment union, and final elaboration to (+)-Spongistatin 1
| Chris Sfouggatakis, Dimitar Gotchev, Wenyu Zhu, Shohei Shirakami, Victoria Doughty, Clay Bennett, and Amos B. Smith III. Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, PA 19104 |
| The spongistatins (a.k.a. altohyrtins) comprise an important family of architecturally unique bis-spiroketal macrolides that display extraordinary (subnanomolar) antitumor activities against a variety of highly chemo-resistant tumor cell lines. Due to their remarkable biological profile and extremely limited supply, the spongistatins have been the focus of considerable attention among the chemical and biological communities. Recently, we have achieved a preparatively useful synthesis of the advanced ABCD fragment (–)-4, taking advantage of our multicomponent dithiane coupling tactic. Wittig union with the EF phosphonium salt (+)-3, followed by macrolactonization and global deprotection afforded (+)-spongistatin 1 (1). A summary of these results, as well as a modified synthesis of (+)-3 will be presented. 
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Total Synthesis, Process R&D, Combinatorial, Bioorganic, Physical Organic Chemistry
8:00 PM-10:00 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- Hall D, Poster
Sci-Mix
8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix
Division of Organic Chemistry
The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004
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