ORGN 396 |
Intramolecular formal aza-[3 + 3] cycloaddition approach for the synthesis of immunosuppressant FR901483
| Elena P. Sizova and Richard Hsung. Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455 |
| Immunosuppressant FR901483 (1) was isolated in 1996 from the fermentation broth of Cladobotrym sp. No.112311 by Sakamoto and coworkers, and displays potent, selective immunosuppressive activity in vitro, such as inhibition of purine nucleotide biosynthesis. The synthesis of the tricyclic core of 1 has attracted the attention of several synthetic groups. We were drawn to the possibility that the azaspiro[4.5]decane nucleus may be constructed utilizing an intramolecular formal aza-[3 + 3] cycloaddition of 2. To demonstrate the feasibility of this approach, vinylogous amides 3 were prepared through a 12-step pathway. We envision the construction of the desired heterocycles 4 to be accomplished via an intramolecular formal aza-[3 + 3] cycloaddition of the iminium salt’s of 3. 
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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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