Abstract
The evolution of a strategy culminating in an efficient, enantioselective synthesis of the potent microtubule-stabilizing agent FR182877 is described. Guided by a proposed biogenesis of this complex natural product, a solution emerged that involved the first reported example of a double transannular DielsAlder reaction to fashion the key elements of its hexacyclic structure. This pivotal transformation creates a complex pentacycle from a 19-membered macrocyclic pentaene, forming seven new stereogenic centers in a fully diastereocontrolled fashion. The efficiency of the approach ultimately enabled the preparation of multigram quantities of the direct precursor of FR182877 for conversion to the relatively unstable natural product when required. The reactivity of the strained, bridgehead olefin of this secondary metabolite with biologically relevant nucleophiles is also described.
Original language | English (US) |
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Pages (from-to) | 5393-5407 |
Number of pages | 15 |
Journal | Journal of the American Chemical Society |
Volume | 125 |
Issue number | 18 |
DOIs | |
State | Published - May 7 2003 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- General Chemistry
- Biochemistry
- Catalysis
- Colloid and Surface Chemistry