6995-12-6Relevant academic research and scientific papers
Furans in synthesis. II.1 total syntheses of (±)- and (-)-fastigilin C
Tanis, Steven P.,Robinson, Edward D.,McMills, Mark C.,Watt, William
, p. 8349 - 8362 (2007/10/02)
Fastigilin C (2), a complex helenanolide, has been reported to exhibit cytotoxic and antineoplastic activity, thus making it an attractive target for total synthesis. We wish to report the first total syntheses of (±)- and (-)-fastigilin C ((±)-and (-)-2). As a result of our interest in the utilization of furan-terminated cyclizations as the key step in the construction of diverse ring systems, we envisioned (eq 1) furan 3 as the precursor to bicyclo[5.3.0]decane furan 4, which should afford 2. In the forward direction, a Mukaiyama Michael-aldol protocol affords 3 with complete control of relative stereochemistry. A mercury(II)-mediated-furan-terminated cyclization gives 4, which is ultimately converted (17 steps, 24.6% overall yield) to (±)-fastigilin C ((±)-2). A porcine pancreatic lipase mediated resolution of 4-hydroxy-2-methyl-2-cyclopentenone leads to (S)-(+)-4-methoxy-2-methyl-2-cyclopentenone, which is converted (17 steps) to (-)-fastigilin C ((-)-2) in 14% overall yield.
