Combined directed ortho metalation/cross-coupling strategies: synthesis of the tetracyclic A/B/C/D ring core of the antitumor agent camptothecin.
A convergent synthesis of the A/B/C/D ring fragment 5 of camptothecin using a combination of directed ortho metalation and Negishi cross-coupling is described. The key features of the synthetic sequence are an anionic ortho-Fries rearrangement (10 --> 12), a Negishi cross-coupling (7 --> 6), and a terminal modified von Braun reaction (16 --> 5) that leads to tetracyclic derivative 5 in 7 steps and 11% overall yield.
Nguyen
Tam
T
The Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
Wicki
Markus A
MA
Snieckus
Victor
V
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002166:Camptothecin / Q000138:chemical synthesis*; D002384:Catalysis; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin