Synthesis of Tetracyclic ABCD Ring Cores of Camptothecins

Significance

A concise synthetic sequence has been developed for the parent and substituted ABCD ring cores of the camptothecin family of alkaloids. This two-step synthesis starts by N-alkylation of the 2-pyridone 1 with 3-bromo-1-phenylpropyne (Curran’s protocol: D. P. Curran and co-workers Tetrahedron Lett. 1995, 36, 8917-8920) to give 2, followed by DBU-induced cyclization, presumably involving an intramolecular hetero-Diels-Alder reaction, to produce the target tetracyclics 3 in good overall yield. The scope and limitations of this method were not sufficiently investigated.