Introduction.. Camptothecin (CPT, 1) 2 and related compounds 3 have recently returned to the forefront of experimental cancer treatment. 4 Good evidence regarding their biomolecular target and mode of action has been produced. 5 Furthermore, previously unrecognized antiviral properties 6 and modulation of protein synthesis v have now been observed for 1 and related natural products. Not surprisingly, renewed biomedical interest, scarcity of the natural product, and difficulties encountered in the preparation of derivatives with a better pharmacological profile directly from 1, have stimulated a flurry of new synthetic activity in the CPT area)
The numerous syntheses of CPT known to date s rest largely 9 on four strategic ideas, depicted in Scheme 1 as retrosynthetic paths A -D. Of these, paths A 'ยฐ and B 1' emerged during the "classical" era of CPT chemistry, and the fact that new and ever more efficient developments of these themes continue to appear 12 is a testament to the soundness of the original formulations and the vision of their formulators. Routes C 8c'8d and D 8f may be termed "contemporary" and reflect recent advances in synthetic technology.