Practical formal total synthesis of (rac)- and (S)-camptothecin

Org Biomol Chem. 2006 Feb 7;4(3):498-509. doi: 10.1039/b514147h. Epub 2005 Dec 22.

Abstract

A practical, efficient and scalable formal total synthesis of (rac)- and (S)-camptothecin is described, which proceeds via the known DE ring building blocks 19 and (S)-19, respectively. The racemic synthesis starts from diethyl oxalate and uses straightforward carbonyl chemistry in order to generate the pyridone ring system. 19 was formed in 8.4% overall yield over 9 linear steps avoiding any chromatographic purification. The asymmetric version of this approach encompassed a diastereoselective Grignard addition to the enantiomerically pure alpha-ketoester 30 in order to generate the (S)-configured quaternary stereocenter. The auxiliary could be recycled in high yield and was successfully reused multiple times. The final steps paralleled the racemic approach. (S)-19 was thus prepared in 9.4% overall yield (er = 95 : 5) over 10 steps.

MeSH terms

  • Camptothecin / chemical synthesis*
  • Camptothecin / chemistry*
  • Molecular Structure

Substances

  • Camptothecin