Boehmeriasin A as new lead compound for the inhibition of topoisomerases and SIRT2

• We describe two synthetic approaches to the alkaloid boehmeriasin A.
• Anti-proliferative activity in 5 cell lines indicates activity at the nanomolar range.
• Topoisomerases and SIRT2 are identified as biological targets.
• Experimental data are supported by docking studies.

Two synthetic approaches to boehmeriasin A are described. A gram scale racemic preparation is accompanied by an efficient preparation of both the pure enantiomers using the conformationally stable 2-piperidin-2-yl acetaldehyde as starting material. The anti-proliferative activity in three cancer cell lines (CEM, HeLa and L1210) and two endothelial cell lines (HMEC-1, BAEC) indicates promising activity at the nanomolar range. Topoisomerases and SIRT2 are identified as biological targets and the experimental data has been supported by docking studies.

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