Synthesis and biological evaluation of (−)-kunstleramide and its derivativesThe authors declare no competing interests.Electronic supplementary information (ESI) available: 1H and 13C spectra of all new compounds are available. See DOI: 10.1039/c6md00606j

Stereoselective total synthesis of (−)-kunstleramide, a cytotoxic dienamide from the bark of Beilschmiedia kunstleri gamble, has been accomplished by using Keck's asymmetric allylation and Trost isomerization as key reactions. Application of the developed strategy for the synthesis of a series of amide analogues ( 8-22 ) was also reported. Furthermore, the synthesized compounds were evaluated for their in vitro anti-proliferative activities against human epithelial lung carcinoma (A549), human epithelial cervical cancer (HeLa), human breast adenocarcinoma (MCF7) and human neuroblastoma (IMR32) cell lines using the SRB assay. All the compounds show moderate anti-proliferative activity against all cell lines. Some of the piperazine derivatives ( 17-22 ) strongly inhibit the growth of breast cancer cells with IC 50 values of 8-20 μM. Stereoselective synthesis of (−)-kunstleramide and its amide derivatives has been achieved and they have been evaluated for their in vitro anti-proliferative activities against various cell lines.