Novel and efficient synthesis of 22-alkynyl-13,24(23)-cyclo-18,21-dinorchol-22-en-20(23)-one analogues.

The efficient synthesis of some 22-alkynyl-13,24(23)-cyclo-18,21-dinorchol-22-en-20(23)-ones was investigated. 22-Iodocyclo-18,21-dinorcholenones were prepared from cyclo-18,21-dinorcholenones using I(2)/DMAP/pyridine system firstly. The cross coupling reaction of 22-iodocyclo-18,21-dinorcholenones and 1-alkynes was carried out efficiently catalyzed by tetrakis(triphenylphosphine) palladium/cuprous iodide in the presence of base diisopropylethylamine. This strategy offered a very straightforward and efficient method for access to conjugated alkynyl cyclo-18,21-dinorcholenones from the cyclo-18,21-dinorcholenones and 1-alkynes in excellent overall yields. Evaluation of the synthesized compounds for cytotoxicity against KB, HeLa, MKN-28 and MCF-7 cell lines showed that the 22-alkynylcyclodinorchoenones possessing hydroxylethyl and hydroxylmethyl mono-substituted side chain at the end of alkynyl group have significantly inhibition activity.