Synthesis of new simplified hemiasterlin derivatives with α,β-unsaturated carbonyl moiety.

Chinh Pham The (1) , Tuyet Anh Dang Thi (1) , Thi Phuong Hoang (1) , Quoc Anh Ngo (1) , Duy Tien Doan (1) , Thu Ha Nguyen Thi (1) , Tham Pham Thi (1) , Thu Ha Vu Thi (1) , M Jean (2) , P van de Weghe (2) , Tuyen Nguyen Van (1)

1 VAST - Vietnam Academy of Science and Technology
2 ISCR - Institut des Sciences Chimiques de Rennes

In this Letter, we report a convenient and efficient method for the synthesis of new simplified derivatives of hemiasterlin in which the α,α-dimethylbenzylic moiety A is replaced by α,β-unsaturated aryl groups as Michael acceptor. Most of these derivatives have a strong cytotoxic activity on three human tumor cell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a high cytotoxicity against KB and Hep-G2 cancer cell lines comparable to paclitaxel and ellipticine.

Domaines: Chimie organique

Chinh Pham The, Tuyet Anh Dang Thi, Thi Phuong Hoang, Quoc Anh Ngo, Duy Tien Doan, et al.. Synthesis of new simplified hemiasterlin derivatives with α,β-unsaturated carbonyl moiety.. Bioorganic and Medicinal Chemistry Letters, 2014, 24 (10), pp.2244-6. ⟨10.1016/j.bmcl.2014.03.091⟩. ⟨hal-01114407⟩