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Synthesis of new hemiasterlin derivatives with α,β-unsaturated carbonyl-thiophene groups in fragment A

Pham The Chinh, Pham Thi Tham, Nguyen Van Tuyen

Abstract


Hemiasterlin, an antimitotic tripeptide, exhibits cytotoxicity in the nanomolar range against a variety of cultured human and murine cell lines. For this reason, the synthesis of new hemiasterlin derivatives has attracted a lot of interest in the organic chemistry community recently. In this article, we synthesized new simplified derivatives of hemiasterlin in which the α,α-dimethylbenzylic group in fragment A is replaced by α,β-unsaturated  carbonyl-thiophene group. These new compounds will be prepared by classical peptide coupling approach between the carboxylic acid fragments A 12 and dipeptide 13. We expect that this derivative will possess interesting biological activities due to the high reactivity of the α,β-unsaturated  carbonyl group as Michael receptor with biological nucleophiles, such as DNA, RN5A, and enzymes.

Keywords.Synthesis, hemiasterlin, α,β-unsaturated; tripeptides, nanomolar.


Keywords


Synthesis, hemiasterlin, α,β-unsaturated; tripeptides, nanomolar

References


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