Macrocyclic ketone analogues of halichondrin B

This paper is dedicated to memory of Bruce F. Wels, our friend and colleague
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Abstract

Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.

Graphical abstract

Synthesis and SAR studies of structurally simplified analogues of marine natural product halichondrin B resulted in the discovery of E7389, a new potential antitumor agent currently undergoing Phase I clinical trials.

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