Efficient Synthesis of ESI-09, A Novel Non-cyclic Nucleotide EPAC Antagonist

Haijun Chen; Chunyong Ding; Christopher Wild; Huiling Liu; Tianzhi Wang; Mark A White; Xiaodong Cheng; Jia Zhou

doi:10.1016/j.tetlet.2013.01.024

Efficient Synthesis of ESI-09, A Novel Non-cyclic Nucleotide EPAC Antagonist

Tetrahedron Lett. 2013 Mar 20;54(12):1546-1549. doi: 10.1016/j.tetlet.2013.01.024.

Authors

Haijun Chen¹, Chunyong Ding, Christopher Wild, Huiling Liu, Tianzhi Wang, Mark A White, Xiaodong Cheng, Jia Zhou

Affiliation

¹ Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, United States.

Abstract

A concise and efficient synthetic approach to producing a novel non-cyclic nucleotide EPAC antagonist ESI-09 and its new analogs is reported. Key features of the synthesis include a mild and reliable one-pot procedure for an isoxazole synthon, as well as a modified one-pot protocol for the cyanomethyl ketone key intermediate. The synthesis requires inexpensive starting materials and only three linear steps for the completion in a total yield of 53%.

Keywords: EPAC antagonist; ESI-09; cyanomethyl ketone; isoxazole; modified Kowalski's protocol.

Abstract

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