A Practical Synthesis of the Kappa Opioid Receptor Selective Agonist (+)-5R,7S,8S-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxospiro[4,5]dec-8-yl]ben­zeneacetamide (U69,593)

Timothy McElroy; James B. Thomas; George A. Brine; Hernán A. Navarro; Jeffrey Deschamps; F. Ivy Carroll

doi:10.1055/s-2008-1032185

PAPER

A Practical Synthesis of the Kappa Opioid Receptor Selective Agonist (+)-5R,7S,8S-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxospiro[4,5]dec-8-yl]benzeneacetamide (U69,593)

Timothy McElroy^a, James B. Thomas^a, George A. Brine^a, Hernán A. Navarro^a, Jeffrey Deschamps^b, F. Ivy Carroll*^a
^a Organic and Medicinal Chemistry, Research Triangle Institute, P. O. Box 12194, Research Triangle Park, NC 27709, USA
Fax: +1(919)5418868; e-Mail: fic@rti.org;
^b Laboratory for the Structure of Matter, Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375-5341, USA

Abstract

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Abstract

A novel approach to the synthesis of the kappa opioid receptor agonist U69,593 has been developed. This approach improves upon current literature methods by substituting stable and isolable cyclic sulfates for the unstable epoxides. The new approach provides access to gram quantities of the target compound and displays excellent control of the relative stereochemistry. The absolute stereochemistry as well as biological activity of the U69,593 produced by this new method was verified using X-ray crystal structure analysis and binding assays for the kappa opioid receptor.

Key words

U69,593 - kappa opioid agonist - X-ray crystal structure - synthesis - receptors

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References

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A Practical Synthesis of the Kappa Opioid Receptor Selective Agonist (+)-5R,7S,8S-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxospiro[4,5]dec-8-yl]ben­zeneacetamide (U69,593)

A Practical Synthesis of the Kappa Opioid Receptor Selective Agonist (+)-5R,7S,8S-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxospiro[4,5]dec-8-yl]benzeneacetamide (U69,593)