Synthesis and antileishmanial activity of the core structure of cristaxenicin A

Hitoshi Fumiyama; Tomoko Sadayuki; Yasutaka Osada; Yasuyuki Goto; Yoichi Nakao; Seijiro Hosokawa

doi:10.1016/j.bmcl.2016.06.061

Synthesis and antileishmanial activity of the core structure of cristaxenicin A

Bioorg Med Chem Lett. 2016 Sep 1;26(17):4355-7. doi: 10.1016/j.bmcl.2016.06.061. Epub 2016 Jul 7.

Authors

Hitoshi Fumiyama¹, Tomoko Sadayuki¹, Yasutaka Osada², Yasuyuki Goto², Yoichi Nakao³, Seijiro Hosokawa⁴

Affiliations

¹ Department of Applied Chemistry, Faculty of Advanced Science and Engineering, Waseda University, Ohkubo 3-4-1, Shinjuku, Tokyo 1658555, Japan.
² Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 1138657, Japan.
³ Department of Chemistry and Biochemistry, Faculty of Science and Engineering, Waseda University, Ohkubo 3-4-1, Shinjuku, Tokyo 1658555, Japan; Research Institute for Science and Engineering, Waseda University, Ohkubo 3-4-1, Shinjuku, Tokyo 1658555, Japan.
⁴ Department of Applied Chemistry, Faculty of Advanced Science and Engineering, Waseda University, Ohkubo 3-4-1, Shinjuku, Tokyo 1658555, Japan; Research Institute for Science and Engineering, Waseda University, Ohkubo 3-4-1, Shinjuku, Tokyo 1658555, Japan.

PMID: 27476143
DOI: 10.1016/j.bmcl.2016.06.061

Abstract

The core structure of cristaxenicin A having trans-fused dihydropyran and nine membered ring has been synthesized and evaluated the antileishmanial activity. The dihydropyran ring was synthesized by [4+2] cycloaddition reaction between an unsaturated aldehyde and a β-alkoxy-α,β-unsaturated ketone. The nine membered ring possessing α,β-unsaturated aldehyde was constructed by the intramolecular NHK reaction followed by the Mitsunobu rearrangement. The racemic core structure of cristaxenicin A was evaluated the anti-leishmanial activity with an IC50 value of 2.4μM.

Keywords: Antileishmanial; Cristaxenicin A; Nine-membered ring; Synthesis; [4+2] cycloaddition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiprotozoal Agents / chemical synthesis
Antiprotozoal Agents / chemistry
Antiprotozoal Agents / pharmacology
Diterpenes / chemical synthesis*
Diterpenes / chemistry
Diterpenes / pharmacology*
Inhibitory Concentration 50
Leishmania / drug effects*
Molecular Structure

Substances

Antiprotozoal Agents
Diterpenes
cristaxenicin A