Issue 7, 2005
From the journal:

Organic & Biomolecular Chemistry

Synthesis of 5′-methylenearisteromycin and its 2-fluoro derivative with potent antimalarial activity due to inhibition of the parasite S-adenosylhomocysteine hydrolase1

Chieko Takagi,a   Makoto Sukeda,a   Hye-Sook Kim,b   Yusuke Wataya,b   Saori Yabe,c   Yukio Kitade,c   Akira Matsudaa  and  Satoshi Shuto*a  

* Corresponding authors

a Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, Japan
E-mail: shu@pharm.hokudai.ac.jp
Fax: +81-11-706-4980
Tel: +81-11-706-3229

b Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama, Japan

c Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu, Japan

Abstract

5′-Methylenearisteromycin (5) and its 2-fluoro derivative 6, which were designed as antimalarial agents because of their AdoHcy hydrolase inhibition, were synthesized from D-ribose, using a stereoselective intramolecular radical cyclization as the key step to construct the carbocyclic structure. These compounds were evaluated as AdoHcy hydrolase inhibitors with the recombinant human and malarial parasite enzymes. Although 5 and 6 were both potent inhibitors of the malarial parasite AdoHcy hydrolase, the 2-fluoro derivative 6 proved to be superior due to its lower inhibitory effect on the human enzyme. In addition, 6 was identified as a potent antimalarial agent using an in vitro assay system with Plasmodium falciparum.

Graphical abstract: Synthesis of 5′-methylenearisteromycin and its 2-fluoro derivative with potent antimalarial activity due to inhibition of the parasite S-adenosylhomocysteine hydrolase1

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Article information

DOI
https://doi.org/10.1039/B418829B
Article type
Paper
Submitted
16 Dec 2004
Accepted
07 Feb 2005
First published
28 Feb 2005

Org. Biomol. Chem., 2005,3, 1245-1251

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Synthesis of 5′-methylenearisteromycin and its 2-fluoro derivative with potent antimalarial activity due to inhibition of the parasite S-adenosylhomocysteine hydrolase

C. Takagi, M. Sukeda, H. Kim, Y. Wataya, S. Yabe, Y. Kitade, A. Matsuda and S. Shuto, Org. Biomol. Chem., 2005, 3, 1245 DOI: 10.1039/B418829B

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