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Synthesis 2007(15): 2397-2403  
DOI: 10.1055/s-2007-983768
PAPER
© Georg Thieme Verlag Stuttgart · New York

Selective Synthesis of ent-15-epi-F 2t -Isoprostane and a Deuterated Derivative

Manami Shizuka, Marc L. Snapper*
Department of Chemistry, Eugene F. Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA
Fax: +1(617)5521442; e-Mail: marc.snapper@bc.edu;
Further Information

Publication History

Received 8 March 2007
Publication Date:
12 July 2007 (online)

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Abstract

Isoprostanes are an emerging class of lipid metabolites whose physiological properties are not well understood. The selective synthesis of ent-15-epi-F2t-isoprostane, an isomer active in a preliminary screening assay is described. The synthesis features a regioselective cross-metathesis on an enantiomerically enriched divinyl cyclopentyl intermediate to selectively differentiate the side-chains of the target. The route provides the isoprostane, as well as a d 4-labeled analogue, in 14 steps from readily available starting material­s.

Key words

asymmetric synthesis - metathesis - olefination - lipids

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17

Regioselectivity was determined by COSY NMR.

19

Selectivity was determined by 1H NMR (estimated detection limits of 20:1) by comparison with authentic samples of each diastereomer.

24

More details on the setup and results of the GC/MS detection assay may be obtained by contacting the authors.

27

Data shown for a 74% yield reaction. Yields range from
70-90%, depending on catalyst purity.

28

This compound is the major isomer; however, it is in a mixture of isomers of lower deuterium incorporation.