Molecules 2012, 17(2), 2091-2102; doi:10.3390/molecules17022091
Communication

Total Synthesis of Flocoumafen via Knoevenagel Condensation and Intramolecular Ring Cyclization: General Access to Natural Products

1,†, 2,†, 2, 2, 2, 3,* email and 2,* email
Received: 4 January 2012; in revised form: 9 February 2012 / Accepted: 14 February 2012 / Published: 21 February 2012
(This article belongs to the Section Organic Synthesis)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.
Keywords: flocoumafen; Knoevenagel condensation; tetralone; 2D NMR analysis; computer simulation
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MDPI and ACS Style

Jung, J.-C.; Lim, E.; Lee, Y.; Min, D.; Ricci, J.; Park, O.-S.; Jung, M. Total Synthesis of Flocoumafen via Knoevenagel Condensation and Intramolecular Ring Cyclization: General Access to Natural Products. Molecules 2012, 17, 2091-2102.

AMA Style

Jung J-C, Lim E, Lee Y, Min D, Ricci J, Park O-S, Jung M. Total Synthesis of Flocoumafen via Knoevenagel Condensation and Intramolecular Ring Cyclization: General Access to Natural Products. Molecules. 2012; 17(2):2091-2102.

Chicago/Turabian Style

Jung, Jae-Chul; Lim, Eunyoung; Lee, Yongnam; Min, Dongguk; Ricci, Jeremy; Park, Oee-Sook; Jung, Mankil. 2012. "Total Synthesis of Flocoumafen via Knoevenagel Condensation and Intramolecular Ring Cyclization: General Access to Natural Products." Molecules 17, no. 2: 2091-2102.

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