Next Article in Journal
In Vitro Antibacterial and Time-Kill Assessment of Crude Methanolic Stem Bark Extract of Acacia mearnsii De Wild against Bacteria in Shigellosis
Previous Article in Journal
Regulated Expressions of MMP-2, -9 by Diterpenoids from Euphorbia formosana Hayata
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,*  and 2,*
Received: 4 January 2012 / Revised: 9 February 2012 / Accepted: 14 February 2012 / Published: 21 February 2012
(This article belongs to the Section Organic Synthesis)
Download PDF [316 KB, 18 June 2014; original version 18 June 2014]

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 flocoumafen; Knoevenagel condensation; tetralone; 2D NMR analysis; computer simulation
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.

Supplement

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

Cited By

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert