Dimer-selective retinoid

The short and efficient stereospecific synthesis of the dimer-selective retinoid X receptor modulator was carried out in the laboratory of L.G. Hamann. The synthetic sequence began with the von Pechmann reaction between tetramethyltetrahydronaphthol and ethyl acetoacetate in 75% sulfuric acid solution. The desired coumarin was formed regioselectively and isolated in high yield. 

Hamann, L. G. An Efficient, Stereospecific Synthesis of the Dimer-Selective Retinoid X Receptor Modulator (2E,4E,6Z)-7-[5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2- (n-propyloxy)naphthalen-3-yl]-3- methylocta-2,4,6-trienoic Acid. J. Org. Chem. 2000, 65, 3233-3235. 

Martin, G., Poirier, H., Hennuyer, N., Crombie, D., Fruchart, J. C., Heyman, R. A., Besnard, P., and Auwerx, J. (2000). Induction Of The Fatty Acid Transport Protein 1 and Acyl-Coa Synthase Genes by Dimer-Selective Rexinoids Suggests That the Peroxisome Proliferator-Activated Receptor-Retinoid X Receptor Heterodimer is Their Molecular Target./ Bid. Chem. 275, 12612-12618. 

Retinoic X receptors (RXR, a, (3 and " (), also termed rexinoid receptors, are usually classified among orphan receptors, but belong to the thyroid/retinoid family. RXR is an obligatory partner dimerizing with other thyroid/retinoid receptors. RXR selectively bind the 9-cis isomer of retinoic acid, whereas RAR bind aU-tran retinoic acid as well as its 9-cis isomer. RXR selective agonists are termed rexi-noids, like bexarotene used as an antineoplastic in the treatment of cutaneous T-cell lymphoma and the cutaneous lesions of T-cell lymphomas and Kaposi s sarcoma. 

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