Asymmetric synthesis of the stereoisomers of 11,12,15( S)-trihydroxyeicosa-5( Z),8( Z),13( E)-trienoic acid, a potent endothelium-derived vasodilator

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 19; pp. 4987 - 4990
• Main Authors: Falck, J.R., Barma, Deb, Mohapatra, Suchismita, Bandyopadhyay, A., Reddy, Komandla Malla, Qi, Jianjun, Campbell, William
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 04.10.2004; Elsevier
• Subjects: Biological and medical sciences; Cardiovascular system; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Chromatography, High Pressure Liquid; Eicosanoic Acids - chemical synthesis; Eicosanoic Acids - chemistry; Endothelium, Vascular - metabolism; Gas Chromatography-Mass Spectrometry; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Science & Technology; Stereoisomerism; Vasodilator Agents - chemical synthesis; Vasodilator Agents - chemistry; Vasodilator agents. Cerebral vasodilators; CELLS; ARTERIES; RABBIT AORTA; 15-LIPOXYGENASE; IDENTIFICATION; Vasodilator agent; Hydroxyacid; Asymmetric synthesis; Stereospecificity; Fatty acids; In vitro; Biological activity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.07.019

The four stereoisomers 11,12,15( S)-THETA were prepared by a triply convergent, asymmetric route that exploited the stereospecific, copper mediated cross-coupling of α,β-dialkoxystannanes and the utility of dialkylthionocarbamates as orthogonal alcohol protective groups. Only 11( R),12( S),15( S)-THETA was comparable to natural material by HPLC, GC/MS, and in vitro bioassay. The four stereoisomers of the endothelial-derived vasorelaxant 11,12,15( S)-trihydroxyeicosatrienoic acid [ 1, 11,12,15( S)-THETA] were prepared by a triply convergent, asymmetric route that exploited the stereospecific, copper mediated cross-coupling of α,β-dialkoxystannanes with organic electrophiles and the utility of dialkylthionocarbamates as orthogonal alcohol protective groups. Only 11( R),12( S),15( S)-THETA was comparable to natural material by HPLC, GC/MS, and in vitro bioassay.