Preparation of 16-formylestradiol and the 16-(alpha-methylenebutanolide) derivative
1Department of Chemistry, University of Technology, Loughborough, Leicestershire, England.
Abstract:
Routes to the preparation of 16-formylestradiol are described. Estrone was converted to (E)-16-methoxymethylene estrone via the 16-hydroxymethylene estrone. Reduction of the methoxymethylene estrone with NaBH4 in the presence of CeCl3 gave 16-methoxymethylene estradiol. Deprotection by acid afforded the desired 16-formylestradiol. Attempts to prepare the 16-formylestradiol via the 16-butylthiomethylene derivative gave only 16-formylestra-1,3,5(10),16-tetraen-3-ol, and a route through the 16-dimethoxymethyl derivative gave a mixture of the 16-formyltetraen-3-ol and the 16-formylestradiol in low yield. The 16-formylestradiol was subsequently converted to the alpha-methylene lactone conjugate, 4-(3,17 beta-dihydroxyestra-1,3,5(10)trien-16-yl)-2-methylene-4-butanol ide by reaction with methyl alpha-(bromomethyl) acrylate and zinc.
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