Preparation of 16-formylestradiol and the 16-(alpha-methylenebutanolide) derivative.
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.
Akanni
O A
OA
Department of Chemistry, University of Technology, Loughborough, Leicestershire, England.
Marples
B A
BA
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis; D000107:Acetylation; D001894:Borohydrides; D002586:Cesium; D002712:Chlorides; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D004963:Estrenes / Q000138:chemical synthesis; D004970:Estrone / Q000031:analogs & derivatives / Q000737:chemistry*; D006851:Hydrochloric Acid; D009682:Magnetic Resonance Spectroscopy
D001894:Borohydrides; D002712:Chlorides; D004963:Estrenes; C082685:16-formylestradiol; C082686:16-methoxymethylene estrone; C082687:4-(3-hydroxyestra-1,3,5(10)-tetraen-16-yl)-2-methylene-4-butanolide; D002586:Cesium; D004970:Estrone; D004958:Estradiol; C025364:sodium borohydride; C028019:cesium chloride; D015107:4-Butyrolactone; D006851:Hydrochloric Acid