A novel synthesis of 14α, 15α-methylene estradiol (J 824)

• Published in: Steroids Vol. 60; no. 4; pp. 308 - 315
• Main Authors: Siemann, Hans-J., Droescher, Peter, Undeutsch, Bernd, Schwartz, Sigfrid
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 1995; Elsevier Science
• Subjects: 14α, 15α-methylene estradiol; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; estrogens; Exact sciences and technology; hapten; Organic chemistry; Preparations and properties; steroid synthesis; Steroids; tritium labeling; estrogens; 14α, 15α-methylene estradiol; steroid synthesis; tritium labeling; hapten; Pentacyclic compound; Sonochemical reaction; Steroid; Stereoselectivity; Radiolabelling; Regioselectivity; Estrogen; Phenols; Tritium; Aromatic compound; Hydrogen Isotopes; Hapten
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/0039-128X(94)00046-F

A novel approach to the synthesis of the orally active estrogen 14α, 15α-methylene estradiol ( 8, J 824) is described, starting with 3-methoxy-estra-1,3,5(10),8,14-pentaen-17α-ol( 5). The 14α, 15α-methylene bridge was sonochemically introduced by regioselective and stereoselective Simmons-Smith methylenation of the 14-double bond. Birch reduction of the 8-double bond provided the desired 8β-H. 9α-H steroid, whereas ionic hydrogenation afforded the 8β-H, 9β-H isomer, together with an epimerization of the 17α-hydroxy group. Oxidation of the Birch product yielded the corresponding 17-oxo steroid, which gave the title compound by diborane reduction. For radioimmunoassay development the 6-(O-carboxymethyl)-oximino derivative of 8 was prepared as hapten and the 2-hydroxy derivative of 8 was synthesized as a potential metabolite of 8, and 8 was tritium labeled as well.