A novel synthesis of 14 alpha, 15 alpha-methylene estradiol (J 824).
A novel approach to the synthesis of the orally active estrogen 14 alpha,15 alpha-methylene estradiol (8, J 824) is described, starting with 3-methoxy-estra-1,3,5(10),8,14-pentaen-17 alpha-ol (5). The 14 alpha, 15 alpha-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 8 beta-H, 9 alpha-H steroid, whereas ionic hydrogenation afforded the 8 beta-H, 9 beta-H isomer, together with an epimerization of the 17 alpha-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.
Division of Research and Development, Jenapharm GmbH, Germany.
H J
HJ
Siemann
P
P
Droescher
B
B
Undeutsch
S
S
Schwarz
D002396:Catechols / Q000737:chemistry / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D045166:Estradiol Congeners / Q000138:chemical synthesis*; D006241:Haptens / Q000737:chemistry; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D006914:Hydroxysteroids / Q000737:chemistry; D009153:Mutagens; D010084:Oxidation-Reduction; D014316:Tritium; D015032:Zinc / Q000737:chemistry
D002396:Catechols; D045166:Estradiol Congeners; D006241:Haptens; D006847:Hydrocarbons, Iodinated; D006914:Hydroxysteroids; D009153:Mutagens; D014316:Tritium; C050886:14,15-methylene estradiol; C027946:methylene iodide; D004958:Estradiol; D015032:Zinc; C034221:catechol