Synthesis of estrogen sulfamates: compounds with a novel endocrinological profile.
Estrogen sulfamates are promising hormones by oral administration. Therefore, generally applicable and convenient methods for the multigram synthesis of these derivatives are desirable. Numerous estra-1,3,5(10)-trienes derived from estrone, estradiol. 14 alpha,15 alpha-methylenestradiol, ethinylestradiol, and estriol have been esterified with sulfamoyl chloride and N-methylsulfamoyl chloride by a novel approach involving the use of 2,6-di-tert-butylpyridines as bases and chemoselective hydroxy group protections. These pathways circumvent the nonselective formation of esters and side reactions by in situ generated azasulfenes. For toxicological and clinical studies a new synthesis of estrone sulfamate on a 100-g scale was developed using dimethylformamide as the solvent and base.
Schwarz
S
S
Division of Research and Development, Jenapharm GmbH, Jena, Germany.
Thieme
I
I
Richter
M
M
Undeutsch
B
B
Henkel
H
H
Elger
W
W
D004958:Estradiol / Q000031:analogs & derivatives / Q000737:chemistry; D004964:Estriol / Q000031:analogs & derivatives / Q000737:chemistry; D004967:Estrogens / Q000138:chemical synthesis* / Q000737:chemistry; D004970:Estrone / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013451:Sulfonic Acids / Q000737:chemistry*
D004967:Estrogens; D013451:Sulfonic Acids; D004970:Estrone; D004958:Estradiol; C005741:sulfamic acid; D004964:Estriol