TY - JOUR
T1 - Preparation of 14,15-secoestra-1,3,5(10)-trien-15-ynes, inhibitors of estradiol dehydrogenase
AU - Auchus, Richard J.
AU - Palmer, James O.
AU - Carrell, H. L.
AU - Covey, Douglas F.
N1 - Funding Information:
supported by National Institutes of Health Grants CA-23582, CA-10925, CA-06927, RR-05539, and CA-22780: by the Endowment Research Fund, the Jewish Hospital of St. Louis: and by an appropriation from the Commonwealth of Pennsylvania. D.F.C. is the recipient of Research Career Development Award CA-00829, and R.J.A. received support from National Research Service Award GM-07805, both from the National Institutes of Health. Assistance was provided by both the Washington University High Resolution NMR Facility (supported in part by NIH I SI0 RR00204 and a gift from the Monsanto Co.) and by the Washington University Mass Spectrometry Service Facility (supported by NIH RR00954).
PY - 1989
Y1 - 1989
N2 - The conversion of estrone to 14,15-secoestratrien-15-ynes, inactivators of estradiol dehydrogenase from human term placenta, is described. The optically pure precursor 7-acetoxy-octahydro-2-phenanthrenecarboxylic acid methyl ester is prepared from estrone in five steps and 40% yield. The unsubstituted propargylic secoestratriene diol, a mechanism-based inactivator of estradiol dehydrogenase, and the corresponding acetylenic ketone, an affinity label inactivator of the same enzyme, arise from the phenanthrene ester in three and four steps. The propargylic secoestratriene diol also competes with [3H]estradiol for binding to calf uterus estrogen receptor and possesses weak uterotrophic activity.
AB - The conversion of estrone to 14,15-secoestratrien-15-ynes, inactivators of estradiol dehydrogenase from human term placenta, is described. The optically pure precursor 7-acetoxy-octahydro-2-phenanthrenecarboxylic acid methyl ester is prepared from estrone in five steps and 40% yield. The unsubstituted propargylic secoestratriene diol, a mechanism-based inactivator of estradiol dehydrogenase, and the corresponding acetylenic ketone, an affinity label inactivator of the same enzyme, arise from the phenanthrene ester in three and four steps. The propargylic secoestratriene diol also competes with [3H]estradiol for binding to calf uterus estrogen receptor and possesses weak uterotrophic activity.
UR - http://www.scopus.com/inward/record.url?scp=0024399420&partnerID=8YFLogxK
U2 - 10.1016/0039-128X(89)90147-5
DO - 10.1016/0039-128X(89)90147-5
M3 - Article
C2 - 2772972
AN - SCOPUS:0024399420
SN - 0039-128X
VL - 53
SP - 77
EP - 96
JO - Steroids
JF - Steroids
IS - 1-2
ER -