Collect. Czech. Chem. Commun.
1992, 57, 463-471
https://doi.org/10.1135/cccc19920463
Synthesis of o-Carboranylmethyl Ethers of Steroids as Potential Target Substrates for Boron Neutron Capture Therapy
Lenka Schneiderováa, Oldřich Štroufa, Bohumír Grünera, Vladimír Pouzarb, Pavel Drašarb, Richard Hamplc and Irena Kimlovád
a Institute of Inorganic Chemistry, Czechoslovak Academy of Sciences, 160 00 Prague 6
b Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6
c Institute of Endocrinology, 116 94 Prague 1
d Chair of Radiology, Biophysics and Nuclear Medicine, Faculty of Medicine III, Charles University, 100 34 Prague 10
Abstract
o-Carboranylmethyl ethers of steroids were synthesized by insertion of steroidal 2-propynyloxy derivatives into 6,9-bis(acetonitrile)decaborane (12). This reaction afforded compounds with estrane and androstane skeleton, potentionally useful in boron neutron capture therapy of hormone-sensitive forms of cancer: 17β-o-carboranylmethyl ether of estradiol IXb (yield 14%) and 3β- and 17β-carboranylmethyl ethers of androstenediol Vb and VIIb (yield 12% and 13%, respectively). Jones oxidation afforded carboranyl derivative of androsten-17-one VIb in 75% yield. As shown by a study of insertion of 3β-(2-propynyloxy)cholest-5-ene (IVa), the low yields of the insertion reaction cannot be increased by change in the reaction conditions. The relative binding affinity of compound IXb to estrogen receptor from rat uterine and human breast tumor cytosol was 3.0 and 0.29% respectively, of that of estradiol.
