SYNTHESIS OF NOVEL 21-TRIFLUOROPREGNANE STEROIDS - INHIBITORS OF 17-ALPHA-HYDROXYLASE 17,20-LYASE (17-ALPHA-LYASE)/

Novel 21-trifluoropregnenolone (6), 21-trifluoroprogesterone (7) and r elated compounds 4a and 8 have been synthesized in high yields from 3 beta-acetoxyandrost-5-ene-17 beta-carbaldehyde (3). The key reaction w as the conversion of 3 into the 21-trifluoromethyl-20-alcohol as a dia stereomeric mixture (4) by trifluoromethyltrimethylsilane (TMS-CF3) in the presence of tetrabutylammonium fluoride (TBAF). All compounds, in cluding 6 and 7, were unambiguously characterized by IR, H-1 and F-19 NMR, high-resolution mass spectrometry (HRMS), and elemental analysis. On this basis, we concluded that the only report of an earlier synthe sis of 6 and 7(13) is erroneous. Enzyme inhibition studies showed that 20 xi-hydroxy-21-trifluoropregn-4-en-3-one (8) is a potent inhibitor (IC50 value = -0.6 mu M) of rat 17 alpha-hydroxylase/17,20-lyase. (C) 1997 by Elsevier Science Inc.