INHIBITORS OF STEROL SYNTHESIS - TRITIUM-LABELED 26-HYDROXYCHOLESTEROL OF HIGH SPECIFIC ACTIVITY FROM A BY-PRODUCT OF THE CLEMMENSEN REDUCTION OF DIOSGENIN

(25R)-26-Hydroxycholesterol (I) was synthesized in six steps from (22Z ,25R)-cholesta-5,22-diene-3 beta,26-diol (II) in 31% overall yield. Th e 26-tert-butyldiphenylsilyl ether of II was converted via its 3 beta- tosylate to (22Z,25R)-6 beta-methoxy-26-(tertbutyldiphenylsilyloxy) -3 alpha,5-cyclo-5 alpha-cholest-22-ene (V). Removal of the 26-silyl gro up of V gave (22Z,25R)-6 beta-methoxy-3 alpha,5-cyclo-5 alpha-cholest- 22-en-26-ol, which was hydrogenated over platinum oxide and then hydro lyzed to I. Catalytic reduction in the presence of deuterium or tritiu m gas gave [H-2]-I or [H-3]-I, respectively. Analysis of the [H-2]-I b y mass spectrometry showed that all the deuterium was located in the s terol side chain, mainly as d(2), d(3), and d(4) species. The H-2 and C-13 nuclear magnetic resonance (NMR) spectra of[2H]-I indicated that most of the deuterium was located at C-22 and C-23, with lesser amount s at C-24 and minor amounts at C-20, C-21, C-25, and C-27. NMR spectra of [H-2]-I and its alpha-methoxy-alpha-(trifluoromethyl)phenylacetate diester showed no detectable 20S epimer and similar to 2% of the 25S epimer. The [H-3]-I was prepared analogously to [H-2]-I using carrier- free tritium and showed a specific activity of 16.9 Ci/mmol. All synth etic intermediates were characterized fully by H-1 and C-13 NMR, and r epresentative H-1-H-1 coupling constants are given for the ring A prot ons of i-steroids. - Ni, Y., A. Kisic, W. K. Wilson, and G. J. Schroep fer, Jr. Inhibitors of sterol synthesis. Tritium-labeled 26-hydroxycho lestero1 of high specific activity from a byproduct of the Clemmensen reduction of diosgenin.