Configulation at C-23 in 5.BETA.-cholestane-3.ALPHA.,7.ALPHA.,12.ALPHA.,23-tetrol excreted by patients with cerebrotendinous xanthomatosis.

Chemical Synthesis of the Epimeric (23R)‐ and (23S)‐Fluoro Derivatives of Bile Acids via Horner–Wadsworth–Emmons Reaction

“…Epoxidation of 4a and 4b with m-chloroperbenzoic acid (m-CPBA) in the presence of NaHCO 3 at room temperature [16] gave the 24-nor-22,23-epoxides (5a and 5b) in good isolated yields (85 and 83 %). Subsequent oxidative-cleavage of the 22,23-epoxide ring in 5a and 5b with orthoperiodic acid (HIO 4 ) in THF at room temperature [16] afforded the corresponding C 22 23,24-dinor-22-aldehyde derivatives (6a and 6b) in isolated yields of 43 and 45 %, respectively. When 6a and 6b were subjected to the Horner-Wadsworth-Emmons reaction with triethyl 2-fluoro-2-phosphonoacetate in the presence of LiCl and 1,8-diazabicyclo [5,4,0]undec-7-ene (DBU) as base-sensitive reagents [17], the reaction proceeded smoothly to give the more thermodynamically stable (E)-isomer of the C 24 α-fluoro-α,β-unsaturated esters (7a and 7b) in reasonable isolated yields of 70 and 72 %.…”

“…The crystals contain about 1.5 molecule of water per molecule of 1b-S, likely from methanol used for recrystallization that had not been dried prior to use. Thus, the X-ray analysis provided directly the absolute configuration at C-23, in analogy with hydroxylated derivatives epimeric at C-23, C-25, C-22/C-25 or C-24/C-25 of bile acids and bile alcohols [14,[21][22][23][24], and conclusive evidence for the stereochemical assignment of 1b-S as the (23S)-configuration, which was the secondary-eluted peak in Fig. 3 (2); 1b-R was therefore assigned as (23R).…”