Absolute configuration of pentahydroxy bile alcohols excreted by patients with cerebrotendinous xanthomatosis: a circular dichroism study

• Main Authors: B Dayal, G Salen, G S Tint, V Toome, S Shefer, E H Mosbach
• Format: Article
• Language: English
• Published: Elsevier 1978-02-01
• Series: Journal of Lipid Research
• Subjects: Cotton effects; epimeric bile alcohols
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520415561

The absolute configurations of the C27 pentahydroxy bile alcohols present in bile and feces of two patients with cerebrotendinous xanthomatosis (CTX) were determined by circular dichroism (CD) spectroscopy. The CD spectra of 5β-cholestane-3α,7α,12α,24α,25-pentol in the presence of Eu(fod)3 [tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato) europium (III)] exhibited a negative Cotton effect and was assigned to 24R absolute configuration. Conversely, 5β-cholestane-3α,7α,12α,24β,25-pentol showed a strong positive Cotton effect and was assigned the 24S configuration. These assignments were based upon comparison with a model compound, 5-cholestene-3β,24(R),25-triol, whose single-crystal X-ray structure has been determined. The importance of these data is to establish a structural mechanism for the conversion of 5β-cholestane-3α,7α,12α,24S, 25-pentol rather than 5β-cholestane-3α,7α,12α,24R, 25-pentol into cholic acid in man as well as in animals.