Kihira K, Morioka Y, Hoshita T
J Lipid Res. 1981 Nov;22(8):1181-7.
(22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids were synthesized, starting from chenodeoxycholic acid, in order to establish the chemical structure of haemulcholic acid, which has been found in certain fish as the major bile component. Oxidative decarboxylation of diformoxylated chenodeoxycholic acid with lead tetraacetate yielded 24-nor-5 beta-chol-22-ene-3 alpha, 7 alpha-diol, which was hydroxylated to form a mixture of (22R and 22S)-24-nor-5 beta-cholane-3 alpha, 7 alpha, 22,23-tetrols. Lead tetraacetate oxidation of the mixture yielded 3 alpha, 7 alpha-dihydroxy-23,24-dinor-5 beta-cholan-22-a1. A Reformatsky reaction of the dihydroxydinorcholanal with bromoacetate resulted in the formation of a mixture of (22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids. The bile acids epimeric at C-22 were resolved by silica gel column chromatography, and their configurations of C-22 were assigned by a modification of Horeau's method and 13C-nuclear magnetic resonance spectroscopy. By direct comparison with synthetic bile acids, the naturally occurring haemulcholic acid was shown to be (22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acid.
以鹅去氧胆酸为起始原料合成了(22R和22S)-3α,7α,22-三羟基-5β-胆烷-24-酸，目的是确定在某些鱼类中作为主要胆汁成分发现的鲷胆酸的化学结构。用四乙酸铅对二甲醛化鹅去氧胆酸进行氧化脱羧反应，得到24-降-5β-胆-22-烯-3α,7α-二醇，将其羟基化形成(22R和22S)-24-降-5β-胆烷-3α,7α,22,23-四醇的混合物。该混合物经四乙酸铅氧化得到3α,7α-二羟基-23,24-二降-5β-胆烷-22-醛。二羟基二降胆醛与溴乙酸进行Reformatsky反应，生成(22R和22S)-3α,7α,22-三羟基-5β-胆烷-24-酸的混合物。通过硅胶柱色谱法拆分了在C-22处的差向异构体胆汁酸，并通过改进的Horeau方法和13C核磁共振光谱确定了它们在C-22处的构型。通过与合成胆汁酸直接比较，表明天然存在的鲷胆酸为(22S)-3α,7α,22-三羟基-5β-胆烷-24-酸。
