Methyl cholate

Cholic acid may be converted in several steps into the 3,9-epoxy-carboxyIic acid (246) which has the ABC ring system of batrachotoxin. The synthesis of 24-nor-5a-cholic acid from methyl cholate involved the Barbier-Wieland degradation of the side-chain and treatment of the resultant 24-nor-5/3-cholic acid with Raney nickel. A major product of this reaction was the 5a-3-oxo-compound (247) which... 

Cyclodextrin-substituted molecular channel approaches have now been extended to include acyl substituents through a covalent bond formation. Stearoyl and methyl cholate-substituted cyclodextrins 10 and 11, respectively, have been synthesized. It may be worthwhile commenting on the molecular design of methyl cholate-substituted a-cyclodextrin. All of the ether groupings are convergent at the inner side of the steroidal backbone of a bent structure to make the molecule amphiphilic. Once the cyclodextrin derivative is incorporated into the membrane phase, it may easily be expected that the ether parts are assembled inside the channel in the sea of hydrophobic lipid molecules and the hydrophobic steroidal skeletons cover its outside to stabilize the inner hydrophilic pore (Figure 13). 

As expected, axial OH groups were easier to differentiate from equatorial ones than equatorial OH groups from one another. In the case of methyl cholate 66a, a standard reagent (pyridine, 50) does a good job. But in the glucose derivative 67a, the two equatorial OH groups are much more similar to one another. Therefore it is not surprising that they react with almost the same rate in the uncatalyzed reaction. When pyridine (50) was used as catalyst, the acylation of the 2-position (67c) was preferred by a factor of 4 but also a bis-acylated product 67d was formed. Concave pyridine 3r showed the best results. With a selectivity of 9 1, the 2-acylated product 67c was formed and no diacylated product 67d could be determined. 

Acylation catalyst.2 4-Pyrrolidinopyridine (1), like N,N-dimethyl-4-pyridinamine (3, 118-119), is a very effective catalyst for acylation of sterically hindered alcohols. In a typical procedure, the alcohol is treated with a carboxylic acid anhydride and an equimolar amount of the dialkylaminopyridine at room temperature. In preparations on a larger scale, 1 eq. of triethylamine is added to bind the acid formed in the acylation. For example, methyl cholate is converted into the triacetate at room temperature within 2 hr. using 4-pyrrolidinopyridine as catalyst. Acetylation with Ac20/pyridine at room temperature affords only the 3,7-diaeetate (the 12a-hydroxyl group is axial).3 4-Dialkylaminopyridines are particularly useful catalysts for acylation of add-sensitive tertiary alcohols such as linalool (2), which can be acetylated in 80% yield by this new procedure. 

Selective conversion of methyl cholate into the 3,7-diacetate was accomplished by dissolving 50 g. of ester in 100 ml. of dioxane and 100 ml. of pyridine, cooling to room temperature, and adding 150 ml. of acetic anhydride. After standing at 26-28° for 20 hrs., 200 ml. of water was added, and the mixture warmed to effect solution... 

The prolinamide 8 is synthesized from methyl cholate. The diamide 9 containing two prolyl residues is said to fulfill the demand for cross-aldol condensation of aldehydes. ... 

Scott, J.L. Solid-vapour reactions of cholic acid and methyl cholate with acetonitrile Stmctures and reaction kinetics. J. Chem. Soc.. Perkin Trans. 2 1995. 495. 

Goonewardena, W. Miyata, M. Takemoto, K. Onedimensional inclusion polymerization of diene and vinyl monomers by using methyl cholate as a host. Polym. J. 1993. 25. 731. 

Miki. K. Masui, A. Kasai, N. Shibakami. M. Takemoto, K. Miyata, M. Stmctures of 1 1 addition compounds of methyl cholate with methanol and with 2-propanol. Acta Crystallogr., C. 1992. 48. 503. 

Hassounea H, Rhlaloub T and Vercherea J F (2009), Mechanism of transport of sugars across a supported liquid membrane using methyl cholate as mobile carrier , Desalination, 242,84-95. 

With the elucidation of the elementary formula of cholic acid, a number of investigators began to contribute toward the nature of the functional groups. Hoppe-Seyler (16), for instance, showed that cholic acid was a mono-carboxylic acid which yielded a monomethyl or monoethyl ester, that the three remaining oxygen atoms were present as hydroxyl groups and that, under proper conditions, it was possible to obtain the triacetate of methyl cholate (17). The elucidation of the structure of the bile acids was carried out by Wieland and his co-workers, beginning in 1912 (18). 

The order of reactivity of the hydroxyl groups toward acetylation or hydrolysis is Cg>>C7>Ci2. Thus methyl cholate when treated with acetyl chloride in pyridine will yield the 3-acetoxy-7,12-dihydroxy compound, then the 3,7-diacetoxy-12-hydroxy ester, and finally 3,7,12-triacetoxy methyl cholate as the severity of the reaction conditions increases. The reactivity at these positions vis-d-vis reduction or hydrogenation is also Cg>C,>Ci2. 

On the other hand, methyl allocholate and methyl cholate are not separated by crystallization (19, 19a, 47). Karavolas et al. (28) achieved a separation of 91 % of allocholic acid from cholic acid by repeated crystallization from benzene, acetone, aqueous methanol, and benzene-acetone. Final separation was effected by chromatography on Florisil. 

Kallner (66) studied the stereospecific formation of 5a steroids by the reduction of 3-keto- -derivatives with Li in liquid ammonia (Fig. 7). Oppenauer oxidation of methyl cholate provided the 3-dehydro derivative IX which was hydrolyzed to the free acid (X) and the product dehydrogenated with Se02 to the dihydroxy-3-ketochol-4-enoic acid (XI). The unsaturated acid (XI) was reduced with Li in liquid ammonia, and the product methylated to provide a mixture from which XII was separated from the desired ketone... 

Selective acetylation at positions 3a and 7a of methyl cholate (XXVa, 25 g) is effected in benzene (125 ml) containing acetic anhydride (30 ml) and pyridine (30 ml). The mixture is kept at room temperature for 24 hr and then poured into ice water in a separatory funnel. The benzene layer is washed... 

A somewhat better yield of 7-ketoIithocholic acid can be obtained by an alternative procedure, in which the 3a-hydroxyl group of chenodeoxy-cholic acid is protected from chromic oxidation by the formation of succinic ester. The procedure of Heusser and Wuthier (53) for the preparation of 3a-succinic ester of methyl cholate requires the use of succinic anhydride in pyridine. The use of pyridine is obnoxious in many respects, and it is omitted in the following modified procedure for the preparation of 7-ketolithocholic acid. 

The values in the two columns refer to chromatoplates developed 14 cm from the starting line. Mobilities are given relative to that of methyl cholate. Absolute mobility of this compound 2.5 cm. The values in the right column are those obtained after treatment of the compounds listed in the left column with BF3- methanol (see 131). 

Deoxycholic acid Methyl cholate Silica gel G Silica gel G... 

Broderick, S., Davis, A. P. and Williams, R. P. (1998) The Triamino-analogue of Methyl Cholate A Facial Amphiphile and Scaffold with Potential for Combinatorial and Molecular Recognition Chemistry, Tetrahedron Lett. 39, 6083-6086. 

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