Cholic acid molecular structure

FIGURE 7.12 Cholic acid. Its 11 chirality centers are those carbons at which stereochemistry is indicated in the structural drawing at the left. The molecular model at the right more clearly shows the overall shape of the molecule. 

Figure 26.13 Expression for three-axial chirality of cholic acid molecule, (a) A molecular structure of cholic acid, (b) a space-filling model of cholic acid with the three-axial chirality expression, as in the case of (c) a vertebrate amimal.

With this information in hand, it seemed reasonable to attempt to use force field methods to model the transition states of more complex, chiral systems. To that end, transition state.s for the delivery of hydrogen atom from stannanes 69 71 derived from cholic acid to the 2.2,.3-trimethy 1-3-pentyl radical 72 (which was chosen as the prototypical prochiral alkyl radical) were modeled in a similar manner to that published for intramolecular free-radical addition reactions (Beckwith-Schicsscr model) and that for intramolecular homolytic substitution at selenium [32]. The array of reacting centers in each transition state 73 75 was fixed at the geometry of the transition state determined by ah initio (MP2/DZP) molecular orbital calculations for the attack of methyl radical at trimethyltin hydride (viz. rsn-n = 1 Si A rc-H = i -69 A 6 sn-H-C = 180°) [33]. The remainder of each structure 73-75 was optimized using molecular mechanics (MM2) in the usual way. In all, three transition state conformations were considered for each mode of attack (re or ) in structures 73-75 (Scheme 14). In general, the force field method described overestimates experimentally determined enantioseleclivities (Scheme 15), and the development of a flexible model is now being considered [33]. 

A macrocyclic resorcin[4]arene with four hydrophobic substituents in the axial position provides an ion-conducting molecular pore by tail-to-tail dimerization.Because the pore size and characteristics of the entry way are defined explicitly by the molecule, only one conductance level is observed. The relatively simple structure is amenable to systematic structural modifications and is, therefore, appropriate in establishing the structure-function relationships. When a methyl ether derivative of cholic acid was employed as the axial substituent,the conductance was increased by 50% to 9.9 pS, compared with the value 6.1 pS observed for 1 with simple alkyl substituents. The cation and anion selectivity ratio Pk/Pc was 20 for 2. showing a significantly larger selectivity factor compared to 8 for 1. A hydrophilic molecular plane of methoxy substituents certainly contributes to the increase of conductance and a higher cation and anion selectivity by the arrangement of a more hydrophilic environment at the central pore. Both ion channels exhibited moderate preferences compared to Na by a facior of ca. 3. The aromatic moiety provides a weak electric field... 

Mylius. F. Uber die cholsaure. Chem. Ber. 1887. 20, 1968. Johnson, P.L. Schaefer, J.P. The crystal and molecular structure of an addition compound of cholic acid and ethanol. Acta Crystallogr.. B 1972. 28. 3083. 

Some steroids, such as cholic acid, progesterone and testosterone were already mentioned in the chapters discussing aldehydes, ketones and carboxylic acids. The most common steroid in humans is cholesterol. Although the compound has been discovered in the eighteenth century its complete molecular structure was determined only in the middle of the last century. Cholesterol appears in most of tissues and it has a special role in the regulation of blood circulation. An imbalance of cholesterol in the organism can cause serious health problems similar to arthero-sclerosis. The cholesterol molecule, like other steroids, is formed by a particular biosynthetic pathway from the terpene precursors, squalene and lanosterol. Since cholesterol has 27 carbon atoms, 3 atoms less than the triterpene squalene (which has 30 C-atoms), 3 C-atoms are eliminated during the biosynthetic process. 

Most steroids, such as cholesterol, have all trans fusions or have olefins at a fusion (as in cholesterol or testosterone) or aromatic rings (as in estrone). Either way, the flat, fra/js-decalin shape is maintained, making these generally lipophilic molecules adopt an elongated, disk-like structure. A major role of cholesterol is to insert into and thereby stabilize cell membranes, and no doubt the molecular shape is crucial to this function. There are exceptions, such as cholic acid (a component of bile) which adopts one cis ring fusion. This cis ring fusion alters the molecular shape considerably, and also creates an interesting juxtaposition of the three hydroxyls. 

Zhang J, Junk MJN, Luo J, Hinderberger D, Zhu XX (2010) 1,2,3-Triazole-containing molecular pockets dtaived from cholic acid the influence of structure on host-guest coordination properties. Langmuir 26 13415—13421... 

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