Cholesterol chiral center

Cholesterol is derived from the steroid skeleton by adding a hydroxyl group at C3, methyl groups at CIO and C13, an eight-carbon alkyl group at C17, and introducing a double bond between carbon atoms 5 and 6.1 have taken some pains to indicate the stereochemistry at each of the eight chiral centers in this molecule its shape matters. 

Exercise 5-4 How many chiral centers are evident in the structure of cholesterol Identify them by the number of the carbon atom. 

Some of the CH2 crosspeaks are degenerate, meaning that the two protons have the same ll chemical shift (d and r). This can be a coincidence, but it is more likely to happen in a flexible chain, so we would suspect carbons 22-24 in cholesterol, although 22 is less likely because it is next to a chiral center. 

Cholesterol belongs to a class of natural products called steroids, which are characterized by the presence of one five-membered and three six-membered rings fused together in the same pattern as cholesterol. This structure has eight chirality centers, so there are 2s = 256 stereoisomers. Only one of these is cholesterol. Another is the enantiomer of cholesterol, and the other 254 are diastereomers of cholesterol. Of the 256 possibilities, nature produces only one cholesterol. 

Chiral centers, more than one, lljf Chiral stereomer, 69 Cholesterol, chirality in, 81 Cinnamaldehyde, 328 Cis-trans interconversion, 111 Cis-trans isomerism, in cyclic compounds, 163 Claisen condensation, 394 rearrangement, 439 Cleavage, oxidative, 117 Clemmensen reduction, 219, 311 Coenzyme A, 354 Collins reagent, 264 Collision frequency, 39 Configuration, 72 relative, 76 Conformation, 51 Conformational diastereomers, 78 enantiomers, 78 stereomers, 78... 

The choice of an irreversible color-induction reaction requires more ingenuity and greater care in execution. If the extended molecular unsaturation required to produce the color is too exhaustive, the chiral centers could be systematically eliminated, and must be avoided. Reaction conditions are much more unfavorable. Reagents are generally toxic and corrosive, and reaction conditions are anhydrous, e.g., the measurement of plasma cholesterol using a modified Chugaev reagent. ... 

The major rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A reductase (HMG-CoA reductase), has been a therapeutic target for many research groups. A synthesis of the functionalized thiophene 172, prepared for its biological activity, illustrates the utility of 162 for the introduction of one of the hydroxy chiral centers present in the molecule. This chiral center is then exploited for the introduction of the second chiral hydroxy center. Treatment of aldehyde 169 with the double anion of 162 at —95 °C in THF affords as the major product 170 (98.8 1.2). Treatment of the adduct with excess tert-butylacetate enolate at — 78 °C followed by acidic work-up furnishes the jS-hydroxyketone 171 in 86% isolated yield. Chelation-controlled reduction of the ketone, accomplished by initial complexation of the ketone and the hydroxy group with triethylborane followed by sodium borohydride addition, provides the desired dihydroxyester 172 (Scheme 39) [47]. 

Fig. 12-4 Cholesterol and some structural nomenclature. (A) Cholesterol structure showing key aspects of bonding at chiral centers. (B) The numbering system used in the 4-ring structure.

The compounds shown here are widely used in medicine. Ampicillin is an antibiotic, and simvastatin is a cholesterol-lowering drug. Locate the chirality centers in each. 

In some cases, particularly natural products with many chiral centers, it is convenient to name the mirror image of a substance having a trivial or common name by simply indicating that the structure is the enantiomer (en t-) of the natural compound. The enantiomer of cholesterol (67) is therefore... 

So far we have mainly considered chiral molecules that contain only one chirality center. Many organic molecules, especially those important in biology, contain more than one chirality center. Cholesterol (Section 23.4B), for example, contains eight chirality centers. (Can you locate them ) We can begin, however, with simpler molecules. Let us consider 2,3-dibromopentane, shown here in a two-dimensional bond-line formula. 2,3-Dibromopentane has two chirality centers ... 

Cholesterol, having eight chirality centers, hypothetically could exist in 2 (256) stereoisomeric forms, yet biosynthesis via enzymes produces only one stereoisomer. 

Part of the difficulty in assigning an absolute structure to cholesterol is that cholesterol contains eight tetrahedral chirality centers. This feature means that 2, or 256, possible stereoisomeric forms of the basic structure are possible, only one of which is cholesterol ... 

Designate with asterisks the eight chirality centers of cholesterol. 

The natural occurrence of 24,25- and 25,26-dihydroxyvitamin D metabolites has led to studies of their synthesis and configurational assignment via the initial preparation of the correspondingly substituted cholesterol derivatives. Initial approaches to these compounds were carried out on oxidized forms of A24- or A25-steroids (98, 142, 154, 155, 169, 170) or by reduction of the ketol (46) (5i). In these cases, almost equal amounts of the diasteroisomeric epoxides or diols were obtained because the newly formed asymmetric position was too distant from a chiral center (i. e., at C-17 or C-20) for stereoselective induction. 

Look up the formula diagram for cholesterol, (a) How many optical isomers are allowed by the chiral centers (b) Are the isomers anticipated in nature with equal likelihood in nature Please discuss. 

Label the eight chiral centers in cholesterol. How many stereoisomers are possible for a molecule with this many chiral centers ... 

Cholesterol has eight chiral centers, and a molecule with this number of chiral centers can exist as 2, or 256, stereoisomers (128 pairs of enantiomers). Only one of these stereoisomers is known to exist in nature the stereoisomer with the configuration shown in Figure 26.8. 

Cholesterol has eight chirality centers, giving rise to a family of 2 stereoisomers (256 stereoisomers). The specific stereoisomer shown has only one enantiomer and 254 diastereomers, although the structure shown is the only stereoisomer produced by nature. 

Atorvastatin is sold under the trade name LIpItor and is used for lowering cholesterol. Annual global sales of this compound exceed 13 billion. Assign a configuration to each chirality center in atorvastatin ... 

Molecular models are much more difficult for type C3, where the chiral centers are located inside the mesogenic axis. Small changes of the orientation of the main axis of the molecule can cause large changes of the chiral properties, thus, they are very sensitive to small changes of pressure, temperature, or concentration. Inversion of the helix [33] or of the spontaneous polarization [34] is quite common. Even cholesterol chloride and iodide have a different sense of the cholesteric helical pitch [36], and the first observation of helix inversion was done with a steroid compound [37]. 

A newer type of cholesterol drugs is based upon the direct inhibition of the uptake of free cholesterol from the small intestine. Perhaps the most prominent in this class is ezetimibe (Zetia , Schering-Plough Corporation). Note that there are three chiral centers and therefore 2 or 8 possible stereoisomers. The stereoisomers exhibit different cholesterol absorption inhibition and therefore a single stereoisomer, as depicted, is administered [18]. 

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