Conformational diastereomers enantiomers

Problem 9.17 Give your reasons for selecting the isomers of dimethylcyclohexane shown in Figs. 9-8 to 9-12 that exist as (a) a pair of configurational enantiomers, each of which exists in one conformation (ft) a pair of conformational diastereomers (c) a pair of configurational enantiomers, each of which exists as a pair of conformational diastereomers (d) a single conformation (c) a pair of conformational enantiomers. ... 

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... 

Butane exists as three conformational isomers, one anti and two gauche (Sec. 3.5). The gauche conformers, II and III, are mirror images of each other, and hence are (conformational) enantiomers. Conformers I and II (or I and III) are not mirror images of each other, and hence are (conformational) diastereomers. 

For convenience, we laid down (Sec. 4.20) the following ground rule for discussions and problems in this book unless specifically indicated otherwise, the terms stereoisomers," ""enantiomers," and ""diastereomers" will refer only to configurational isomers, including geometric isomers, and will exclude conformational isomers. The latter will be referred to as conformational isomers," con-formers, conformational enantiomers, and conformational diastereomers. ... 

To summarize, then, 1,2-dimelhyIcycIohexane exists as a pair of (configurational) diastereomers the cis- and trans-iaomers. The m-isomer exists as a pair of conformational enantiomers. The irans-homcr exists as a pair of configurational enantiomers, each of which in turn exists as two conformational diastereomers (axial -axial and equatorial-equatorial). 

Stereoisomers also include conformational isomers, in which different isomers are generated through rotations about bonds. Conformational isomers are often called con-formers. Eclipsed and staggered ethane are typical examples. Note that a conformational isomer need not be an energy minimum— the eclipsed conformation of ethane is an energy maximum, for example. Conformational isomers can be either enantiomeric or diastereomeric.The two gauche forms of butane are conformational enantiomers, but the gauche and the anti forms of butane are conformational diastereomers (Rg. 4.57). 

If compounds have the same topology (constitution) but different topography (geometry), they are called stereoisomers. The configuration expresses the different positions of atoms around stereocenters, stereoaxes, and stereoplanes in 3D space, e.g., chiral structures (enantiomers, diastereomers, atropisomers, helicenes, etc.), or cisftrans (Z/E) configuration. If it is possible to interconvert stereoisomers by a rotation around a C-C single bond, they are called conformers. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Consider the stereochemical relationships between these flexible stereoisomers. A flexible molecule is chiral only if each of its conformers is chiral and if no two conformers are mirror images. Which, if any, of the stereoisomers are chiral Rexible chiral molecules are enantiomers only if each of their conformers are mirror-images. Which, if any, of the stereoisomers are enantiomers and which are diastereomers ... 

Now, consider the physical properties of these stereoisomers. Enantiomers should have many of the same physical properties, such as energy and dipole moment, but diastereomers should not. Obtain the energy of each conformer and use equation (1) to calculate the composition of a large sample of each stereoisomer at 298 K. Then, obtain the dipole moment of each conformer and use equatiori (2) to calculate the dipole moment of a large sample of each stereoisomer at 298 K. Do enantiomers have the same dipole moment Do diastereomers have different dipole moments ... 

It must be kept in mind that the ( )-diastereomer is a mixture of enantiomers that were not separable by reverse phase HPLC. Since the method for separation of (+)- and meso-diastereomers (reverse phase HPLC, C-18 column) is based on the difference in conformation between isomers (related ultimately to their differential attraction to the column), it is unlikely that the two enantiomers of the (+ )-diastereomer have different conformations at the air-water interface. It is not known, however, how the energetics of compression and expansion will differ for films cast from either R,R or S,S enantiomer from those cast from the racemic mixture. 

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