Chiral centers, reducing number

The degree of control of stereochemistry that is necessary depends on the nature of the molecule and the objective of the synthesis. The issue becomes of critical importance when the target molecule has several stereogenic centers, such as double bonds, ring junctions, and chiral centers. The number of possible stereoisomers is 2", where n is the number of stereogenic centers. Failure to control stereochemistry of intermediates in the synthesis of a compound with several centers of stereochemistry will result in a mixture of stereoisomers, which will, at best, lead to a reduced yield of the desired product and may generate inseparable mixtures. 

Section 7 12 For a particular constitution the maximum number of stereoisomers is 2" where n is the number of structural units capable of stereochemical variation—usually this is the number of chirality centers but can include E and Z double bonds as well The number of stereoisomers is reduced to less than 2" when there are meso forms... 

Another route to a methyl-branched derivative makes use of reductive cleavage of spiro epoxides ( ). The realization of this process was tested in the monosaccharide series. Hittig olefination of was used to form the exocyclic methylene compound 48. This sugar contains an inherent allyl alcohol fragmenC the chiral C-4 alcohol function of which should be idealy suited to determine the chirality of the epoxide to be formed by the Sharpless method. With tert-butvl hydroperoxide, titanium tetraisopropoxide and (-)-tartrate (for a "like mode" process) no reaction occured. After a number of attempts, the Sharpless method was abandoned and extended back to the well-established m-chloroperoxybenzoic acid epoxida-tion. The (3 )-epoxide was obtained stereospecifically in excellent yield (83%rT and this could be readily reduced to give the D-ribo compound 50. The exclusive formation of 49 is unexpected and may be associated with a strong ster chemical induction by the chiral centers at C-1, C-4, and C-5. 

These adverse conditions have elicited considerable efforts to reduce the number of chiral centers as well as hydroxyl groups with the simultaneous introduction of useful functional groups (10, 13-15). One approach involves the shortening of the aldose carbon chain, or, more simply, its bisection, as exemplified by the use of D-mannitol-derived 2,3-Oisopropylidene-D-glyceraldehyde. Whilst this product and its L-ascorbic acid-derived enantiomer have developed into popular enantiopure three-carbon synthons (16), it may be objected that the photosynthetic achievement of Nature which graciously provides us with six-carbon compounds, is utilized rather inefficiently, clearly pointing towards elaboration of synthons from sugars with retention of the carbon chain. 

Minor amounts of the further dehydrogenated estranes equilin (9-1) and equilenin (9-2) are to be found in pregnant mare s urine (Scheme 3.9). The chiral centers at Cg and C9, it should be noted, have been replaced by trigonal carbon atoms devoid of chirality in equilenin. The reduced number of possible enantiomers of 9-2 led to the selection of this compound as the target for an early total synthesis. 

By arbitrarily assigning a particular configuration to the chirality center at C-5, Fischer realized that he could determine the configurations of C-2, C-3, and C-4 relative to C-5. This reduces the number of structural possibilities to the eight that we now call D-hexoses. 

When a molecule has two chiral centers that are identically substituted, the number of stereoisomers is reduced from four to three, as is well known for the case of tartaric acid. The three stereoisomers are the d and l forms (enantiomers) and the diastereomeric meso form. The meso form is superimposable on its mirror image, since it has a plane of symmetry and is achiral and optically inactive. The three possible stereoisomers of tartaric acid are shown below ... 

Certain molecules containing two or more chiral centers have special symmetry properties that reduce the number of stereoisomers to fewer than the maximum number predicted by the 2" rule. One such molecule is 2,3-dihydroxybutanedioic acid, more commonly named tartaric acid. 

Figure 1. Chemical structures of lipid A-diphosphate (A) and two antagonistic lipid A-diphosphate molecules, (B and C). Lipid A-diphosphate from E. coli is a 1,4-di-phosphorylated P-1,6-linked D-glucosamine disaccharide with four residues of amide-and esterified R-(-)-3-hydroxy fatty acids ( denotes the chiral centers in the hydroxy fatty-acid esters, apart form the chiral and epimeric carbons in the disaccharide moieties which are not marked). The antagonistic lipid A-diphosphate molecules shown in (B) and (C) contain the same disaccharide as in (A) however, they differ in the number anchored carbohydrate positions and the number of chiral fatty-acid chains but the chain lengths is the same (C J. The corresponding monophosphate of lipid A is only phosphorylated at the reducing end of the disaccharide.

The molecular helices and propellers discussed above contain no center of chirality, and the P and M nomenclature is thus the only way of describing their absolute configuration. This nomenclature, however, is also applicable to some series of chiral compounds which display several centers of chirality. As will be discussed in Section 6, the presence in a molecule of two or more centers of chirality usually implies the existence of several stereoisomers, but steric reasons may reduce down to two the possible number of stereoisomeric forms. Thus, 2,3-epoxycyclohexanone contains two asymmetric carbon atoms, but for steric reasons only two stereoisomers, namely the (2S 3S)-(—)- and the (2/ 3/J)-( + )-enantiomer, exist the former is depicted in diagram XL [49]. 

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