Stereochemistry enantiomers

Gunter Helmchen Glossary of Problematic Terms in Organic Stereochemistry, Enantiomer 1(1), vier nicht numerierte Seiten nach S. 84 (1996)... 

Another important disadvantage is the insufficient representation of stereochemistry enantiomers show exactly the same autocorrelation descriptor values. 

Compiled from E. Eliel and S.H. Wilen (1994) Stereochemistry of Organic Compounds, Wiley-Inter-science, New York, USA G. Helmchen (1996) Glossary of Problematic Terms in Organic Stereochemistry, Enantiomer 1 C.A. Challener (ed.) (2001) Chiral Intermediates, Ashgate Publishing Cointany, Burlington, USA. 

Strategy Problem 7 Synthesis of a single enantiomer. Many compounds such as pharmaceuticals, flavourings, and insect control chemicals must not only have the right relative stereochemistry but must be optically active too if tliey are to be of any use. Consider the strategy of synthesising one enantiomer ... 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

Streptirnidone is an antibiotic and has the structure shown How many diastereomers of streptimidone are possible" How many enantiomers" Using the E Z and R S descnptors specify all essential elements of stereochemistry of streptimidone... 

Fischer projections and d-l notation are commonly used to describe car bohydrate stereochemistry The standards are the enantiomers of glycer aldehyde... 

Before leaving this biosynthetic scheme notice that PGE2 has four chirality cen ters Even though arachidomc acid is achiral only the stereoisomer shown m the equa tion IS formed Moreover it is formed as a single enantiomer The stereochemistry is controlled by the interaction of the substrate with the enzymes that act on it Enzymes offer a chiral environment m which biochemical transformations occur and enzyme catalyzed reactions almost always lead to a single stereoisomer Many more examples will be seen m this chapter... 

Stereochemistry (Chapter 7) Chemistry in three dimensions the relationship of physical and chemical properties to the spatial arrangement of the atoms in a molecule Stereoelectron ic effect (Section 5 16) An electronic effect that depends on the spatial arrangement between the or bitals of the electron donor and acceptor Stereoisomers (Section 3 11) Isomers with the same constitu tion but that differ in respect to the arrangement of their atoms in space Stereoisomers may be either enantiomers or diastereomers... 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

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. 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

Next, examine the lowest-unoccupied molecular orbital (LUMO) for the cation. The components of the LUMO (its lobes ) identify locations where the cation might bond to a water molecule. How many lobes are associated with C 7 For each lobe, draw the alcohol that will be produced (show stereochemistry). How many alcohol enantiomers will form If more than one is expected, decide which wiU form more rapidly based on the relative sizes of the lobes. 

One interesting phenomenon was the effect of the boron substituent on enantioselectivity. The stereochemistry of the reaction of a-substituted a,/ -unsatu-rated aldehydes was completely independent of the steric features of the boron substituents, probably because of a preference for the s-trans conformation in the transition state in all cases. On the other hand, the stereochemistry of the reaction of cyclopentadiene with a-unsubstituted a,/ -unsaturated aldehydes was dramatically reversed on altering the structure of the boron substituents, because the stable conformation changed from s-cis to s-trans, resulting in production of the opposite enantiomer. It should be noted that selective cycloadditions of a-unsubsti-tuted a,/ -unsaturated aldehydes are rarer than those of a-substituted a,/ -unsatu-... 

One of the following molecules (a)-(d) is D-erythrose 4-phosphale, an intermediate in the Calvin photosynthetic cycle by which plants incorporate C02 into carbo- hydrates. If D-erythrose 4-phosphate has R stereochemistry at both chirality centers, which of the structures is it Which of the remaining three structures is the enantiomer of D-erythrose 4-phosphate, and which are diastereomers ... 

Most of the biochemical reactions that take place in the body, as well as many organic reactions in the laboratory, yield products with chirality centers. Fo example, acid-catalyzed addition of H2O to 1-butene in the laboratory yield 2-butanol, a chiral alcohol. What is the stereochemistry of this chiral product If a single enantiomer is formed, is it R or 5 If a mixture of enantiomers i formed, how much of each In fact, the 2-butanol produced is a racemic mix ture of R and S enantiomers. Let s see why. 

Divalent sulfur compounds are achiral, but trivalent sulfur compounds called sulfonium stilts (R3S+) can be chiral. Like phosphines, sulfonium salts undergo relatively slow inversion, so chiral sulfonium salts are configurationally stable and can be isolated. The best known example is the coenzyme 5-adenosylmethionine, the so-called biological methyl donor, which is involved in many metabolic pathways as a source of CH3 groups. (The S" in the name S-adenosylmethionine stands for sulfur and means that the adeno-syl group is attached to the sulfur atom of methionine.) The molecule has S stereochemistry at sulfur ana is configurationally stable for several days at room temperature. Jts R enantiomer is also known but has no biological activity. 

One of the most important reasons for using tosylates in S j2 reactions is stereochemical. The S]s]2 reaction of an alcohol via an alkyl halide proceeds with hvo inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol via a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.5 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships. 

The reactions of allylboronates 1 (R = H or CH3) may proceed either by way of transition state 3, in which the a-substituent X adopts an axial position, or 4 in which X occupies an equatorial position. These two pathways are easily distinguished since 3 provides 7 with a Z-olefin, whereas 4 provides 8 with an E-olefinic linkage. There is also a second fundamental stereochemical difference between these two transition states 7 and 8 are heterochirally related from reactions in which 1 is not racemic. That is, 7 and 8 arc enantiomers once the stereochemistry-associated with the double bond is destroyed. Thus, the selectivity for reaction by way of 3 in preference to 4, or via 6 in preference to 5 in reactions of a-subsliluted (Z)-2-butenylboronate 2, is an important factor that determines the suitability of these reagents for applications in enantioselective or acyclic diastereoselective synthesis. 

A similar case of enolatc-controlled stereochemistry is found in aldol additions of the chiral acetate 2-hydroxy-2.2-triphenylethyl acetate (HYTRA) when both enantiomers of double deprotonated (R)- and (S)-HYTRA are combined with an enantiomerically pure aldehyde, e.g., (7 )-3-benzyloxybutanal. As in the case of achiral aldehydes, the deprotonated (tf)-HYTRA also attacks (independent of the chirality of the substrate) mainly from the /te-side to give predominantly the t/nii-carboxylic acid after hydrolysis. On the other hand, the (S)-reagcnt attacks the (/ )-aldebyde preferably from the. S7-side to give. s wz-carboxylic acids with comparable selectivity 6... 

The title compound is a key C6 building block. Several labs have prepared novel a-amino acids, biological probes and other interesting compounds using the D-diepoxide as a key intermediate.3 An efficient route to the L-enantiomer provides a pathway to compounds with the opposite configuration, one not readily available from commercial sources, and a valuable probe of stereochemistry in biological systems and reaction mechanism. 

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