Enantiomers, also compounds

Racemic Compounds existing as a racemate, or a 50-50 mixture of two enantiomers also denoted as dl or ( + ). Racemates are also called racemic mixtures. 

An interesting structure-taste study of sweet Ao-vanillyl derivatives has been published <1998JFA4002, 2001QSA3>. It was found that only one enantiomer of each pair proved to be sweet, the other being tasteless. The R-(+)-enantiomer of compound 129 was the sweetest molecule among the variety tested with a relative sweetness, RS, of 20000 (RS = [sucrose]/[compound]). (The 6 -(—(-enantiomer was also tasteless.) As in these Ao-vanillyl derivatives, the difference in the taste of two enantiomers seems to be general and helps in defining receptor-active sites. 

The introduction of branches also makes it possible to have stereoisomers. Compounds with a single methyl branch at any position other than carbon 2 or the exact center of the chain can exist as one of two possible enantiomers, whereas compounds with two or more branches have a number of different stereoisomers (e.g., enantiomers, me so isomers, or diastereomers). Generic reactions that produce racemic mixtures or mixtures of stereoisomers will be discussed first, followed by descriptions of methods used to make individual stereoisomers. 

The reluctance of phenyl-substituted methylenecyclopropanes to rearrange to products in which the phenyl group is located at the exocyclic methylene group was also demonstrated with l-methylene-2-phenylcyclopropane and l-methyl-2-methylene-l-phenylcyclopropane. When used as single enantiomers, both compounds underwent facile racemization at 100 C in chloroform without formation of benzylidenecyclopropane or (l-phenylethylidene)cyclo-propane. Similar results were obtained when a mixture of as- and tra i-l-methyl-2-methyl-ene-3-phenylcyclopropane (Table 1, R = R = R = R = H R = Me R = Ph) was isomerized under thermal or photochemical conditions. 

In the example below, one enantiomer of compound is acylated by a lipase and the other by a phosphine-catalysed process.10,33 We want the lipase to catalyse the reaction between vinyl pivalate 58 and the R-alcohol, and the phosphine to catalyse the acylation of the S-alcohol using the polymer-bound anhydride 60. But, the lipase must not use the polymer-bound anhydride or the wrong enantiomer of alcohol will end up polymer-bound. Similarly, the phosphine must not react with the vinyl pivalate. Fortunately, the phosphine does not react with the vinyl pivalate and the lipase, which is insoluble, cannot interact with the polymer bound material. Also, the lipase will be kept away from the potentially damaging F-acyIphosphon iurn intermediates. The conditions are described as a Three-Phase System . The three phases are the solution phase and the two separate insoluble phases of the polymer bound anhydride and the cross-linked lipase. 

Molecular ellipticity is analogous to specific rotation in that two enantiomers have exactly opposite values at every wavelength. Two enantiomers also show CD spectra having opposite signs. A compound with several absorption bands may show both positive and negative bands. Figure 2.3 illustrates the CD curves for both enantiomers of 2-amino-1 -phenyl-1 -propanone." ... 

Am. (a) Constitutional isomers (b) cis-tram isomers which are also categorized as optical isomers (diastereomers) (c) enantiomers (d) different compounds which are not isomers (e) enantiomers (/) same compound (g) cis-tram isomers (diastereomers). 

Enantiomers also are referred to as chiral compounds, antipodes, or enantiomorphs. When introduced into an asymmetric, or chiral, environment, such as the human body, enantiomers will display different physicochemical properties, producing significant differences in their pharmacokinetic and pharmacodynamic behavior. Such differences can result in adverse side effects or toxicity, because one or more of the isomers may exhibit significant differences in absorption (especially active transport), serum protein binding, and metabolism. With the latter, one isomer may be converted into a toxic substance or may influence the metabolism of another drug. To discuss further the influence of stereochemistry on drug action, some of the basic concepts of stereochemistry need to be reviewed. 

Given that the S-enantiomer of compound 233 is readily available in essentially enantiomerically pure form the work shown above constimtes a formal total synthesis of the unnatural or (—)-enantiomer of the title alkaloid. Since the alcohol R-233 will almost certainly be available by closely related means, the chemistry presented here should also allow access to the naturally occurring enantiomeric forms of various Aspidosperma alkaloids. 

The different enantiomers of optically active compounds have identical chemical and physicochemical properties, except their different influence on the rotation of polarized light. However, a binding site is a chiral environment that discriminates between the different enantiomers as if they were completely different molecules optical enantiomers also differ in their metabolism. Thus, stereochemistry plays an important role in the biological activity of drugs. 

Some carbocyclic nucleoside phosphonates have been described. There has been a further report on compounds of type 208 (see Vol. 28, p. 291), with both purine and pyrimidine bases. Although initially made as racemates, a precursor diol could be resolved by enantioselective acetylation using a lipase and vinyl acetate.The triphosphate analogues 209 (B=Gua, Ade) have been made from the previously-described monophosphonates (Vol. 29, p. 285), and the cyclopropyl-fused diphosphate analogues 210 (X=CH2 and O) were also reported, along with their enantiomers. Trani-compounds of type 211 (n=l-3) have been made as racemates,and so have the related cw-isomers (n=l or 2). ... 

The protonated species (73/74) presumably also served as precursor to the 4P-deuteriotri-0-methylfisetinidol (82) by delivery of hydride ion from the P-face in a predominant Sn2 mode. Compound (82) persistently formed also when fisetinidol-(4a- 8)- and (4p- 8)-catechin hepta-O-methyl ethers (68) and (70) were treated with Na(CN)BD3 in TEA. This observation prompted an investigation of the structural features of the substrates that direct the stereochemistry of the delivery of hydride ion at C(4) in intermediates of type (73/74). Whereas treatment of the epifisetinidol-(4p- 8)-catechin hepta-O-methyl ether (85) with Na(CN)BD3 afforded the 4P-deuteriotri-0-methylepifisetini-dol (87) (18.5%), tetra-O-methylcatechin (75) (32%) and the (25)-l,3-dideuterio-l,3-diarylpropan-2-ol [6%, enantiomer of compound (80)], the nEfisetinidol-(4p- 8)-catechin hepta-O-methyl ether (86) gave 4a-deuteriotri-O-methyl- nf-fisetinidol [13%, the enantiomer of compound (82)], tetra-O-methylcatechin (75) (24%) and the (25)-l,3-dideuterio-l,3-diarylpropan-2-ol [12%, enantiomer of (80)]. 

The compounds represented by structures 1 and 2 are enantiomers. The compounds represented by structures 3 and 4 are also enantiomers. But what is the isomeric relation between the compounds represented by 1 and 3 ... 

A new route to intermediates useful for the synthesis of cis chrysanthemic acid has been reported (Scheme 22)/ The enantiomer of compound (67) was also described. 

The Cahn-Ingold-Prelog (CIP) rules stand as the official way to specify chirahty of molecular structures [35, 36] (see also Section 2.8), but can we measure the chirality of a chiral molecule. Can one say that one structure is more chiral than another. These questions are associated in a chemist s mind with some of the experimentally observed properties of chiral compounds. For example, the racemic mixture of one pail of specific enantiomers may be more clearly separated in a given chiral chromatographic system than the racemic mixture of another compound. Or, the difference in pharmacological properties for a particular pair of enantiomers may be greater than for another pair. Or, one chiral compound may rotate the plane of polarized light more than another. Several theoretical quantitative measures of chirality have been developed and have been reviewed elsewhere [37-40]. 

Our discussion to this point has been limited to molecules m which the chirality center IS carbon Atoms other than carbon may also be chirality centers Silicon like carbon has a tetrahedral arrangement of bonds when it bears four substituents A large number of organosilicon compounds m which silicon bears four different groups have been resolved into their enantiomers... 

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. 

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

Diaziridines also show slow nitrogen inversion, and carbon-substituted compounds can be resolved into enantiomers, which typically racemize slowly at room temperature (when Af-substituted with alkyl and/or hydrogen). For example, l-methyl-3-benzyl-3-methyl-diaziridine in tetrachloroethylene showed a half-life at 70 °C of 431 min (69AG(E)212). Preparative resolution has been done both by classical methods, using chiral partners in salts (77DOK(232)108l), and by chromatography on triacetyl cellulose (Section 5.08.2.3.1). 

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