Diastereoisomers: definition

Chiral centres encountered in anaesthetics usually have carbon or quaternary nitrogen as the chiral centre. Any compound which contains more than one chiral centre is termed a diastereoisomer by definition. 

One can define diastereoselectivity as the formation of diastereoisomers in a non-statistical ratio in any chemical transformation (formation of transition states included). Such a definition concerns equilibrium as well as nonreversible reactions. An asymmetric synthesis in a restricted sense can be considered as a reaction leading to a product containing at least one new stable dissymmetric center with a definite chirality. Such a reaction may take place in the coordination sphere of a metal ion. First of all the following question has to be answered which are the structural properties in the architecture of the coordination sphere that lead to the following phenomenona ... 

Diastereoisomerism is observed when two or more chiral elements appear in the same system. Isolation and characterization of enantiomers or diastereoisomers depend on the structural stability of the chiral element. Therefore the conformation of a chelate ring must generally be considered as labile. The structural stability of the configuration around the metal center and the stability of an asymmetric coordination atom depends on the nature of the central metal atom. In most cases an optically active ligand molecule can be considered as configurationally stable. The presence of a stable chiral element can induce definite chirality in another element which, taken separately, would be labile. 

When we talk about two chiral diastereoisomers, we have no choice but to draw the structure of one enantiomer of each diastereoisonier, because we need to include the stereochemical information to distinguish them, even if we re talking about a racemic mixture of the two enantiomers. To avoid confusion, it s best to write something definite under the structure, such as (meaning racemic) under a structure if it means this diastereoisomer but not this enantiomer of this diaster eoiso mer . 

We have termed the major diastereoisomer anti because the two substituents (Me and OH) are on opposite sides of the chain as drawn. There is no formal definition of anti and syn they can only really be used in conjunction with a structural drawing. 

The other point concerns syn and anti. We said earlier that there is no precise definition of these terms they are a useful way of distinguishing two diastereoisomers provided the structure of at least one of them is presented in diagrammatic form. For aldol products the convention is that syn or anti refers to the enolate substituent (the green Me in the last example) and the new hydroxy) group, provided the main chain is in the plane of the paper, the way we have encouraged you to draw molecules. 

In a study of the highly purified alanine racemase of E. coli, Lambert and Neuhaus determined significant differences in the maximal velocities and the Michaelis-Menten constants of the substrates in the forward (L - dl) and reverse directions (d - dl) [37]. From these data the value calculated for Keq is 1.11 0.15. The time course of the reaction showed that in 10 min with L-alanine as substrate ca. 0.09 jumol of D-alanine were formed. With the same amount of enzyme (750 ng) and in the same time period, ca. 0.05 jamol of L-alanine were formed from D-alanine. Similar results have been reported for the same enzyme from S. faecalis and for proline racemases [37]. Thus, in these cases, there are definite kinetic differences, as expected for the existence of two diastereoisomers formed between enzyme and two substrate enantiomers. 

Irradiation of the MeO signal (2.07) should give an NOE and reveal which of H and is on the same side of the ring and may show that is also on the same side. Irradiation of H and in turn (you were given the NMR shifts of this part of the molecule so you could see that, fortunately, H, tf, and Y are well separated in the NMR spectrum) should give definite information on the relative stereochemistry. The original work shows clearly that the compound is one diastereoisomer but which one was not determined. 

You need to ask which is the first chiral intermediate Can it be conveniently resolved Will the hirality survive subsequent steps The first intermediate is chiral but it enolizes very readily and the rnol is achiral so that s no good. The second compound is definitely chiral but it has three chiral entres and these are evidently not controlled. We should have to separate diastereoisomers before resolution and that would be a waste of time since all the diastereoisomers give the next mtermediate. 

It can be seen that the stereoisomers with configuration (17 ,27 ) and (15,25) are related as enantiomers, and the (17 ,25) and (15,27 ) stereoisomers are also related as enantiomers. What then is the relationship between the stereoisomers of 1 with configurations (17 ,25) and (17 ,27 ), for example With respect to each other, these have one stereogenic centre of common, (17 ), configuration, and the other of opposite, (25) and (27 ), configuration. Clearly these stereoisomers are not enantiomers. Instead, they are related as diastereoisomers and the same can be said for the (15,27 ) and (15,25) stereoisomers. The most concise definition, given in the plural, is diastereoisomers are stereoisomers that are not enantiomers . 

Although it has been generally accepted diat diastereoisomers give virtually identical mass-spectra, Vink and coworkers have shown, with the aid of a computer, that peak intensities exhibit minor, but definite, differences that depend on the configuration of the sugar. Havlicek and colleagues also commented on the influence of stereochemistry on the m.s. of pyranose derivatives. 

The enzymatic conjugation using rat liver cytosol produces a mixture of the 4- and 5-thioether conjugates. However, the diastereoisomers of the conjugates are not formed in equal amounts. With a purified enzyme from the Little River Skate, an equal mixture of the 4- and 5-thioether conjugates are produced. But in this case, only one of the diastereoisomers of each positional isomer is produced. Product analysis of the SH conjugates obtained from C-labeled BP-4,5-oxide (4,5- C) established some definite stereochemical requirements for the catalytic step (12). 

---