Absolute configuration of

All the double bonds are cis and the absolute configuration of the chirality center is S Wnte a stereochemically accurate representation of ectocarpene... 

The same cannot be said about reactions with alkyl halides as substrates The conver Sion of optically active 2 octanol to the corresponding halide does involve a bond to the chirality center and so the optical purity and absolute configuration of the alkyl halide need to be independently established... 

Techniques for determining the absolute configuration of chiral molecules were not developed until the 1950s and so it was not possible for Eischer and his contemporaries to relate the sign of rotation of any substance to its absolute configuration A system evolved based on the arbitrary assumption later shown to be correct that the enantiomers... 

FIGURE 1.19 Viewing angle as a means of designating the absolute configuration of compounds with a chiral axis, (a) (R )-2-Butanol (sequence clockwise) (b) (fi)-2-butanol (sequence counterclockwise). 

Chemical conversion of compounds to intermediates of known absolute configuration is a method routinely used to determine absolute configuration (86). This is necessary because x-ray analysis is not always possible suitable crystals are required and deterrnination of the absolute configuration of many crystalline molecules caimot be done because of poor resolution. Such poor resolution is usually a function of either molecular instability or the complex nature of the molecule. For example, the relative configuration of the macroHde immunosuppressant FK-506 (105) (Fig. 8), which contains 14 stereocenters, was determined by x-ray crystallographic studies. However, the absolute configuration could only be elucidated by chemical degradation and isolation of L-pipecoUc acid (110) (80). 

ORD and CD also provide a basis by which the absolute configuration of a compound may be correlated with that of a known compound of similar stmcture by observing changes in degree of rotation with wavelength (87). 

Similar degradation reactions were used to estabUsh the absolute configuration of mocimycin (kirromycin) (1, R = H) (46), the constitution of which had been described previously (7,47). The chemical stmctures of most other subsequentiy discovered elfamycins have been deterrnined spectroscopically and assignments of absolute configurations are not complete. The elfamycin stmctures shown in Figure 1 have complete stereochemical details that have been in part ascertained experimentally and in part are assumed to correspond to the aurodox topography. 

Among the modem procedures utilized to estabUsh the chemical stmcture of a molecule, nuclear magnetic resonance (nmr) is the most widely used technique. Mass spectrometry is distinguished by its abiUty to determine molecular formulas on minute amounts, but provides no information on stereochemistry. The third most important technique is x-ray diffraction crystallography, used to estabUsh the relative and absolute configuration of any molecule that forms suitable crystals. Other physical techniques, although useful, provide less information on stmctural problems. 

Nitrogen chirality may also be produced by the action of an achiral peroxyacid on a Schiff base containing a chiral amine (75JOC3878). In this case the oxaziridine contains a configurationally known centre of chirality relative to this, absolute configurations of the centres of chirality at nitrogen and carbon, and thus the complete absolute configuration of the molecule, can be determined (see Section 5.08.2.2). 

The absolute configuration of naturally occurring 5(-)-azetidine-2-carboxylic acid has been established (73CL5), and the DL form has been resolved (69JHC993). ORD and CD curves have been determined for 2-methylazetidine and an octant rule has been proposed for the N-chloro- and N-cyano-2-methylazetidines (74T39). 

If a molecule contains several asymmetric C atoms, then the diastereomers show diastereotopic shifts. Clionasterol (28a) and sitosterol (28b) for example, are two steroids that differ only in the absolute configuration at one carbon atom, C-24 Differing shifts of C nuclei close to this asymmetric C atom in 28a and b identify the two diastereomers including the absolute configuration of C-24 in both. The absolute configurations of carboxylic acids in pyrrolizidine ester alkaloids are also reflected in diastereotopic H and C shifts which is used in solving problem 54. 

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

The spatial aiiangement of substituents at a chirality center is its absolute configuration. Neither the sign nor the magnitude of rotation by itself can tell us the absolute configuration of a substance. Thus, one of the following structures is (-l-)-2-butanol and the other is (—)-2-butanol, but without additional infonnation we can t tell which is which. 

An elaborate network connecting signs of rotation and relative configurations was developed that included the most important compounds of organic and biological chemistry. When, in 1951, the absolute configuration of a salt of (3-)-taitaiic acid was... 

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