Octant rule

CD was utilized to obtain the solvent dependency of the conformation of the cation-lonophore complex as well as Kp s. Saturation Isotherms were plotted from linear computer fits of 1/[cation] versus 1/ArJ the slopes yielded Kjj s while extrapolation of Rq to infinite cation concentration provided the rJ s of the cation-saturated lonophore. It Is Important to note that the cation Itself is a significant vlnclnal moiety, which by virtue of Its charge, polarizability and location with respect to the chromophore of concern, can modify the rotational strength of the chromophore. 

X-ray crystallographic studies confirm that all cationic complexes of carboxylic lonophores have their llgandlng atoms oriented toward a central cavity. The extent to which this conformation would be altered in the absence of a bound cation due to the mutual electrostatic repulsion of the dipolar oxygen atoms would, in turn, be modulated by the mobility of the backbone supporting the ligands. 

We conclude that the dynamics of molecular conformation associated with sallnomycin complexatlon In all likelihood extend at least to the other naturally occurring carboxylic lonophores. The influence of lonophore environment, e.g. solvent, on lonophore conformation Is particularly significant when considering the environmental continuum encountered by an lonophore when trans-versing a biological membrane. 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

The extension to lonophore selectivity of a hypothesis based on analogy with the rigid matrices of Ion selective glasses (19) 

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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). 

The optical rotatory dispersion curves of steroidal ketones permit a distinction to be made between the conformations, and assignment of configuration is possible without resorting to chemical methods (see, e.g. ref. 36) which are often tedious. The axial halo ketone rule and, in the more general form, the octant rule summarize this principle and have revealed examples inconsistent with the theory of invariable axial attack in ketone bromination. 2-Methyl-3-ketones have been subjected to a particularly detailed analysis. There are a considerable number of examples where the products isolated from kinetically controlled brominations have the equatorial orientation. These results have been interpreted in terms of direct equatorial attack rather than initial formation of the axial boat form. 

The effect of an a-substituted oxirane group on the optical rotatory dispersion of steroidal ketones should be interpreted with caution an inverted octant rule for a-epoxy ketones has been proposed/although recent data indicate that the normal octant rule may still be valid. 

The -position of the cyclopropane ring was established by the observed negative circular dichroism curve (Ae — 2.03 in dioxane at 298 m/i) and consideration of the inverse octant rule for cyclopropyl ketones. ... 

The procedure is widely applicable and highly reliable. For example, the configuration of bicyclo[2.2.2]oct-5-ene-2-carboxylic acid (6) was correctly assigned applying Horeau s method to bicyclo[2.2.2]octan-2-ol (7) derived from 6. Conversely, on the basis of the octant rule, the wrong sign for the Cotton effect of 8 was predicted (see p 430)235. 

The octant rule has been tested by various theoretical approximations12-18 and thoroughly empirically analyzed by Kirk and Klyne19 22. Two generalizations of importance with regard to configurational applications of the octant rule can be given. 

Cotton effects due to unsymmetrical heteroatom ring-substituted cyclohexanones have also been recorded34. However, direct application of the octant rule to determine the absolute configuration of heterocyclohexanones such as 8 is not recommended30. 

In /(,y-unsaturated ketones overlap of the olefinic rc-orbital with the orbitals of the carbonyl group leads to enhancement of both the isotropic absorption and the Cotton effect of the n-71 band. The generalized" octant rule predicts a large positive n-71 Cotton effect when the C = C bond in /j.. -imsatijrated ketones of cisoidgeometry appears in a positive octant [Figure 6 (a)]43. 

Figure 6. Generalized octant rule for /l.v-unsaturated ketones. Reprinted from Tetrahedron, 42, 777 (1986) with kind permission of Pergamon Press Ltd, Headington Hill Hall, Oxford 0X3 OBW. UK..

These chiroptical properties are compatible with the prediction made by Scott s octant rule 47) which says that both compounds, which have polymethylene bridges in the (—)-regions (see 52), should exhibit (—)-Cotton effects. 

After decarboxylation, enolization in the alternative mode would cause racemization. However, this reasoning does not explain why 199 was racemized. The racemic a-aminoketones were eventually resolved via their bromocamphorsulfonates. Optically pure (—)-indolizidin-l-one (196) was reduced with lithium aluminum hydride to the alcohol, tosylated, and again reduced to (+)-indolizidine [Eq. (28)]. Since indolizidine obtained from R-pipecolic acid [Eq. (29)] was levorotatory, it followed that the absolute configuration of the original ketone was S.254 The optical rotatory dispersion (ORD) curve of the S(-)-ketone showed a strong negative Cotton effect as predicted by the octant rule. 

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