Isosteric equivalence

Isosteric equivalence, 77, 149 benzene and thiophene, 52 carbon and nitrogen, 399 Isothiouronium salts, as source of thiols, 44 Isothipendyl, 430 Isoxazole synthesis, 126 Isoxsuprine, 69 Ivanov reagent, 92, 93... 

Substances that are isosteric equivalents of substances that are toxic or pharmacologically active may also possess these biological properties. It is also possible that biological properties may be bestowed, exacerbated, or attenuated when isosteric modifications are made. This point is illustrated by the following examples. 7-Methyl-benz[a]anthracene (36) is a known carcinogen, whereas 7-methyl-l-fluorobenz[o]... 

The imidazole ring or an isosteric equivalent is required to mimic the Hiss side chain of angiotensin II. 

Weik and Rademann have described the use of phosphoranes as polymer-bound acylation equivalents [65]. The authors chose a norstatine isostere as a synthetic target and employed classical polymer-bound triphenylphosphine in their studies (Scheme 7.54). Initial alkylation of the polymer-supported reagent was achieved with bromoacetonitrile under microwave irradiation. Simple treatment with triethyl-amine transformed the polymer-bound phosphonium salt into the corresponding stable phosphorane, which could be efficiently coupled with various protected amino acids. In this acylation step, the exclusion of water was crucial. 

Replacement of the carbamate group with isosteric functionalities such as an IV-methyl carbamate, urea, or amide group clearly confirmed the favorable qualities of the carbamate group [57], While the introduction of a urea group, as in case of iV-9-(tert-butylcarbamoyl)-9-desoxy-9-aminoquinine selector, instead of carbamate functionality turned out to be virtually equivalent in terms of enantiorecognition capabilities [57,58], the enantiomer separation potential was severely lost on iV-methylation of the carbamate group, like in 0-9-(N-me hy -N-tert-butylcarbamoyl)quinine [32,58], or its replacement by an amide, such as in case of Af-9-(pivaloyl)-9-desoxy-9-aminoquinine selector [57,58], For example, enantioselectivities dropped for DNB-alanine from 8.1 for the carbamate-type CSP, over 6.6 for thein-ea-type CSP, to 1.7 for the amide-type CSP, and 1.3 for the A -methyl... 

Also here the equilibria can be formally given by formulas equivalent to (17) and (20). In the first case A/i0,o —27 kcal./mole and a 20 kcal./ mole. Contrary to the case with nickel, the isosteric heats fit closely to the results of both plots at higher coverages but deviate markedly at lower ones, the heterogeneous model giving the best fit here. 

The activation energy for intra-crystalline diffusion for n-butane is 30 kj mol" [72,74,89], For the isosteric heat of adsorption values of =38 kJ mol" are reported by Kapteyn and by Vroon, which value is considerably lower than other values (=50 kJ mol ) reported in literature. For CH4 a good agreement between Ccdculated and measured fluxes is obtained, for n-butane the agreement is reasonable to bad at low pressure and good at higher pressure. A difficult problem is the value of the saturation concentration. In many cases no reliable experimental data are known and theoretical estimates have to be made usually imder the questionable assumption that is independent of temperature. For n-butane the theoretical sorption capacity of MFI/silicalite equals about 2.1x10 mol g" (equivalent to 12 molecules per unit cell). 

More extensive and accurate data and additional calculations are necessary to obtain s , e , and from isotherm data over what is required to get the differential energy and entropy from the isosteric equation. The first complete calculation of ss, e and , as well as the differential quantities, has recently been made by Hill, Emmett, and Joyner (95). This paper shows in detail how the methods of this section can be applied in practice. Using heats of immersion, Harkins and Jura (96) made earlier equivalent calculations, but the relationship of their calculated quantities to the thermodynamic functions of the adsorbed molecules was not pointed out until recently by Jura and Hill (92). 

Luche conditions have also been utilized in the synthesis of an electrophilic galactose equivalent, specifically for preparation of an O-linked glycopeptide isostere in the laboratory of Randall L. Halcomb.19 To accomplish this goal, per-acetylated cyclohexone 17 was reduced using NaBUi and CeCl3 to produce psuedoequatorial cyclohexenol 18. The reaction produced a 30 1 ratio of diastereomers favoring the product of axial hydride addition. 

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