I-Amino effect

The formation of an N-hydroxyquinoxaline-2,3-dione 104 from an (2-nitrophenyl)sarcosine 103 by the action of aqueous alkali could be accounted for by invoking a I-amino effect (Scheme 34) (87TL6363). 

In 1913 Werner 2 described a new series of optically active cobalt compounds containing two asymmetric cobalt atoms in the molecule, the tetraethylenediamino-/i-amino-nitro-dicobaltic salts. The resolution is effected by treating tetraethylencdiamino - /x - amino - nitro-dicobaltic bromide with silver d-bromo-camphor sulphonate and fractionally crystallising the product. 

Tsai et al. (2) determined that blue phosphorescent organic light-emitting devices consisting of 2,2 -bis(A,A-disubstituted amino)-9,9 -spirobifluorenes, (I), were effective as hole transporting materials and had efficiencies of up to 16%, 30.6 cd/A and 26.7 lm/W. 

For substituents with —I, +M effects, the orienting effect of such substituents (halogens, alkoxy, thioalkoxy, amino, alkylamino, etc.) is similar to that of alkyl groups. If the substituent is in position 2, further substitution occurs at position 5 if it is in position 3, substitution occurs preferentially at 2, unless the steric requirement forces the incoming substituent to position 5. 

Reduction of isoxazolines, i-amino alcohols. Lithium aluminum hydride reduction of the ready available isoxazolines 1 is effected with unusually high 1,3-asymmetric induction (equation I). The stereoselectivity is not affected drastically by the presence of a hydroxyl group in the side chains at C3 or C5, but isoxazolines bearing a 4a-hydroxyl group are reduced almost entirely to the erythro ( fi)-diastereomer.1... 

Aggarwal and coworkers have studied the electrophilic behavior of enantiomerically pure N-p-toluenesulfinimines and N-tert-butanesulfinimines in the asymmetric Baylis-Hillman reaction with methyl acrylate with and without Lewis acids [26], In the presence of In(OTf)3 good yields and high diastereoselectivities have been achieved providing an effective route to /i-amino-a-methylene esters. 

It is significant that the reaction mixture was worked up by removal of the unreacted ester by hexane extraction and concentration of the aqueous layer to obtain the desired (i )-amino acid. The process has a high throughput and was easy to handle on a large scale. However, because of the nature of a batch process, the enzyme catalyst could not be effectively recovered, adding significantly to the cost of the product. In the further scale up to 100-kg quantity productions, the resolution process was performed using Sepracor s membrane bioreactor module. The enzyme was immobilized by entrapment into the interlayer of the hollow-fiber membrane. Water and the substrate amino ester as a neat oil or hexane solution were circulated on each side of the membrane. The ester was hydrolyzed enantioselectively by the enzyme at the membrane interface, and the chiral acid product... 

In a 3-I. beaker a paste is made from 82 g. (0.21 mole) of 88 per cent technical Chicago add (i-amino-8-naphthol-2,4-disul-fonic add) (Note 3) and 500 cc. of water, and solution effected by the addition of 8 g. (0.2 mole) of sodium hydroxide in 30 cc. of water, testing with litmus toward the end and leaving the reaction still add (Note 4). The solution is cooled to 18° by the addition of ice, and just before the coupling 35 g. (0.33 mole) of anhydrous sodium carbonate is added. 

One further point inductive effects and resonance effects don t necessarily act in the same direction. Halogen, hydro.xyl, alko.xyl, and amino substituents, for instance, have electron-H /l7/i/nnv//i inductive effects because of the electro-negativity of the —X, -O, or -N atom bonded to the aromatic ring but have electron-donating resonance effects because t)f the lone-pair electrons on those same —X, —O, or —N atoms. When the hvo effects act in opposite directions, the stronger of the two dominates. 

Vudkoff, M-, Uaikhin, Y Nissim, I., Grunstein, K and Nissim, I. (1997). Effects of ketone bodies on astrocyte amino acid metabolism. /. Wfurnclrepn, 69, 682-692. 

It is evident that although much is now known about these type I t-amino-effect reaction pathways involving C=C substituents, the synthetic applications have barely been touched. The predictable stereochemistry and remarkable specificity of the reactions await further development. 

This review of necessity brings together disparate information not always recognized as part of the /-amino effect principle. Consequently, some examples in the literature may have been overlooked. I apologize to those whose work I have not acknowledged and would be glad to hear from them for the next update. 

Carbidopa is an inhibitor of aromatic i.-amino acid decarboxylase, the enzyme that converts levodopa to dopamine. Since it does not enter the CNS, the drug acts only on the enzyme present in peripheral tissues (eg, liver). The use of carbidopa in combination with levodopa decreases the dose requirement and reduces peripheral side effects of levodopa. The answer is (C). 

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