Other Nitrobenzyl Reagents

To circumvent these difficulties, Horton and Tucker 196) synthesized a water-soluble reagent, dimethyl (2-hydroxy-5-nitrobenzyl)-sulfonium bromide (132) which, like HNB-Br, can react selectively with tryptophan residues of proteins in aqueous solution, but in the absence of organic solvent. 

Although the sulfonium reagent is rapidly hydrolyzed in neutral and alkaline solutions, it is relatively stable in acidic aqueous solutions. 

Consequently, it has been found convenient to dissolve an appropriate excess of the reagent in water prior to its addition to a buffered solution of the protein. An alternative is simply to add the reagent as a solid. 

However, even more complex alkylations of the indole ring by the water soluble sulfonium reagent had to be expected, since methylation reactions have to be taken into account. 

Heinrich et al. 167) studied the reaction of (132) with the model compound N-acetyl-tryptophan amide at a constant pH of 4.7. At least ten different reaction products could be detected some of them were expected on the basis of the results obtained by previous workers. However, in the case of N-acetyl-tryptophan amide, the most stable and abundant product was found to be a compound (134) bearing a 2-piperidone ring system, which could arise from a cyclization of the presumed intermediate (133) in the reaction. 

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Other reductions. A mixed hydride of ratio 1 1 is superior to lithium aluminum hydride alone for the reduction of nitriles to amines. Unlike lithium aluminum hydride, the mixed reagent does not reduce nitro groups. Thus p-nitrobenzaldehyde is reduced by mixed hydride to p-nitrobenzyl alcohol in 75% yield. Whereas lithium aluminum hydride tends to remove halogen atoms, this reduction is retarded or prevented by the presence of aluminum chloride. Thus (8-bromopropionyl chloride is reduced by a 1 1 mixed hydride to 3-bromo-1-propanol in 77% yield in the absence of AlClj the yield is 44%. ... 

Other o-nitrophenol-containing resins have been prepared with the aim of increasing the distance between the reactive center and the macromolecular backbone, which should accelerate the active ester formation by achieving an easier approach of the reagents. Thus, the Friedel-Crafts alkylation of styrene-divinyl-benzene copolymer with 4-hydroxy-3-nitrobenzyl chloride promoted by aluminium trichloride gave 4-hydroxy-3-nitrobenzylated polystyrene (70) (approximately 30% of the aromatic rings of the polymer were substituted according to elemental... 

Figure 15.4 Examples of caged compounds and other photoactivatable drugs, (a) and (b) on photolysis the o-nitrobenzyl protecting group detaches and releases ATP and cAMP, respectively (c) photosensitive chelator. The cis form of the molecule binds Zn2+ but the trans form does not (d) frequently used photosensitive calcium chelators. Nitr-2 (R = CH3), Nitr-5 (R = H) (e) ICYP-diazirine, a photoaffinity reagent that becomes covalently attached to p-adrenergic receptors upon photolysis.

Compound 37 was condensed with tryptamine perchlorate in the presence of sodium cyanoborohydride to provide the secondary amine 38. On the other hand, the aldehyde 37 was stirred with silica gel in methylene chloride to afford the epimer, which on reductive condensation with tryptamine perchlorate gave 39. Lactamization of 38 and 39 gave the lactams 40 and 41, respectively. Reaction of 40 and 41 with Lawesson s reagent gave the corresponding thio-lactams 42 and 43, which were treated with p-nitrobenzyl bromide to afford the crude salts 44 and 45. Reduction of 44 and 45 with sodium borohydride afforded (-)-tetrahydroalstonine (3) and (-)-ajmalicine (1), respectively. 

There are a large number of reagents which form derivatives with phenols which can be readily crystallized and separated. Those commonly used include p-nitrobenzyl bromide, chloroacetic acid, p-toluenesulfonyl chloride, phenyl isocyanate, and benzoyl chloride. An extensive list of the melting points of these and other derivatives suitable for the characterization of phenols is given by Johnson, Shennan, and Reed (54) who also describe the methods of preparation of the compounds. 

Spande, T. F., M. Wilchek, and B. Witkop The Reaction of Derivatives of Tryptophan, Tryptamine, and Other Indoles with 2-Hydroxy-5-nitrobenzyl Bromide (Koshland s Reagent). J. Amer. Chem. Soc. 90, 3256-3258 (1968). 

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