Schiff base reduction with sodium

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

Glutaraldehyde is the most popular b/s-aldchydc homobifunctional crosslinker in use today. Flowever, a glance at glutaraldehyde s structure is not indicative of the complexity of its possible reaction mechanisms. Reactions with proteins and other amine-containing molecules would be expected to proceed through the formation of Schiff bases. Subsequent reduction with sodium cyanoborohydride or another suitable reductant would yield stable secondary amine... 

Figure 14.21 Aldehyde-particles can be reacted with amine-containing proteins or other molecules to form intermediate Schiff bases, which can be stabilized by reduction with sodium cyanoborohydride.

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary iminium salt. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

To keep the probe specifically at the primary amine side chains, we have used pyrenecarboxaldehyde and attached it covalently to polyethylenimine by reduction with sodium borohydride of the Schiff base formed between the probe aldehyde and the polymer primary amine. Such reductive alkylation has been used widely with primary amines of enzymes.43,44 For three different adducts to the polymer, the extent of coupling with pyrene, expressed relative to units of monomer residues,... 

Amino acids undergo a condensation reaction with pyridoxal in alkaline medium to form a Schiff base which can be converted into stable pyridoxyl-amino acids by catalytic reduction or by reduction with sodium tetrahydroborate. The reactions involved are illustrated in Fig. 4.46. The resulting derivatives can be detected in quantities as low as 5-10"10 moles by fluorescence at 332 nm (excitation) and 400 nm (emission). Column chromatography may be used to separate die pyridoxyl-amino acid derivatives [93,94]. 

The ketone groups of aldosterone, corticosterone, and cortisol were derivatized with p-hydrazinobenzoic acid. The resulting carboxylic acid derivatives could be linked to BSA with water-soluble carbodiimide. Aldehydes can be conjugated to proteins directly by Schiff base formation followed by stabilization of the bond by reduction with sodium borohy-dride. Pyridoxal and pyridoxal phosphate are examples of haptens conjugated in this manner. ... 

When primary amines react with a-acylaminoketones the resulting Schiff bases can be cyclized in the presence of phosphoryl chloride, phosphorus pentachloride, or triphenylphosphine and triethylamine in hexachloroethane to give 1-substituted imidazoles (11) (Scheme 2.1.4). The starting a-acyl-aminocarbonyls are readily prepared from a-amino acids by reduction with sodium amalgam [31, 32] or by the Dakin-West reaction [33, 34], which is most conveniently conducted in the presence of 4-(AUV-dimethylamino)pyridine (DMAP) as an acylation catalyst [35 37]. 

The absolute configuration of the structurally unique fungal metabolite mycosporins was determined in the laboratory of J.D. White by means of enantioselective total synthesis." In the endgame of the synthetic effort, the Staudinger reaction was used to elaborate the side chain. The cyclic vinyl azide was first converted to a stable vinyl iminophosphorane, which was subsequently reacted with benzyl glyoxylate to afford the corresponding Schiff base. Reduction of the imine was achieved with sodium cyanoborohydride. 

Although Schiff base formation can be performed with amine groups, the low stability of the bond in aqueous conditions makes hydrazide a better alternative. Hydrazides can be introduced on the sensor surface via reaction of hydrazine or carbohydrazine to carboxylic groups after activation with EDC/NHS (Fig. 11) [32]. The hydrazide-aldehyde bond forms rapidly and is relatively stable in neutral to alkaline conditions, but disintegrates slowly in acidic buffers. If necessary, the bond can be further stabilized by reduction with sodium cyanoborohydride at pH 4. 

Oxidation of Sephadex G-50 or Enzacryl polyacetal using periodate affords aldehydic pol5nners with which the primary amino groups of the amino acid moieties in aminoacyl-tRNA form Schiff bases, and coupling is rendered irreversible by reduction with sodium cyanoborohydride. Hence, only the amino-acylated tRNA molecules in a mixture are retained, and the tRNA may subsequently be released by washing with ammonium bicarbonate buffer, thus affording a convenient method for the separation of isoacceptor tRNA species. ... 

In our study on the substrate specificity of FDP aldolase, the compound 3-deoxy-3-fluorohydroxyacetone-l-phosphate was found not a substrate for the enzyme it was an inhibitor for the enzymatic cleavage of fructose-1, 6-diphosphate. The was determined to be 3 mM (Figure 4). When sodium borohydride was added to the mixture of aldolase and 3-deoxy-3-fluorohydroxyacetone-l-phosphate, no inactivation of aldolase was observed, indicating that a Schiff base is not formed. The Schiff base intermediate in the mixture of DHAP and aldolase has previously been trapped by reduction with sodium borohydride to inactivate the enzyme (8). The inhibitor may be useful for study of the active site of the enzyme. 

An additional type of derivative that is often used for glycan profiling and analysis is the modification of the reducing end with a chromophore, usually achieved by the formation of a Schiff base with an aromatic amine, and subsequent reduction with sodium borohydride to stabilize the initially formed product by its conversion to a saturated amine. This procedure was initially developed for HPLC analysis with ultraviolet detection, but it is also appropriate for MS analysis because the substituted amino group represents a site for charge localization that simplifies the fragmentation pattern and also provides the opportunity to introduce a stable isotope label for quantitative purposes (54). 

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