Schiffbase formation

Figure 9.11 demonstrates the Schiffbase formation reaction for class II aldolases, which are mainly found in prokaryotes E.coli aldolase uses a zinc ion to ionize the carbonyl group of DHAP (Alan Berry, University of Leeds) it is now Figure 9.12. 

Schiffbase formation followed, by reduction a cis-trans isomerization is necessary to suitably position the amine and aldehyde groups... 

Sherman, W.R., Rasheed, A., Mauck, L.A., and Wiecko, J., 1977, Incubations of testis myoinositol-1 -phosphate synthase with D-(5-180)glucose 6-phosphate and with H2180 show no evidence of Schiffbase formation. J. Biol. Chem. 252 5672-5676. 

Some examples of DKR based on racemization of secondary alkyl amine via Shiff base were shown in Scheme 5.9. Schiffbase formation of a-amino carboxylic esters significantly increases the acidity of the a-proton in comparison to that of the parent amino acid, thus enabling enantiomer-selective hydrolysis and ammonoly-sis through DKR [23]. For example, chymotrypsin catalyses the hydrolysis of a Schiff base of phenylalanine ethyl ester and an aromatic aldehyde (Scheme 5.9, Equation 5.6) [23b]. In this particular case, natural phenylalanine precipitates, leaving the aldehyde and unhydrolysed enantiomeric ester in solution. Addition of l,4-diazabicyclo[2.2.2]octane (DABCO) (as the Bronsted base) allows DKR to take place by promoting racemization of the Schiffbase. Similarly, Novozym 435... 

Formation of /1-lactams by the reaction of an acid chloride, a SchifFbase and a tertiary amine (Eq. 62) appears to involve multiple pathways, some of which are very fast at higher temperatures. When conducted in open vessels in unmodified micro-wave ovens, high level irradiation leads to preferential formation of the trans -lactams (55%) whereas, at low power, the cis isomer was obtained as the only product (84%). The failure of the cis isomer to isomerize to the trans compounds is an example of induced selectivity. 

Recently, Maeda and coworkers utilized the (S, S) -le-catalyzed asymmetric alkylation of phenylglycine-derived Schiffbase 42 (R1 = Ph) for the stereoselective synthesis of a 4-hydroxy-2-phenylproline framework [27]. After hydrolysis and transesterification, the resulting (S)-49 was derivatized to its N-tosylate 50. Subsequent treatment of 50 with Br2 in CH2C12 resulted in the formation of y-lactone 51 with high diastereos-electivity this was then treated with NaH in methanol to give essentially pure (2 S,4R)-4-hydroxy-2-phenylproline derivative 52 in 80% yield from 50 (Scheme 5.25). 

Dilution has a significant effect in reducing the rate of the reaction, and the formation of Schiffbases is slowed down, although not entirely stopped once the compound has been diluted in alcohol. Methyl anthranilate occurs naturally in many essential oils together with aldehydes such as citral without forming Schiffbases owing to the low concentration of both materials. 

Formation of this carbinolamine bond is revealed by the continuous electron density that connects the aldehyde group of the antibiotic to Hm A2103 in the unbiased electron density maps obtained for each of the 16-membered macrolides studied to date, each of which has an aldehyde group extending from C6. Not surprisingly, that continuous electron density feature is absent in the unbiased electron density map calculated for the structure of the 15-membered macrolide azithromycin which has no aldehyde group at C6. The electron density feature is consistent with formation of a carbinolamine bond and not with a SchifFbase, consistent with the expected chemical reactivity between exocyclic amines and aldehydes (Fig. 4.9) [21]. 

The a subunit catalyzes the formation of indole from indole-3-glycerol phosphate, whereas each P subunit has a PLP-containing active site that catalyzes the condensation of indole and serine to form tryptophan. The overall three-dimensional structure of this enzyme is distinct from that of aspartate aminotransferase and the other PLP enzymes already discussed. Serine forms a Schiff base with this PLP, which is then dehydrated to give the Schiffbase of aminoacrylate. This reactive intermediate is attacked by indole to give tryptophan. 

The stoichiometry of the reductive half-reaction is shown in Equation (2). The initial step in this reaction, as depicted in Figure 13, involves the nucleophilic attack of the primary amine substrate at C5 of oxidized TPQ (Figures 13(a) —> 13(b)). This results in the formation of a substrate Schiffbase (Figure 13(b)). In the next step, an active site base (a conserved aspartic acid) abstracts a proton to form a carbanion species (Figure 13(c)), which quickly rearranges to form a product Schiffbase (Figure 13(d)). The product aldehyde is formed by... 

Rosseinsky and coworkers reported the postmodification of IRMOF-3 with sali-cylaldehyde by imine condensation, leading to the formation of the MOF-supported Schiffbase with 13% yield. The resulting salicylidene-functionalized IRMOF-3 was used as an N-O ligand for a vanadium oxide complex and characterized by liquid-state NMR and PXRD analyses. The obtained MOF-supported vanadium catalyst was found to be active for cyclohexene a-oxidation with tBuOOH, although both conversion and TOF were relatively low, a possible problem involving framework coUapse was identified [118]. 

SchiffBase lshifs- A reaction intermediate compound characteristic of reactions involving amines in general formula is RNH-CO-N = CH2 often used in formation of ureaformaldehyde polymers. (Smith MB, March J (2001) Advanced organic chemistry, 5th edn. Wiley,... 

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