Oxidative activation structural motif

Early proposals suggested [72] that catalase contains a p-oxo-bis(p-carboxylato)-dimanganese core. The UV-Vis spectra of this structural motif present in model complexes exhibit 480-520 nm d-d absorptions [73] similar to the UV-Vis absorption bands of manganese catalases. The EPR studies of oxidized T. ther-mophilus catalase [74] also suggested a MnIIIMnI" p-oxo-bis(p-carboxy 1 ato) core as a possible structural motif for the active site. 

Bestatin 6a (Figure 3.6.8) is the lead structure of a family of highly potent protease inhibitors containing the 3-amino-2-hydroxy-4-phenylbutanoic acid as the active, isosteric motif, mimicking the tetrahedral intermediate formed during amide bond cleavage [31]. Several clinically employed HIV-protease inhibitors are from this class of compound. The oxidized a-keto-/ -amino derivatives have also... 

Oxidizing polymers and polymer-supported carbanion equivalents, in particular, have been employed successfully for preparation of protease inhibitor collections as a practically relevant example. With peptide aldehydes and differently substituted a-hydroxy-jS-amino carbonyl moieties two inhibitory motifs have been prepared with hitherto unprecedented ease and efficiency. Now it remains to be demonstrated that the synthetic methodology as introduced here is capable of assisting the identification of novel biologically active structures. 

Many natural products display structural motifs biosynthetically derived from ortho-quinol precursors, and some even feature ortho-quinol moieties in their final structural arrangement [1, 6]. Asatone (7) and related neolignans can be put forward as classic examples of complex natural products derived from cyclodimerization of oxidatively activated simple phenol precursors (Figure 5) biomimetic syntheses of 7 have accordingly been accomplished by anodic oxidation (Section 15.2.1) and by Pelter oxidation (Section 15.2.2) of the naturally occurring phenol 9 [34, 36]. 

Copper Catalysts Direct oxidative functionalization of tertiary amines is of importance both enzymatically and synthetically. The combination of CuBr—TBHP has proved to be as an efficient system in the oxidative activation of sp3 C—H bonds adjacent to a nitrogen atom [10]. Various types of cross-dehydrogenative coupling (CDC) reactions have been developed, including compounds with activated methylene groups [11], indoles [12], and terminal alkynes (Scheme 11.2) [13]. Because 1,2,3,4-tetrahydroisoquinoline derivatives are important structure motifs of natural... 

The 2.0-A crystal structure revealed that DsbA contains a thioredoxin-like fold (Martin et al., 1993). The thioredoxin fold includes a central /3-sheet formed by four antiparallel /3-strands. The central /3-sheet is flanked by a perpendicular helix and two helices on the opposite side (Martin, 1995). Compared to thioredoxin, DsbA contains an additional /l-strand in the central (6-sheet and the insertion of a 65-residue helical domain (Fig. 1). Such insertions are commonly observed within the thioredoxin family (Martin, 1995 McCarthy etal., 2000). Most members of the thioredoxin superfamily are involved in disulfide exchange reactions, and contain a redox-active CXXC motif in their active site. The CXXC motif participates in disulfide exchange reactions by going through reversible cycles of oxidation and reduction. In this motif, the... 

Oxidation of Met residues has significantly affected biological activity in some instances (subtilisin, E. colt ribosomal protein L12), but has shown no effect in others (ribonuclease, Kunitz trypsin inhibitor). As is the case with degradation at Asx, the rate of oxidation at select residues within a protein is dependent upon higher-order structure, presumably because of solvent inaccessibility or steric hindrance. Howevei unlike the case of Asx degradation, there are no primary sequence or other structural motifs found to strongly correlate with oxidation of Met. Other amino add residues susceptible to oxidation are Cys, His, Trp, and Tyr. 

Benzolactones are important structural motifs in natural products and biologically active compounds. Gallardo-Donaire and Martin reported an efficient Cu(OAc)2-catalyzed synthesis of benzolactones under mild conditions (Scheme 8.115). The intramolecular C-H hydroxylation of 2-arylbenzoic acids afforded benzolactones in moderate to good yields using (PhC02)2 as the oxidant [190]. 

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