Side-chain oxidation, biological

Biological activity is interestingly maintained even in the face of the total omission of a carbonyl group from the side chain. Oxidation of the free alcohol from fluoropred-nisolone acetate (15-2) under more drastic conditions than those used in the preceding... 

The synthesis of unnatural amino acids and peptides is of great interest since it offers the possibility to design new biologically active protein analogues. One of the possible interesting transformations is side chain oxidation of amino acids, for which MTO can be used. It is reported that various /V-Boc protected amino acids such as methionine (Met), cysteine (Cys), and tryptophan (Trp) can be oxidized with the MT0/H202 system [108]. 

Androgens, the male sex hormones, proved far more elusive that either the estrogens and progestins since they occur at much lower concentrations in biological fluids. The bioassay used to track the isolation in this case comprised the capon unit . This was the amount of extract that produced a 20% increase in the surface of a rooster s comb. The 15 mg of pure crystalline testosterone isolated in 1931 came from about 15 0001 of urine. The structural investigations of this series relied on the then newly discovered side chain oxidations of cholestanol (13-1) (Scheme 1.13). This method in essence comprised fairly drastic oxidation of reduced cholesterols of known stereochemistry at the A-B junction to afford in fairly low yield products in which the side chain at Cn had been consumed to leave behind a carbonyl group. One of these products proved to be identical with androsterone (13-2). That compound had in turn been obtained from a sequence of reactions starting from dehydroepiandrosterone (13-3) that had been isolated from male urine. 

Benzene oxide and compounds derived from it are carcinogenic and can react with DNA to induce mutations This difference m the site of biological oxidation—ring versus side chain—seems to be responsible for the fact that benzene is carcinogenic but toluene is not... 

The stereocontroUed syntheses of steroid side chains for ecdysone, cmstecdysone, brassinoHde, withanoHde, and vitamin D have been reviewed (185). Also, other manuscripts, including reviews on the partial synthesis of steroids (186), steroid dmgs (187—189), biologically active steroids (190), heterocychc steroids (191), vitamin D (192), novel oxidations of steroids (193), and template-directed functionali2ation of steroids (194), have been pubhshed. 

The significance of protein oxidation became paramount with the advent of recombinant protein biologies used as human therapeutics. Careful characterization of protein stability is essential to maintaining the efficacy of protein pharmaceuticals. If even a single side chain amino acid residue becomes oxidized, then a protein therapeutic may not have the same activity in vivo as the unmodified protein. 

Harry B. Gray and Walther Ellis,13 writing in Chapter 6 of reference 13, describe three types of oxidation-reduction centers found in biological systems. The first of these, protein side chains, may undergo oxidation-reduction reactions such as the transformation of two cysteine residues to form the cystine dimer as shown in equation 1.28 ... 

By permanganate oxidation long side chains are broken down to carboxyl groups attached to the ring. The biological degradation of oj-aryl-fatty acids proceeds in accordance with the fi-oxidation rule (F. Knoop). 

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