Oxidation alpha

The final method for constructing epidithiodiketopiperazine motifs relied on the nucleophilic thiolation of /V-acyliminium ions. Access to alpha-oxidized diketopi-perazine structures was central to this approach, and key developments were made in this regard. Schmidt first demonstrated the feasibility of this ionization approach in 1973 by conversion of proline anhydride to its diacetate using Pb(OAc)4 [42], Hydrolysis of the acetates, ionization of the hemiaminals with zinc chloride in the presence of hydrogen sulfide, and oxidation with iodine provided the epidisulfide of interest. In 1975, Matsunari reported access to alpha-methoxy diketopiperazines,... 

D-bifunctional protein deficiency [5], 2-methyl acyl-CoA racemase (AMACR) deficiency [3] and sterol carrier protein (SCP-x) deficiency [6], the disorders of etherphospholipid biosynthesis (dihydroxyacetone phosphate acyltransferase and alkyl- dihydroxyacetone phosphate synthase deficiency) [2], the disorders of phytanic acid alpha-oxidation (Refsum disease) [15], and the disorders of glyoxylate detoxification with hyperoxaluria type 1 as caused by alanine glyoxylate aminotransferase deficiency as a sole representative. 

Alpha oxidation and omega oxidation. Animal tissues degrade such straight-chain fatty acids as palmitic acid, stearic acid, and oleic acid almost entirely by (3 oxidation, but plant cells often oxidize fatty acids one carbon at a time. The initial attack may involve hydroxylation on the a-carbon atom (Eq. 17-3) to form either the d- or the L-2-hydroxy add.17 18-32 323 The L-hydroxy acids are oxidized rapidly, perhaps by dehydrogenation to the oxo acids (Eq. 17-3, step b) and oxidative decarboxylation, possibly utilizing H202 (see Eq. 15-36). The D-hydroxy acids tend to accumulate... 

Brown SP, Brochu MP, Sinz CJ, MacMillan DWC (2003a) The direct and enantioselective organocatalytic alpha-oxidation of aldehydes. J Am Chem Soc 125 10808-10809... 

Eldjarn L, Stokke O, Try K. 1966. Alpha-oxidation of branched chain fatty acids in man and its failure in patients with Refsum s disease showing phytanic acid accumulation. Scand J Clin Lab Invest 18 694-695. 

Oxabicyclic ketones have also been further derivatized to the alpha-oxidation products which are in turn cleaved, offering still another option for carbon-carbon bond scission. For example, hydroxyketone 114, available in > 98 % ee from the parent ketone, was cleaved by lead tetraacetate to afford an excellent yield of the hydroxyester 115, a key intermediate in Noyori s synthesis of showdomycin, Eq. 86 [121,129]. In this case, the ozonolysis of the silyl enol ether of the parent ketone led to complex mixtures, demonstrating the complementarity of these approaches. 

M18. Meyer, D. J., and Ketterer, B., 5a,6a-Epoxy-cholestan-3p-ol (cholesterol alpha-oxide) A specific substrate for rat liver glutathione transferase B. FEBS Lett. 150, 499-502 (1982). 

Jansen, G.A., Wanders, R.J.A. 2006. Alpha-oxidation. Biochim. Biophys. Acta 1763 1403-1412. 

FATTY ACID ALPHA-OXIDATION ENZYMOLOGY AND DEFICIENCIES IN MAN... 

Watkins, P.A., Howard, A.E. Mihalil S.J. (1994) Biochim. Biophys. Acta 1214, 288-294. Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. 

Mihalik, S.J., Rainville, A.M. Watkins, P.A. ( 995)Eur. J. Biochem. 232, 545-551. Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. 

Croes, K., Casteels, M, de Hoffmann, E., Mannaerts,GP. Van Veldhoven,PP. (1996) r. J. Biochem. 240, 674 83. alpha-Oxidation of 3-methyl-substituted fatty acids in rat liver. Production of formic acid instead of C02, cofactor requirements, subcellular localization and formation of a 2-hydroxy-3-methylacyl-CoA intermediate. 

Jansen, G.A., Mihalik, SJ., Watkins, P.A., Moser, H.W., Jakobs, C, Denis, S. Wanders, R.J.A. (19%) Biochem. Biophys. Res. Commun. 229, 205-210. Phytanoyl-CoA hydroxylase is present in human liver, located in peroxisomes, and deficient in Zellweger syndrome direct, unequivocal evidence for the new, revised pathway of phytanic acid alpha-oxidation in humans. 

Croes, K., Casteels, M., Asselberghs, S., Herdewijn, P, Marmaerts, GP. Vanveldhoven, P.P. (1997) FEBS. Lett. 412, 643-645. Formation of a 2-methyl-branched fatty aldehyde during peroxisomal alpha-oxidation. 

Tsai, S.C., Avigan, J. Steinberg, D. (1969) J. Biol. Chem. 244, 2682-2692. Studies on the alpha oxidation of phytanic acid hy rat liver mitochondria. 

Poulos, A., Sharp, R, Singh, H., Johnson, D.W., Carey, W.E. Easton, C. (1993) Biochem. J. 292, 457 61. Formic acid is a product of the alpha-oxidation of fatty acids by human skin fibroblasts deficiency of formic add production in peroxisome-deficient fibroblasts. 

Singh, 1., Pahan, K., Dhaunsi, G.S., Lazo, O. Ozand, P. (1993) J. Biol. Chem. 268, 9972-9979. Phytanic acid alpha-oxidation. Differential suhcellular localization in rat and human tissues and its inhibition by nycodenz. 

Wanders, R.J. van Roermund, C.W. (1993) Biochim. Biophys. Acta 1167, 345-350. Studies on phytanic acid alpha-oxidation in rat liver and cultured human skin fibroblasts. 

PHYH Phytanoyl-CoA hydroxylase (Refsum disease) Lipid metabolism/fatty acid alpha-oxidation... 

Mead, J.F., Levis, G.M. Alpha oxidation of the brain fatty acids. Biochem. biophys. Res. Commun. 9, 231-234 (1962)... 

Alpha-oxidation of fatty acids has also been reported in plants, a process which involves sequential removal of one carbon at a time from free fatty acids of chain length ranging from C13 to Cig- It is unlikely that complete oxidation of fatty acids occurs in this manner, and the physiological significance of this pathway is obscure. It could well serve to shorten odd-chain fatty acids to even lengths and thus allow their degradation by jS-oxidation. 

The commonest polymethyl-branched fatty acid is probably phytanic or 3,7,11,15-tetramethylhexa-decanoic acid, which is a metabolite of phytol, and can be found in trace amounts in many animal tissues. It becomes a major component of the plasma lipids in Refsum s syndrome, a rare condition in which there is a deficiency in the enzymatic fatty acid alpha-oxidation system. Lough [562] has reviewed the occurrence and biochemistry of this and other isoprenoid fatty acids. Similar fatty acids are present in the lipids of the preen gland of birds and in those of tubercle bacilli. 

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