Biological hydroxylation

G.S. Boyd u. R.M.S. Smellic, Biological Hydroxylation Mechanisms, Academic Press, London New York... 

Ullrich, V. Cytochrome P450 and Biological Hydroxylation Reactions. 83, 67-104 (1979). 

II Gunsalus, I.C., Pederson, T.C. and Sligar S.G. Oxygenase-catalyzed biological hydroxylations. Ann. Rev. Biochem. 

These oxidation states attract attention because Fe(IV) and Fe(V) cation radical porphyrins are active intermediates in biological hydroxylation. In strong base, Fe(IV) is produced from Fe(III) by powerful oxidants and Fe(V) arises from radical reduction of Fe(VI)... 

The synthesis of 6a-methyldigitoxigenin acetate (394) has been reported according to Scheme 19.198 Pregn-4-en-21-ol-3,20-dione was converted into its 6a-methyl derivative (387) using a previously described five-step reaction sequence biological hydroxylation furnished the 14a,12-diol (388) and reduction of the derived 21-acetate gave the 5/3-dihydro-steroid (389). Dehydration furnished the A14-olefin (390) which was converted into the 21-mesylate and thence into the lactone (391) by reaction with the monoethyl ester of malonic acid. The crude lactone was decarbox-ylated, reduced to the 3/3-alcohol (392), and converted into the bromohydrin (393) via its 3/3-acetate and thence by debromination into 6a-methyldigitoxigen 3-acetate... 

The results with the tritiated tryptophan samples further indicate that hydrox-ylation at the carbon which corresponds to C-3 of tryptophan occurs with loss of the pro-R hydrogen, i.e. hydroxylation with retention of configuration. This result was probably to be expected for it is a well-founded rule that biological hydroxylation occurs with retention of configuration, and this then is an additional example from the field of secondary metabolites. 

This functionalization has been used for a synthesis of cortisone from cor-texolone that is an attractive alternative to biological hydroxylation. Thus irradiation of (5) and lodobenzene dichloride gives, after dehydrohalogenation and saponification, the unsaturated alcohol (6). Hydroboration, oxidation, and deprotection of (6) affords dihydrocortisone, which had been converted previously into cortisone acetate and prednisolone acetate. 

Aminophosphonic acids play an important role in living systems. The first acid to be found naturally, namely (2-aminoethyl)phosphonic acid (also known as ciliatine, 2AEPH, and jS-Ala ) , has been followed more recently by 2-amino-5-phosphonopent-2-enoic acid, isolated from Streptomyces plumbens, and (2-amino-l-hydroxyethyl)phosphonic acid, isolated from Acanthamoeba castellani and formed through the biological hydroxylation of (2-aminoethyl)phosphonic acid. Many acids are inhibitors of enzymes important in carboxylic acid biochemistry. Ala is a potent inhibitor of a racemase from Gram-positive bacteria (the corresponding phosphinic acid 99 is not). Phosphinothricin... 

Such cyclic peroxides have been proposed as intermediates in photochemical and chemiluminescent reactions of aromatic compounds with oxygen (4, 5, 44) and in the biological hydroxylation of aromatic compounds (22, 23, 34). In dilute ferrous ion solution the cyclic peroxides could decompose ionically to give a predominantly electrophilic distribution of substituted phenols, while at higher concentrations the ferrous ion would cleave the peroxide bond homolytically this, followed by loss of water, would give a more random pattern of substituted phenols. 

Cytochrome P4S0 and Biological Hydroxylation Reactions Table 1. Cytochrome P450-dependent monooxygenases... 

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