Steroidal substrates, oxidative transformations

Iglesias-Arteaga and coworkers have reported several (diacetoxyiodo)benzene-promoted oxidative transformations of steroidal substrates (Schemes 3.148 and 3.149) [468 71]. In particular, the treatment of (25f )-3a-acetoxy-5p-spirostan-23-one (370) with (diacetoxyiodo)benzene in basic methanol leads to F-ring contraction via Favorskii rearrangement to afford product 371 (Scheme 3.148) [468],... 

A series of oxidative transformations with iodylbenzene as the co-oxidant of vanadyl bis(acetylacetonate) have been reported [1116-1118]. In the presence of VO(acac)2, iodylbenzene oxidizes A -steroids into epoxides a radical mechanism was suggested for this reaction. Epoxidation of cholest-5-ene-3-one occurred with high a-selectivity, while the remaining substrates gave mainly p-epoxides. Oxidation of trans-dehydroepiandrosterone acetate (818) afforded epoxide 819 (Scheme 3.323) [1116]. 

The natural series of steroids is not necessarily the preferred substrate for aU microorganisms. Greenspan and collaborators (Ap-28) have described oxidation of 17 -hydroxysteroids with Flavobacterium dehydrogenans and -dehydrogenations with Corynebacterium hoagii, which resulted in the transformation of both d and I substrates. 

CYB5A, yielding dehydroepiandrosterone (DHEA), which enters the circulation as DHEA sulfate (DHEAS), a substrate for P450 3A7 in the fetal liver below dashed line in box). In the plaeenta, steroid sulfatase removes the sulfate from 16a-hydroxyDHEAS, and 3PHSD1 oxidizes and isomerizes 16a-hydroxyDHEA, to yield 16a-hydroxyandrostenedione. Placental P450aro and 17PHSD1 catalyze the final transformations to 16a-hydroxyestrone and estriol, respectively. 

Since the beginning of enzyme catalysis in microemulsions in the late 1970s, several biocatalytic transformations of various hydrophilic and hydrophobic substrates have been demonstrated. Examples include reverse hydrolytic reactions such as peptide synthesis [44], synthesis of esters through esterification and transesterification reactions [42,45-48], resolution of racemic amino acids [49], oxidation and reduction of steroids and terpenes [50,51], electron-transfer reactions, [52], production of hydrogen [53], and synthesis of phenolic and aromatic amine polymers [54]. Isolated enzymes including various hydrolytic enzymes (proteases, lipases, esterases, glucosidases), oxidoreductases, as well as multienzyme systems [52], were anployed. 

The substrate can be either endogenous, i.e. involved in the biosynthesis or the biodegradation (steroid, fatty acid) or exogenous, i.e. come from the environment (drug, pesticide, solvent, etc.). In the latter case, the transformation of an exogenous substrate into a hydroxylated derivative affords its solubilization in the aqueous medium, in order to remove it from the body. In particular, the substrate can be, for instance, an alkane (methane mono-oxygenase) oxidized to an alcohol, or an alkene oxidized to an epoxide. The redox mediation chain (see the above section) can be schematized as follows in the case of cytochrome P450 ... 

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