Steroids Baeyer-Villiger reaction

While the oxidation of ketones by peracids (Baeyer-Villiger reaction) has been used in steroids mainly for ring cleavage, it has occasionally been applied to 20-ketopregnanes for conversion to 17-acetoxy- or hydroxyandros-tanes. The synthetic utility of this method is limited since reactive double bonds and other ketones are incompatible with the reagent. 

More recently, permaleic acid has been recommended as a very satisfactory reagent for the Baeyer-Villiger reaction. It reacts almost as fast as trifluoroperoxyacetic acid and does not require buffering. Unfortunately, neither of these two reagents has been used extensively on 20-keto steroids a patent claims the conversion of progesterone to testosterone acetate with trifluoroperoxyacetic acid, but a later communication describes the ready reaction of 3-keto-A" -steroids with this reagent. 

Hydroxylation and Baeyer-Villiger reactions carried out by monooxygenation are important in the degradation of a range of terpenoids and steroids. The aerobic degradation of limonene can take place by a number of reactions several of which involve hydroxylation at allylic positions... 

Baeyer-Villiger reactions of steroid ketones [61] have been... 

The Baeyer-Villiger reaction is also effected by biochemical oxidation using the enzyme cyclohexanone oxygenase from Acinetobacter strain NCIB 9871. Cyclohexanone is thus converted into e-caprolactone [1043], and phenylacetone (l-phenyl-2-propanone) is transformed into benzyl acetate. The formation of benzyl acetate from phenylacetone involves the same migration as that in oxidation with peroxytrifluoroacetic acid (equation 387) [1034]. More examples of biochemical Baeyer-Villiger reactions occur in diketones and steroids see equation 397). 

The Baeyer-Villiger reaction of hydroxy ketones and unsaturated diketones is very common in steroids, where it occurs preferentially at the keto group on C-17 and leaves the carbonyls in position 3 intact. 

A detailed examination of OSO4 reactions with A -steroids has been reported." The A-ring conformation of the reactant or derived complex is important in determining the stereoselectivity of these reactions, and the major role of the proximate substituents is to anchor the appropriate conformation favouring a- or /3-attack. Studies on the stereochemistry of electrophilic attack on cholest-5-en-3-one continue." As with bromine chloride," appreciable /3-attack occurs and the 5/3,6j8-epoxide was isolated along with the previously reported 5a,6a-epoxide and the Baeyer-Villiger product, the A-homo-enol lactone (58). Base-catalysed... 

The mono-oxygenases which catalyse a series of oxidations such as hydroxylation, epoxidation, heteroatom oxidation and Baeyer-Villiger oxidation (Figure 2.24), depend on NADH or NADPH and cofactors usually Fe or Cu. A particularly important reaction is the direct incorporation of molecular oxygen into non-activated carbon centres, such as in synthesis of important steroidal drags by microbial 11 dr-hydroxylation of... 

The microbial reaction sequence to testololactone (24) involves an intermediate ester 23 from the first Baeyer-Villiger oxidation that ordinarily undergoes hydrolysis by the esterases present in the fermentation environment. However, the tendency of the ester to undergo hydrolysis and further conversion can be blocked by the use of the potent esterase inhibitor diisopropylfluorophosphate. Most of the reported work417-421 with steroids is concerned with the oxidation of 22 to acetate 23. 

Two different modes of reaction have been reported for steroidal A -3-ketones 20). Potassium persulphate in sulphuric acid gave the 4 0xa"3 ketone (23), considered to arise by an initial Baeyer-Villiger oxidation to the unsaturated lactone (21) as an enol lactone of the C(g)-aldehyde (22) this could suffer further degradation through a second Baeyer-Villiger attack on the aldehyde group [64], Other. workers [6 ] used peroxytrifluoroacetic acid and obtained the 5a-carboxy--4"Oxa 3-ketone (25) and the bridged product (26), apparently derived by an internal aldol condensation of the intermediate lactone-aldehyde (24). 

Alkaline hydrogen peroxide reacts with a jS-unsaturated ketones by a different reaction sequence, exemplified by the behaviour of "A-nor-testosterone 27) [7 ]. The reagent first converts the steroid into the corresponding epoxy-ketone 28) by the mechanism discussed on p. 201, and only then brings about a Baeyer-Villiger oxidation of the ketone function to give the epoxy-lactone (29) as the major product. 

The first indication of the existence of so-called Baeyer-Villiger monooxygenases (BVMOs) was reported in the late 1940s [56]. It was observed that certain fungi were able to oxidize steroids via a BV reaction [56], but two decades elapsed before the first BVMOs were isolated and characterized [57, 58]. All characterized BVMOs contain a flavin cofactor that is vital for the catalytic activity of the enzyme, Furthermore, NADH or NADPH cofactors are needed as electron donors. Careful inspection of all available biochemical data on BVMOs has revealed that at least two discrete classes of BVMOs exist, types I and II [59]. 

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