Sterols side chain degradation

Figure 9.2 Generalised metabolic sequences of sterol side chain degradation by micro-organisms.

Rosloniec KZ, Wilbrink MH, Capyk JK, Mohn WW, Ostendorf M, van der Geize R, Dijkhuizen L, Eltis LD (2009) Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHAl. Mol Microbiol 74 1031-1043... 

Bacterial removal of sterol side chains is carried out by a stepwise P-oxidation, whereas the degradation of the perhydrocyclopentanophenanthrene nucleus is prevented by metaboHc inhibitors (54), chemical modification of the nucleus (55), or the use of bacterial mutants (11,56). P-Sitosterol [83-46-5] (10), a plant sterol, has been used as a raw material for the preparation of 4-androstene-3,17-dione [63-05-8] (13) and related compounds using selected mutants of the P-sitosterol-degrading bacteria (57) (Fig. 2). 

Barbier-Wieland degradation. Stepwise carboxylic acid degradation of aliphatic acids (particularly in sterol side chains) to the next lower homo log. The ester is converted to a tertiary alcohol that is dehydrated with acetic anhydride, and the olefin oxidized with chromic acid to a lower homologous carboxylic acid. 

Selective degradation of tiie sterol side chain... 

Microbial cleavage of sterol side-chains has been reviewed. Nocardia sp. M29-40 is reported to degrade /8-sitosterol to the hydroxyhexahydroindanone... 

Production Testosterone and its derivatives as well as the unnatural A. and anabolic agents are industrially produced currently either by total synthesis or from an-drost-4-ene-3,17-dione, obtained by microbial side chain degradation from sterols. 

Although the yeast sterol ergosterol (I) is at the present time not so cheap as diosgenin and its side-chain degradation to pregnane derivatives is more involved, it exhibits the marked advantage over all other readily available ring C unsubstituted steroids in that it already possesses the A -diene system, which in the other instances has first to be introduced. 

Steroids and sterols Hydroxylation, dehydrogenation, side chain degradation, hydrolysis, peroxidation, reduction, isomerization, and conjugation Maxon (1985)... 

Processing Raw Materials. Along with the aforementioned chemical methods of processing steroid raw materials, microbial transformations have been and are used in a number of commercial degradation processes. The microbial degradation of the C17 side chain of the two most common sterols, cholesterol (2) and P-sitosterol (41), is a principal commercial method for the preparation of starting materials in Japan and the... 

Figure 9.3 The figure shows the degradation of the side chain of sterols which have substitutions at C-19. Removal of the C-19 methyl group (eg 19 norchoiesta-1,3,5 (10) triene-3-ol) also prevents ring breakdown. Note, however, hydroxylation of C-19 does not prevent all ring modifications.

The organism would probably grow quite well. The structure shown is simply analogous to the acetyl ester of cholesterol except that the side chain has been removed. The organism would, presumeably, degrade the sterol nucleus by its normal route. 

The organism would probably only show slight growth. It would be able to degrade the side chain in the normal way, but the hydroxyl group in position 19 blocks the metabolism of the sterol nucleus. Thus only a small portion of the molecule can be catabolised. 

Degradation of the sterol stigmasterol to progesterone is achieved by the sequence shown in Figure 5.120. The double bond in the side-chain allows cleavage by ozonolysis, and the resultant aldehyde is chain shortened via formation of an enamine with piperidine. This can be selectively oxidized to progesterone. In this sequence, the ring A transformations are carried out as the... 

Recently, special microbial mutants have been developed which are able to degrade the C-17 side chain of sterols, such as cholesterol (5) and sitosterol, with simultaneous introduction of a 9a-hydroxyl group. 

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