Sitosterol, degradation

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). 

Szederkenyi, F. Ambrus, G. Horvat, G. Ilkov, E. N-Methoxy N,0-bis-TMS carbamate as a derivatization reagent for the gas chromatography of sitosterol degradation products. J. Chromatogr. 1988, 446, 253-257. 

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... 

Sterols are seldom detected in archaeological residues due to their low concentration and the tendency to undergo chemical degradation. In any case, the presence of sterols or of their oxidation products in a sample can help distinguish between animal and plant lipid materials cholesterol is the most abundant animal sterol, while campesterol and sitosterol are the two major plant ones. 

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. 

These mutants are protected by several patent publications, e.g., Mycobacterium species CBS174 obtained from Mycobacterium species NRRL, Mycobacterium vaccae ZIMET 11052175 obtai ned from M. vaccae NRRL-B-3805, Mycobacterium roseum sp. nov. 1108/1 176, and Mycobacterium fortuitum NRRL-B-8119177 obtained from M.fortuitum ATCC 6842. Furthermore, Mycobacterium fortuitum NRRL-B-12433178, a double mutant obtained from M. fortuitum NRRL-B-8119, is able to partially degrade the side chain of sitosterol (7), with concomitant 9a-hydroxylation, to give the pregnadiene-20-carboxylic acid 8. 

Sitosterol (24-ethylcholesterol) is degraded to desmosterol (A -cholesterol) in the silkworm Bombyx mori, through the (245,285)-epoxide. The stereochemical features of the isomeric 24,28-epoxides and the derived 24,28-glycols have been worked out by a combination of physical and chemical methods. a,/8-Epoxyoximes give trans-a-alkyl-/8-hydroxy-ketones by reaction with lithium dialkylcup-rate and deoximation, a procedure with potentialities for alkylation in steroid chemistry. ... 

SITOSTEROL Sitosterol is another phytosterol and is an analogue of stigmasterol with a saturated side chain. It is obtained from soy oil and com oil. The side chain cannot be degraded chemically, but microbiologically it is possible to produce intermediates of valne to the steroid industry. Sitosterol can therefore be used as a starting material for the synthesis of steroid hormones. 

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

Besides cholesterol, other S. such as pregnane derivatives, bile acids, and phytosterols are also degraded, principally to androsta-l,4-diene-3,17-dione. These microbial processes have been developed in the last two decades to an industrial process for the degradation of cholesterol and sitosterol (about 100(XK) t/a of each) to androsta-l,4-diene-3,17-dione (ADD), an-drost-4-ene-3,17-dione (AD), and 9a-hydroxy-AD for use in the partial synthesis of hormonally more active S. . 

At the end of the I970 s the microbial processes for side chain degradation of cholesterol and sitosterol to androsta-1,4-diene-3,17-dione, androst-4-ene-3,17-dione, and its 9a-hydroxy derivative had been developed to such a state of industrial efficiency that these new raw material sources now serve for the economic production of most of the medically important S. The only exceptions are some corticosteroids, especially those with substituents at C-16, which are still prepared from steroid sapogenins, and a number of 19-nor-S. for which high-yield total syntheses are available. For details on the analysis of S., see Lit.. ... 

Like the flatworms, insects cannot synthesize steroids and so they degrade the plant steroids, stigmasterol and sitosterol, to obtain their essential cholesterol. The special enzymes used for this purpose are suitable targets for selective attack, because most other forms of life synthesize their steroids de novo. 

From the ether-soluble fraction, Takahashi etal. 134, 135) isolated sitosterol-P-D-glucoside, sitosterol, p-elemene (96), eremophilene (97) and a new polyacetylenic alcohol named panaxynol (98), the structure of which was elucidated as heptadeca-l,9(Z)-diene-4,6-diyn-3-ol by degradative and synthetic procedures. It is identical with carotatoxin from carrots 136) and falcarinol from Falcaria vulgaris 137). Recently two other polyacetylenic alcohols, 9,10-epoxy-3-hydroxyheptadeca-l-en-4,6-diyne [(99), panaxydol] 138) and heptadeca-l-en-4,6-diyn-3,9-diol (100) 139) were isolated from Ginseng roots by Wrobel et al. 

Japanese Patent 30915 (1964) Derwent Abstr. 19, 293). Degradation of cholesterol, sitosterol, or stigmasterol by Corynebacterium simplex and other known 1-dehydrogenating species, in the presence of agents which chelate copper or iron, to give 4-androstene 3,17-dione, l,4-androstadiene-3,17-dione, and other products. 

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