Sterol side chain

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). 

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

Dias, A.C.P, Cabral, J.M.S. and Pinheiro, H.M. (1994) Sterol side-chain cleavage with immobilized Mycobacterium cells in water-immiscible organic solvents. Enzyme and Microbial Technology, 16, 708-714. 

There is a single report of the dealkylation of a sterol side-chain in the whelk Buccinum undatum [52]. This organism also transformed 3H-lanosterol (33) to cholesterol (1), thus indicating its capability for de novo sterol biosynthesis. 

A comparative calculation of sterol side-chain chemical shifts using both GP and LA rules (394) showed that both are suitable, but the LA results are slightly preferable for signal assignments. It should be noted that revised LA coefficients have been suggested recently (395). The original LA coefficients are given in Table 25. 

Crist, B.V. Li, X. Bergquist, P.R. Djerassi, C. (1983) Isolation, partial synthesis, and determination of absolute configuration of pulchrasterol. The first example of double bioalkylation of the sterol side chain at position 26. J. Org. Chem., 48,4472-9. 

Slotte JP, Jungner M, Vilcheze C, Bittman R (1994) Effect of sterol side-chain structure on sterol-phosphatidylcholine interactions in monolayers and small unilamellar vesicles. Biochim Biophys Acta Biomemhr 1190 435 143... 

Steroids isolated from sponges frequently contain substantially modified side chains, such as those with high degrees of alkylation or other unusual functionalization. Biosynthetic studies have been performed on the mechanism and scope of sterol side-chain dealkylation in sponges ... 

For cholesterol absorption, one can take advantage of the fact that plant sterols (phytosterols) are poorly absorbed by mice and humans despite close structural similarity to cholesterol. Beta sitosterol, for example, differs from cholesterol only by the addition of an ethyl group to carbon 24 of the sterol side chain (see Fig. 10.1). This reduces absorption to 6% (34, 35) as compared to 60-80% for cholesterol. Sitostanol, which has a saturated C5-C6 bond in addition to the ethyl group, is only absorbed at 3% (34, 35) and is widely used as a non-absorbed sterol marker (Fig. 10.1). 

A24(25)-COmp0und, which is then reduced to give the saturated sterol side-chain. This route is further supported by a recent identification of stigmasta-7,24-dien-3/3-ol in higher plants.167 A similar pathway of alkylation operates for the biosynthesis of clionasterol [(24S)-(95)] from cycloartenol in the yellow-green alga Monodus subter-raneus, with the exception that direct reduction of a A24(28)-sterol [cf. (98)], rather than isomerization and then reduction, appears to occur.168... 

Figure 26 (a) The oxidation of alcohols to aldehydes via an hemiacetal intermediate (b) The sterol side chain cleavage reaction via a diol note the formation of an O-based radical intermediate... 

Extensive use is now being made of n.m.r. for structural studies involving sterol side-chains. The separate assignments of C-26 and C-27 in the C n.m.r. spectrum of cholesterol, based upon C-enriched material of biosynthetic origin,have been confirmed by conversion of kryptogenin [(25/ )-3/8,27-dihydroxycholest-5-ene-16,22-dione (12)] into (25S)-27-deuteriocholesterol... 

In addition to animal cholesterol, approximately 200 to 300 mg of plant sterols are ingested daily. The most common plant sterol is P-sitosterol. Plant sterols differ from cholesterol only by small variations on the sterol side chain. Despite their close similarity to cholesterol, plant sterols are poorly absorbed. When plant sterols are administered in amounts of 5 to 15g/day, they significantly inhibit the absorption of cholesterol. Although the mechanism for reducing cholesterol absorption has not been determined, plant sterols have been used therapeutically in patients with elevated plasma cholesterol levels. 

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. 

Steroidal and other rigid alcohols have been used to derive a four-parameter equation for the calculation of 13C chemical shifts due to substitution by the OH group.57 Calculated 13C chemical shifts for all the likely saturated sterol side-chains with from seven to eleven carbon atoms have been tabulated and compared, where possible, with published data.58 Good agreement is found in most cases, with standard deviations of ca. 1 p.p.m. Only C-20, attached to the steroid nucleus, showed serious deviations (ca. + 5 p.p.m.) from calculated values. The results will be useful in future structural assignments of new sterols. 

Selective degradation of tiie sterol side chain... 

Fig. 4. Mechanisms involved in alkylating the 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... 

Synthesis of sterol side chain. Polish chemists have prepared 25-hydroxy-cholesterol (6) from zl -3jS-acetoxyandrostene-17-one (2) in 42% overall yield as formulated. The key step involves alkylation of the anion of the ester (3)... 

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