Ergosterol hydrogenation

Ergosterol (a triene) rapidly takes up 1 mole of hydrogen selectively to give 5a,6-dihydroergosterol, recrystallized from methanol-chloroform, mp 173-174°. 

We have already reported that the use of cyclohexanol at 140°C in the hydrogenation of ergosterol over Cu/A1203 gives the 5(5 derivative with an 81% selectivity owing to an intramolecular hydrogen transfer reaction, whereas direct H2 addition over the same catalyst gives the 5a isomer with 89% selectivity (10) (Scheme 1). 

The biosynthetic pathway of ergosterol is shown in Figure 15 to explain the steps of inhibition by morpholines the accumulating sterols are framed. Inhibition of the A -reduction by fenpropimorph should lead to an accumulation of 4,4-dimethyl- A8, -ergo-statriene-ol. However, C -demethylation and side chain hydrogenation are obviously able to occur with the accumulating sterol as substrate... 

Solvent quality controls the hydrogenation of ergosterol (or its acetate) over Raney nickel.116 When pure ethyl acetate is used, for example, reduction proceeds smoothly to 5a -ergost-7-en-3/3-ol, but the presence of a little acetaldehyde, 4-dimethylaminobenzaldehyde, dimethylaniline, or a similar contaminant, stops the reaction at the 7,22-diene stage. 

Imidazoles (ketoconazole, miconazole, fenticonazole, clotrimazole, isoconazole, tioconazole) interfere with fungal oxidative enzymes to cause lethal accumulation of hydrogen peroxide they also reduce the formation of ergosterol, an important constituent of the fungal cell wall which thus becomes permeable to intracellular constituents. Lack of selectivity in these actions results in important adverse effects. 

Bond.— Side chain dehydrogenation is reviewed by Lederer. Unlike the dehydrogenations of the steroid nucleus, introduction of the Irons A -double bond of ergosterol and related steroids does not require the presence of a or A -double bond. However, the suggested formation of ergosta-5,7,22,24(28)-tetraen-3) -ol is supported by incorporation studies. The stereochemistry of this process is species-dependent. In protozoa Ochromonas tetrahymena) the (22R)- and (23S)-hydrogens of cholesterol are lost, i.e. the hydrogens at these positions derived from [2R- H,3R]- and [3R,5R-... 

In yeast, however, the 7a-hydrogen is lost in the A A step. This reaction is inhibited in bramble tissue cultures by the fungicide AY9944. The wide distribution in fungi of considerable amounts of A - -sterols such as ergosterol (12-H) may be due to the absence or low activity of the A reductase in these organisms. The existence of lichesterol (II), a A -sterol has not yet been rationalized biosynthetically. 

An isomerization step is also involved in the hydrogen transfer reaction of steroidal homoallylic alcohols which takes place in the presence of Cu/AlaOa 12). This process recently allowed us to obtain 95% 5P Isomer in the hydrogenation of ergosterol under inert atmosphere while 98% 5a isomer was obtained under Ha pressure with the same catalyst [3],... 

In ergosterol, the Cio methyl group is 3 (coming out of the plane of the paper — solid lines), and the Cs hydrogen is a (going behind the plane of the paper — dotted lines). In stereoisomer IX, both the Cio methyl and the Cg hydrogen are a, while in stereoisomer X, both are 3 ... 

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