22-hydroxylated steroid side chains

They are used to prepare heterocycles such as 1,2-dihydropyridines, the pyrrolizidine alkaloid (+)-isoretronecanol and J-butyrolactone, and couple with allyIX to give 1,5-dienes. ot-EthoxybutenylSnBu is intermediate in the preparation of dihomoallyl ethers, and Me vSnCH2 allyl ethers provide for chiral transfer in the stereospecific synthesis of hydroxylated steroid side chains. The... 

Further exploration125 of the stereochemistry associated with modification of the steroidal side-chain into that of steroidal alkaloids such as solanidine (139) and tomatidine (140) has revealed that on formation of the furan ring in (140) tritium in the 16/8-configuration of cholesterol [as (143)] is retained but appears now in the 16a-configuration. Retention of the tritium excludes a C-16-oxo-intermediate, and the fact that an inversion of configuration is observed excludes hydroxylation with normal retention of configuration. Examination of the fate of the cholesterol 16/S-proton on incorporation into solanidine (139) revealed that during solanidine biosynthesis this proton is lost. 

Numerous squalamine analogs have been prepared and examined for biological activity (Figure 9.1). The squalamine structure has been varied through the length of the polyamine chain [41-44] the nature of the anionic functional group [41] the position of the polyamine [43-45], sulfate [45,46], and free hydroxyl [41,43,44,47] on the steroid scaffold the stereochemistry and substitution at C-3, C-7, and C-24 [41-44] the length of the steroid side chain [41,45,46] and the unsaturation of the steroid [43,44]. 

A. The enzyme sterol 27-hydroxylase catalyzes the hydroxylation of carbon 27 of the steroid side chain in the conversion of cholesterol to the primary bile acids. It is a mitochondrial, cytochrome P450 enzyme that has a broad specificity and can act on cholesterol as well as its reduced and hydroxylated metabolites. A deficiency in this enzyme leads to decreased bile acid synthesis and increased conversion of cholesterol to cholestanol. 

Hydroxylation corresponds to hydroxylation of one of the two terminal methyl groups in the steroid side chain. Since such a substitution creates an asymmetric... 

Salmond of the Upjohn Company has reported several methods for the preparation of 25-hydroxycholesterol from the intermediate aldehyde (52). In a most efficient process the aldehyde was condensed with the Wittig reagent (59) obtained in three easy steps from isoprene. The product diene (61) could be selectively oxidized at the 24,25-double bond to give epoxide (62) as a mixture epimeric at C-24. Catalytic hydrogenation concomitantly reduced the 22,23-double bond and the epoxide to give the 25-hydroxylated cholesterol side chain. Reversal of the /-steroid ether... 

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

A significant fraction of the body s cholesterol is used to form bile acids Oxidation m the liver removes a portion of the CsHi7 side chain and additional hydroxyl groups are intro duced at various positions on the steroid nucleus Cholic acid is the most abundant of the bile acids In the form of certain amide derivatives called bile salts, of which sodium tau rocholate is one example bile acids act as emulsifying agents to aid the digestion of fats... 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

The interconversion of alcohols to ketones is a common biochemical reaction. The introduction of hydroxyl groups into toe steroid nucleus and side chain creates a variety of secondary alcohols. Some of these, especially at positions 3, 7, 11 and 17 are frequently oxidised to ketones. 

Sterols are steroid alcohols. They have a P-positioned hydroxyl group at C-3 and one or more double bonds in ring B and in the side chain. There are no further oxygen functions, as in the carbonyl and carboxyl groups. 

---