11 P-Hydroxy steroid

The same electron transfer system operates in the 22-, 20-, and 18-hydroxylations as well as in the 11 -hydroxylation. Further, the identical electron transfer system appears to be pertinent to the system of steroid hydroxylation in testis and ovary. 22-, 20-, 18-, and 11 p-hydroxy-lases are all distributed in the mitochondrial fraction of adrenal cortex, whereas 21- and 17-hydroxylases are located in the microsomal fraction. The electron transfer system in the microsomal steroid hydroxylation has not yet been established. 

In man, hydrocortisone gives mainly 5(3 metabolites, whereas 11 (3-hydroxyandrostenedione, which is also secreted by the adrenal cortex, gives mainly 5 a metabolites. Thus, if hydrocortisone is administered, it would be expected to decrease the normal ratio of 5a to 5P metabolites. Hence, the ratio of 5a to 5 P metabolites in the 11-oxygenated-17-oxo steroid metabolites of hydrocortisone and of 11 P-hydroxy-... 

Stewart, P.M., A.M. Wallace, R. Valentino, et al. 1987. Mineralocorticoid activity of liquorice 11-beta-hydroxy steroid dehydrogenase deficiency comes of age. Lancet 2(8563) 821-824. 

The steroids aldosterone, cortisone, cortisol, 11-P-hydroxyandrostenedione, corticosterone, and rostenedione, 11-desoxycorticosterone, 17-hydroxy-progesterone, and progesterone have been performed on Ultrasphere ODS using methanokwater.19 Ranitidine N-[2-[[[5-[(dimethylamino)methyl]-2-furanyl]-methyl]thio]ethyl]-N1-methyl-2-nitro-l,l-ethenediamine has been separated using a p-Bondapak C18 column operated with acetoni-trile methanol water buffered with triethylamine phosphate.117 Pyridoxal-5 -phosphate and other B6 vitamers, including pyridoxamine phosphate, pyri-doxal, pyridoxine, and 4-pyridoxic acid, were separated as bisulfite adducts... 

The adrenal glands secrete over 50 different steroids, the most important of which are aldosterone and hydrocortisone. Aldosterone causes salt retention in the body. It is not commercially available. Hydrocortisone is useful for its anti-inflammatory and antiallergic activity. Cortisone and its derivatives have similar activity and it is reduced in vivo to hydrocortisone. The two substances are used to treat rheumatoid arthritis. The 11-P-hydroxyl of hydrocortisone is believed to be of major importance in binding to the receptors of enzymes. Anti-inflammatory activity is significantly Increased by various substituents 6a-fluoro, 9a-fluoro, 21-hydroxy, 2a-methyl, 9a-chloro, and a double bond at C-1. 

Fig. 6.12. Gradient CEC separation of derivatized neutral steroids. (Reprinted with permission [38], Copyright 2000 Elsevier). Conditions Column 35 cm (active length 25 cm) x 100 pm i.d., mobile phase gradient of acetonitrile-water-240 mmol/L phosphate buffer pH 3 from 35 60 5 to 65 30 50 in 15 min 600 V/cm injection 100 V/cm for 10 s. Peaks labeling reagent 1, progesterone 2, 11 P-hydroxyandrosterone 3, dehydroisoandrosterone and equiline 4, estrone 5, androsterone 6, 19-hydroxy-4-androsterone-3,17-dione 7, 5-a-androstan-17-one 8.

Fig. 44.22. Biosynthesis of the adrenocorticoids from cholesterol. The enzymes involved are (a) side chain cleavage, b) 17a-hydroxylase, (c) 5-ene-3p-hydroxy-steroid dehydrogenase, (cf) 3-oxosteroid-4,5-isomerase, (e) 21-hydroxylase, (f) 11 p-hydroxylase, and (g)...

Hydroxy steroids are important as direct precursors to 19-norsteioids, but are not readily obtainable by microbial hydroxylation without additional nuclear substitution. However a strain of Pellicularia filamentosa ° will 19-hydroxylate cortexolone (82 equation 28) successfully. 11 Hydroxylation of cortexolone derivatives can be accomplished in up to 86% yield using a mutant strain of CurvuUuia lu-naffl (PERM P-8515). O... 

The Schering synthesis of a A9,11-intermediate, essentially by dehydration of an 1 la-hydroxy intermediate, always resulted in the formation of approximately 10% (frequently more) of an unwanted A11,12-olefine. Formation of this impurity not only diverted valuable starting steroid into useless product, but also caused purification problems in later process steps. Although dehydration of 9 a-hydroxysteroids can lead to formation of a A8,9-olefine impurity (see (footnote 92(a)), this unwanted reaction has been shown to be avoidable [see Beaton, J. M., Huber, J. E., Padilla, A. G., and Breuer, M. E. U.S. Patent 4,127,596, 1978 (to Upjohn) and VanRheenen, V., and Shephard, K. P. J. Org. Chem., 1979, 44, 1582.]... 

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