Corticosterone acetate

A photochemical partial synthesis of aldosterone (19) made the hormone available on an industrial scale for the first time (114). Corticosterone acetate (51 acetate) is treated with nitrosyl chloride in pyridine at 20°C to yield the 11-nitrite (115). Irradiation of (115) leads to rearrangement with formation of the C g-oxime (116). Removal of the oxime residue with nitrous acid furnishes aldosterone (19) in excellent yield. 

Favorably situated carbonyl groups under certain circumstances, interact with the newly formed oxime. Thus, during the irradiation of corticosterone acetate-11-nitrite (27, R = NO), the nitrone12 (33) was formed the latter was also obtained from the oxime by thermal treatment and by heating at reflux in a polar solvent. This transformation is represented as outlined (30-33). 

Among the numerous applications of this reaction reported over four decades, some typical examples of the functionalization are outlined in Schemes 3 to 10. Thus, Scheme 3 outlines the well-known Barton transformation of corticosterone acetate nitrite into aldosterone acetate oxime which, with nitrous acid, gives aldosterone 12-acetate [4]. The yield of 18-oxime is, however, rather low (21 %), since attack by the 11/3-alkoxyl radical on C-19 competes with the desired attack on C-18. Incorporation of the 1,2-double bond into the nitrite prevented undesired C-19 attack by the radical and a far better yield (47 %) of 18-oxime was achieved [5] (Scheme 4). This example may indicate that the Barton reaction is sensitive to... 

Scheme 3. Transformation of corticosterone acetate nitrite into aldosterone 21-acetate.

For the synthesis14 of 11-deoxy-corticosterone acetate, a convenient starting material was the readily available alcohol 39. On photolysis under oxygen, the corresponding nitrite gave the desired nitrate 40. Standard oxidation, hydrolysis and Oppenauer oxidation gave 18-nitrate 41 which was readily reduced under mild conditions with zinc dust to give the 18-... 

Barton reaction In the Barton reaction " a methyl group in the 7 -position to an OH group is converted into an oxime group. For example, corticosterone acetate (2.45) on reaction with nitrosyl chloride (NOCl) in pyridine forms its 1 l -nitrite 2.46, which on photolysis in toluene gives aldosterone acetate oxime (2.47) in 21% yield. Treatment of 2.47 with nitrous acid (HNO2) gives aldosterone acetate (2.48) (Scheme 2.40). 

Pyka separated six selected steroids (corticosterone acetate, 11-dehydrocorticosterone acetate, corticosterone,... 

Trihydroxy-5a-pregnan-20-one 30,11(1,21 -triliydroxy-20-oxo-5o-pregnane Reichstein s substance R. Cj,Hw04 mol wt 350.48. C 71.96%. H 9.78%. O 18.26%. Isolation from adrenal glands Reichstein, von Euw, l civ Chim. Acta 21, 1197 (1938) Reichstein. ibid. 1490. Partial synthesis by hydrogenation of corticosterone acetate Pataki Cl of., J. 

Ehrenstein M. Investigations on steroids. VIII. Lower homo log ues of hormones of the pregnane series 10-nor-11-desoxy corticosterone acetate and 10-norprogesterone. J Org Chem 1944 9 435-456. 

The steroids corticosterone acetate, 11-dehydrocortisone acetate, corticosterone, 11-dehydrocorticosterone, hydrocortisone, and cortisone have been separated by RP-HPTLC. The chromatographic data (Bm) and partition coefficient (logF) values of the compounds have been correlated with the numerical values of topological indices. The most accurate predictions of the Bm and logF values of the selected steroids were achieved by the use of monoparametric equations employing the topological index... 

Pyka separated six selected steroids (corticosterone acetate, 11-dehydrocorticosterone acetate, corticosterone, 11-dehydrocorticosterone, hydrocortisone, and cortisone) by RP-HPLC on Separon Six Cig column. Column void time was determined using the peak derived from a solution of sodium nitrite in methanol. The mobile phase was prepared from analytical grade methanol and redistilled water (3 2, v/v). The Randic (, Wiener... 

Normally the reaction of thiols with carbonyls, saturated or unsaturated, leads to the formation of dithioacetals when acid catalysts such as zinc chloride or p-toluene-sulphonic acid are present (see section II.A. 1). Occasionally, under special reaction conditions thioenol ethers have been formed using these same catalysts but never in the presence of acid-sensitive substituents. Pyridine hydrochloride as the catalyst has been successfully used to give excellent yields of the thioenol ethers of A -3-ketosteroids even in the presence of sensitive groups . Thus, desoxy-corticosterone acetate (92) was converted to its 3-benzylthioenol ether... 

The Barton nitrite photolysis was used in the conversion of nitrite of corticosterone acetate (5) to 6 during the synthesis of aldosterone actetate. ... 

These examples are the most weU-known applications of the reaction found by Barton as well as by his colleagues. The irradiation of corticosterone acetate nitrite affords aldosterone acetate oxime, which with nitrous acid gives aldosterone 12-acetate (Scheme 13). The overall yield, however, is rather low (15%) because an attack by the lip-alkoxyl radical on C19 competes with the desired attack on CIS. The incorporation of the 1,2-double bond into the nitrite could avoid an undesired C19 attack by the radical a far better yield (47%) of 19-oxime was achieved, as shown in Scheme 14. These examples of the functionalization may indicate that the Barton reaction is sensitive to structural changes and that the distance and conformation requirements between the alkoxyl radical and the methyl group, which are in a 1,3-diaxial relationship, is rather strict (Scheme 14). 

Aq. NaBH4 added dropwise at 20 to a stirred soln. of corticosterone acetate in dimethylformamide, and the product isolated after 1 hr. zl -pregnen-ll, 20), 21-triol-3-one 20) -acetate. Y 77%.—Mild base catalysis is strikingly effective in promoting acyl migration in the above case. F. e. without acyl group migration s. D. Taub, R. D. Hoffsommer, and N. L. Wendler, Am. Soc. 81, 3291 (1959). 

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