The inhibition of 11β-hydroxylation of deoxycorticosterone by metopirone in bovine adrenal perfusions

Levy, Harold; Hwa, Chung; Cargill, D. Innes; Carlo, James J.

doi:10.1016/0039-128x(65)90080-2

Cited by 16 publications

(1 citation statement)

References 15 publications

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“…The structure of 18-OH-DOC was demonstrated by Birmingham and Ward to be in the 20->-18-cyclohemiketal form by near infrared.1 In spite of this there has been confusion in the literature concerning the structure of 18-OH-DOC. 16 For example, Diminguez17 as well as others have observed that there are two interconvertible forms of 18-OH-DOC during paper chromatography. Authentic, crystalline, and chemically synthesized 18-OH-DOC has been said to exhibit the same interconversion when dissolved in polar solvent for an extended time.17 Dominguez argued that the possibility that the structure of the crystalline, chemically synthesized compound is the 18-OH-DOC (presumably in the keto form) and that it interconverts to the hemiketal form in solution cannot be entirely ruled out.…”

Section: Scheme IImentioning

confidence: 97%

18-Hydroxy-11-deoxycorticosterone. Chemical synthesis, structure, and circular dichroism

Li¹,

Birmingham²,

Chan³

1976

J. Org. Chem.

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Hydroxy-11 -deoxycorticosterone (18-OH-DOC) has been prepared in two steps from 18-hydroxyprogesterone in high yield. 18-Hydroxyprogesterone has in turn been prepared in ~20% yield by photolysis of the ethylene ketal of deoxycorticosterone 21-acetate followed by acidic and then basic hydrolysis and column chromatography. The circular dichroic spectra of 18-OH-DOC and related compounds are reported. From the induced circular dichroism of 18-OH-DOC with Pr(dpm)s, it is concluded that 18-OH-DOC has the 20-»-18-cyclohemiketal structure with C-20 having the R configuration.18-Hydroxy-ll-deoxycorticosterone (18-OH-DOC) was first isolated and identified as a naturally occurring steroid from incubated sectioned rat adrenal by Birmingham and Ward in 19611 and by Péron in the same year.2 It was characterized to be in the 20-»-18-cyclohemiketal form. The in vivo secretion of 18-OH-DOC in rats was demonstrated by Cortes et al.3 The endogenous formation of 18-OH-DOC has also been demonstrated in the camel by Race and Wu in 1964,4 and in man by Melby and collaborators,5,6 who isolated and identified 18-OH-DOC from human adrenal vein blood. They obtained levels comparable to those of aldosterone and deoxycorticosterone in normal subjects, and elevated levels in patients suffering from various forms of hypertension, including Cushing's syndrome and essential hypertension.Because of the possibly important role of 18-OH-DOC in the etiology of essential hypertension,7 a careful study of the structure and the biological activities of 18-OH-DOC appears to be necessary. To this end, we embarked on a synthesis of 18-OH-DOC so that a reasonable amount of the steroid may be at hand. When we began our synthetic work, the synthesis of 18-OH-DOC had been described by Pappo in 1959 only in a preliminary communication8 and in U.S. Patents.9 It involves a 15-step synthesis starting from the alkaloid conessine. This ingenious but long synthesis was, however, not practical in our hands. We decided to adopt a simpler synthesis of 18-OH-DOC starting from 18-hydroxyprogesterone according to Scheme II. This route to 18-OH-DOC has been reported by us in preliminary form.10 Recently, several groups have reported on similar preparations with varying degrees of success.11,12 In this paper, we wish to describe in greater detail our synthesis, and some physicochemical studies on 18-OH-DOC and related compounds. Chemical Synthesis. A. 18-Hydroxyprogesterone. As the immediate precursor for the synthesis of 18-OH-DOC, we chose the structurally similar steroid 18-OH-progesterone

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Section: Scheme IImentioning

confidence: 97%

18-Hydroxy-11-deoxycorticosterone. Chemical synthesis, structure, and circular dichroism

Li¹,

Birmingham²,

Chan³

1976

J. Org. Chem.

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Über die adrenale Steroid‐Biosynthese in vitro. III. Selektive Hemmung der Nebennierenrinden‐Funktion

Kahnt

Neher

1966

Helvetica Chimica Acta

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Volumen 49, Fasciculus 1 (1966) -No. 82-83 725 azides with an hexapeptide. The two latter have been obtained from the hexapeptide by the recurring method, using active trichlorophenyl esters.Comparison of the biological activities of these compounds with those of the corresponding analogues still bearing the a-amino group shows that suppression of this amino group decreases the pressoric/antidiuretic ratio of these compounds.Laboratoires de Chimie pharmaceutique SANDOZ S. A., BAle BIBLIOGRAPHIE

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Hydroxylation of reichstein's compound s with cell-free preparations from Curvularia lunata

Zuidweg¹

1968

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metaboli

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The inhibition of 11β-hydroxylation of deoxycorticosterone by metopirone in bovine adrenal perfusions

Cited by 16 publications

References 15 publications

18-Hydroxy-11-deoxycorticosterone. Chemical synthesis, structure, and circular dichroism

18-Hydroxy-11-deoxycorticosterone. Chemical synthesis, structure, and circular dichroism

Über die adrenale Steroid‐Biosynthese in vitro. III. Selektive Hemmung der Nebennierenrinden‐Funktion

Hydroxylation of reichstein's compound s with cell-free preparations from Curvularia lunata

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