Steroid oxides as potential precursors in the biosynthesis of estrogens

“…Androst-4-ene-3.17-dione, 19-dl (19-dl-2b) Jones' oxidation of 19-dl-& (0.16g) afforded 19-dl-2b (0.12 g, 76%); lH nmr included signals at 6 0.92 (3H, s, C-18H), 1.22 (2H, s, C-19H), and 5.8 (IH, s, C-4H) ppm; 2Hnmr: see Table 1; ms mle (%): 287 (loo), 272 (14), 269 (13), 259 (20), 245 (96). Isotopic content: see Table 1.…”

Section: (28) 273 (5) 247 (28) 125 (100) Isotopic Content: Seementioning

confidence: 99%

“…2) (7-9), 2P hydroxylation to give 24 (10,11), enzymic "Baeyer-Villiger" oxidation to give the ester 25 (12), or epoxidation to 26 (13,14). The possible involvement of a As steroid via a 5,6 epoxide has also been suggested (13). The proposed pathways for the aromatization of the aldehyde 22 are based on the experimental observations of the release of C-19 as formate (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Several of the mechanisms proposed for the aromatization of 22 have included intermediates in which the A4 double bond is rearranged to the A5(10)position (1,13) or the position (13), and so a knowledge of the fate of the C-4 and C-6 hydrogens of 2a or 2b during conversion to the estrogens is desirable. In addition, the use of C-19-deuterium labelled steroids enables the kinetic isotope effect, kH/kD at C-19, for the aromatization to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Enzymic aromatization of deuterium labelled testosterone and androst-4-ene-3,17-dione

Holland¹,

Taylor²

1981

Can. J. Chem.

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The preparation and aromatization by human placental microsomes of androst-4-ene-3-ones labelled with deuterium at C-4, C-6α, C-6β, C-16, and C-19 is described. Deuterium nmr spectra are reported for these compounds and for a sample of a 1,2-dideuterated androst-4-ene-3-one; the latter is formed nonstereospecifically by reduction of the C-1(2) double bond of a Δ1,4-diene-3-one. Aromatization by placental microsomes occurs with retention of deuterium at C-4 and C-6, but with some loss from C-16. The aromatization of 19-d1 and 19,19,19-d3 steroids in the presence of 16,16-d2 steroids has been carried out to determine the deuterium isotope effect for the oxidative removal of C-19. The values obtained (kH/kD for 19-d1 = 2.3, kH/kD for 19,19, 19-d3 = 3.2) are a combination of primary and secondary effects, but suggest that oxidation at C-19 is a rate-limiting reaction of the biosynthetic sequence.The fungus Pellicularia filamentosa NRRL 2727, reported to hydroxylate androst-4-ene-3,17-dione at C-19, gave only the products of hydroxylation at C-11α, C-11β, and C-14.

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Design and action of steroidal aromatase inhibitors

Parish

1996

J Americ Oil Chem Soc

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The biosynthesis of estrogens involves three sequential hydroxylations, progressing from cholesterol, that are mediated by an enzyme complex referred to as aromatase. The last steps in this sequence involve aromatization of the A ring of the steroid nucleus. Compounds that inhibit aromatase have potential applications in the treatment of advanced estrogen‐dependent mammary carcinoma and prostatic hyperplasia. The enzyme aromatase is currently a priority target for the development of active‐site directed inhibitors. A number of steroid inhibitors may inactivate aromatase by diverse interactions with the enzyme and include competitive inhibitors, affinity labelling agents, and mechanism‐based inhibitors (“suicide substrates”). By designing steroidal analogs with substituents at various positions on the steroid nucleus, information has been obtained on the structural requirements needed for favorable interactions with the enzymatic sites.

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Steroid oxides as potential precursors in the biosynthesis of estrogens

Cited by 5 publications

References 21 publications

19-Hydroxy-steroids. Part 7. Boron trifluoride-catalysed reactions of 19-hydroxy- and 19-acetoxy-5,6-epoxy-steroids

19-Hydroxy-steroids. Part 7. Boron trifluoride-catalysed reactions of 19-hydroxy- and 19-acetoxy-5,6-epoxy-steroids

Enzymic aromatization of deuterium labelled testosterone and androst-4-ene-3,17-dione

Design and action of steroidal aromatase inhibitors

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