IMPROVED PREPARATION OF 14β-Hydroxyprogesterone

Templeton, J. F.; Yan, Yuhao

doi:10.1080/00304949209355689

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…3β-Acetoxypregna-5,14-dien-20-one (12b) 51 and 3β-Acetoxy-17R-pregna-5,14-dien-20-one (13b). 200 mg 11b (0.56 mmol) was diluted in 40 mL xylene.…”

Section: -Hydroxyiminopregnamentioning

confidence: 99%

“…Treatment of 11b with NH 2 OH and deprotection of 11a gave the oxime 11 . For the preparation of compound 12 the method of Templeton and Yan was applied, treating 11b with tri- n -butyltin hydride under irradiation (sunbeam lamps). TLC monitoring revealed the formation of a side product, which was determined by 1 H NMR as the 17α-isomer of the desired Δ14-ketone.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Evaluation of Novel Steroidal Oxime Inhibitors of P450 17 (17α-Hydroxylase/C17−20-Lyase) and 5α-Reductase Types 1 and 2

et al. 2000

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17 alpha-Hydroxylase/C17-20-lyase (P450 17, CYP 17) and 5 alpha-reductase are the key enzymes in androgen biosynthesis and targets for the treatment of prostate cancer and benign prostatic hyperplasia. In the search of inhibitors for both enzymes, 23 pregnenolone- or progesterone-based steroids were synthesized bearing an oxime group connected directly or via a spacer to the steroidal D-ring. Tested for inhibition of human and rat P450 17, some pregnenolone (9, 11, 14) and a series of progesterone compounds (17-20) turned out to be highly active inhibitors of the human enzyme. The most active compound was Z-21-hydroxyiminopregna-5, 17(20)-dien-3 beta-ol (9) showing K(i) values of 44 and 3.4 nM for the human and rat enzymes, respectively, and a type II UV-difference spectrum indicating a coordinate bond between the oxime group and the heme iron. In contrast to the pregnenolones which showed no inhibition of 5 alpha-reductase isozymes 1 and 2, the progesterones 16, 17, 20, 21, and 23 showed marked inhibition, especially toward the type 2 enzyme. Compounds 17 and 20 were identified as potent dual inhibitors of both P450 17 and 5 alpha-reductase. Tested for selectivity, the most potent P450 17 inhibitors 9, 10, and 14 showed no or only marginal inhibition of P450 arom, P450 scc, and P450 TxA(2). Selected compounds were tested for inhibition of the target enzymes using whole-cell assays. Compounds 9-11 strongly inhibited P450 17 being coexpressed with NADPH-P450 reductase in E. coli cells, and 16, 20, and 23 markedly inhibited 5 alpha-reductase expressed in HEK 293 cells. Tested for in vivo activity, 9 (0.019 mmol/kg) decreased the plasma testosterone concentration in rats after 2 and 6 h by 57% and 44%.

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“…3β-Acetoxypregna-5,14-dien-20-one (12b) 51 and 3β-Acetoxy-17R-pregna-5,14-dien-20-one (13b). 200 mg 11b (0.56 mmol) was diluted in 40 mL xylene.…”

Section: -Hydroxyiminopregnamentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Synthesis and Evaluation of Novel Steroidal Oxime Inhibitors of P450 17 (17α-Hydroxylase/C17−20-Lyase) and 5α-Reductase Types 1 and 2

et al. 2000

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“…For the synthesis, see: Templeton & Yan (1992); Fell & Heathcock (2002). For background on hecogenin, see: Ranu & Samanta (2003).…”

Section: Related Literaturementioning

confidence: 99%

“…The title compound was prepared according to the literature method (Fell & Heathcock, 2002;Templeton & Yan 1992).…”

Section: S2 Experimentalmentioning

confidence: 99%

3β,12β,14α-Trihydroxypregnan-20-one

Shi

2009

Acta Cryst E

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The title compound, C21H34O4, is a steriod of the pregnane family prepared by the sequential oxidation and reduction of 3β,12β-diacetoxy-20-ethylenedioxypregnan-14-ene. The conformations of the six-membered rings are close to chair forms, while the five-membered ring adopts an envelope conformation. All the rings are trans-fused and an intramolecular O—H⋯O hydrogen bond occurs. In the crystal structure, intermolecular O—H⋯O hydrogen bonds link the molecules into a two-dimensional network.

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“…54 The stereoselective generation of cis and trans AB-junctions in steroids can be achieved by palladiumcatalysed [Pd(OAc),PBu,] hydrogenolysis of 3a-formyloxy-A5steroids (leading to the m-cis configuration) or 3P-formyloxy-A5-steroids (leading to the AB-trans config~ration).~~ An improved preparation of A6* 14-7-ketones consists of a regioselective one-pot oxidation of A7-steroids with SeO, in acetic acid (without isolating the intermediate 7a-acetoxy-A87 14steroid), followed by CrO, oxidation to give the 8a,l4a-epoxy-7-oxosteroid. Reduction of the latter with zinc in acetic acid provides (53) or (54) in 38 YO and 43 YO overall yield, respectively. They are suitable starting compounds for the synthesis of 14asubstituted steroids.…”

Section: Unsaturated Compoundsmentioning

confidence: 99%