A Preparation of Progesterone-4-C<sup>14</sup>

Thompson, Lee M.; Yates, C.H.; Odell, AL

doi:10.1021/ja01633a093

Cited by 9 publications

(1 citation statement)

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“…One of the earliest examples of this strategy was in the synthesis of labelled steroids, wherein an unlabelled methylene was replaced with a radiocarbon in a three-step protocol [85,86] (Scheme 5): (i) oxidative degradation of an α,β-unsaturated enone to an enol-lactone; (ii) [ 14 C]methyl Grignard addition to give a diketone; (iii) acid or base catalyzed cyclization to regenerate original enone, now labelled at C-4 [78,87].…”

Section: [ 14 C]methyl Sulfonium Saltsmentioning

confidence: 99%

Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors

McCarthy

2000

CPD

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Over the past decade, the increased chemical complexity of new drug candidates has resulted in a parallel need to develop innovative syntheses of carbon-14 labelled pharmaceuticals. Faced with short time-lines and a limited number of labelled precursors, radiochemists have addressed this challenge by developing new reagents and adapting existing technology to labelled syntheses. Selected examples from the recent radiochemical literature illustrate some of the creative strategies used to rapidly solve these synthetic challenges. Examples describing the handling and use of common small molecule reagents, such as carbon-14 labelled carbon dioxide, methyl iodide, cyanide, acetic acids, sulfur and phosphorous stabilized ylides for the synthesis of labelled steroids, prostanoids, nucleosides, pyridines, quinolines, benzazepines and other heterocycles are presented. Several general strategies for radiolabelling are also discussed including the degradation strategy for accessing necessary intermediates and precursors, the radiolabelling of aromatic substrates, transition metal mediated cross-couplings, and the use of chiral auxiliaries for the enantioselective syntheses of radiolabelled pharmaceuticals.

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Section: [ 14 C]methyl Sulfonium Saltsmentioning

confidence: 99%

Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors

McCarthy

2000

CPD

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Syntheses and Uses of Isotopically Labelled Dienes and Polyenes

Zieliński¹,

Kańska²

2009

Patai's Chemistry of Functional Groups

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Introduction Synthesis of Dienes and Polyenes Labelled with Stable Isotopes Synthesis and Uses of Dienes and Polyenes Labelled with Tritium Synthesis and Uses of Dienes and Polyenes Labelled with Radioisotopes of Carbon Synthesis and Uses of Dienes and Polyenes Labelled with Heavy Radioisotopes Isotope Effect Studies with Dienes and Polyenes Acknowledgements

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Synthesis of carbon‐14 and tritiated steroidal 5α‐reductase inhibitors

Shu

Heys

1994

Labelled Comp Radiopharmac

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Summary17P-[N-( 1 , l -Dimethylethyl)carbamoyl]androsta-3,5-diene-4-~~C-3-carboxylic acid ([14C]SK&F 105657) was prepared via a three-step sequence (t-butyl amidation, triflation and carbomethoxylation) starting from androst-4-en-3-one-4-14C-1 7p-carboxylic acid. Its A-ring aromatic analog 17P-[N-(1,1 -dimethylethyl)carbamoyl]estra-1,3,5-(1 O)-triene-3-carboxylic acid (SK&F 105656) was labeled with tritium by means of iridium-mediated exchange methodology.Key Words: 5a-Reductase inhibitors, ring-labeled steroids, iridium-mediated tritium exchange, and 3H NMR. I n t r o d u c t i o nRecent efforts in searching for improved therapeutic agents to treat benign prostatic hyperplasia (BPH) in the aging male population led to the discovery of a series of unsaturated 3-carboxysteroids.1 ,2 These compounds bind to the enzyme human prostatic steroid 5a-reductase via a novel enzyme-NADP+-inhibitor ternary complex, and inhibit the biosynthesis of 5 a -d i h y d r o t e s t o~t e r o n e . 3~4 The latter, though it is essential for normal prostatic growth to reach puberty, also brings about the undesired effect of organ enlargement at a later age, causing, among other physiological symptoms, the indicative blockage of the urinary tract. Suppression of 5a-dihydrotestosterone synthesis would shrink prostate size and provide a potential cure for BPH.1,2 Being potent inhibitors of normal substrate binding to the human prostatic 5a-reductase, SK&F 105657 (1) and the A-ring aromatic analog SK&F 105656 (2), both with a 17P-t-butylcarboxamide, were targeted for further investigation. Experiments designed to profile their

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A Preparation of Progesterone-4-C¹⁴

Cited by 9 publications

References 1 publication

Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors

Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors

Syntheses and Uses of Isotopically Labelled Dienes and Polyenes

Synthesis of carbon‐14 and tritiated steroidal 5α‐reductase inhibitors

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A Preparation of Progesterone-4-C14

Cited by 9 publications

References 1 publication

Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors

Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors

Syntheses and Uses of Isotopically Labelled Dienes and Polyenes

Synthesis of carbon‐14 and tritiated steroidal 5α‐reductase inhibitors

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Product

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A Preparation of Progesterone-4-C¹⁴