Synthesis of multi carbon-13 labeled dexamethasone

Crowe, David F.; Christie, P. H.; DeGraw, Joseph I.; Fujiwara, Allan N.; Grange, Emma; Lim, Peter; Tanabe, Masato; Cairns, Thomas; SKELLY, G.

doi:10.1016/s0040-4020(01)91549-2

Cited by 9 publications

(9 citation statements)

References 21 publications

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“…One major drawback of this semisynthetic approach 33 of dexamethasone 49 multiply labeled with 13 C atoms is the availability of the starting material, 16-methylcorticoid 52, which is restricted to a few suppliers in limited quantities and at high prices. Nevertheless, 16-methylcorticoid 52 could be easily prepared from commercially available prednisone 45 via the key precursor tetraene 53 [21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione (price around 25 g/€500)] (Scheme 9).…”

Section: Scheme 8 Retrosynthetic Analysis Of Degraw and Co-workers Apmentioning

confidence: 99%

“…[37][38][39] The degradation of the A,B-ring system of 16-methylcorticoid 52 to prepare the key -enol lactone 51 is outlined in Scheme 10. 33 After protection of the 1,3-dihydroxyacetone side chain at C17 of 52 as the bis(methylenedioxy) (BMD) derivative 56 under standard conditions, followed by A-ring aromatization and concomitant demethylation with zinc in water containing DMF, 40,41 the resulting 3-hydroxyestratetraene 57 was treated with Me 2 SO 4 to provide the 3methyl ether 58 in 35% overall yield after crystallization. Next, Birch reduction of 58 with Li in NH 3 at -78 °C provided the reduction of the C9-C11 double bond to afford the protected derivative 59 in nearly quantitative yield, as a sin-…”

Section: Scheme 8 Retrosynthetic Analysis Of Degraw and Co-workers Apmentioning

confidence: 99%

“…At this stage, the A,B-ring system of [ 13 C 3 ]-dexamethasone 49 was reconstructed from enol lactone 51 with [ 13 C 3 ]-5-(diethylphosphono)pentan-2-one ethylene ketal 50 (Scheme 12). In the experimental section of this publication, 33…”

Section: Syn Thesismentioning

confidence: 99%

“…32 Steroidal enol lactone 46 was treated with 14 Unfortunately, this approach is not suitable for the introduction of multiple labeled carbon atoms into the A ring of steroids. In 1983, DeGraw and co-workers 33 successfully utilized the Fujimoto-Belleau reaction to introduce up to five 13 C atoms into the A ring of the steroid skeleton to prepare [1,2,3,4,10-13 C 5 ]-dexamethasone 49 and its [2,3,4-13 C 3 ]-49 isotopologue from enantiopure -lactone 51 (prepared starting from 16-methylcorticoid 52) with [1,2,3,4,5-13 C 5 ]-5-(diethylphosphono)pentan-2-one ethylene ketal 50 and its isotopologue [1,2,3-13 C 3 ]-50, respectively (see Scheme 8). In this approach, the crucial issue is the access to the desired C,D-steroid nucleus, some of which have been obtained through microbial degradation of sterols 34 or by multistep synthesis.…”

Section: Introduction Of 13 C Atom(s) With 13 C-labeled 5-(diethylphomentioning

confidence: 99%

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Synthesis of 13C-Labeled Steroids

Dénès

Farard²,

Lebreton

2019

Synthesis

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Due to the wide spectrum of biological activities of steroids, the detection and quantification of steroidal residues in various biological materials are crucial for drug development, doping prevention, and environmental protection. In addition, the analytical technique of stable isotopic dilution (SID) by Liquid Chromatography-Mass Spectrometry (LC-MS) requires 13C-labeled steroids as standards to provide accurate and reproducible steroid quantification. In this context, the synthesis of 13C-labeled steroids is reviewed. The approaches based on partial synthesis starting from commercially available steroids have been, by far, the most commonly employed strategy.1 Introduction2 Hemisynthesis of 13C3-Labeled Steroids via Partial Degradation of the A Ring2.1 Degradation of the A Ring to an Enol Lactone2.1.1 Introduction of 13C Atom(s) via Claisen Condensation: Turner’s Strategy2.1.2 Introduction of 13C Atom(s) with 13C-Labeled 5-(Diethylphosphono)pentan-2-one Ethylene Ketal Based on the Fujimoto–Belleau Reaction2.2 Degradation of the A Ring and Introduction of 13C Atom(s) with [13C3]-1-(Triphenylphosphoranylidene)propan-2-one3 Construction of the A Ring from an α,β-Unsaturated Ketone with 13C-Labeled 1-Iodo-3,3-(ethylenedioxy)butane as Electrophile4 Construction of the A and B rings: Stork’s Strategy5 Hemisynthesis with Introduction of 13C Atom(s) in the C17 Side Chain6 Conclusion

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Section: Scheme 8 Retrosynthetic Analysis Of Degraw and Co-workers Apmentioning

confidence: 99%

Section: Scheme 8 Retrosynthetic Analysis Of Degraw and Co-workers Apmentioning

confidence: 99%

Section: Syn Thesismentioning

confidence: 99%

Section: Introduction Of 13 C Atom(s) With 13 C-labeled 5-(diethylphomentioning

confidence: 99%

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Synthesis of 13C-Labeled Steroids

Dénès

Farard²,

Lebreton

2019

Synthesis

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“…The keto acid 15, which was obtained through ozonolysis of 14 in CH 2 Cl 2 at -78 °C in the presence of a small amount of pyridine, and treatment with 30% hydrogen peroxide overnight, was then dehydrated with acetic anhydride and sodium acetate to provide the enol lactone derivatives 16a and 16b. 16 Reaction of 16a and 16b with methyllithium in anhydrous THF at -35 °C for 2 hours, fol- The two hydroxyl groups of 12 were protected to give 11 in an excellent yield. Under Wasserman oxidation conditions, 18,19 11 was transformed to 10 via 18 in a high yield.…”

Section: Scheme 2 Retrosynthetic Analysis Of 319-dihydroxyjolkinolidmentioning

confidence: 99%

Synthesis of Novel 3,19-Dihydroxyjolkinolides and Related Derivatives Starting from Andrographolide

Wang

Yang

et al. 2016

Synthesis

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The jolkinolides are a series of naturally occurring ent-abietane diterpenes with potent antitumor activity, which have been isolated from the genus Euphorbia. We describe the first method for the total synthesis of 3,19-dihydroxyjolkinolide and its derivatives. The strategy for the synthesis of 3,19-dihydroxyjolkinolide A has 12 steps with an overall yield of 4.3%. The synthesized compounds were evaluated for their antitumor activity in nine kinds of tumor cell lines.

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TheBirch Reduction of Aromatic Compounds

Rabideau

Marcinow²

1992

Organic Reactions

131

138

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The reduction of aromatic compounds by alkali metals in liquid ammonia represents an important method for the preparation of partially unsaturated six‐membered rings. The reaction was discovered by Wooster and Godfrey, but the major development resulted from the efforts of A. J. Birch, and the reaction has since come to bear his name. Although a variety of metals can be used, the most common are sodium and lithium, and, to a lesser extent, potassium. Cosolvents such as ether or tetrahydrofuran (THF) are often used to improve solubility, and weak acids such as alcohols may be employed during the reaction as proton sources. The latter are necessary for the reduction of benzene and its unactivated derivatives. Improvement in experimental procedures by Wilds and Nelson, the application to polynuclear compounds by Hückel and later by Harvey, and the development of methods for the alkylation of the anions generated in this process (i.e., reductive alkylation) have made this reaction an important approach to the synthesis of a wide variety of organic compounds.

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Synthesis of multi carbon-13 labeled dexamethasone

Cited by 9 publications

References 21 publications

Synthesis of 13C-Labeled Steroids

Synthesis of 13C-Labeled Steroids

Synthesis of Novel 3,19-Dihydroxyjolkinolides and Related Derivatives Starting from Andrographolide

TheBirch Reduction of Aromatic Compounds

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