Synthesis of 13C-Labeled Steroids

Fabrice Dénès; Julien Farard; Jacques Lebreton

doi:10.1055/s-0037-1611914

Synthesis, Table of Contents

Synthesis 2019; 51(23): 4311-4337
DOI: 10.1055/s-0037-1611914

review

Synthesis of ¹³C-Labeled Steroids

Fabrice Dénès

^aUniversité de Nantes, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France Email: jacques.lebreton@univ-nantes.fr

,

Julien Farard

^bAtlanChim Pharma, 3, Rue Aronnax, 44800 Saint Herblain, France Email: jacques.lebreton@atlanchimpharma.com

,

Jacques Lebreton∗

^aUniversité de Nantes, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France Email: jacques.lebreton@univ-nantes.fr

^bAtlanChim Pharma, 3, Rue Aronnax, 44800 Saint Herblain, France Email: jacques.lebreton@atlanchimpharma.com

› Author Affiliations

Abstract

All articles of this category

This review is dedicated to the memory of Dr Anaïs Fournial

Abstract

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 Introduction

2 Hemisynthesis of ¹³C₃-Labeled Steroids via Partial Degradation of the A Ring

2.1 Degradation of the A Ring to an Enol Lactone

2.1.1 Introduction of ¹³C Atom(s) via Claisen Condensation: Turner’s Strategy

2.1.2 Introduction of ¹³C Atom(s) with ¹³C-Labeled 5-(Diethylphosphono)pentan-2-one Ethylene Ketal Based on the Fujimoto–Belleau Reaction

2.2 Degradation of the A Ring and Introduction of ¹³C Atom(s) with [¹³C₃]-1-(Triphenylphosphoranylidene)propan-2-one

3 Construction of the A Ring from an α,β-Unsaturated Ketone with ¹³C-Labeled 1-Iodo-3,3-(ethylenedioxy)butane as Electrophile

4 Construction of the A and B rings: Stork’s Strategy

5 Hemisynthesis with Introduction of ¹³C Atom(s) in the C17 Side Chain

6 Conclusion

Key words

steroids - ¹³C-labeled compounds - hemisynthesis - stable isotope labeling

Full Text

References

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