Scalable synthesis of the aroma compounds d6-β-ionone and d6-β-cyclocitral for use as internal standards in stable isotope dilution assays

Mosaferi, Shabnam; Jelley, Rebecca E.; Fedrizzi, Bruno; Barker, David

doi:10.1016/j.tetlet.2020.152642

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…For example, deuterated acetone, in addition to being an NMR solvent, is an attractive building block for the introduction of a gem-ditrideuteromethyl fragment. This moiety is recovered in the labeled aroma fragment β-ionone 380 as well as in a leukotriene C4 synthase inhibitor. 381 MK 3814 was investigated as a potential treatment for Parkinson's disease.…”

Section: Multistep Syntheses With Deuterium Incorporationmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017−2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

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Section: Multistep Syntheses With Deuterium Incorporationmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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“…This purification process resulted in the isolation of a molecule, I-4 (2.8 mg, t R = 40 min). This molecule, I-4 , was identified as β -cyclocitral by comparing the MS and 1 H NMR spectral data with the previous literature [ 30 , 31 ]. HR ESI-TOF-MS m/z [M+H] + 153.1217; 1 H NMR (500 MHz, Chloroform-d) Δ 10.13 (s, 1H), 2.19 (t, J = 6.3 Hz, 2H), 2.09 (s, 3H), 1.67–1.58 (m, 2H), 1.47–1.41 (m, 2H), 1.20 (s, 6H).…”

Section: Methodsmentioning

confidence: 87%

β-Cyclocitral from Lavandula angustifolia Mill. Exerts Anti-Aging Effects on Yeasts and Mammalian Cells via Telomere Protection, Antioxidative Stress, and Autophagy Activation

Shan,

Mo,

et al. 2024

Antioxidants

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We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of β-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notable increases in the telomerase content, telomere length, and the expression of the telomeric shelterin protein components telomeric-repeat binding factor 2 (TRF2) and repressor activator protein 1 (RAP1). More interestingly, CYC reversed H2O2-induced telomere damage and exhibited strong antioxidant capacity. Moreover, CYC improved the survival rate of BY4741 yeast under oxidative stress induced by 6.2 mM H2O2, increasing the antioxidant enzyme activity while reducing the reactive oxygen species (ROS), reactive nitrogen species (RNS), and malondialdehyde (MDA) levels. Additionally, CYC enhanced autophagic flux and free green fluorescent protein (GFP) expression in the YOM38-GFP-ATG8 yeast strain. However, CYC did not extend the RLS of K6001 yeast mutants, such as Δsod1, Δsod2, Δcat, Δgpx, Δatg2, and Δatg32, which lack antioxidant enzymes or autophagy-related genes. These findings reveal that CYC acts as an anti-aging agent by modifying telomeres, oxidative stress, and autophagy. It is a promising compound with potential anti-aging effects and warrants further study.

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“…6b). Additionally, we utilized the developed method to access deuterated Bezafibrate (19) 57 , a medication used to regulate lipid levels in the blood. Treatment of d2-TT salt 2f with aryl bromide 4b resulted in the efficient formation of the 5fb product.…”

Section: Synthetic Applicationsmentioning

confidence: 99%

“…This technique enables the introduction of both deuterium atoms and functional groups in a single step, resulting in the construction of a target molecule with easily controllable deuterated sites and a high level of deuterium incorporation. Although this method has been utilized in the synthesis of deuterium-containing drugs [16][17][18][19][20] , its progress has been hindered by the limited availability of readily accessible deuterated reagents. Alkyl halides (I, Br, and Cl) and pseudohalides (OTs, OTf) are widely applied and abundant electrophilic alkylation reagents within the realm of organic synthesis.…”

mentioning

confidence: 99%

Metallaphotoredox deuteroalkylation utilizing thianthrenium salts

Jiao,

Zhang,

Wang

et al. 2024

Nat Commun

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Deuterium labeling compounds play a crucial role in organic and pharmaceutical chemistry. The synthesis of such compounds typically involves deuterated building blocks, allowing for the incorporation of deuterium atoms and functional groups into a target molecule in a single step. Unfortunately, the limited availability of synthetic approaches to deuterated synthons has impeded progress in this field. Here, we present an approach utilizing alkyl-substituted thianthrenium salts that efficiently and selectively introduce deuterium at the α position of alkyl chains through a pH-dependent HIE process, using D2O as the deuterium source. The resulting α-deuterated alkyl thianthrenium salts, which bear two deuterium atoms, exhibit excellent selectivity and deuterium incorporation in electrophilic substitution reactions. Through in situ formation of isotopically labelled alkyl halides, these thianthrenium salts demonstrate excellent compatibility in a series of metallaphotoredox cross-electrophile coupling with (hetero)aryl, alkenyl, alkyl bromides, and other alkyl thianthrenium salts. Our technique allows for a wide range of substrates, high deuterium incorporation, and precise control over the site of deuterium insertion within a molecule such as the benzyl position, allylic position, or any alkyl chain in between, as well as neighboring heteroatoms. This makes it invaluable for synthesizing various deuterium-labeled compounds, especially those with pharmaceutical significance.

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Scalable synthesis of the aroma compounds d6-β-ionone and d6-β-cyclocitral for use as internal standards in stable isotope dilution assays

Cited by 5 publications

References 33 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

β-Cyclocitral from Lavandula angustifolia Mill. Exerts Anti-Aging Effects on Yeasts and Mammalian Cells via Telomere Protection, Antioxidative Stress, and Autophagy Activation

Metallaphotoredox deuteroalkylation utilizing thianthrenium salts

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