Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids

Kelleher, Fintan; Proinsias, Keith ó

doi:10.1016/j.tetlet.2007.05.064

Cited by 11 publications

(6 citation statements)

References 12 publications

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“…However, the initial Brønsted-catalyzed allylation under reflux conditions to produce compound 5 resulted in disappointingly low yields, mainly due to self-condensation of serine under the employed conditions. Alternatively, the first protection of the amino group of serine 3 with a trityl group to produce 4 , and subsequent allylation afforded 5 in 42% yield over two steps, comparable to an earlier literature report 34 . The protected serine 5 was treated with MsCl under reflux conditions for 48 h to cleanly afford aziridine 6 in good yield comparable to the Thr analogue 32 , 33 .…”

Section: Resultssupporting

confidence: 83%

Fine-tuning of lysine side chain modulates the activity of histone lysine methyltransferases

Temimi

Merx

Noortwijk

et al. 2020

Sci Rep

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Histone lysine methyltransferases (KMTs) play an important role in epigenetic gene regulation and have emerged as promising targets for drug discovery. However, the scope and limitation of KMT catalysis on substrates possessing substituted lysine side chains remain insufficiently explored. Here, we identify new unnatural lysine analogues as substrates for human methyltransferases SETD7, SETD8, G9a and GLP. Two synthetic amino acids that possess a subtle modification on the lysine side chain, namely oxygen at the γ position (KO, oxalysine) and nitrogen at the γ position (KN, azalysine) were incorporated into histone peptides and tested as KMTs substrates. Our results demonstrate that these lysine analogues are mono-, di-, and trimethylated to a different extent by trimethyltransferases G9a and GLP. In contrast to monomethyltransferase SETD7, SETD8 exhibits high specificity for both lysine analogues. These findings are important to understand the substrate scope of KMTs and to develop new chemical probes for biomedical applications.

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Section: Resultssupporting

confidence: 83%

Fine-tuning of lysine side chain modulates the activity of histone lysine methyltransferases

Temimi

Merx

Noortwijk

et al. 2020

Sci Rep

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“…Classically substituted sulfonamides may be formed from amines and sulfonyl chlorides, by direct alkylation of sulfonamides with alkyl halides, or through reductive amination . The Mitsunobu reaction has also been employed to convert an alcohol into a sulfonamide. ,, Given the high level of interest in sulfonamides, it is perhaps unsurprising that new, more atom-economical catalytic methods for their formation have continued to evolve. Many of these methods employ transition metal catalysts, including the hydroaminations of alkenes, C–H activation methods, metal catalyzed additions to N -sulfonyl imines, , alkylation via π-allyl metal complexes, and alkylation of alcohols via borrowing hydrogen methods .…”

mentioning

confidence: 99%

Alkylation of Sulfonamides with Trichloroacetimidates under Thermal Conditions

Wallach

Chisholm

2016

J. Org. Chem.

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An intermolecular alkylation of sulfonamides with trichloroacetimidates is reported. This transformation does not require an exogenous acid, base, or transition metal catalyst, instead the addition occurs in refluxing toluene without additives. The sulfonamide alkylation partner appears to be only limited by sterics, with unsubstituted sulfonamides providing better yields than more encumbered N-alkyl sulfonamides. The trichloroacetimidate alkylating agent must be a stable cation precursor for the substitution reaction to proceed under these conditions. Graphical abstractThe sulfonamide functional group has played an important role in the development of numerous pharmaceuticals. While best known as antibiotics, sulfonamide scaffolds provide a diverse range of biological activity including antitumor, antiviral, diuretic, antiinflammatory and anti-hypertensive properties. 1 Summaries of the top selling pharmaceuticals clearly demonstrate that sulfonamides are well represented in these valuable structures. 2 Data on recently approved pharmaceuticals indicate that sulfonamides continue to be popular in drug discovery, 3 with recent publications in the medicinal chemistry field corroborating that the investigation of sulfonamide-containing structures is ongoing. 4 Sulfonamides also have proven useful in agricultural and insecticidal applications. 5

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“…11 During the aziridine ring-opening reactions it was found that there were issues with the regioselectivity of the reactions, depending on the choice of N-protecting group and ester group at the aziridine 2-position. Since the initial results…”

mentioning

confidence: 99%

Synthesis of orthogonally protected 1,2-diaminopropanoic acids by ring-opening of 3-unsubstituted N-activated aziridine 2-carboxylates with para-methoxybenzylamine: a study of the regioselectivity of the reaction

O’Brien¹,

Kelleher²

2013

Tetrahedron Letters

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Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids

Cited by 11 publications

References 12 publications

Fine-tuning of lysine side chain modulates the activity of histone lysine methyltransferases

Fine-tuning of lysine side chain modulates the activity of histone lysine methyltransferases

Alkylation of Sulfonamides with Trichloroacetimidates under Thermal Conditions

Synthesis of orthogonally protected 1,2-diaminopropanoic acids by ring-opening of 3-unsubstituted N-activated aziridine 2-carboxylates with para-methoxybenzylamine: a study of the regioselectivity of the reaction

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