Nucleophilic ring opening of aziridines

Stamm, H.

doi:10.1002/(sici)1521-3897(199905)341:4<319::aid-prac319>3.0.co;2-9

Cited by 102 publications

(17 citation statements)

References 66 publications

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“…Here, electronic properties play a major role and fluorine-18 was seen to attack preferably at the quaternary carbon of the aziridine ring rather than the secondary carbon. Partial positive charge on nitrogen of the aziridine ring weakens the nitrogen-to-quaternary carbon bond [49] and the resulting partial positive charge on the quaternary carbon may be further stabilized by the lone pair of the carboxylate oxygen. We believe that these factors facilitate nucleophilic attack preferentially at the quaternary carbon [50].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

Basuli

Shi

et al. 2012

Nuclear Medicine and Biology

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Introduction The small molecule 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid (NST732) is a member of the ApoSense® family of compounds, capable of selective targeting, binding and accumulation within cells undergoing apoptotic cell death. It has application in molecular imaging and blood clotting particularly for monitoring anti-apoptotic drug treatments. We are investigating a fluorine-18 radiolabeled analog of this compound for positron emission tomography studies. Methods We prepared the tosylate precursor methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(tosyloxymethyl)butanoate (4) to synthesize fluorine-18 labeled NST732. Fluorination reaction of the tosylate precursor in 1:1 acetonitrile, dimethylsulfoxide with tetrabutyl ammonium fluoride (TBAF) proceeds through an aziridine intermediate (4A) to afford two regioisomers 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-fluorobutanoate (5) and methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoate (6). Acid hydrolysis of the fluoromethylbutanoate (6) isomer produced NST732. As the fluorination reaction of the tosylate precursor proceeds through an aziridine intermediate (4A) and the fluorination conceivably could be done directly on the aziridine, we have separately prepared an aziridine precursor (4A). Fluorine-18 labeling of the aziridine precursor (4A) was performed with [18F]tetrabutyl ammonium fluoride to afford the same two regioisomers (5 and 6). The [18F]2-((5-dimethylamino)naphthalene-1-sulfonamido)methyl)-2-fluorobutanoic acid (NST732) was then obtained by the hydrolysis of corresponding [18F]-labeled ester (6) with 6N hydrochloric acid. Results Two regioisomers obtained from the fluorination reaction of aziridine were easily separated by HPLC. The total radiochemical yield was 15 ± 3% (uncorrected, n = 18) from the aziridine precursor, in a 70 min synthesis time with a radiochemical purity > 99%. Conclusion Fluorine-18 labeled aposense coumpound [18F]NST732 is prepared in moderate yield by direct fluorination of an aziridine precursor.

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Section: Resultsmentioning

confidence: 99%

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

Basuli

Shi

et al. 2012

Nuclear Medicine and Biology

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“…For a discussion of the pyramidalized geometry of N-sulfonylamides, see: Ohwada et al (1998). By regioselective ring opening reactions, countless nitrogencontaining compounds are accessible, see: Stamm (1999); Schneider (2009). For consecutive ring-opening reactions of aziridines by triethylamine, see: Golz & Strohmann (2015).…”

Section: Related Literaturementioning

confidence: 99%

Crystal structure of 1-[(2,4,6-triisopropylphenyl)sulfonyl]aziridine

2015

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The title compound, C17H27NO2S, exhibits a distorted geometry of the aromatic ring with elongated bonds at the ipso-C atom. The S atom deviates from the aromatic ring plane by 0.393 (4) Å. Similar to this, the adjacent isopropyl groups are bent out of the aromatic ring plane by −0.125 (4) and −0.154 (4) Å. Even the distant isopropyl group in para-position to the sulfonyl moiety shows a slight deviation from the ring plane of 0.111 (5) Å. These distortions, which are caused by the bulky substituents, can also be observed in related sulfonylaziridine structures.

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“…Moreover, the preparation of the required cysteine- and aziridine-derived reaction partners is concise and well-established . Various bases, as well as Lewis acids, have been successfully applied for aziridine ring-opening reactions with carbon, nitrogen, sulfur, oxygen, and halogen nucleophiles. , To the best of our knowledge, BF 3 ·OEt 2 is the only Lewis acid that has ever been utilized in the attack of cysteine-derived nucleophile on aziridine. However, as mentioned above, since these reactions typically require large excesses of BF 3 ·OEt 2 , long reaction times, display intolerance toward acid labile protecting groups, and proceed in relatively poor yields, this reaction is unsuitable for large-scale synthesis of β-MeLan derivatives.…”

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Scalable Synthesis of Orthogonally Protected β-Methyllanthionines by Indium(III)-Mediated Ring Opening of Aziridines

Gentry

Murphy

et al. 2019

Org. Lett.

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Lantibiotics are a class of peptide antibiotics with activity against most Gram-positive bacteria. Lanthionine (Lan) and β-MeLan are unusual thioether-bridged, non-proteinogenic amino acids, which are characteristic features of lantibiotics. In this paper, we report the facile stereoselective synthesis of β-methyllanthionines with orthogonal protection by nucleophilic ring opening of aziridines. This method leads to an expedient access to β-methyllanthionines and allows production of over 30 g of β-methyllanthionine in a single batch.

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Nucleophilic ring opening of aziridines

Cited by 102 publications

References 66 publications

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

Crystal structure of 1-[(2,4,6-triisopropylphenyl)sulfonyl]aziridine

Scalable Synthesis of Orthogonally Protected β-Methyllanthionines by Indium(III)-Mediated Ring Opening of Aziridines

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