Synthesis of Ψ[CH(RF)NH]Gly-peptides: The dramatic effect of a single fluorine atom on the diastereocontrol of the key aza-Michael reaction

Bigotti, Serena; Meille, Stefano Valdo; Volonterio, Alessandro; Zanda, Matteo

doi:10.1016/j.jfluchem.2008.06.018

Cited by 18 publications

(11 citation statements)

References 14 publications

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“…As expected, the X group on the ester function of the nucleophile has a negligible effect (compare entries 7 and 8). Finally, the effect of the bulkiness of the R side chains of 3 was investigated performing the reaction with different a-amino acid esters (entries [16][17][18][19][20][21]. Accordingly, the bulkier is the R group the higher resulted to be the diastereoisomeric ratio of the process, as exemplified by R = iso-propyl (entries 7 and 8) as compared to benzyl (entry 20), iso-butyl (entry 21) and methyl (entry 16).…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, the bulkier is the R group the higher resulted to be the diastereoisomeric ratio of the process, as exemplified by R = iso-propyl (entries 7 and 8) as compared to benzyl (entry 20), iso-butyl (entry 21) and methyl (entry 16). An important effect of the stereogenic sec-butyl sidechain is more than likely in the case of L-Ile-OMe (entries 18,19), so these results should be weighed in a different manner. In an attempt to improve further the diastereoselectivities, we undertook a series of experiments lowering the temperature of the reaction.…”

Section: Methodsmentioning

confidence: 99%

“…The stereochemistry of the minor diastereoisomer 5a was assessed by X-ray diffraction (see ESI †), 18 whereas the configurations of the other adducts 4 and 5 were confidentially assigned on the basis of their spectroscopic features in comparison with those of 4a and 5a. In fact, the 19 F NMR signals of the fluorinated group of the major diasteroisomers 4 were always observed at higher fields than those of the minor diastereoisomer 5 (see Experimental Section).…”

Section: Methodsmentioning

confidence: 99%

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Ψ[CH(CF3)NH]Gly-peptides: synthesis and conformation analysis

et al. 2009

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Psi[CH(CF(3))NH]Gly peptides, a conceptually new class of peptidomimetics having a stereogenic trifluoroethylamine group as a natural peptide-bond surrogate, have been synthesized by stereoselective addition of alpha-amino acid esters to trans-3,3,3-trifluoro-1-nitropropene. Long range nuclear Overhauser effects, detected via ROESY experiments, provided evidence that model Psi[CH(CF(3))NH]Gly-tetrapeptides incorporating a trifluoroethylamine mimic of the dipeptide loop Pro-Gly can be represented by an ensemble of unfolded and folded conformations. The latter are driven by the formation of a hydrogen bond between a carbonyl group and the aminic proton of the trifluoroethylamine unit. MD calculations indicate a population of conformers which adopt folded beta turn structures for all the L-peptides; on the other hand, a D-stereochemistry at the Pro residue induces a natural folding towards a beta hairpin conformation driven by the formation of a second hydrogen bond, regardless of the stereochemistry of the stereogenic peptide bond surrogate.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ψ[CH(CF3)NH]Gly-peptides: synthesis and conformation analysis

et al. 2009

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“…В останні два десятиліття пред-метом особливої уваги дослідників стали їх α-фто-роалкіловмісні аналоги -унікальні синтетичні блоки для побудови різноманітних типів фторо-ваних аміносполук [6][7][8]. Описані в літературі під-ходи до їх отримання зазвичай базуються на при-єднанні аміносполук до 3,3,3-трифторо-1-нітро-пропену (реакція аза-Міхаеля) [9][10][11][12][13]. Нещодав-но з'явились перші повідомлення про можливість використання для цієї цілі реакції аза-Генрі за уча-стю фтороалкілованих іміносполук, зокрема, N-за-міщених трифторометилальдімінів [14] та фто-роалкіл-α,β-ненасичених N-трет-бутилсульфініл-кетімінів [15].…”

Section: 1-трифторопропан-2-ил)кар-баматы; N-(3-амино-111-трифтороunclassified

Synthesis and some transformations of alkyl N-(2-aryl-3-nitro-1,1,1-trifluoropropan-2-yl)carbamates

Tkachuk¹,

Мельніченко²,

Kovalchuk³

et al. 2014

J. org. pharm. chem.

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Робота присвячена отриманню та дослідженню перетворень нових поліфункціональних фторовмісних синтез-блоків -алкіл N-(3-нітро-1,1,1-трифторопропан-2-іл) N-(2-АРИЛ-3-НИТРО-1,1,1-ТРИФТОРОПРОПАН-2-ИЛ -трифтороэтилиденкарбаматы; N-(3-нитро-1,1,1-трифторопропан-2-ил) кар-баматы; N-(3-амино-1,1,1-трифторопропан-2-ил)карбаматы; 4-трифторометилимидазолидин-2-оны; 3,3,3-трифторопропан-1,2-диамины Работа посвящена получению и исследованию преобразований новых полифункциональных фторсо-дер-жащих синтез-блоков -алкил N-(3-нитро-1,1,1-трифторопропан-2-ил) SYNTHESIS AND SOME TRANSFORMATIONS OF ALKYL N-(2-ARYL 6H 2 O leads to selective reduction of the nitro group and formation of the corresponding alkyl N-(3-aminopropan-2-yl)carbamates. The presence of amino group in their structure considerably affects the chemical shifts of diastereotopic methylene protons. Their signals in the 1 H NMR spectra are upfield (about 2 ppm difference in comparison with nitro derivatives). Alkyl N-(3-aminopropan-2-yl)carbamates in refluxing toluene in the presence of DBU were easily transformed into 4-trifluorometylimidazolidyn-2-ones by intramolecular cyclization. In its turn, tert-butyl N-(3-aminopropan-2-yl)carbamates when treating with hydrogen chloride in dioxane readily gave 3,3,3-trifluoropropan-1,2-diamines through Boc protecting group cleavage. СИНТЕЗ И НЕКОТОРЫЕ ПРЕВРАЩЕНИЯ АЛКИЛ

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“…However, to date, most fluorine-containing peptide modifications involve the introduction of trifluoromethyl or difluoromethylene into molecules [ 14 – 18 ]. Only a few examples have been reported of the preparation and bioassay of pseudopeptides and peptidomimetics bearing difluoromethyl groups.…”

Section: Introductionmentioning

confidence: 99%