Heterocyclisation des α-acylaminoamides—IV

Clerin, Daniel; Kille, G.; Fleury, Jean‐Pierre

doi:10.1016/s0040-4020(01)97026-7

Cited by 29 publications

(17 citation statements)

References 5 publications

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“… 6 , 10 , 28 , 29 Hammett substituent effects arising from R 2 (alkyl or aryl) might be expected to be operative in the cyclization of 19 to 20 or in the acid-catalyzed ring opening of 21 to 3 . 30 …”

Section: Resultsmentioning

confidence: 99%

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

et al. 2014

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Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent’s Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis.

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Section: Resultsmentioning

confidence: 99%

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

et al. 2014

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“…in previous reviews (1,2 (100) labeling experiments were invoked to distinguish between the two possible pathways (96). Interestingly, when R1 = p-N02Ph, pathway a (eq 97) was operative to the extent of 100%.…”

Section: Aminooxazolesmentioning

confidence: 92%

Oxazole chemistry. A review of recent advances

Turchi¹

1981

Ind. Eng. Chem. Prod. Res. Dev.

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“…Multicomponent reaction followed by post-functionalization constitutes a powerful approach to access rapidly the structural diversities. 15 Taking advantage of the instability of aminooxazoles under acidic conditions, 16,17 the oxazole 4 was readily transformed into the corresponding constrained dipeptide as two separable diastereoisomers 13 in 91% yield (trifluoroacetic acid in THF-water 1:1, Scheme 2). This represents one of the shortest routes to attach an amino acid residue onto the C-1 position of the isoquinoline.…”

Section: Figurementioning

confidence: 99%

A Three-Component Synthesis of (1,3-Oxazol-2-yl)-1,2-dihydro(iso)quinoline and its further Structural Diversifications

Tron¹,

Zhu²

2005

Synlett

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A Reissert-type three-component synthesis of 1,3-oxazol-2-yl-1,2-dihydro(iso)quinoline is developed using a-isocyano b-phenyl propionamide as an isonitrile input. The structure of this multicomponent adduct is further diversified taking advantage of the rich chemistry of oxazole.Quinoline and isoquinoline derivatives are important classes of hetertocycles. 1 Their ubiquitous occurrence in nature and their wide spectrum of biological activities make them the prime targets in medicinal chemistry and the search of new and efficient synthetic routes has attracted attention of synthetic chemists for years. 2 For the functionalization of quinolines, isoquinolines and related aromatic azines, the Reissert reaction remained one of the most powerful tools. 3 The reaction can be considered as a multicomponent reaction (MCR) 4 where adducts are formed from an azine, an acyl chlorides and sodium cyanide via a N-acyliminium intermediate.The ability of isonitrile to undergo facile a-addition with a nucleophile and an electrophile under mild conditions made it a popular reactant for the development of novel MCRs. The eminent example is the classic Ugi four-component reaction which converts an aldehyde, an amine, an acid and an isonitrile into a-acetamidoamide in one step with good to excellent yield. 5 Recently, Lavilla and coworkers extended the Ugi-4CR to (iso)quinoline and demonstrated that N-acylated aromatic azine, is susceptible to nucleophilic attack of isocyanide leading, after hydrolysis, to the a-carbamoylated 1,2-dihydroazine. 6,7 On the other hand, Mironov et al. have independently developed a three-component synthesis of 2,3-dihydro-10H-pyrrolo[2,1-a]isoquinoline-1-one by reaction of isoquinoline, gem-diactivated olefines and isocyanides. 8 Earlier, Morel and his co-workers developed a three-component synthesis of fused imidazolium and dihydropyrimidinium salt by reaction of methylchlothioimidate, pyridine and isocyanides. 9,10 Based on these observations, we report herein a three-component synthesis of (1,3-oxazol-2-yl)-1,2-dihydro(iso)quinoline by exploiting the unique reactivity of a-isocyano acetamides. 11 Further structural-diversification of this adduct is also delineated based on the chemical reactivity of oxazole. Scheme 1As shown in the Scheme 1, the reaction of isoquinoline (1), methyl chloroformate (2) and morpholinyl-a-isocyano-b-phenylpropionamide (3) under slightly modified Lavilla's conditions (CH 2 Cl 2 , -40°C, 4 Å molecular sieves) 12 provided the expected compound 4 in 76%. 13

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Heterocyclisation des α-acylaminoamides—IV

Cited by 29 publications

References 5 publications

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

Oxazole chemistry. A review of recent advances

A Three-Component Synthesis of (1,3-Oxazol-2-yl)-1,2-dihydro(iso)quinoline and its further Structural Diversifications

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