N-Alkylation of N-arylsulfonyl-α-amino acid methyl esters by trialkyloxonium tetrafluoroborates

Marco, Rosaria De; Gioia, Maria Luisa Di; Liguori, Angelo; Perri, Francesco; Siciliano, Carlo; Spinella, Mariagiovanna

doi:10.1016/j.tet.2011.10.042

Cited by 29 publications

(23 citation statements)

References 70 publications

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“…The temperature of the capillary was set at 220 °C. 1 H and 13 C NMR spectra were recorded at 298 K on a Bruker Avance 300 MHz spectrometer, using CDCl 3 and referred to internal tetramethylsilane …”

Section: Methodsmentioning

confidence: 99%

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

et al. 2018

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Chemotherapy is used for the treatment of all stages of breast cancer, including the metastatic stage of the disease. Treatment regimens are generally tailored for each patient′s particular situation. However, chemotherapeutic agents are the leading cause of serious drug‐related adverse effects; moreover, drug resistance often occurs. In this study, we designed and synthesized a new series of N‐alkylcarbazoles derived from ellipticine, an alkaloid with a carbazole skeleton initially used in the treatment of metastatic breast cancer and later dismissed because of poor aqueous solubility and severe side effects. After evaluating the binding modes of our class of newly synthesized compounds with human topoisomerase II (hTopo II), we performed hTopo II decatenation assays, identifying compound 4 f (2‐(4‐((3‐chloro‐9H‐carbazol‐9‐yl)pentyl)piperazin‐1‐yl)‐N,N,N‐trimethylethanammonium iodide) as a good inhibitor. Moreover, 4 f and 4 g (2‐(4‐((3‐chloro‐9H‐carbazol‐9‐yl)hexyl)piperazin‐1‐yl)‐N,N,N‐trimethylethanammonium iodide) showed a good anti‐proliferative activity toward breast cancer cells, causing apoptosis by activation of the caspase pathway. Interestingly, the activity of these two compounds on triple‐negative MDA‐MB‐231 cells, which tend to be highly metastatic and aggressive, is strictly connected to the observed inhibition of hTopo II.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

et al. 2018

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“…It is well known that N‐arylsulfonylation is a common protection strategy for α‐amino acids. The diazomethylation of N‐arylsulfonylated substrates gave variable yields, which depends on the acidity of the N‐H (Table ) . With the 4‐NO 2 substituent, the yield was quantitative (entry 1).…”

Section: Methylation By Using Conventional Reagentsmentioning

confidence: 99%

“…The diazomethylationo fN -arylsulfonylated substrates gave variable yields, which depends on the acidity of the N-H (Table 20). [182] With the 4-NO 2 substituent, the yield was quantitative (entry 1). A halide (F,C l) atom in the 4-position gave low yields (entries2, 3), whereas with ane lectron-donatings ubstituent (Me, OMe), the yields were poor (entries 4, 5).…”

Section: Trimethyloxoniumtetrafluoroborate(me 3 Obf 4 )A Nd Diazomethmentioning

confidence: 99%

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

Chen

2018

Chemistry A European J

177

115

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Methylation is a well‐known structural modification in organic and medicinal chemistry. This review summarizes recent advances in methylation by categorizing specific methylation reagents. The challenges of mono N‐methylation of aliphatic amines and N‐methylation of peptides are discussed. This review will be useful for chemists wanting to select the appropriate reagents for methylation chemistry. Based on the large diversity of methylation reagents and their wide scope, this review also broadens perspectives on which strategies to select for utilizing a particular methylation, resulting in an increased flexibility in synthetic route planning.

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“…As a result of the high reactivity of diazomethane, it became the reagent of choice due to low nucleophilicity of the α‐nitrogen atom. After successful methylation, the NBS group was removed conveniently using mercaptoacetic acid in the presence of sodium methoxide to give the desired N ‐Me analogs …”

Section: N‐methylation Of Amino Acids and Peptidesmentioning

confidence: 99%

N‐methylation in amino acids and peptides: Scope and limitations

et al. 2018

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Active pharmaceutical ingredients (APIs) can be divided into two types, namely chemical and biological entities. Traditionally, the former has been associated with the so-called small molecules. The revival of peptides in pharmaceutical industry results from their importance in many biological roles. However, low metabolic stability and the lack of oral availability of most peptides is the main drawback for peptide to fulfill that paradigmatic situation. In this regard, efforts are being channeled into addressing this issue by introducing restrictions into the flexible peptide backbone, mainly through N-methyl amino acids (NMAAs) or development of small cyclic peptides. In many cases, both the above restrictions are combined with the aim to enhance oral availability. The synthesis of NMAAs is complex and their introduction into the peptide chain brings additional synthetic challenges and also sometimes leads to side-reactions. Here we discuss the most efficient methods for the synthesis of NMAAs (either in solution or in solid phase) and also their introduction into peptide sequences. Special attention is also given to the detection of side reactions and the most efficient way to prevent them.

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N-Alkylation of N-arylsulfonyl-α-amino acid methyl esters by trialkyloxonium tetrafluoroborates

Cited by 29 publications

References 70 publications

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

N‐methylation in amino acids and peptides: Scope and limitations

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