128424-93-1

Basic information

• Product Name: L-Leucine, N-[5-[(2-amino-1-methyl-2-oxoethyl)amino]-2,4-dinitrophenyl]-, (S)-
• CAS NO: 128424-93-1
• Molecular Formula: C15H21N5O7
• Molecular Weight: 383.361
• Mol File: 128424-93-1.mol
• Article Data: 57

Chemical Properties

• CAS DataBase Reference: L-Leucine, N-[5-[(2-amino-1-methyl-2-oxoethyl)amino]-2,4-dinitrophenyl]-, (S)-(CAS DataBase Reference)
• NIST Chemistry Reference: L-Leucine, N-[5-[(2-amino-1-methyl-2-oxoethyl)amino]-2,4-dinitrophenyl]-, (S)-(128424-93-1)
• EPA Substance Registry System: L-Leucine, N-[5-[(2-amino-1-methyl-2-oxoethyl)amino]-2,4-dinitrophenyl]-, (S)-(128424-93-1)

Safety Data

• Hazardous Substances Data: 128424-93-1(Hazardous Substances Data)

Upstream product

• 95713-52-3 N-(2,4-dinitro-5-fluorophenyl)-L-alaninamide 
• 1037224-63-7 mollamide C 

Relevant articles and documents

Mariannamides A and B, new cyclic octapeptides isolated from Mariannaea elegans NBRC102301

Two new cyclic octapeptides, mariannamides A (1) and B (2), have been isolated from Mariannaea elegans NBRC102301, a Pinus densiflora-derived filamentous fungus. Their structures were elucidated to be cyclo-(L-Leu1-L-Pro1-L-Pro2-L-Leu2-L-Ile1-L-Pro3-L-Val1-L-Ile2) and cyclo-(L-Leu1-L-Pro1-L-Pro2-L-Leu2-L-Ile1-L-Pro3-L-Val1-L-Val2) based on spectroscopic data and Marfey's method. Mariannamide A (1) promoted mRNA expression of sirtuin 1 (SIRT1) in C2C12 cells, a mouse skeletal muscle myoblast cell line, and showed the antimicrobial activity against Escherichia coli and Cryptococcus neoformans.

Cyclic tetrapeptides from the marine strain Streptomyces sp. PNM-161a with activity against rice and yam phytopathogens

Two cyclotetrapeptides, henceforth named Provipeptides A (1) and B (2), along with five known diketopiperazines (3–7) were isolated from the liquid culture of marine Streptomyces sp. 161a recovered from a sample of sea grass Bryopsis sp. The structures of cyclotetrapeptides and diketopiperazines (DKPs) were established by 1D and 2D NMR data, MS, and by comparison with literature data. The absolute stereochemistry of compounds cyclo-(l-Pro-l-Leu-d-Pro-l-Phe) 1 and cyclo-(-Pro-Ile-Pro-Phe) 2 was established by the Marfey’s method. Compound 1 showed antibacterial activity against rice phytopathogenic strains Burkholderia glumae (MIC = 1.1 mM) and Burkholderia gladioli (MIC = 0.068 mM), compound 2 was active only against B. glumae (MIC = 1.1 mM), and DKP cyclo-[l-Pro-l-Leu] 5 showed to be active against B. gladioli (MIC = 0.3 mM) and B. glumae (MIC = 2.4 mM). Compounds 1 and 2 showed 65% and 50% inhibition of Colletotrichum gloeosporioides (yam pathogen) conidia germination, respectively at a concentration of 1.1 mM.

Cytotoxic Orbitide from the Latex of Croton urucurana

The bioactive ethyl acetate phase obtained from the latex of Croton urucurana Baillon afforded a novel orbitide (1), [1-9-NαC]-crourorb A1, that proved active against NCI-ADR/RES (ovary, multidrug-resistance phenotype) cells with the same potency as doxor

Auyuittuqamides A-D, Cyclic Decapeptides from Sesquicillium microsporum RKAG 186 Isolated from Frobisher Bay Sediment

Four new cyclic decapeptides, auyuittuqamides A-D (1-4), were obtained from Sesquicillium microsporum RKAG 186 obtained from marine sediment collected from the intertidal zone of Frobisher Bay, Nunavut, Canada. The structures of the compounds were elucida

Bioactive compounds from the aerial parts of brachystemma calycinum and structural revision of an octacyclopeptide

Four new cyclic peptides, brachystemins F - I (1 - 4), and 11 known compounds were isolated from the aerial parts of Brachystemma calycinum. The absolute configurations of compounds 1 - 4 were assigned using Marfey's method. The structure of compound 5 was revised from cyclo(Pro1 - Phe 2 - Leu3 - Ala4 - Thr5 - Pro 6 - Ala7 - Gly8) to cyclo(Pro1 - Pro2 - Ala3 - Gly4 - Leu5 - Ala 6 - Thr7 - Phe8) with QTOF/MS and X-ray diffraction analysis. The N-containing compounds were assessed for their inhibitory effects on the secretion of monocyte chemokine ligand 2 (CCL-2), interleukin 6 (IL-6), and collagen IV against high-glucose-stimulated mesangial cells. Compound 5 was evaluated for its effects on collagen I, reactive oxygen species (ROS), superoxide anion (O2?-) production, and cell viability in mesan ial cells, and on nitric oxide (NO) production in macrophage cells.

Seven new and two known lipopeptides as well as five known polyketides: The activated production of silent metabolites in a marine-derived fungus by chemical mutagenesis strategy using diethyl sulphate

AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1-7) and two known (8-9) lipopeptides were isolated together with five known polyketides 10-14 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A-G (1-7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1.-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1-14 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 1-14 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.

Streptopyrazinones A?D, rare metabolites from marine-derived Streptomyces sp. ZZ446

Secondary metabolites from marine-associated actinomycetes are important source for the discovery of novel bioactive compounds. In this study, an actinomycete Streptomyces sp. ZZ446 was isolated from coastal soils and different media were used to culture this isolated marine actinomycete. It has been found that this actinomycete in the liquid medium of 2216 E with sea salt produced five new compounds of streptopyrazinones A?D (1–4) and N-acetyl-L-isoleucine-L-leucinamide (5) as well as six known diketopiperazines (6–11) and one alkaloid (12). Structures of the new compounds were determined by extensive NMR analyses, HRESIMS data, electronic circular dichroism (ECD) calculation, chemical degradation, Marfey's method, and X-ray diffraction analysis. This type of streptopyrazinones A?D (1–4) is rarely found in the natural resources. New compounds 1–5 showed activity in inhibiting the growth of Candida albicans and methicillin-resistant Staphylococcus aureus.

Inhibitors of serine proteases from a Microcystis sp. Bloom material collected from timurim reservoir, Israel

Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were isolated from the hydrophilic extract of bloom material of Microcystis sp. collected from the Timurim water reservoir in Israel. The structures of compounds 1 and 2 were determined using 1D and 2D NMR spectroscopy and HR ESI MS and MS/MS techniques. Micropeptin TR1058 (1) was extremely unstable under the isolation conditions, and several degradation products were identified. NMR analysis of aeruginosin TR642 (2) revealed a mixture of eight isomers, and elucidation of its structure was challenging. Aeruginosin TR642 contains a 4,5-didehydroaraginal subunit that has not been described before. Micropeptin TR1058 (1) inhibited chymotrypsin with an IC50 of 6.78 μM, and aeruginosin TR642 (2) inhibited trypsin and thrombin with inhibition concentration (IC50) values of 3.80 and 0.85 μM, respectively. The structures and biological activities of the new compounds are discussed.

Determination of absolute structures of cyclic peptides, PF1171A and PF1171C, from unidentified ascomycete OK-128

Two cyclic peptides, PF1171A (1) and PF1171C (2), were isolated from okara that had been fermented with unidentified ascomycete OK-128. Their absolute configurations were determined by Marfey's method. These peptides showed paralytic activity against silkworms.

Cytotoxic and antimicrobial compounds from the marine-derived fungus, penicillium species

The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the previously reported cyclo(R-Pro–S-Phe) (3) and cyclo(R-Pro–R-Phe) (4). The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS). The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities.

Mollamides B and C, cyclic hexapeptides from the indonesian tunicate Didemnum molle

Two new cyclic hexapeptides, mollamides B (1) and C (2), were isolated from the Indonesian tunicate Didemnum molle along with the known peptide keenamide A (3). The structures were established using 1D and 2D NMR experiments. The relative configuration of mollamide B at the thiazoline moiety was determined using molecular modeling coupled with NMR-derived restraints. Their absolute configuration was determined using Marfey's method. The new peptides have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, anti-Mtb, and anti-inflammatory activities. Keenamide A and mollamide B show cytotoxicity against several cancer cell lines.

Secondary metabolites from the endophytic fungi Penicillium polonicum and Aspergillus fumigatus

Two new compounds, rhodostegone (1) from endophytic fungus Penicillium polonicum and cyclo-(L-Val-L-Leu) (2) from Aspergillus fumigatus, together with six known diketopiperazines (3-8), were isolated. The structures of these compounds were characterized through a combination of extensive IR, MS, NMR, and CD analysis.

Three bioactive cyclic dipeptides from the Bacillus sp. N strain associated with entomopathogenic nematode

In continuation of our search for new bioactive secondary metabolites from Bacillus cereus associated with entomopathogenic nematode (EPN), three cyclic dipeptides (CDPs), cyclo(l-Leu-d-Arg) (1), cyclo(2-hydroxy-Pro-l-Leu) (2), and cyclo(l-Val-l-Pro) (3) were purified from the ethyl acetate extract of B. cereus. The chemical structure of the compounds was identified by 1D, 2D NMR and HR-ESI-MS. Cyclo(l-Leu-d-Arg) recorded best antifungal activity and the highest activity was recorded against Cryptococcus neoformans (1 μg/mL), which is better than the standard antifungal agent amphotericin B. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used for finding cell proliferation inhibition and cyclo(l-Leu-d-Arg) recorded significant activity against breast cancer cell line (MDAM-B231) (IC50 value: 25 μM) and the three cyclic dipeptides recorded no toxicity against normal human cell (fore skin (FS) normal fibroblast) up to 50 μM except cyclo(l-Val-l-Pro). Cyclo(l-Leu-d-Arg) induced significant morphological changes and DNA fragmentation associated with apoptosis in MDAM-B231 cells by acridine orange/ethidium bromide staining and flow cytometry analysis. Out of three cyclic dipeptides tested only cyclo(2-hydroxy-Pro-l-Leu) recorded significant antioxidant activity. The hydroxyl radical scavenging activity of cyclo(2-hydroxy-Pro-l-Leu) is greater than BHA, the standard antioxidant agent. Cyclo(l-Leu-d-Arg) was isolated for the first time from a natural source with a d-arginine residue. To the best of our knowledge, this is the first time that the bioactivity of the isolated cyclic dipeptides is reported against medically important fungi and cancer cells. This study is a significant contribution to the knowledge of cyclo(l-Leu-d-Arg) from B. cereus as potential sources of new drugs in the pharmacological industry, especially as potent antifungal and anticancer agent.

Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics

Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.

Cytotoxic cyclic depsipeptides from the Australian marine sponge Neamphius huxleyi

Three new cyclic depsipeptides, neamphamides B (2), C (3), and D (4), were isolated from the Australian sponge Neamphius huxleyi. The planar structural characterization of these molecules was elucidated using 2D NMR experiments and ESI-FTICR-MSn. Their configurations were determined by Marfey's method and J-based NMR analysis. These new metabolites inhibited the growth of human cell lines (A549, HeLa, LNCaP, PC3, and NFF) with IC50 values ranging from 88 to 370 nM. However, neamphamide D causes A549 cell proliferation at subcytotoxic doses and should be treated cautiously as a cytotoxic compound.

Antibacterial low-molecular-weight compounds produced by the marine bacterium Rheinheimera japonica KMM 9513T

Strain KMM 9513T was isolated from a sediment sample collected from the Sea of Japan seashore and selected due to its ability to inhibit indicator bacterial growth. The strain KMM 9513T has been recently described as a novel species Rheinheimera japonica. This study was undertaken to determine which substances produced by strain KMM 9513T could be responsible for its antimicrobial activity. Eight compounds were obtained from an ethyl acetate extract of R. japonica KMM 9513T. The structures of five diketopiperazines (4–8) and diisobutyl-, dibutyl- and bis(2-ethylhexyl) phthalates (1–3) were established on the basis of detailed interpretation of NMR data, by Marfey method and optical rotation data. The structures of diketopiperazines were determined as cyclo-(l-valyl-l-proline), cyclo-(l-valyl-d-proline), cyclo-(l-phenylalanyl-l-proline), cyclo-(l-leucyl-l-proline), and cyclo-(l-phenylalanyl-d-proline). Compounds 1–3, 5 and 8 revealed antimicrobial activities against Bacillus subtilis and/or Enterococcus faecium and Staphylococcus aureus. In this paper, we describe the isolation and structural elucidation of the isolated compounds 1–8. This is the first report of the characterisation of low molecular weight antibacterial metabolites produced by a member of the genus Rheinheimera.

Wollamides: Antimycobacterial cyclic hexapeptides from an australian soil Streptomyces

A soil Streptomyces nov. sp. (MST-115088) isolated from semiarid terrain near Wollogorang Station, Queensland, returned two known and two new examples of a rare class of cyclic hexapeptide, desotamides A and B (1 and 2) and E and F (3 and 4), respectively, together with two new d-Orn homologues, wollamides A and B (5 and 6). Structures were assigned by detailed spectroscopic and C3 Marfey's analysis. The desotamides/wollamides exhibit growth inhibitory activity against Gram-positive bacteria (IC50 0.6-7 μM) and are noncytotoxic to mammalian cells (IC50 >30 μM). The wollamides exhibit antimycobacterial activity (IC50 2.8 and 3.1 μM), including reduction in the intracellular mycobacterial survival in murine bone marrow-derived macrophages.

Identification of an Anti-MRSA Cyclic Lipodepsipeptide, WBP-29479A1, by Genome Mining of Lysobacter antibioticus

Lysobacter are ubiquitous in the environment but remain largely underexplored, although the bacteria are considered "peptide specialists". Here, we identified a new cyclic lipodepsipeptide, WBP-29479A1 (1), through genome mining of L. antibioticus ATCC 29479. 1 is biosynthesized by a large NRPS gene cluster, and its structure, including the six nonproteinogenic residues and 3-hydroxy fatty acid, was determined by extensive spectroscopic analyses and chemical derivatization. 1 exhibits potent anti-MRSA activity in a menaquinone-dependent manner.

Highly sensitive determination of amino acids by LC-MS under neutral conditions

Peptide drug leads possess unusual structural features that allow them to exert their unique biological activities and ideal physicochemical properties. In particular, these peptides often have D-amino acids, and therefore the absolute configurations of t