42002-99-3

Upstream product

• 68078-09-1 N-methylproline 
• 64-17-5 ethanol 
• 475-11-6 N-methyl-L-proline 
• 147-85-3 L-proline 
• 475-11-6 N-methyl-D-proline 
• 344-25-2 D-Prolin 
• 50-00-0 formaldehyd 
• 5817-26-5 ethyl (2S)-pyrrolidine-2-carboxylate 
• 172223-81-3 5-(Hydroxy-methyl-amino)-pentanoic acid ethyl ester 
• 14660-52-7 ethyl 5-bromovalerate 
• 172223-88-0 C₂₀H₂₆NO₄P 

Downstream Products

• 61609-41-4 1-Methyl-2-acetoxymethyl-pyrrolidin 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke

Stachydrine is a natural product with multiple protective biological activities, including those involved in preventing cancer, ischemia, and cardiovascular disease. However, its use has been limited by low bioavailability and unsatisfactory efficacy. To address this problem, a series of stachydrine derivatives (A1/A2/A3/A4/B1/B2/B3/B4) were designed and synthesized, and biological studies were carried out in vitro and in vivo. When compared with stachydrine, Compound B1 exhibited better neuroprotective effects in vitro, and significantly reduced infarction size in the model of the middle cerebral artery occlusion rat model. Therefore, Compound B1 was selected for further research on ischemic stroke. [Figure not available: see fulltext.].

ANTIBIOTIC COMPOUNDS

The present invention relates to antibiotic compounds of formula (I), to compositions containing these compounds and to methods of treating bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Gram-positive and/or Gram-negative bacteria, and in particular in the treatment of infection with, and diseases caused by, Neisseria gonorrhoeae.

Synthesis of a series of amino acid derived ionic liquids and tertiary amines: Green chemistry metrics including microbial toxicity and preliminary biodegradation data analysis

A series of l-phenylalanine ionic liquids (ILs), l-tyrosine ILs, tertiary amino analogues and proposed transformation products (PTPs) have been synthesised. Antimicrobial toxicity data, as part of the green chemistry metrics evaluation and to supplement preliminary biodegradation studies, was determined for ILs, tertiary amino analogues and PTPs. Good to very good overall yields (76 to 87%) for the synthesis of 6 ILs from l-phenylalanine were achieved. A C2-symmetric IL was prepared from TMS-imidazole in a one-pot two-step method in excellent yield (91%). Synthesis of the l-tyrosine IL derivatives utilised a simple protection group strategy by using an extra equivalent of the bromoacetyl bromide reagent. Improvements in the synthesis of the α-bromoamide alkylating reagent from l-phenylalanine were achieved, directed by green chemistry metric analysis. A solvent switch from dichloromethane to THF is described, however the yield was 15% lower. Antimicrobial activity testing of l-phenylalanine ILs, l-tyrosine ILs, tertiary amino analogues and PTPs, against 8 bacteria and 12 fungi strains, showed that no compound had a high antimicrobial activity, apart from an l-proline analogue. In this exceptional case, the highest toxicity (IC95 = 125 and 250 μM) was observed towards the two Gram positive strains Staphylococcus aureus and Staphylococcus epidermidis respectively. High antimicrobial activity was not found for the other bacteria or fungi strains screened. The limitations of the antimicrobial activity study is discussed in relation to SAR studies. Preliminary analysis of biodegradation data (Closed Bottle Test, OECD 301D) is presented. The pyridinium IL derivative is the preferred green IL of the series based on synthesis, toxicity and biodegradation considerations. This work is a joint study with Kümmerer and co-workers and the PTPs were selected as target compounds based on concurrent biodegradation studies by the Kümmerer group. For the comprehensive biodegradation and transformation product analysis see the accompanying paper.

Characterization of N-methylated amino acids by GC-MS after ethyl chloroformate derivatization

Methylation is an essential metabolic process in the biological systems, and it is significant for several biological reactions in living organisms. Methylated compounds are known to be involved in most of the bodily functions, and some of them serve as biomarkers. Theoretically, all α-amino acids can be methylated, and it is possible to encounter them in most animal/plant samples. But the analytical data, especially the mass spectral data, are available only for a few of the methylated amino acids. Thus, it is essential to generate mass spectral data and to develop mass spectrometry methods for the identification of all possible methylated amino acids for future metabolomic studies. In this study, all N-methyl and N,N-dimethyl amino acids were synthesized by the methylation of α-amino acids and characterized by a GC-MS method. The methylated amino acids were derivatized with ethyl chloroformate and analyzed by GC-MS under EI and methane/CI conditions. The EI mass spectra of ethyl chloroformate derivatives of N-methyl (1–18) and N,N-dimethyl amino acids (19–35) showed abundant [M-COOC2H5]+ ions. The fragment ions due to loss of C2H4, CO2, (CO2 + C2H4) from [M-COOC2H5]+ were of structure indicative for 1–18. The EI spectra of 19–35 showed less number of fragment ions when compared with those of 1–18. The side chain group (R) caused specific fragment ions characteristic to its structure. The methane/CI spectra of the studied compounds showed [M + H]+ ions to substantiate their molecular weights. The detected EI fragment ions were characteristic of the structure that made easy identification of the studied compounds, including isomeric/isobaric compounds. Fragmentation patterns of the studied compounds (1–35) were confirmed by high-resolution mass spectra data and further substantiated by the data obtained from 13C2-labeled glycines and N-ethoxycarbonyl methoxy esters. The method was applied to human plasma samples for the identification of amino acids and methylated amino acids. Copyright

Intramolecular Nucleophilic Substitution on Nitrogen A New Heterocyclic Synthesis

A series of 5-(diphenylphosphinyloxyamino)valeric acid esters has been prepared.Their treatment with appropriate bases led to cyclization to proline derivatives.The reaction constitutes the first reported case of intramolecular nucleophilic substitution o