Enantioselective Synthesis of Atropisomeric Amides by Dynamic Resolution: Thermodynamic Control with a Proline-Derived Diamine Resolving Agent

By exploiting the thermal instability about the Ar–CO axis at high temperature, atropisomeric amides can be dynamically resolved to provide material with up to 96.5 % ee in 70–80 % overall yield from racemic starting material. The amides are coupled with a diamine resolving agent and equilibrated to single diastereoisomers. Hydrolysis returns enantiomerically enriched amide (see reaction scheme).     

Halogen Bonding in Haspin-Halogenated Tubercidin Complexes: Molecular Dynamics and Quantum Chemical Calculations

Haspin, an atypical serine/threonine protein kinase, is a potential target for cancer therapy. 5-iodotubercidin (5-iTU), an adenosine derivative, has been identified as a potent Haspin inhibitor in vitro. In this paper, quantum chemical calculations and molecular dynamics (MD) simulations were employed to identify and quantitatively confirm the presence of halogen bonding (XB), specifically halogen∙∙∙π (aromatic) interaction between halogenated tubercidin ligands with Haspin. Consistent with previous theoretical finding, the site specificity of the XB binding over the ortho-carbon is identified in all cases. A systematic increase of the interaction energy down Group 17, based on both quantum chemical and MD results, supports the important role of halogen bonding in this series of inhibitors. The observed trend is consistent with the experimental observation of the trend of activity within the halogenated tubercidin ligands (F < Cl < Br < I). Furthermore, non-covalent interaction (NCI) plots show that cooperative non-covalent interactions, namely, hydrogen and halogen bonds, contribute to the binding of tubercidin ligands toward Haspin. The understanding of the role of halogen bonding interaction in the ligand–protein complexes may shed light on rational design of potent ligands in the future.     

Direct determination of non-steroidal anti-inflammatory drugs by column-switching LC-MS

A method for determination of 16 non-steroidal anti-inflammatory drugs (NSAIDs) in human plasma samples without time-consuming sample pre-treatments was developed. The system consisted of two pumps for mobile phase delivery, a six-port switching valve, a pre-column (Oasis HLB Cartridge Column), and a reversed phase analytical column (COSMOSIL 3C18-MS-II). The analytes were trapped on the precolumn and subsequently separated on the analytical column. The present method allowed on-line sample clean-up and enrichment, leading to improved sensitivity without any tedious sample preparation. The recoveries of NSAIDs from human plasma by column-switching were greater than 72.6%. The total analysis time for a single analytical run was approximately 11 min. The detection limits of NSAIDs were 0.0025 to 0.2 microg/mL using the selected ion monitoring mode.     

Determination of inorganic anions in natural water by microcolumn ion chromatography with on-column enrichment.

An on-column enrichment method was developed for the rapid determination of inorganic anions in natural water. The system was assembled from a syringe pump, a six-port switching valve with a sample-enrichment loop, a separation column and a UV detector. The enrichment efficiency of the system was tested by using inorganic anions as samples. The limits of detection were between 0.6 and 7.7 microg/L. The system was applied to the determination of anions in river and pond-water samples.     

2-pyrazinylnitrene and 4-pyrimidylnitrene. Ring expansion to 1,3,5-triazacyclohepta-1,2,4,6-tetraene and ring opening to (2-Isocyanovinyl)carbodiimide

Tetrazolo[1,5-a]pyrazine/2-azidopyrazine 9T/9A undergo photolysis in Ar matrix at cryogenic temperatures to yield 1,3,5-triazacyclohepta-1,2,4,6-tetraene 21 as the first observable intermediate, and 1-cyanoimidazole 11 and (2-isocyanovinyl)carbodiimide 22 as the final products. The latter tautomerizes to 2-(isocyanovinyl)cyanamide 23 on warming to 40 K. The same intermediate 21 and the same final products are obtained on matrix photolysis of the isomeric tetrazolo[1,5-c]pyrimidine/4-azidopyrimidine 24T/24A. These photolysis results as well as those of the previously reported thermal ring contraction of (15)N-labeled 2-pyrazinyl- and 4-pyrimidylnitrenes to 1-cyanoimidazoles can all be rationalized in terms of selective ring opening of 21 or nitrine 10 to a nitrile ylide zwitterion 28 prior to formation of the final products, 11 and 22. The results are supported by high-level ab initio and DFT calculations (CASPT2-CASSCF(6,6), G3(MP2), and B3LYP/6-31+G) of the energies and IR spectra of the intermediates and products.     

Total Synthesis of (±) Flavipucine

In 1972 we proposed¹ structure 3 for flavipucine, an antibiotic from an Aspergillus flavipes strain. Later we reported² a novel reaction of 6-methyl-4-hydroxy-2-pyridone with α keto aldehydes which provided 1a from isobutylglyoxal and it was stated that we believed 1a would serve as a key intermediate in the total synthesis of flavipucine 3.