Synthesis of marine alkaloids leucettamines B and C by β-lactam ring rearrangement

A new method for the synthesis of marine alkaloids leucettamines B and C from Leucetta sp. sponges is described. The key step is the base-promoted rearrangement of β-lactam into imidazolone ring. Leucettamines B and C as well as their N-benzoyl derivatives were obtained in high yields. Single-crystal structures of both leucettamines B and C were determined by X-ray diffraction confirming Z-configuration of double bond at 4-position of imidazolone.     

Selective electrochemical CO bond cleavage of β-O-4 lignin model compounds mediated by iodide ion

The electrochemically oxidative cleavage of lignin β-O-4 model compounds mediated by iodide ion has been studied. The results indicate that electrolytic conditions play a predominant role in determining the distribution of cleavage products. The preparative-scale electrolysis proceeds in a simple undivided cell, employing a catalytic amount of NaI as the redox mediator and supporting electrolyte in methanol. Under these conditions, the C_βO bond is selectively cleaved with 2,2-dimethoxy-2-arylacetaldehyde being the main product. In some cases, the reaction gives a good yield of cleavaged products. The results further demonstrate that the indirect electrolysis mediated by halide is a versatile approach for chemical transformation.     

A useful ring transformation route to novel thiazepino[7,6-b]indoles from monochloro-β-lactam-fused 1,3-thiazino[6,5-b]indoles,analogues of cyclobrassinin

The Staudinger ketene-imine cycloaddition reactions of cyclobrassinin phytoalexin analogues 2-aryl-4,9-dihydro-1,3-thiazino[6,5-b]indoles with chloroacetyl chloride as a ketene source were investigated under different conditions. Both β-lactam ring formation and the N-chloroacetylation of the indole moiety took place. The indole N-chloroacetyl group can be easily removed by treatment in the presence of silica gel in methanol at reflux temperature. The selective β-lactam formation can be also achieved in certain cases under milder Staudinger conditions. The treatment of azeto[2,1-b]thiazino[6,5-b]indole-1-one derivatives with sodium ethoxide in ethanol provided the novel thiazepino[7,6-b]indole ring systems in a one-step ring transformation. The structures of the new ring systems were determined by means of IR and NMR spectroscopy.     

Synthesis and characterization of Rosuvastatin calcium impurity A; a HMG-CoA reductase inhibitor

During the process development for multistep synthesis of Rosuvastatin calcium several impurities were obtained along with the final Rosuvastatin calcium. Out of this; synthesis of impurity A (acetone adduct) a minor impurity of Rosuvastatin calcium (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[[(2-hydroxy-2-methylpropyl)sulfonyl(methyl)amino]-6-(1-methylethyl)-pyrimidin-5-yl]-3,5-dihydroxyheptenoicacid hemicalcium salt, is described. The synthesis of impurity A has been accomplished in 6 steps; starting from formation of β-hydroxy sulfonamide as the key intermediate and followed by using convenient routes with overall yield of 13.5%. The target compound can be used as the reference substance of impurity of the Rosuvastatin calcium.     

Rapid,efficient and solvent-free synthesis of (un)symmetrical xanthenes catalyzed by recyclable sulfated polyborate

The present study describes a rapid, simple and straightforward approach to the synthesis of 1,8-dioxo-octahydroxanthenes, 14-phenyl-14H-dibenzo[a,j]xanthene and tetrahydrobenzoxanthene-11-ones under solvent-free conditions using sulfated polyborate as a highly efficient catalyst. The procedure offers several advantages including cleaner reaction profile, mild reaction condition, economic, recyclable and environmentally benign catalyst, high yields, simple experimental and workup procedures. While non-extractive work up/purification, along with reusability of catalyst make this method economically affordable for large scale.     

Phosphoprotein Analysis by MALDI-TOF Mass Spectrometry using On-Probe Tandem Proteolysis and Dephosphorylation

In this investigation, methods based on on-probe enzymatic cleavage matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOF-MS) analyses have been developed, allowing the rapid assignment of phosphorylation sites within phosphoproteins. The procedures involved robotic sample deposition of a phosphoprotein, such as intact bovine β-casein, on stainless steel or gold MALDI plates, on-probe proteolysis with trypsin for 10–180?s at 37°C, on-probe dephosphorylation for 1–10?min at 37°C with alkaline phosphatase, followed by differential mass spectrometry with peptide mass mapping. The dephosphorylation conditions were initially optimized using in-solution tryptic digestion of the phosphoprotein performed in the presence of MS-compatible anionic surfactant sodium 3-[(2-methyl-2-undecyl-1,3-dioxolan-4-yl)methoxy]-1-propanesulfonate. Two methods of trypsin deactivation were investigated, cooling and quenching by acidification, which resulted in the surfactant either staying intact or becoming cleaved, respectively. Since the surfactant had no detrimental effects on dephosphorylation of phosphopeptides, the acidification and neutralization steps were not included in the final analytical method. A protocol, comprising on-probe tandem, surfactant-aided proteolysis for 3?min followed by on-probe dephosphorylation for 10?min was thus established, allowing the rapid identification of location and sequence of phosphopeptides within a phosphoprotein by these procedures.     

A rapid and highly efficient Michael addition of methoxybenzenes and indoles to α,β-unsaturated ketones using BF3·OEt2 as a catalyst

An efficient and general protocol is described for the Michael addition of α,β-unsaturated ketones with electron-rich arenes/indoles to give alkylated arenes/indoles under mild reaction condition at room temperature. Shorter reaction time, convenient and good isolated yields are the significant features of this protocol. Moreover, the procedure is environmentally benign in nature and applicable to variety of arenes/indoles as well as α,β-unsaturated ketones.     

A new umpolung for direct γ-regioselective nucleophilic addition of alcohols to γ-enolizable α,β-unsaturated aldehydes

A direct γ-regioselective nucleophilic addition of alcohols toward γ-enolizable α,β-unsaturated aldehydes was developed using a catalytic amount of MeSO₃H (30 mol%) and a stoichiometric amount of chloranil (1.0 equiv) as the oxidant. The addition of hexafluoroisopropanol (HFIP) was found to accelerate this cross-dehydrogenative coupling, furnishing diverse alcoholic adducts with high γ-regio- and E-stereoselectivities.     

Utilizing Paper-Based Devices for Antimicrobial-Resistant Bacteria Detection

Antimicrobial resistance (AMR), the ability of a bacterial species to resist the action of an antimicrobial drug, has been on the rise due to the widespread use of antimicrobial agents. Per the World Health Organization, AMR has an estimated annual cost of USD 34 billion in the US and is predicted to be the number one cause of death worldwide by 2050. One way AMR bacteria can spread, and by which individuals can contract AMR infections, is through contaminated water. Monitoring AMR bacteria in the environment currently requires that samples be transported to a central laboratory for slow and labor intensive tests. We have developed an inexpensive assay using paper-based analytical devices (PADs) that can test for the presence of β-lactamase-mediated resistance. To demonstrate viability, the PAD was used to detect β-lactam resistance in wastewater and sewage and identified resistance in individual bacterial species isolated from environmental water sources.     

Aqueous microwave-assisted DMAP catalyzed synthesis of β-phosphonomalonates and 2-amino-4H-chromen-4-ylphosphonates via a domino Knoevenagel-phospha-Michael reaction

An aqueous microwave (mw)-assisted DMAP catalyzed one-pot highly efficient route to synthesize β-phosphonomalonates and 2-amino-4H-chromen-4-yl phosphonates has been demonstrated via the domino Knoevenagel-phospha-Michael reaction of aryl aldehyde/salicylaldehyde, malononitrile/ethyl cyanoacetate and alkyl phosphite ester. Optimization of reaction conditions were performed by using conventional and microwave synthetic approaches. This conversion proceeded smoothly to deliver the desired product in good to excellent yields (75–95%) in a short reaction time (10–12 min). The present methodology is very simple, environmentally benign, high yielding and has very well demonstrated the synergistic effect of water and microwaves.