Field evaluation of the CATT/Trypanosoma brucei gambiense on blood-impregnated filter papers for diagnosis of human African trypanosomiasis in southern Sudan.

Most Human African Trypanosomiasis (HAT) control programmes in areas endemic for Trypanosoma brucei gambiense rely on a strategy of active mass screening with the Card Agglutination Test for Trypanosomiasis (CATT)/T. b. gambiense. We evaluated the performance, stability and reproducibility of the CATT/T. b. gambiense on blood-impregnated filter papers (CATT-FP) in Kajo-Keji County, South-Sudan, where some areas are inaccessible to mobile teams. The CATT-FP was performed with a group of 100 people with a positive CATT on whole blood including 17 confirmed HAT patients and the results were compared with the CATT on plasma (CATT-P). The CATT-FP was repeated on impregnated filter papers stored at ambient and refrigerated temperature for 1, 3, 7 and 14 days. Another 82 patients with HAT, including 78 with a positive parasitology, were tested with the CATT-FP and duplicate filter paper samples were sent to a reference laboratory to assess reproducibility. The CATT-FP was positive in 90 of 99 patients with HAT (sensitivity: 91%). It was less sensitive than the CATT-P (mean dilution difference: -2.5). There was no significant loss of sensitivity after storage for up to 14 days both at ambient and cool temperature. Reproducibility of the CATT-FP was found to be excellent (kappa: 0.84). The CATT-FP can therefore be recommended as a screening test for HAT in areas where the use of CATT-P is not possible. Further studies on larger population samples in different endemic foci are still needed before the CATT-FP can be recommended for universal use

Total Synthesis of Amphidinolide F

Orchestrated yet nonconsonant: The challenge posed by the “umpoled” 1,4-dioxygenation pattern characteristic for the polyketide frame of amphidinolide F was mastered by a late-stage ring-closing alkyne metathesis followed by a directed transannular hydration under the aegis of a carbophilic π-acid catalyst. This concordant strategy enabled a concise total synthesis of this enticing marine natural product

Direct Amidation of Esters via Ball Milling

The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent

Continuous Preparation and Use of Dibromoformaldoxime as a Reactive Intermediate for the Synthesis of 3-Bromoisoxazolines

We report the multistep continuous process for the preparation of dibromoformaldoxime (DBFO) as a precursor to generate 3-bromoisoxazolines. We also report process improvements that afford a productivity of over 620 mmol h−1 of DBFO.We would like to thank Syngenta Crop Protection AG (CB) and the EPSRC (SVL, grant nos. EP/K009494/1, EP/ M004120/1, and EP/K039520/1) for financial support

Direct Amidation of Esters via Ball Milling

The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent

A Comment on Continuous Flow Technologies within the Agrochemical Industry

The agrochemical sector operates on a large scale within a highly complex environment. Cost-effective production on an increasing scale in a sustainable fashion imposes massive constraints on the industry. Here we offer a perspective on flow chemistry, with literature highlights showing how the application of this technology can impact chemical processes (especially at the early stages of R&D) for agrochemicals, with clear benefits in comparison with a traditional batch vessel, be it safety, quality, or throughput. The value of flow chemistry for the business is clear, and the number of examples reported in the literature will undoubtably continue to increase in the agrochemical industry

Data supporting "Continuous preparation and use of dibromoformaldoxime as a reactive intermediate for the synthesis of 3-bromoisoxazolines"

NMR file

Supplementary material to "Flow Synthesis of Cyclobutanones via [2+2] Cycloaddition of Keteneiminium Salts and Ethylene Gas"

A flow chemistry process for the synthesis of 2-substituted cyclobutanones, via [2+2] cycloaddition of keteneiminium salts and ethylene gas, is reported

Flow synthesis of cyclobutanones via\textit{via} [2 + 2] cycloaddition of keteneiminium salts and ethylene gas

A flow chemistry process for the synthesis of 2-substituted cyclobutanones, $\textit{via}$ [2+2] cycloaddition of keteneiminium salts and ethylene gas, is reported. Our approach uses rapid and mild reaction conditions to access a diverse array of products with good to excellent yield, alongside a good level of functional group compatibility.The authors would like to thank Syngenta Crop Protection (CB) and the EPSRC (SVL, grants EP/K009494/1, EP/M004120/1 and EP/K039520/1) for financial support

Concise Total Syntheses of Amphidinolides C and F

The marine natural products amphidinolide C (1) and F (4) differ in their side chains but share a common macrolide core with a signature 1,4-diketone substructure. This particular motif inspired a synthesis plan predicating a late-stage formation of this non-consonant (“umpoled”) pattern by a platinum-catalyzed transannular hydroalkoxylation of a cycloalkyne precursor. This key intermediate was assembled from three building blocks (29, 41 and 47 (or 65)) by Yamaguchi esterification, Stille cross-coupling and a macrocyclization by ring-closing alkyne metathesis (RCAM). This approach illustrates the exquisite alkynophilicity of the catalysts chosen for the RCAM and alkyne hydroalkoxylation steps, which activate triple bonds with remarkable ease but left up to five other π-systems in the respective substrates intact. Interestingly, the inverse chemoselectivity pattern was exploited for the preparation of the tetrahydrofuran building blocks 47 and 65 carrying the different side chains of the two target macrolides. These fragments derive from a common aldehyde precursor 46 formed by an exquisitely alkene-selective cobalt-catalyzed oxidative cyclization of the diunsaturated alcohol 44, which left an adjacent acetylene group untouched. The northern sector 29 was prepared by a two-directional Marshall propargylation strategy, whereas the highly adorned acid subunit 41 derives from D-glutamic acid by an intramolecular oxa-Michael addition and a proline-mediated hydroxyacetone aldol reaction as the key steps; the necessary Me3Sn-group on the terminus of 41 for use in the Stille coupling was installed via enol triflate 39, which was obtained by selective deprotonation/triflation of the ketone site of the precursor 38 without competing enolization of the ester also present in this particular substrate