A Robust and Scalable Continuous Flow Process for Glycerol Carbonate

We report a robust continuous flow procedure for the synthesis of glycerol carbonate (2‐GLC) from green reagents glycerol and dimethyl carbonate (DMC), mediated by an inexpensive polymer‐supported base catalyst using methanol as co‐solvent. High conversion and selectivity were obtained, while residence times were typically shorter than 10 minutes

Two-chamber reactors and flow chemistry as valuable tools in organic synthesis

In this thesis, an attempt was made to develop organic synthesis methodology involving dangerous gases. The idea was to provide tools to the academic and industrial research society to work in a safe manner with these products. In general, in an academic lab setting, organic reactions involving gaseous reagents are avoided because of both practical and safety concerns. Therefore, alternatives for these reactions are needed. A convenient and safe method was developed to generate carbon monoxide, a synthetically useful but highly dangerous gas. The gas is formed in a closed system where it is consumed as well. This new method uses formic acid, mesyl chloride and triethylamine to generate carbon monoxide, 3 commodity chemicals available in every organic synthesis lab and is one of the cheapest ways known to generate carbon monoxide on laboratory scale. This methodology was applied by means of a two-chamber reactor to the development of minimalist α-helix peptidomimetics, scaffolds that can display amino acid side chains in a geometrically similar way as a protein α-helix. Palladium catalyzed aminocarbonylation reactions were used to assemble the helix mimetics. Previously unreported pyrazine based oligoamide α-helix mimetics were generated in this fashion. Next, the use of sulfur dioxide as reactant in organic synthesis was examined. Facing similar problems as with carbon monoxide, we developed a method for the large scale laboratory synthesis of DABSO, a common gas surrogate for sulfur dioxide, again making use of two-chamber reactors. Finally, flow chemistry was used to expand classic batch synthetic tools. In a first example, the use of a carbon monoxide precursors was explored in flow using at tube in tube reactor setup. Another example involves the application of flow chemistry to the synthesis of glycerol carbonate from glycerol. Glycerol is an industrial waste product of the production of biodiesel while glycerol carbonate is considered a green chemical.status: publishe

A Convenient Multigram Synthesis of DABSO Using Sodium Sulfite as SO2 Source

A convenient synthesis of DABCO·(SO2)2 (abbreviated as DABSO) is reported. Using a two-chamber set-up, sulfur dioxide is generated in one chamber and consumed in the other. This closed system overcomes safety issues related to working with toxic SO2 gas. Pressure build-up is avoided by gradually generating the gas using sodium sulfite as precursor. Moreover, only near-stoichiometric amounts of SO2 are required for this protocol. The use of anhydrous solvents is not necessary and every step is performed at room temperature. A scale-up was carried out on a 10 gram scale which, after overnight drying, resulted in a quantitative yield.status: publishe

A Robust and Scalable Continuous Flow Process for Glycerol Carbonate

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim With glycerol being a bulk waste product, the interest in converting it to other value-added products is steadily increasing. A scalable continuous flow process was developed for the synthesis of glycerol carbonate (2-GLC) from glycerol and dimethyl carbonate on a hydroxide functional resin. High conversion and selectivity were obtained while the residence times were typically shorter than 10 min. Continuous production of 2-GLC was achieved in high throughput and with improved processing metrics, creating the foundations for a production level process.status: publishe

Low-cost instant CO generation at room temperature using formic acid, mesyl chloride and triethylamine

Three low-cost standard lab chemicals, formic acid, mesyl chloride and triethylamine, were used for instant carbon monoxide (CO) generation at room temperature. Subsequently this gas was implemented in palladium-catalysed aminocarbonylation chemistry. Moreover, 13C-enriched formic acid was used as one of the most economical CO precursors for 13C-carbonyl labelling.crosscheck: This document is CrossCheck deposited related_data: Supplementary Information identifier: Cedrick Veryser (ORCID) identifier: Cedrick Veryser (ResearcherID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: The accepted version of this article will be made freely available after a 12 month embargo period history: Received 7 January 2016; Accepted 3 February 2016; Advance Article published 15 February 2016; Version of Record published 30 March 2016status: publishe

Carbonylation as a novel method for the assembly of pyrazine based oligoamide alpha-helix mimetics

The design and synthesis of oligoamide α-helix peptidomimetics is reported. The oligoamide type systems are prepared in a modular fashion by coupling the monomers using palladium-catalyzed carbonylation chemistry. This enabled us to use substrates with a low nucleophilicity, leading to previously unreported pyrazine based oligoamide α-helix mimetics. The proof of principle is given by synthesizing a small set of compounds. Various end-capping groups were introduced and also a mixed multimer was successfully prepared.crosscheck: This document is CrossCheck deposited related_data: Supplementary Information related_data: Crystal Structure Data identifier: Philippe Gilles (ORCID) identifier: Cedrick Veryser (ORCID) identifier: Cedrick Veryser (ResearcherID) identifier: Luc Van Meervelt (ORCID) identifier: Wim M. De Borggraeve (ORCID) identifier: Wim M. De Borggraeve (ResearcherID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0) history: Received 30 October 2016; Accepted 29 November 2016; Accepted Manuscript published 29 November 2016; Advance Article published 2 December 2016; Version of Record published 4 January 2017status: publishe

Carbonylation as a novel method for the assembly of pyrazine based oligoamide alpha-helix mimetics

Carbonylative assembly of pyrazine based oligoamide alpha-helix mimetics.</p

Control of mosquito larvae with TMOF and 60 kDa Cry4Aa expressed in Pichia pastoris

Cry4Aa 678 amino acids fragment (60 kDa) was cloned into Escherichia coli. After induction with IPTG the 60 kDa Cry4Aa fragment was purified by Ni chromatography, separated by SDS PAGE and identified by mass spectrometry (MS/MS). The 60 kDa Cry4Aa fragment exhibited high toxicity towards Ae. aegypti larvae. The earlier results [1] show that Pichia pastoris yeast cells expressing tmfA (synthetic gene coding for the Trypsin Modulating Oostatic Factor of Ae. aegypti) together with E. coli cells expressing Bti toxin genes (cry4Aa, cry11Aa, cyt1Aa and p20) are synergistic. Therefore, P. pastoris, which synthesizes high amounts of heterologous proteins was genetically engineered to produce TMOF and Cry4Aa. Codon-optimized synthetic genes, cry4Aa-tmfA, gst-cry4Aa-tmfA, tmfA and gfptmfA that were expressed by P. pastoris and fed to Ae. aegypti larvae caused 90% mortality. GST (glutathione-S-transferase) enhanced the activity of Cry4Aa-TMOF and protected it from heat denaturation and GFP (Green Fluorescent Protein)- TMOF allowed us to follow yeast cells consumption by individual larva using fluorescent microscopy. This report shows for the first time that 60 kDa Cry4Aa and TMOF expressed together in P. pastoris are highly toxic to Ae. aegypti larvae