Application notes

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The following application notes show the range of synthesis that are possible with the Vapourtec system.

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Synthesis of N-methylated peptides in continuous flow

Application Note 81 – December 2025

Peptides incorporating N-methyl amino acids are notoriously difficult to synthesize by conventional batch SPPS, often leading to long cycle times, high deletion levels, and reduced crude purity. In Application Note 81, Vapourtec demonstrates a validated fast-flow SPPS (FF-SPPS) protocol using Oxyma/DIC activation that enables reliable incorporation of N-methylated and other sterically hindered residues.

Peptide-Builder

High throughput synthesis of peptides with high crude purity

Application Note 80 – December 2025

High-throughput fast-flow synthesis delivers sixteen 16-mer peptides at ~90% crude purity, with real-time monitoring and fully unattended weekend operation on the Peptide-Builder.

CSTR

Suzuki-Miyaura coupling using CSTRs

Application Note 79 – February 2025

This application note demonstrates the benefits of using a cascade of continuous stirred-tank reactors (CSTR) to perform heterogeneous Suzuki-Miyaura couplings including: Short residence time, high conversion and Simple set up to change residence time and catalytic loading.

  • Heterogeneous catalysis

Cleaving Oligonucleotides

Cleavage of oligonucleotides in continuous flow

Application Note 78 – February 2025

Prepared by scientists from Novo Nordisk, this application note demonstrates the benefits of continuous flow in the cleavage and deprotection of oligonucleotides, reducing this process to as little as 2.5 min residence time, regardless of the scale. Also offering safety and purity improvements.

Solid-phase oligonucleotide synthesis

Solid-phase oligonucleotide synthesis DNA 9-mer

Application Note 77 – July 2024

Continuous flow synthesis offers a powerful opportunity to transform oligonucleotide production, yet challenges around resin behaviour, mass transfer, and reagent efficiency have limited its adoption. In this application note, Vapourtec demonstrates how its Variable Bed Flow Reactor (VBFR) technology enables efficient solid-phase oligonucleotide synthesis under continuous flow conditions. By actively controlling resin packing and eliminating channelling, the VBFR delivers consistent reaction performance and efficient washing throughout the synthesis. Using a 9-mer DNA sequence as a model, the system achieves ~77% crude purity and 82% isolated yield in under 4.5 hours, highlighting a robust, scalable approach to oligonucleotide synthesis.

Enzymatic synthesis of melatonin in flow

Enzymatic synthesis of melatonin in flow

Application Note 76 – July 2024

Melatonin is a hormone that regulates the human’s body sleep cycle and it is prescribed as insomnia relief medication. This application note demonstrates how the Paradisi Research Group synthesised melatonin under very mild conditions in decagram scale via an enzymatic process. By packing an immobilised enzyme acetyltransferase from Mycobacterium smegmatis (MsAcT), melatonin was synthesised with a throughput of 37 g/day.

CSTR

Controlled Stevens oxidation – CSTR

Application Note 75 – January 2024

Efficient mixing is critical to the success of biphasic reactions—yet it remains a persistent challenge in scale-up. In this application note, we demonstrate how Vapourtec’s continuous stirred-tank reactors (CSTRs) overcome these limitations, enabling robust and scalable biphasic chemistry. Using the biphasic esterification of an aldehyde via Stevens oxidation as a model system, we show how a cascade of CSTRs delivers rapid reaction times of ~1 minute while achieving a throughput exceeding 5 kg/day of the desired building block.

CSTR

Scale up of a SNAr reaction to >10 kg a day with CSTRs

Application Note 74 – December 2023

Scaling reactions that generate solids is a major challenge in flow chemistry, often leading to precipitation and reactor blockage in tubular systems. In this application note, Vapourtec shows how continuous stirred-tank reactors (CSTRs) overcome these limitations. Using a nucleophilic aromatic substitution that produces insoluble product and fluoride salt, a cascade of CSTRs achieves full conversion at high concentration without blockage, delivering throughput exceeding 10 kg per day.

Use of CSTR for biphasic reaction scale up

Use of CSTR for biphasic reaction scale up

Application Note 73 – June 2022

Vapourtec has teamed up with UK based reactor manufacturer Stoli Chem to demonstrate a new range of continuous stirred tank reactors for continuous flow applications. In this application note we demonstrate how a biphasic reaction can be scaled up to kilos/day under very mild conditions using the SABRe reactor. The mixing provided by this reactor enabled a throughout of ~8 mol/day, equating to 1.4 kg/day.

  • General synthesis

VBFR Mount

Cleaving peptides in flow

Application Note 72 – November 2021

In this application note, we demonstrate how safe, fast, and reliably a peptide is cleaved from a resin in continuous flow. Different cleavage conditions were evaluated using Glucagon-like peptide-1 (GLP-1) as an example peptide. By using the Variable Bed Flow Reactor (VBFR), the packing density of the resin was controlled throughout the reaction, minimising dilution and eliminating the channelling of reagents. Temperature, residence time, and cleavage cocktail were evaluated. The optimised protocol yielded GLP-1 with a crude purity of 82 % in only 30 minutes, compared to a traditional batch reaction taking between 2 to 4 hours.