Final Report Summary - FLOW-CHEMISTRY (Development of new flow chemistry methodology: Application into total synthesis of spirangien natural products and analogues thereof.)
Project context and objectives
The development of new methods and reaction protocols in order to make new carbon-carbon bonds is of paramount importance to organic chemistry. To do this, the area of natural product synthesis has played a key role, providing new strategies in order to implement the key functionality required in a target molecule. Natural products incorporating heterocyclic motifs are of particular interest as they usually present high bioactive behaviour. In addition, their structural complexity represents a synthetic challenge in organic chemistry. Therefore, efficient methods for the construction of these molecules are of great importance.
Currently, it is no longer sufficient simply to be able to make complex molecules rather than making them as efficiently as possible. Therefore it is necessary to develop new methodologies that can circumvent the problems associated with traditional batch chemistry. For this reason, the use of flow chemistry has been implemented.
Project outcomes
In doing this, several advantages become apparent:
- a) the use of a contained environment means that high pressures and temperatures can be achieved, whilst toxic, odorous or hazardous reagents would be less problematic;
- b) microfluidic channels can potentially result in enhanced reactivity;
- c) exothermic processes and reactive intermediates can be readily assimilated by the equipment. In a broader sense, we can also anticipate lower solvent usage and less waste product generation which can lead to safer working practices. Furthermore, the use of automated machinery for synthesis is an attractive concept insofar as the requisite material can be made in the quality and quantity needed over a 24h/7-day period, meaning a more efficient use of expensive laboratory space.
The aim of this project was to integrate traditional batch process chemistry with automated continuous flow technologies in order to achieve the total synthesis of several natural products bearing heterocycles in their structure. Thus, we envisioned we could revolutionise the way traditional total synthesis is done by using flow technologies where they showed a great advantage to traditional batch techniques. The chosen target molecules were Spirangien A, O- Methyl siphonazole and ()-Hennoxazole A.
The development of new methods and reaction protocols in order to make new carbon-carbon bonds is of paramount importance to organic chemistry. To do this, the area of natural product synthesis has played a key role, providing new strategies in order to implement the key functionality required in a target molecule. Natural products incorporating heterocyclic motifs are of particular interest as they usually present high bioactive behaviour. In addition, their structural complexity represents a synthetic challenge in organic chemistry. Therefore, efficient methods for the construction of these molecules are of great importance.
Currently, it is no longer sufficient simply to be able to make complex molecules rather than making them as efficiently as possible. Therefore it is necessary to develop new methodologies that can circumvent the problems associated with traditional batch chemistry. For this reason, the use of flow chemistry has been implemented.
Project outcomes
In doing this, several advantages become apparent:
- a) the use of a contained environment means that high pressures and temperatures can be achieved, whilst toxic, odorous or hazardous reagents would be less problematic;
- b) microfluidic channels can potentially result in enhanced reactivity;
- c) exothermic processes and reactive intermediates can be readily assimilated by the equipment. In a broader sense, we can also anticipate lower solvent usage and less waste product generation which can lead to safer working practices. Furthermore, the use of automated machinery for synthesis is an attractive concept insofar as the requisite material can be made in the quality and quantity needed over a 24h/7-day period, meaning a more efficient use of expensive laboratory space.
The aim of this project was to integrate traditional batch process chemistry with automated continuous flow technologies in order to achieve the total synthesis of several natural products bearing heterocycles in their structure. Thus, we envisioned we could revolutionise the way traditional total synthesis is done by using flow technologies where they showed a great advantage to traditional batch techniques. The chosen target molecules were Spirangien A, O- Methyl siphonazole and ()-Hennoxazole A.