Chemical engineers synthesise LGA

A TEAM of chemical engineers and chemists has developed a method of synthesising extremely pure levoglucosan (LGA), a rare and expensive sugar which has gone largely untested for commercial uses.

LGA is a naturally-occurring organic compound that is an effective precursor to more complex chemicals which can be built up from smaller pieces like Lego bricks. The team from Rice University, US and the Dalian Institute of Chemical Physics, China says that LGA’s value comes from the options it presents to drugmakers and chemical engineers who specialise in chemical synthesis.

Michael Wong, professor and chair of chemical and biomolecular engineering at Rice said: “Most chemicals are made from oil and gas, but you can't make LGA from petrochemicals. LGA has a very interesting structure that makes it a much better starter molecule than sugar, but it's been hard for researchers to work with LGA when quantities are limited. LGA is so difficult and inefficient to make that whatever small amounts were commercially available were very expensive.”

The current method for making LGA begins with starch subjected to intense heat under oxygen-free conditions. The result is a chemical soup that contains alcohols, acids, other anhydrosugars, aldehydes and furfurals, and a few percent LGA. The soup must be treated further to separate the waste and yield highly pure LGA.

The new method involves alkoxy or phenoxy substitution at the anomeric carbon of glucose prior to fast pyrolysis of the resulting sugar at 600oC. Adding the substituent group ‘locks’ the sugar’s pyranose ring, which results in LGA formation becoming the dominant reaction pathway during pyrolysis. The team obtained 95% purity with the experiments. Wong said the team's process should be far more economical and operationally simpler than the current small-scale route as it reduces a ten-step process to two, significantly cutting the cost.

Wong said LGA is particularly handy because it contains a number of chiral carbons – which come in left-handed and right-handed forms that are not mirror images of one another. Just as specially-shaped Lego bricks are rare but useful to build unique structures, LGA molecules could open up new avenues to synthetic chemists, he added. Glucose also contains chiral carbons, but it is less stable in syntheses.

In a 2004 Department of Energy analysis, LGA was among the 30 most valuable chemicals identified as possible products of biorefineries. Wong says LGA's unique properties could be useful for making ‘green’ plastics (made solely from biomass) if quantity were no longer an issue. He said some drugmakers have looked at using LGA as a building block for making drugs, including some of the widely-prescribed type 2 diabetes drugs known as SGLT2 inhibitors.

The next step will be to scale up the method in order to produce quantities of LGA for potential commercial needs. Funded by the National Science Foundation (NSF), the scaleup work also includes a grant from NSF’s Innovation Corps (I-Corps), for the researchers to explore potential markets for LGA.

Under I-Corps, the team underwent a seven-week process which includes online training with business mentors and interviews with at least 100 potential customers. Wong hinted that he and his research partner may form a startup company if the I-Corps process reveals a significant market.

Green Chemistry, DOI: 10.1039/C6GC01600F