BIOBASED CHEMICALS
The ReSolute plant will be built at Carling-St Avold in northern France
An LGO derivative was used for the production of an investigational drug for the treatment of leukaemia . The initial manufacturing process relied on an 11-step synthesis . The development team was able to reduce this to two , thereby reducing energy use , carbon emissions and wastewater generation . One of the key transformations was the enzymatic reductive amination of the carbonyl group to form the required chiral amine . Oncolys Bipharma has used the LGO platform to synthesise Censavudine , which has been investigated as a novel drug therapy for HIV with greater activity against the less common HIV-2 variant 3 Its patented route allowed for the synthesis of the API in a simpler way , at lower cost and in larger quantities than previous methods . The company used the inherent chirality of the LGO platform as well as the wellestablished chemical reactivity pattern to increase the sustainability of its production process . Despite these recent advances in the sustainable manufacturing of pharmaceuticals using the LGO platform , there are still significant opportunities to use it more widely to intercept key intermediates . For example , straightforward protocols have been developed
for the facile conversion of LGO to substituted butanolides , which are key building blocks for the synthesis of the COVID-19 anti-infective drug Remdesivir and the HIV protease inhibitor Indinavir . 3 These have the potential to increase the sustainable production of not only these drugs but a range of related compounds .
Drug discovery
Beyond pharmaceutical production , LGO has been used extensively for the synthesis of novel , biologically active compounds . These studies take advantage of the rigid , highly functionalised nature of LGO and its well understood chemical reactivity . 1 A series of recent papers has shown that the 1,4-addition of a range of nucleophiles , including thiols , amines , azides and alcohols , to the enone of LGO resulted in a range of biologically active compounds that had anticancer properties . Simple variations in the structure of the nucleophile gave control over both the specific cancer target and the activity of the molecules . In related work , Banwell introduced a 2-nitropyridine motif at the alpha position of LGO to afford a series of compounds with antimicrobial and anti-cancer activities . Cycloaddition reactions are commonly used to selectively functionalise LGO for the synthesis of biologically active compounds . The cycloaddition of nitrones with LGO proceeds in a highly selective manner due to the polarisation of the double bond as well as the 1,6-anhydro bridge . This reactivity has been used to synthesise a series of carbonic anhydrase and RAS activation inhibitors .
Outlook
Continued innovation in drug development , primarily driven by specialty drugs , is driving an expected CAGR of 8 % from 2021 to 2025 . 4 There is also increasing demands from customers and governments for more sustainable pharmaceutical manufacturing . Against this backdrop , Circa is delivering biomass-derived LGO platform molecules , and developing new products and technologies to support the integration of our products into the sustainable production of pharmaceuticals . The Circa Renewable Chemistry Institute at the University of York has been established for this purpose . Circa is also a partner on the EU Horizon-funded project TransPharm , which seeks to develop sustainable production methods for pharmaceuticals products . •
References : 1 : . https :// www . frontiersin . org / articles / 10.3389 / fchem . 2022.902239 / full
2 : . https :// communities . acs . org / t5 / GCI-Nexus-Blog / Merck-team-wins-2022-Peter-J-Dunn-Award-for- Green-Chemistry-and / ba-p / 87165
3 : . K . Nagai , S . Kiguchi , H . Koyama , W . E . Hume & S . Tsujimoto , WIPO . PCT Application WO / 2009 / 084655 4 : . Future of US healthcare post-COVID-19 | McKinsey
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Dr Jason E . Camp
CTO
CIRCA GROUP jason . camp @ circa-group . com www . circa-group . com
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