Unlocking the Potential of Bio-Based Nitrogen-Rich Furanic Platforms as Biomass Synthons.

The demand for new biomass-derived fine and commodity chemicals propels the discovery of new methodologies and synthons. Whereas furfural and 5-hydroxymethylfurfural are cornerstones of sustainable chemistry, 3-acetamido-5-acetyl furan (3A5AF), an N-rich furan obtained from chitin biomass, remains unexplored, due to the poor reactivity of the acetyl group relative to previous furanic aldehydes. Here we developed a reactive 3-acetamido-5-furfuryl aldehyde (3A5F) and demonstrated the utility of this synthon as a source of bio-derived nitrogen-rich heteroaromatics, carbocycles, and as a bioconjugation reagent.

Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents.

In this study were synthesized non-Michael acceptor cyclopentenones (CP) from biomass derivative furfural as anticancer agents. Cyclic enones, both from natural sources and synthetic analogues, have been described as cytotoxic agents. Most of these agents were unsuccessful in becoming valuable therapeutic agents due to toxicity problems derived from unselective critical biomacromolecule alkylation. This may be caused by Michael addition to the enone system. Ab initio studies revealed that 2,4-substituted CPs are less prone to Michael additions, and as such were tested three families of those derivatives. We prepare the new CPs from furfural through a tandem furan ring opening/Nazarov electrocyclization and further functionalization. Experimentally the 2,4-substituted CPs exhibited no reactivity towards sulphur nucleophiles, while maintaining cytotoxicity against HT-29, MCF-7, NCI-H460, HCT-116 and MDA-MB 231 cells lines. Moreover, the selected CP are non-toxic against healthy HEK 293T cell lines and present proper calculated drug-like properties.

Tandem Thio-Michael Addition/Remote Lactone Activation of 5-Hydroxymethylfurfural-Derived δ-Lactone-Fused Cyclopentenones.

The creation of structurally diverse chemical entities from fairly simple biorefinery products remains a challenge. In this work 5-hydroxymethylfurfural (HMF) was identified as a key synthon for preparing highly complex cyclopentenones (CP) via tandem 1,4-addition/elimination/remote lactone activation to external O- and N-nucleophiles in δ-lactone-fused-CPs hotspots. This scaffold was also reactive enough to be incorporated into model cysteine-peptides in low concentrations, paving the way to a potential translation generating complexity in the synthesis of small peptides. The new enones also exhibited activity against intraerythrocytic Plasmodium falciparum (IC50 =1.32 µm).

Greener Strategy for Lupanine Purification from Lupin Bean Wastewaters Using a Molecularly Imprinted Polymer.

Lupanine is an alkaloid used in the pharma industry as a building block or precursor in the synthesis of sparteine and also explored for drug synthesis in the pharma industry as a chiral selector. This alkaloid is found in lupin bean processing wastewaters originated from the debittering process to make these beans edible. In this work, a computational chemistry approach was taken to design molecularly imprinted polymers (MIPs) selecting itaconic acid, a biobased building block, as a functional monomer that can provide higher affinities for lupanine. MIP-1 was prepared using lupanine as the template, itaconic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker by bulk polymerization. Lupanine was concentrated from lupin bean wastewater by nanofiltration, extracted with ethyl acetate, and purified using the synthesized MIP. MIP-1 was able to selectively recognize lupanine and improve the purity of lupanine from 78 to 88%, with 82% recovery of the alkaloid. These results show the potential application of this strategy to render the industrial process more sustainable.