Synthesis of 6'-galactosyllactose, a deviant human milk oligosaccharide, with the aid of Candida antarctica lipase-B.

Research on human milk oligosaccharides (HMOs) has increased over the past decade showing great interest in their beneficial effects. Here we describe a method for the selective deacetylation using immobilised Candida antarctica lipase-B, Novozyme N435 (N435), of pyranose saccharides in organic media with the aim of simplifying and improving the pathways for the synthesis of HMOs. By first studying in depth the deacetylation reaction of peracetylated D-glucose two reaction conditions were found, which were used on different HMO building blocks, peracetylated saccharides and thioglycosides. D-Glucose based saccharides showed selectivity towards the fourth and the sixth position deacetylation. While α-anomer of peracetylated D-galactose remained unreactive and ß-anomer favoured the first position deacetylation. Peracetylated L-fucose, on the other hand, had no selectivity as the main product was fully unprotected L-fucose. Taking the peracetylated D-glucose deacetylation reaction product and selectively protecting the primary hydroxyl group in the sixth position left only the fourth position open for the glycosylation. Meanwhile, the deacetylation product of D-galactose thioglycoside, with the sixth position deacetylated, had both acceptor and donor capabilities. Using the two aforementioned products derived from the N435 deacetylation reactions a deviant HMO, 6'-galactosyllactose (6'-GL) was synthesised.

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates.

An expansion of the solvent-free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent-based synthesis. Herein a new mechanochemical method was developed for nucleophilic substitution of alcohols using fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate (TFFH) and K2 HPO4 as an alcohol-activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 31-91 % yields. The complete stereoinversion occurred for the SN 2 reaction of (R)- and (S)-ethyl lactates. Substitution with halide anions (F- , Br- , I- ) and oxygen-centered (CH3 OH, PhO- ) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients has been demonstrated.

Cyclohexanohemicucurbit[8]uril Inclusion Complexes With Heterocycles and Selective Extraction of Sulfur Compounds From Water.

Solid-phase extraction that utilizes selective macrocyclic receptors can serve as a useful tool for removal of chemical wastes. Hemicucurbiturils are known to form inclusion complexes with suitably sized anions; however, their use in selective binding of non-charged species is still very limited. In this study, we found that cyclohexanohemicucurbit[8]uril encapsulates five- and six-membered sulfur- and oxygen-containing unsubstituted heterocycles, which is investigated by single-crystal X-ray diffraction, NMR spectroscopy, isothermal titration calorimetry, and thermogravimetry. The macrocycle acts as a promising selective sorption material for the extraction of sulfur heterocycles, such as 1,3-dithiolane and α-lipoic acid, from water.