Peter Gillespie ’25

What if simple sugars could be turned into vital medicines? Dr. Ming-Yu Ngai and his team at Stony Brook University are making this dream a reality.  Due to their relevance in cell-cell recognition, protein folding, inflammation, and infection, carbohydrate modification poses an intriguing avenue through which scientists can treat issues from viral infection to malfunctions in protein folding. Changing the character of the second carbon in a carbohydrate (C2) holds great promise, as many medicines, imaging techniques, and chemical processes rely upon unique functional groups attached to this carbon. As such, Dr. Ngai and his research team focus on developing an efficient process for a 1,2-spin-center shift (1,2-SCS), in which the reactive radical (one electron species) shifts from the first to the second carbon in the molecule. 

The novel mechanism relies upon the unique properties of palladium metal complexes. Exposure to blue LED light excites the palladium complexes, which abstract the halogen atom (X) at the C1-position. This process homolytically breaks the C-X bond, meaning one of two electrons in the C-X bond move to the halogen atom to form a bond with the palladium complex while another electron moves to carbon.  The singly occupied orbital of the radical carbon enters a state of hyper-conjugation, in which it interacts with the high-energy orbital of the neighboring acyloxy group. This interaction weakens the C-O bond at the C2-carbon and promotes the switching of the position of the C1-radical and the C2-acyloxy group, forming C2-radical species that can be captured for further C2-functionalization. 

In initial tests using α-glucosyl bromide, the reaction produced the desired product in 94% yield. Unlike catalysts that lack inner-sphere coordination, the palladium complex reversibly binds to C1-carbon, which maintains the integrity of the radical. Both α-bromosugars (sugars with a bromine atom) and α-iodosugars (sugars with an iodine atom) reacted efficiently under the standard conditions. The reaction also proved to be viable for carbohydrates with a diverse array of C6 attachments and for carbohydrates with fused ring structures. It was also applicable in functionalizing C2-carbon with iodine and deuterium, an isotope of hydrogen. Functionalizing carbons with deuterium is promising for modifying pharmaceuticals and utilizing new biomarkers, as deuterium-labeled sugars are frequently used to study biological processes. Additionally, given the influence of C2-iodosugars in directing glycosidic bond formation, this reaction could be helpful in discovering novel bioactive compounds, making this mechanism an important development in carbohydrate editing.

Works Cited: 

[1] M. Ngai, et al., Excited-state palladium-catalyzed 1,2-spin-center shift enables selective C-2 reduction, deuteration, and iodination of carbohydrates. Journal of the American Chemical Society 143, 1728-1734 (2021). doi: 10.1021/jacs.0c11209.

[2] Image 1 retrieved from: https://pixabay.com/photos/lump-sugar-sugar-cubes-sweet-food-548647/

[3] Image 2 retrieved from: https://pxhere.com/en/photo/1220701