Chiral S(VI) functional groups and their preparation. a, Biologically relevant suloximines and sulfonimidamides and general strategies used for their asymmetric preparation. b, Synthetic methods using S-nucleophilic and S-electrophilic strategies for the synthesis of sulfonimidoyls. c, Design of an enantiopure sulfonimidoyl transfer reagent for the modular asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides (this work). LG, leaving the group; PG, protective group; t-BuOK, potassium tert-butoxide; TFA, trifluoroacetic acid. Credit: Natural chemistry (2024). DOI: 10.1038/s41557-023-01419-3
Over the past decade, new sulfur-containing compounds have been significantly developed, used in various industries including pharmaceuticals and agricultural products. Sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides are types of sulfur-containing chemical compounds that have broad potential as therapeutic drugs. However, the process of synthesizing these compounds is complex and presents several limitations.
In a new article published in Natural chemistryMoffitt Cancer Center researchers describe their development of a new reagent that enables a more efficient approach to making sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides that can be used in drugs.
There are four main chemical approaches commonly used to create sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides. Recently, an additional approach called sulfur-fluorine exchange (SuFEx) chemistry has attracted attention. But this approach has several limitations to its widespread use, such as the need to use high pressures.
Moffitt’s research team wanted to develop a more efficient process for creating sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides. Through various experiments and chemical processes, they developed a reagent called t-BuSF that serves as the hub in the SuFEx chemical process to synthesize these sulfur-containing compounds. The use of t-BuSF reduced the number of steps required to manufacture these compounds and improved the reaction times and stability of their chemical precursors.
The researchers further demonstrated the potential utility of t-BuSF in medicinal chemistry in over 70 examples and by preparing five therapeutic targets and intermediates. They showed that t-BuSF was able to create these products in high yields and with fewer synthesis steps.
“Given the cost-effectiveness and chemical space accessible from this reagent platform, it is expected to have positive impacts on discovery sciences, from the development of new drugs and agrochemicals to the discovery of new ligands, organocatalysts and materials,” said Justin Lopchuk. , Ph.D., associate member of the Department of Drug Discovery at Moffitt.
More information:
Shun Teng et al, Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides and sulfonimidamides activated by an enantiopure bifunctional reagent S(VI), Natural chemistry (2024). DOI: 10.1038/s41557-023-01419-3
Provided by the H. Lee Moffitt Cancer Center and Research Institute
Quote: New reagent improves the process of making sulfur-containing compounds that can be used in medicines (January 22, 2024) retrieved January 22, 2024 from
This document is subject to copyright. Apart from fair use for private study or research purposes, no part may be reproduced without written permission. The content is provided for information only.
