Abstract
Sulfoximines are of considerable interest for incorporation into medicinal compounds. A convenient synthesis of N-protected sulfoximines is achieved, under mild conditions, by rhodium-catalyzed transfer of carbamates to sulfoxides. The first examples of 4-membered thietane-oximines are prepared. Sulfoximines bearing Boc and Cbz groups are stable to further cross coupling reactions, and readily deprotected. This method may facilitate the preparation of NH-sulfoximines providing improved (global) deprotection strategies, which is illustrated in the synthesis of methionine sulfoxide (MSO).
Highlights
Sulfoximine derivatives have received the attention of synthetic chemists over several decades.[1]
We report the first preparation of thietane-oximines, and a preparation of methionine sulfoximine (MSO) via the Boc-sulfoximine
Using rhodium catalysis and magnesium oxide as base, we were delighted to observe the direct formation of the N-Boc sulfoximine 2a from sulfoxide 1a in good yield (Table 1, entry 1).[25]
Summary
Sulfoximine derivatives have received the attention of synthetic chemists over several decades.[1]. MSO and buthionine sulfoximine (BSO) are useful tools for the inhibition of the biosynthesis of glutathione (GSH).[7] the more general use of the sulfoximine group in medicinal chemistry follows the development of BAY 1000394, a pan-CDK inhibitor that is currently in phase 1 clinical trials for cancer in patients with advanced solid tumors.[8] In this case, the sulfoximine conferred improved solubility versus a sulfonamide predecessor. Sulfoximines are increasingly intriguing options for inclusion in drug discovery programs.[9] Much of this interest is due to their attractive structural features to improve physicochemical properties These polar and stable functional groups offer hydrogen bond acceptors and donors, aid solubility, introduce asymmetry at the sulfur atom and provide additional points of substitution through the nitrogen atom
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
