Potential peptidic proteasome inhibitors by incorporation of an electrophilic trap based on amino acid derived α-substituted sulfonyl fluorides

Abstract

Peptido sulfonyl fluoride derivatives were designed and synthesized containing a substituent on the alpha position (αPSFs) with respect to the sulfonyl fluoride electrophilic trap. The chemical reactivity of these α-substituted amino sulfonyl fluorides was studied and compared with the previously described β-substituted amino sulfonyl fluorides in order to get a deeper insight into the importance of the immediate structural environment of the sulfonyl fluoride moiety. Unfortunately, the poor solubility of the resulting αPSFs precluded a proper evaluation of their biological activity.

Pyridinium-based fluorosulfonamide reagents enabled photoredox catalyzed radical fluorosulfonamidation

“…Sulfur (VI) fluoride exchange (SuFEx) click chemistry has emerged as a valuable tool in organic synthesis and biochemistry (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Notably, sulfamoyl fluorides have increasingly become pivotal building blocks in the SuFEx domain due to their unique properties, including chemical stability and selective reactivity at the sulfur center (1).…”

Rh-Catalyzed Highly Enantioselective Synthesis of Aliphatic Sulfonyl Fluorides

“…Since the seminal work reported by K. B. Sharpless group in 2014 (Dong et al., 2014a, Dong et al., 2014b), sulfur(VI) fluoride exchange (SuFEx) click reaction has grown into a powerful synthetic tool, attracting increasing interest with wide applications in various disciplines such as polymer chemistry (Dong et al., 2014a, Dong et al., 2014b, Yatvin et al., 2015, Oakdale et al., 2016, Brendel et al., 2017, Gao et al., 2017, Wang et al., 2017, Zhang et al., 2019), surface chemistry (Brooks et al., 2016), bioconjugation (Zelli et al., 2016, Li et al., 2016), protein target identification (Jones, 2018a, Jones, 2018b, Mortenson et al., 2018, Wang et al., 2018a, Wang et al., 2018b, Wang et al., 2018c, Wang et al., 2018d, Zhao et al., 2017), and covalent protein inhibition (Alvarez et al., 2017, Chen et al., 2016a, Chen et al., 2016b, Fadeyi et al., 2017, Gehringer and Laufer, 2019, Hett et al., 2015, Liu et al., 2018, Narayanan and Jones, 2015, Shishido et al., 2017). Sulfonyl fluoride moiety as the sulfur(VI)-containing functional group at the heart of SuFEx methodology is imbued with a stability and chemoselectivity profile that is highly desirable for click chemistry applications (Chinthakindi and Arvidsson, 2018, Mukherjee et al., 2018, Chinthakindi et al., 2016, Kwon and Kim, 2019, Smedley et al., 2018, Leng and Qin, 2018, Thomas and Fokin, 2018).…”

Ethenesulfonyl fluoride derivatives as telomerase inhibitors: structure-based design, SAR, and anticancer evaluation in vitro

“…As we know, chemical environment of the warhead plays a key role in inhibitor design since it enables the tuning of its reactivity and thereby increasing its selectivity and stability 20 , 21 . Among them, vinyl sulfone, which is a dominant electrophilic trap containing unsaturated sulfone Michael acceptor, which could inhibit both the proteasome and cysteine proteases and high selectivity through manipulation of the peptidic portion 22 .…”