Chemoselective bicyclobutane-based mass spectrometric detection of biological thiols uncovers human and bacterial metabolites

Abstract

Sulfur is an essential element of life. Thiol-containing metabolites in all organisms are involved in the regulation of diverse biological processes. Especially, the microbiome produces bioactive metabolites or biological intermediates...

Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update

“…Recently, the reactivity of BCB amides was utilized for a new methodology to irreversibly capture thiol-containing metabolites, which up to now has been notoriously challenging . The chemoselectivity of BCB warheads for cysteine was furthermore corroborated in a study that found that BCB ketone 134 (Figure B) completely reacted with Boc-Cys-OEt in THF under basic conditions in less than 1 h, while protected Tyr only reached significant conversion after more than 50 h, and Lys and Ser did not react at all.…”

Photochemical α-selective radical ring-opening reactions of 1,3-disubstituted acyl bicyclobutanes with alkyl halides: modular access to functionalized cyclobutenes

“…5 The potential energy stored in the bridging bond (66.3 kcal mol −1 (calculated)) 6 has been harnessed for applications in the design or discovery of new reactions, 7 materials science, 8 medicinal chemistry 9 and analytical chemistry. 10 Among them, BCBs carrying an electron withdrawing group at one end of the bridging bond are often used as substrates in ring-opening reactions with polar carbon 11 and heteroatom-based nucleophiles. 12 In most cases, these reactions occur exclusively at the β-position of the bridging bond, leading to the synthesis of multisubstituted cyclobutanes, as shown in the elegant studies by Gaoni, 11 a ,12 a Fox, 11 b , c Baran, 12 c , d Wipf, 12 e Aggarwal, 13 Malins, 12 f Biju, 11 e and others (Scheme 1b).…”

C(sp2)–H cyclobutylation of hydroxyarenes enabled by silver-π-acid catalysis: diastereocontrolled synthesis of 1,3-difunctionalized cyclobutanes

“…In recent years, strain-release driven transformations have recaptured significant attention in synthetic organic chemistry, 8 materials science, 9 analytical chemistry 10 and bioconjugation. 11 As the smallest of fused carbocycles, bicyclo[1.1.0]butanes (BCBs) are highly strained (ring strain energy ∼ 66 kcal mol −1 ) yet bench-stable, synthetically versatile carbocycles.…”