New Fluorous Photoaffinity Labels (F‐PAL) and Their Application in V‐ATPase Inhibition Studies

Abstract

Keywords: Bafilomycin / Concanamycin / Fluorous chromatography / Perfluorinated reagents / Photoaffinity labeling / VATPase inhibitors (Trifluoromethyl)diazirines are well established photoaffinity labels (PAL) used in biochemical investigations to create covalent ligand-receptor bonds. Two new diazirinylbenzoic acids 8b,c with perfluorobutyl and perfluorooctyl chains (F-PAL) were efficiently prepared from p-bromobenzaldehyde and attached to the highly potent and specific V-ATPase inhibitors 21-deoxyconcanolide A (2) and bafilomycin A 1 (5), deriving from the natural product pool from Streptomyces producer strains. The labelled derivatives 17 and 18 were efficiently purified by fluorous solid-phase extraction. Func-

The Binding Site of the V-ATPase Inhibitor Apicularen Is in the Vicinity of Those for Bafilomycin and Archazolid

“…1), and therefore both compounds are more suitable to displace 14 C-D-apicularen. Furthermore, we may exclude binding of D-apicularen to an alternative binding site due to the sheer presence of the attached diazirinyl group, because a control compound modified with a diazirinyl was, in contrast to D-apicularen, not able to inhibit the V-ATPase (39). Surprisingly, an excess of the plecomacrolides bafilomycin or concanamycin also reduced labeling by 14 C-D-apicularen (Fig.…”

Recent Advances in the Preparations and Synthetic Applications of Oxaziridines and Diaziridines

“…Grond and co‐workers synthesized fluorous photoaffinity label (F‐PAL) from 4‐bromoacetophenone 243 via the intermediate diaziridines 244 as mentioned in the Scheme 65. Oxidation of diaziridine 244 with iodine/Et 3 N gave desired product F‐PAL 245 [110] . Interestingly, F‐PAL 245 was able to attach with V‐ATPase inhibitors (Scheme 64) namely 21‐deoxyconcanolide A 246 and bafilomycin A1 247 to deliver 248 and 249 respectively [111] .…”

“…Oxidation of diaziridine 244 with iodine/Et 3 N gave desired product F-PAL 245. [110] Interestingly, F-PAL 245 was able to attach with V-ATPase inhibitors (Scheme 64) namely 21-deoxyconcanolide A 246 and bafilomycin A1 247 to deliver 248 and 249 respectively. [111] The synthesized products were supposed to be applied in the biochemical investigations for the creation of covalent ligandreceptor bond.…”

Synthesis of a PbTx-2 photoaffinity and fluorescent probe and an alternative synthetic route to photoaffinity probes

“…Other groups have performed this diaziridine oxidation step using iodine in the presence of triethylamine 86 , silver oxide 87 and even oxalyl chloride 88 .…”