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Convenient Synthesis of a [1‐ 14 C]Diazirinylbenzoic Acid as a Photoaffinity Label for Binding Studies of V‐ATPase Inhibitors
Author(s) -
Bender Tobias,
Huss Markus,
Wieczorek Helmut,
Grond Stephanie,
von Zezschwitz Paultheo
Publication year - 2007
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200700194
Subject(s) - diazirine , chemistry , benzoic acid , photoaffinity labeling , electrophile , covalent bond , stereochemistry , combinatorial chemistry , enzyme , trifluoromethyl , peptoid , bromide , atpase , binding site , organic chemistry , biochemistry , peptide , alkyl , catalysis
Diazirine‐tagged systems are considered reliable compounds for photoaffinity labeling (PAL) in biochemical studies as they enable investigation and understanding of biological mechanisms through covalent bonding to the target and subsequent detection. 14 C‐labeled 4‐(3‐trifluoromethyl‐3 H ‐diazirin‐3‐yl)benzoic acid ( 11 ) was prepared by a lithium‐bromide exchange on the bis‐silylated 4‐bromophenyldiaziridine 19 with subsequent transformations with electrophiles as key steps of the synthesis. Using 14 CO 2 , which was generated from rather inexpensive Ba 14 CO 3 , the desired diaziridinylbenzoic acid 21 was obtained in 78 % yield based on the employed radioactive material. Oxidation under mild conditions then yielded diazirine 11 in a 100 mg scale. This versatile photoaffinity label was selectively attached to the tetrahydropyrane ring of bafilomycin A 1 ( 2 ) and concanamycin A‐derived 3 , which both specifically inhibit the V‐ATPases. Inhibition assays were performed and revealed that the inhibitory capacities of the labeled derivatives are suitable for PAL studies on this important group of enzymes to elucidate the as yet unknown binding sites. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)