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Synthesis of novel [ 14 C]‐labelled phenylureas bearing photoactive azido and diazirine groups as photoaffinity labels for the herbicide binding site of photosystem two
Author(s) -
Jewess Philip,
Whitelegge Julian P.,
Camilleri Patrick,
Bowyer John R.
Publication year - 1993
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580330713
Subject(s) - diazirine , chemistry , photoaffinity labeling , trifluoromethyl , photosystem ii , reagent , phosphonate , dcmu , stereochemistry , organic chemistry , combinatorial chemistry , photochemistry , photosynthesis , binding site , biochemistry , alkyl
We have synthesised two photoaffinity‐labelling hydrophobic stilbene urea inhibitors of Photosystem 2 (PS2) bearing either an azido group (3‐(3‐(( E )2‐(4‐azidophenyl)ethenyl)‐phenyl)‐1,1‐dimethylurea, azido‐PDU) or a diazirine group (3‐(3‐(( E )2‐(4‐(3‐(trifluoromethyl)‐diazirin‐3‐yl)phenyl)ethenyl)phenyl)‐1,1‐dimethylurea, diazirinyl‐PDU) as well as [ 14 C]‐labelled forms of these compounds. The key step in both syntheses was the formation of the stilbene entity by a Waddsworth‐Emmons reaction of either a trifluoroacetyl‐protected aminobenzaldehyde or a 3‐(trifluoromethyl)‐diazirin‐3‐yl‐substituted benzaldehyde with dimethyl(4‐nitrophenylmethyl)‐phosphonate which gave largely E stereochemistry. The latter compound was made from 4‐bromobenzaldehyde protected as the 1,3 dioxolane. The substituted diazirine was then constructed via Grignard chemistry and an adaptation of a published procedure for the synthesis of diazirines. Reduction of the nitrostilbenes to the respective anilines and conversion to the isocyanates followed by reaction with di[ 14 C]methylamine then gave the required [ 14 C]‐labelled phenylurea photoaffinity reagents. In studies not detailed here both reagents were found to be highly active inhibitors of photosynthetic electron transport before UV irradiation and to covalently label the herbicidebinding protein (D1) of Photosystem 2 after UV treatment. Diazirinyl‐PDU was found to be considerably more sensitive to UV irradiation than azido‐PDU.