2-diazo-3,3,3-trifluoropropionyl chloride: reagent for photoaffinity labeling.

Abstract

ABSTRACT2-Diazo-3,3,3-trifluoropropionyl chloride has been synthesized from trifluorodiazoethane and phosgene. Its derivatives are acid stable, can be used to label enzymes, and undergo photolysis with substantially less rearrangement than do derivatives of other known diazoacyl reagents designed for photoaffinity labeling. In particular, the diazotrifluoropropionyl thioester of methyl N-acetylcysteine undergoes photolysis in methanol with about 40% insertion into the -OH bond of the solvent; by contrast, photolysis of other diazoacyl thioesters gives substantially quantitative Wolff rearrangement. The trifluoro compounds hold promise for the photoaffinity labeling of thiols. Photoaffinity labeling was initiated with the photolysis of diazoacetyl chymotrypsin, prepared from the enzyme and pnitrophenyl diazoacetate (1, 2). Subsequently, this and other photolabile reagents have been applied (3-14) to a wide variety of problems in biochemistry and biology. (For reviews, see refs. 15-18.) Diazoacetates and diazomalonates (6, 7), however, suffer from the disadvantages that they are not acid stable, and that photolysis leads in large measure to the products of the photochemical analog of the Wolff rearrangement (2, 19). Furthermore, attempts to use the diazoesters of thiols, either with glyceraldehyde-3-phosphate dehydrogenaset or model compounds (20), have led only to products of the photochemical Wolff rearrangement or to other products that are not informative from the point of view of photoaffinity labeling. In this paper, we report the synthesis and photolysis of diazotrifluoropropionyl derivatives that are not subject to these limitations.2-Diazo-3,3,3-trifluoropropionyl chloride is easily prepared, and is purified by vacuum distillation; p-nitrophenyl diazotrifluoropropionate is a crystalline solid that can be purified by sublimation. Various

Glycerophospholipid synthesis: improved general method and new analogs containing photoactivable groups.

“…3,3,3-Trifluoro-2-diazopropionyl chloride was synthesized according to the method of Chowdhry et al (18). m-Azidophenol and 4-azido-2-nitrophenol were prepared as described (19).…”

Intermolecular crosslinking of fatty acyl chains in phospholipids: use of photoactivable carbene precursors.

“…We now report on photolytic studies of phospholipids containing these photoactivable groups. We show that carbenes photogenerated from trifluorodiazopropionyl (2) and diazirinophenoxy (3) groups give rise to extensive intermolecular crosslinks by insertion into C-H bonds. The main aim of this paper is the characterization of crosslinked products formed upon photolysis of vesicles prepared from phospholipids containing these carbene precursors.…”

Purinergic Receptors

“…R2 (4) Greater chemical stability and a reduced tendency to Wolff-type rearrangements can be conferred on some diazocarbonyls by substitution at the adjacent carbon atom with another electron-withdrawing group such as ethoxycarbonyl or fluorine (Chowdry et al, 1976). Of the nitrene precursors, the aromatic azides are the most satisfactory, as they are easily synthesized, they are reasonably stable chemically, and they are readily photolysed at wavelength which can be manipulated by additional substitution of the aromatic nucleus.…”