Photochemical Cleavage and Release of Carboxylic Acids from α-Keto Amides

Abstract

Carboxylate groups incorporated at the position alpha to the keto carbonyl of alpha-keto amides 1 were photochemically cleaved in aqueous media to give carboxylic acids in 70-90% yields with quantum yields of 0.3. The cleavage coproducts were diastereomeric hemiacetals 2. Prompt release of acetate and gamma-aminobutyrate (GABA) in buffer was observed by difference FT-IR spectroscopy upon 355 nm laser flash photolysis. The time-constant for release of GABA was <30 ms. [reaction--see text]

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…396 The yield of 219 was found to depend strongly on the type of alkyl substituent on the carbon adjacent to the amide nitrogen. 397 Time-resolved pH-jump experiments showed that the reaction rate is on the microsecond time scale and that carboxylate release occurs in the rate-determining step.…”

1-(Hydroxyacetyl)pyrene a new fluorescent phototrigger for cell imaging and caging of alcohols, phenol and adenosine

“…1 Based on the above unique ability of the phototriggers, they have been utilized in several important applications, including the controlled release of bioactive molecules for studying complex and fast biological processes, 2 photolithography, 3 DNA synthesis, 4 studies of protein folding processes, 5 solid state synthesis, 6 microarray fabrication, 7 synthetic organic chemistry, 8 the controlled release of bioactive volatiles 9 and pesticides. 10 To date a variety of phototriggers such as 2-(dimethylamino)-5-nitrophenol, 11 α-carboxy nitrobenzyl, 12 3-nitro-2-naphthalenemethanol, 13 p-hydroxyphenacyl, 14 α-keto amides, 15 1-acyl-nitroindolines, 16 anthracene-9-methanol, 17 and derivatives of quinoline 18 as well as coumarin 19 have been reported.…”

The Discovery, Development and Demonstration of Three Caged Compounds†

“…The negatively charged site in the zwitterion would possibly be capable of elimination of various leaving group anions. The release of a wide variety of leaving groups has been observed via Norrish Type II-like photoreaction of a-keto amides 5 (35,36), whereby a hydrogen is transferred from the alkyl amide carbon to the keto oxygen, Eq. 3.…”

“…Twenty years ago studies began to explore the potential for expelling leaving group anions from zwitterionic intermediates that would be generated photochemically from α‐keto amides 5 upon photolysis with UV light (14). The impetus for this work was the early photochemical studies of Aoyama (15) and Whitten (16), although photorelease of LG − was not studied in early work.…”