Oxidative [3+2]Cycloaddition of Alkynylphosphonates with Heterocyclic N-Imines: Synthesis of Pyrazolo[1,5-a]Pyridine-3-phosphonates.

A series of pyrazolo[1,5-a]pyridine-3-ylphosphonates were prepared with moderate to good yields by the oxidative [3+2]cycloaddition of 2-subtituted ethynylphosphonates with in situ generated pyridinium-N-imines and their annulated analogs. 2-Aliphatic and 2-Ph acetylenes demonstrate low activity, and the corresponding pyrazolopyridines were achieved with a moderate yield in the presence of 10 mol% Fe(NO3)3·9H2O. At the same time, tetraethyl ethynylbisphosphonate, diethyl 2-TMS- and 2-OPh-ethynylphosphonates possess much greater reactivity and the corresponding pyrazolo[1,5-a]pyridines, and their annulated derivatives were obtained with good to excellent yields without any catalyst. 2-Halogenated ethynylphosphonates also readily reacted with pyridinium-N-imines, forming complex mixtures containing poor amounts of 2-halogenated pyrazolopyridines.

Design and Synthesis of New Acridone-Based Nitric Oxide Fluorescent Probe.

Nitric oxide (NO) is an important signaling molecule involved in a wide range of physiological and pathological processes. Fluorescent imaging is a useful tool for monitoring NO concentration, which could be essential in various biological and biochemical studies. Here, we report the design of a novel small-molecule fluorescent probe based on 9(10H)acridone moiety for nitric oxide sensing. 7,8-Diamino-4-carboxy-10-methyl-9(10H)acridone reacts with NO in aqueous media in the presence of O2, yielding a corresponding triazole derivative with fivefold increased fluorescence intensity. The probe was shown to be capable of nitric oxide sensing in living Jurkat cells.

Photolysis of dimethoxynitrobenzyl-"caged" acids yields fluorescent products.

Carboxylic acids conjugated with 4,5-dimethoxy-2-nitrobenzyl photoremovable protecting group are well known and widely used for biological studies. In this paper, we study the photolysis of likewise "caged" acetic, caprylic and arachidonic acids. Unexpectedly, we observed huge growth of fluorescence emission at ~430 nm during photolysis. Following further UV irradiation, a product with fluorescence at longer wavelength was formed (470 nm excitation / ~500-600 nm emission). While it may be used to monitor the "uncaging", these fluorescent products may interfere with widespread dyes such as fluorescein in biomedical experiments. This effect might be negligible if the photolysis products dissolve in the medium. On the other hand, we observed that arachidonic and caprylic acids derivatives self-organize in emulsion droplets in water environment due to long lipophilic chains. Illumination of droplets by UV rapidly induces orange fluorescence excited by 488 nm light. This fluorescence turn-on was fast (~0.1 s) and apparently caused by the accumulation of water-insoluble fluorescent residuals inside droplets. These self-organized lipophilic structures with fluorescence turn-on capability may be of interest for biomedical and other application. We have identified and hypothesized some compounds which may be responsible for the observed fluorescense.

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines.

An efficient and operationally simple synthesis of 7-deuteropyrazolo[1,5-a]pyridine and 7-deutero-1,2,4-triazolo[1,5-a]pyridine derivatives using α-H/D exchange of 1-aminopyridinium cations in basic D2O followed by a 1,3-cycloaddition of acetylenes and nitriles is presented. A high regioselectivity and a high degree of deuterium incorporation were achieved. The procedure was applied for several 4-R-1-aminopyridinium cations (R = H, Me, OMe).