ABSTRACT
The deployment of small-molecule fluorescent agents plays an ever-growing role in medicine and drug development. Herein, we complement the portfolio of powerful fluorophores, reporting the serendipitous discovery and development of a novel class with an imidazo[1,2-a]pyridinium triflate core, which we term PyrAtes. These fluorophores are synthesized in a single step from readily available materials (>60â examples) and display Stokes shifts as large as 240â nm, while also reaching NIR-I emissions at λmax as long as 720â nm. Computational studies allow the development of a platform for the prediction of λmax and λEm. Furthermore, we demonstrate the compatibility of these novel fluorophores with live cell imaging in HEK293 cells, suggesting PyrAtes as potent intracellular markers.
Subject(s)
Fluorescent Dyes , Humans , Fluorescent Dyes/chemistry , HEK293 Cells , Microscopy, Fluorescence , Salts/chemistry , Molecular StructureABSTRACT
FR252921, FR252922, and FR256523 are a family of potent macrocyclic polyene immunosuppressive agents with a novel mode of action. However, the lack of an efficient and flexible synthesis has hindered further biological studies, mostly due to the fact that the natural products appear to be kinetic isomers regarding the triene moiety. Herein, we report the development and application of an unprecedented, unique domino Suzuki-Miyaura/4π-electrocyclic ring-opening macrocyclization, resulting in a concise, unified, and stereoselective synthetic route to these complex targets in only 10 steps. This in turn enables ready access to a range of unnatural analogues, among which several compounds showed inhibition of T-lymphocyte proliferation at levels equal or superior to those of the natural products themselves.
Subject(s)
Immunosuppressive Agents/chemical synthesis , Lactams/chemical synthesis , Lactones/chemical synthesis , Macrocyclic Compounds/chemical synthesis , Immunosuppressive Agents/chemistry , Lactams/chemistry , Lactones/chemistry , Macrocyclic Compounds/chemistry , Molecular Structure , StereoisomerismABSTRACT
A cyanoborohydride-promoted radical cyclization methodology has been developed to access α-chlorolactams in a simple and efficient way using NaBH3 CN and trichloroacetamides easily available from allylic and homoallylic secondary amines. This methodology allowed the synthesis of a library of α-chlorolactams (mono- and bicyclic), which were tested for herbicidal activity, trans-3-chloro-4-methyl-1-(3-trifluoromethyl)phenyl-2-pyrrolidinone being the most active.
ABSTRACT
A nickel-catalyzed reductive dimerization of bromocyclobutenes to produce unusual and unprecedented cyclobutene dimers was developed. In a stereoconvergent procedure, various bromocyclobutenes were readily dimerized in good yields, with good diastereoselectivities and broad functional group tolerance. Notably, the presence of a carbonyl group in the starting material appears to dictate diastereoselectivity.
ABSTRACT
Cyclobutene lactones hold great potential as synthetic building blocks, yet their preparation by photochemical rearrangement in batch can often be a bottleneck in synthetic studies. We report the use of flow photochemistry as a tool to enable a higher-throughput approach to the synthesis of 2-oxabicyclo[2.2.0]hex-5-en-3-one, which reduces reaction times from 24â h to 10â min. Accordingly, a significantly improved throughput of 144â mg/h (vs 14-21â mg/h in batch) was achieved. Scale-out experiments showed problematic reactor fouling and steps were taken to explore and minimize this effect.
ABSTRACT
A tetracyclic compound with the ABCD ring framework of calyciphylline A-type alkaloids was synthesized from a cis-3a-methyloctahydroindole triggered by a 5-endo radical cyclization. The synthesis required two additional ring-forming steps: the construction of a seven-membered ring by aldol cyclization and the azabicyclic fragment by a radical ring closure of a trichloroacetamide-tethered enol acetate followed by a diastereoselective α-methylation of the lactam group.