The synthesis of a variety of hydroxylactams from w-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1,5-dione 7) to 26 (cyclodipeptide 26e). Ground-state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radials (Scheme 4). Spacer groups investigated were alkyl chains (C3-Cll: 5c-h, lla, 12), ether (16, 18), ester (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intravs. intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cJ products 11 and 12) in contrast to comparable singlet reactions. Except for the lactones 22, all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b), probably the consequence of a strong intramolecular H-bond (Scheme 10).
COMMUNICATIONSdeveloping negative charge is stabilized by the cationic metal center, while in the latter case the developing negative charge is not stabilized by the metal. The metal center in 4 is providing double Lewis acid activation, while the metal center in 5 is providing single Lewis acid activation. We recently showed that a dinuclear metal complex can rapidly cleave an RNA model compound by providing double Lewis acid activation.['] The two methyl groups in the neocuproine ligand should decrease the 0-Cu-0 bond angle in 3, which should facilitate the chelation of phosphate diesters. In octahedral Co"' complexes, the 0-Co-0 bond angles in chelated phosphates are significantly smaller than the 90" angle found in regular octahedral complexes.I91Among simple compounds, lanthanides and their complexes are the most reactive for hydrolyzing nucleic acids.["] However, enzymes use transition metals, Mgz+, or Ca2+ to cleave phosphate esters. Consequently, there is considerable interest in developing simple transition metal, Mg2+, or Ca2+ complexes that efficiently hydrolyze the phosphate diester bonds of RNA. Complex 3 represents by far the most reactive transition metal complex reported to date for hydrolyzing RNA. Experiinen tal ProcedureThe copper chloride complexes [Cu(terpy)CI]CI, [Cu(bpy)CI,], and [Cu(neocuproine)CI,] were prepared by mixing the appropriate ligands with CuCI, in methanol. All of the ligands and CuCI, are soluble in methanol, whereas the complexes precipitate out of the solvent. Cleavage of ApA was monitored by HPLC (Hewlett-Packard 1090). In a typical kinetic experiment, a solution of ApA (0.5m~),3(10m~),andHEPES(10m~) wasallowed toreactatpH 7.0and25"C.Aliquots (50 pL) of the reaction mixture were quenched with 100 mM ethylenediaminetetraacetic acid (EDTA) (50 pL). The quenched solutions (10 pL) were injected onto a C-18 reversed-phase column (5 pm Hypersil maintained at 40'C) and eluted for 5 min with NH,H,PO, (0.2 M at pH 5.5) followed by a 0-50% linear gradient of NH,H2P0, (0.2 M at pH 5.5) and methanol/water (3:2) solutions over 10 min with a flow rate of 0.5 m l m i n -' .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.