Photo Electron Transfer Induced Macrocyclization of N‐Phthaloyl‐ω‐aminocarboxylic Acids

Abstract

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 -' .

Light‐Triggered Transformation of Molecular Baskets into Organic Nanoparticles

“…In the case of baskets functionalized with hydrophobic α‐amino acids, we found that the photo‐induced loss of CO 2 would render these hosts insoluble in water to prompt their precipitation. With six carboxylates within 1 6− , however, we wondered if a light stimulus would trigger their removal to give baskets possessing distinct recognition characteristics and/or solubility (Scheme B). In fact, when N ‐phthaloyl‐glutamic acid 5 2− (10 m m phosphate buffer, pH 7.0) was exposed to 300 nm light (Scheme A) there followed the exclusive formation of cyclized product 6 (Figure S13) .…”

“…With six carboxylates within 1 6− , however, we wondered if a light stimulus would trigger their removal to give baskets possessing distinct recognition characteristics and/or solubility (Scheme B). In fact, when N ‐phthaloyl‐glutamic acid 5 2− (10 m m phosphate buffer, pH 7.0) was exposed to 300 nm light (Scheme A) there followed the exclusive formation of cyclized product 6 (Figure S13) . On the basis of the literature, we speculate that the formation of long‐lived 3 ππ* triplet state of the phthalimide chromophore from 5 2− triggers the removal of α and γ carboxylates to give diradical intermediate which then cyclizes into racemic 6 (the Norrish–Yang reaction).…”

Advanced Methods for the Synthesis of 3-Substituted 1H-Isoindol-1-Ones

“…The synthesis of macrocyclic ring systems was also possible in this way; thus, azacyclotridecane (n = 9) and a 26-membered cyclic dipeptide could be generated in 60% yield from the readily available N-phthaloylamino acid [27]. The synthesis of macrocyclic ring systems was also possible in this way; thus, azacyclotridecane (n = 9) and a 26-membered cyclic dipeptide could be generated in 60% yield from the readily available N-phthaloylamino acid [27].…”

Synthetic Applications of Photoinduced Electron Transfer Decarboxylation Reactions

“…This primary photoproduct was stable when directly excited or tripletsensitized, however, in the presence of base it rapidly cyclized with extrusion of CO 2 to give the benzopyrrolizidine 7. 17 Water was necessary as cosolvent in order to suppress the formation of reduction products simply formed by CO 2 /H-exchange (vide infra).…”