Synthesis and utilization of nitroxide free radicals and their precursors as sensors and possibly biologically active molecules

Nitroxide stable free radicals have found broad app lication as spin labels, low molecular weight antioxidants, MRI contrast agents, co-oxidants, red ox- and pH-sensitive probes and mediators of polymerization. The chemistry of nitroxides invo lves many challenging aspects, including reaction for carbon-carbon bond formation in the pr esence of amphiphilic nitroxide moieties or the synthesis of nitroxide containing hybrid molecu les, for example, nitroxide incorporated biologically active molecules. In the frame of OTKA 104956 project we aimed to achieve new double (spin and fluorescent) redox sensor molecule s and accomplish the synthesis of new paramagnetically modified biomolecules, spin labels , complex forming agents. All these modifications had to be conducted with selective, b ut still more or less effective reactions

Synthesis of Nitroxide-Annulated Carbocycles and Heterocycles

New, pyrroline nitroxide annulated lactones, polycycles, and maleimide were synthesized by classical and microwave-assisted methodology. We report the application of the metathesis reaction in the presence of nitroxide yielding a pyrroline nitroxide condensed 1,4-benzoquinone as a paramagnetic dienophile. The formation of the isoselenazolone-fused pyrroline ring system was examined and different reactivity was observed with pyrrolin-1-oxyl and pyrroline derivatives

Facile syntheses of 3,4-disubstituted pyrroline nitroxides and their further synthetic applications

Lithiation of an alfa,beta-unsaturated pyrroline nitroxide ester with LTMP at the beta-carbon followed by treatment with electrophiles led to a new series of 3,4-disubstituted pyrroline nitroxides, which could be used as valuable paramagnetic building blocks. The new compounds were tested in Sonogashira and Stille cross coupling reactions, which offered methyl 1-oxyl-4-substituted-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-carboxylate radicals for new C-C bond formation in poor to moderate yields. The reaction of an alfa,beta-unsaturated pyrroline nitroxide ester with methyl chloroformate generated diester 2b; the partial hydrolysis product of this reaction was shown to be a key compound for the synthesis of paramagnetic uracil derivative 10

Synthesis of Deprenyl-like nitroxide free radicals and their diamagnetic derivatives

Synthesis of paramagnetically modified deprenyl and oxotremorine is reported. Starting from 5- and 6-membered 2,5-disubstituted nitrones (1, 6) or 4-phenyl-2,5,5-trimethyl-1H-pyrroline 1-oxide (11) deprenyl or oxotremorine like nitroxides were synthesized via Grignard reactions. The corresponding pre-nitroxides with propargylamine structure were achieved by reduction of nitroxides followed by methylation

Synthesis of nem paramagnetic retinal analogues

New paramagnetic retinal analogues have been synthesized by Horner-Wadsworth-Emmons and Wittig reactions. In these new analogues the pyrroline nitroxide moiety is situated in the place of Beta-ionone ring or at the end of the polyene chain

Synthesis of Azoles Condensed with, or Linked to, Nitroxides

Nitroxides connected to indoles, tetrazoles, or 1,3,4-oxadiazoles were synthesized by conventional and microwave-assisted cyclization reactions. New approaches to pyrrole-, pyrazole-, and triazoleannulated nitroxides are described. We showed that Diels–Alder reactions of the N-tert-butoxycarbonyl derivative of (4,4,6,6-tetramethyl- 2,4,6,7-tetrahydro-5H-pyrrolo[3,4-c]pyridin-5-yl)oxidanyl gave polycyclic scaffolds condensed with a six-membered nitroxide

Synthesis of new spin labels for Cu-free click conjugation

New pyrroline nitroxides attached to a terminal acetylenic sulfone, a dibenzocyclooctyne or a cyclooctyne carboxylic acid were synthesized and tested in Cu-free click reactions to conjugate these new spin labels with 4-azido-TEMPO, azidophenylalanine and an azidophenylalanine-containing protein

Synthesis and potential use of 1,8-naphthalimide type O-1(2) sensor molecules

New double (fluorescent and spin) sensor molecules containing 4-amino substituted 1,8-naphthalimide as a fluorophore and a sterically hindered amine (pre-nitroxide) or pyrroline nitroxide as a quencher and radical capturing moiety were synthesized. All sensors were substituted with a diethylaminoethyl side-chain to increase the water solubility. Steady state fluorescence properties of these compounds and their responses to ROS in vitro are reported with perspectives of plant physiology use in vivo