50592-87-5Relevant articles and documents
Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(iii) N-methoxyalkylpyridylporphyrins
Tovmasyan, Artak G.,Rajic, Zrinka,Spasojevic, Ivan,Reboucas, Julio S.,Chen, Xin,Salvemini, Daniela,Sheng, Huaxin,Warner, David S.,Benov, Ludmil,Batinic-Haberle, Ines
, p. 4111 - 4121 (2011)
Cationic Mn(iii) N-alkylpyridylporphyrins (MnPs) are potent SOD mimics and peroxynitrite scavengers and diminish oxidative stress in a variety of animal models of central nervous system (CNS) injuries, cancer, radiation, diabetes, etc. Recently, properties other than antioxidant potency, such as lipophilicity, size, shape, and bulkiness, which influence the bioavailability and the toxicity of MnPs, have been addressed as they affect their in vivo efficacy and therapeutic utility. Porphyrin bearing longer alkyl substituents at pyridyl ring, MnTnHex-2-PyP5+, is more lipophilic, thus more efficacious in vivo, particularly in CNS injuries, than the shorter alkyl-chained analog, MnTE-2-PyP5+. Its enhanced lipophilicity allows it to accumulate in mitochondria (relative to cytosol) and to cross the blood-brain barrier to a much higher extent than MnTE-2-PyP5+. Mn(iii) N- alkylpyridylporphyrins of longer alkyl chains, however, bear micellar character, and when used at higher levels, become toxic. Recently we showed that meta isomers are ～10-fold more lipophilic than ortho species, which enhances their cellular accumulation, and thus reportedly compensates for their somewhat inferior SOD-like activity. Herein, we modified the alkyl chains of the lipophilic meta compound, MnTnHex-3-PyP5+via introduction of a methoxy group, to diminish its toxicity (and/or enhance its efficacy), while maintaining high SOD-like activity and lipophilicity. We compared the lipophilic Mn(iii) meso-tetrakis(N-(6′-methoxyhexyl)pyridinium-3-yl)porphyrin, MnTMOHex-3-PyP5+, to a hydrophilic Mn(iii) meso-tetrakis(N-(2′- methoxyethyl)pyridinium-3-yl)porphyrin, MnTMOE-3-PyP5+. The compounds were characterized by uv-vis spectroscopy, mass spectrometry, elemental analysis, electrochemistry, and ability to dismute O2-. Also, the lipophilicity was characterized by thin-layer chromatographic retention factor, Rf. The SOD-like activities and metal-centered reduction potentials for the MnIIIP/MnIIP redox couple were similar-to-identical to those of N-alkylpyridyl analogs: log k cat = 6.78, and E1/2 = +68 mV vs. NHE (MnTMOHex-3-PyP 5+), and log kcat = 6.72, and E1/2 = +64 mV vs. NHE (MnTMOE-3-PyP5+). The compounds were tested in a superoxide-specific in vivo model: aerobic growth of SOD-deficient E. coli, JI132. Both MnTMOHex-3-PyP5+ and MnTMOE-3-PyP5+ were more efficacious than their alkyl analogs. MnTMOE-3-PyP5+ is further significantly more efficacious than the most explored compound in vivo, MnTE-2-PyP5+. Such a beneficial effect of MnTMOE-3-PyP5+ on diminished toxicity, improved efficacy and transport across the cell wall may originate from the favorable interplay of the size, length of pyridyl substituents, rotational flexibility (the ortho isomer, MnTE-2-PyP5+, is more rigid, while MnTMOE-3-PyP5+ is a more flexible meta isomer), bulkiness and presence of oxygen.
Preparation of Alkyl Ethers with Diallyltriazinedione-Type Alkylating Agents (ATTACKs-R) Under Acid Catalysis
Fujita, Hikaru,Yamashita, Rina,Fujii, Takanori,Yamada, Kohei,Kitamura, Masanori,Kunishima, Munetaka
, p. 4436 - 4446 (2019/07/03)
Diallyltriazinedione-type acid-catalyzed alkylating agents (ATTACKs-R) with 10 different alkyl groups (R), including benzyl, substituted benzyl, allyl, and methyl groups were synthesized. The palladium-catalyzed intramolecular O-to-N allylic rearrangement of 2,4-bis(allyloxy)-6-chloro-1,3,5-triazine was developed to introduce various alkoxy groups into the N,N′-dialkylated triazinedione skeleton. O-Alkylation of alcohols with ATTACKs-R was carried out in 1,4-dioxane in the presence of 2,6-di-tert-butylpyridinium trifluoromethanesulfonate or trifluoromethanesulfonic acid as a catalyst. Six selected ATTACKs-R bearing benzylic R groups were employed to prepare alkyl ethers from primary, secondary, and tertiary alcohols. The reactions of ATTACKs-R bearing an o-nitro-substituted benzyl group tended to afford low yields. Comparison of four different triazinedione-based benzylating reagents suggested that the N,N′-substituents affected the reactivity.
Polar tagging in the synthesis of monodisperse oligo(p-phenyleneethynylene) s and an update on the synthesis of oligoPPEs
Sahoo, Dhananjaya,Thiele, Susanne,Schulte, Miriam,Ramezanian, Navid,Godt, Adelheid
supporting information; experimental part, (2010/11/03)
One important access to monodisperse (functionalized) oligoPPEs is based on the orthogonality of the alkyne protecting groups triisopropylsilyl and hydroxymethyl (HOM) and on the polar tagging with the hydroxymethyl moiety for an easy chromatographic separation of the products. This paper provides an update of this synthetic route. For the deprotection of HOM protected alkynes, γ-MnO2 proved to be better than (highly) activated MnO 2. The use of HOM as an alkyne protecting group is accompanied by carbometalation as a side reaction in the alkynyl-aryl coupling. The extent of carbometalation can be distinctly reduced through substitution of HOM for 1-hydroxyethyl. The strategy of polar tagging is extended by embedding ether linkages within the solubilising side chains. With building blocks such as 1,4-diiodo-2,5-bis(6-methoxyhexyl) less steps are needed to assemble oligoPPEs with functional end groups and the isolation of pure compounds becomes simple. For the preparation of 1,4-dialkyl-2,5-diiodobenzene a better procedure is presented together with the finding that 1,4-dialkyl-2,3-diiodobenzene, a constitutional isomer of 1,4- dialkyl-2,5-diiodobenzene, is one of the byproducts.
