No abstract

Novel di-Mannich bases of cyclovalone derivatives (1) have been synthesized and evaluated their antioxidant activity using DPPH free radical-scavenger method. The structures of the compounds were confirmed on the basis of FT-IR, 1 H-NMR, 13 C-NMR and mass spectral data. The result of antioxidant evaluation showed that di-Mannich derivative of cyclovalone with diethylamine ((2E,6E)-2,6-bis({3-[(diethylamino)methyl]-4-hydroxy-5-methoxyphenyl} methylidene) cyclohexan-1-one) (2a) exhibited the highest antioxidant activity with IC 50 = 39.0 µM. Structure-activity relationship study showed that the higher pKa of the Mannich base, the higher activity (the lower IC 50 ) of the compound.

Site-specific labeling of synthetic peptides carrying N-methoxyglycine (MeOGly) by isothiocyanate is demonstrated. A nonapeptide having MeOGly at its N-terminus was synthesized by the solid-phase method and reacted with phenylisothiocyanate under various conditions. In acidic solution, the reaction specifically gave a peptide having phenylthiourea structure at its N-terminus, leaving side chain amino group intact. The synthetic human β-defensin-2 carrying MeOGly at its N-terminus or the side chain amino group of Lys(10) reacted with phenylisothiocyanate or fluorescein isothiocyanate also at the N-methoxyamino group under the same conditions, demonstrating that this method is generally useful for the site-specific labeling of linear synthetic peptides as well as disulfide-containing peptides.

We herein report a regioselective preparation of 6-and 7-fluoro-1,2,3,4-tetrahydroquinolines by applying the deoxyfluorination strategy, developed by the authors. This method includes the cyclization of catecholamines bearing an N-protecting group to form 7-hydroxy-1-azaspiro[4.5]deca-6,9-dien-8ones and 6,7-dihydroxy-1,2,3,4-tetrahydroquinolines followed by deoxyfluorination, in which the nature of the N-protecting group has a significant effect on both the cyclization and the regioselectivity of the deoxyfluorination reaction. INTRODUCTIONDue to the unique properties of fluorine, including its high electronegativity, very small atomic radius close to that of hydrogen, and its ability to form strong bonds with carbon, the installation of fluorine atoms into bioactive molecules can increase their lipophilicity, bioavailability, and metabolic stability, and so this strategy is frequently used in the discovery of new pharmaceuticals and agrochemicals. 1Fluorine is also of interest since it frequently used as a biological equivalent (i.e., a bioisostere) of either hydrogen or oxygen in drug discovery research. 2 In addition, radioactive [ 18 F]fluorine is useful for positron emission tomography. 3 Among the wide range of fluorinated pharmaceuticals reported to date, aromatic moieties bearing fluorine atoms are particularly common. In terms of their preparation, the classical electrophilic aromatic fluorination reaction employed for the synthesis of fluorobenzene units generally produces a mixture of regioisomers. On the other hand, the ipso-nucleophilic substitution of pre-functionalized aromatic compounds with fluorine, such as via the Halex (halogen exchange) and Balz-Schiemann reactions, proceeds with an excellent regioselectivity, but requires harsh reaction conditions. Recently, an ipso-fluorination method has been devised via arylsulfonium intermediates. 4Transition-metal-catalyzed carbon-fluorine bond forming reactions of pre-functionalized aromatics have also been developed, where copper, palladium, and silver serve as efficient catalysts, 5 while aromatic C-H fluorination is another rapidly growing protocol. 6 The deoxyfluorination of phenolic hydroxy groups is also intriguing for the regio-controlled fluorination of bioactive aromatic molecules due to the ready availability of different phenolic structures as natural products and synthetic compounds. 7Scheme 1. (A) The regio-complementary deoxyfluorination of bridged biaryls and (B) the outline of this work.