Iodine-mediated Oxidative Cyclization Research Articles

Rapid and Highly Productive Assembly of a Disulfide Bond in Solid-Phase Peptide Macrocyclization.

Here we report a highly efficient disulfide-driven peptide macrocyclization in 15 min on a solid support using persulfate as a crucial additive in iodine-mediated oxidative cyclization. The method eliminates the side products of classical iodine-mediated peptide cyclization. It is operationally simple and convenient for cyclizing small to lengthier peptides embodying popular cysteine building blocks in a single step.

Synthesis of 1,3,4-Oxadiazoles by Iodine-Mediated Oxidative Cyclization of Methyl Ketones with 4-Phenylsemicarbazide

AbstractAn efficient one-pot method has been developed to access 5-amino-2-(het)aroyl-1,3,4-oxadiazoles through I2/DMSO-promoted oxidative cyclization of 4-phenylsemicarbazide with (het)aryl methyl ketones under mild conditions. This reaction proceeds smoothly with a wide range of methyl ketones containing various functional groups to give the corresponding products in moderate yields under mild conditions.

Synthesis and Chiroptical Properties of Planar Chiral Azahelicenes Based on [2.2]Paracyclophane.

Three pairs of planar chiral heteroarenes were synthesized using palladium-catalyzed Buchwald-Hartwig coupling and hypervalent iodine-mediated oxidative cyclization from optically pure 4-amino[2.2]paracyclophane. Among them, an enantiomer of planar chiral azahelicene was found to have circularly polarized luminescence activity that was remarkably stronger than that of planar chiral heteroarenes.

Indolyl-α-keto-1,3,4-oxadiazoles: Synthesis, anti-cell proliferation activity, and inhibition of tubulin polymerization

A series of novel indolyl-α-keto-1,3,4-oxadiazole derivatives have been synthesized by employing molecular iodine-mediated oxidative cyclization of acylhydrazones. In vitro anti cell proliferation activity of these derivatives against various cancer cells lines such as human lymphoblast (U937), leukemia (Jurkat & SB) and human breast (BT474) was investigated. Among the synthesized indolyl-α-keto-1,3,4-oxadiazoles 19a-p, only one compound (19e) exhibited significant antiproliferative activity against a panel of cell lines. The compound 19e with 3,4,5-trimethoxyphenyl motif, endowed strong cytotoxicity against U937, Jurkat, BT474 and SB cancer cells with IC50 values of 7.1, 3.1, 4.1, and 0.8 µM, respectively. Molecular docking studies suggested a potential binding mode for 19e in the colchicine binding site of tubulin. When tested for in vitro tubulin polymerizaton, 19e inhibited tubulin polymezations (IC50 = 10.66 µM) and induced apoptosis through caspase 3/7 activation. Further, the derivative 19e did not cause necrosis when measured using lactate dehydrogenase assay.

Natural Product-Based Fungicides Discovery: Design, Synthesis and Antifungal Activities of Some Sarisan Analogs Containing 1,3,4-Oxadiazole Moieties.

A series of sarisan analogs containing 1,3,4-oxadiazole moieties were synthesized by iodine-mediated oxidative cyclization and screened in vitro for their antifungal activities at 50 μg/mL against five phytopathogenic fungi such as Valsa mali, Curvularia lunata, Alternaria alternate, Fusarium solani and Fusarium graminearum. 1,3,4-Oxadiazole derivatives 7e, 7p, 7r, 7t and 7u exhibited potent and a broad spectrum of antifungal activities against at least three phytopathogenic fungi at the concentration of 50 μg/mL. Especially, compound 7r displayed more potent antifungal activities against five phytopathogenic fungi than the positive control hymexazol. The EC50 of 7r against V. mali, C. lunata and A. alternate were 12.6, 14.5 and 17.0 μg/mL, respectively. Additionally, some interesting results of structure-activity relationships (SARs) were also observed.

Iodine-Mediated Oxidative Cyclization of 2-(Pyridin-2-yl)acetate Derivatives with Alkynes: Condition-Controlled Selective Synthesis of Multisubstituted Indolizines

An iodine-mediated oxidative cyclization reaction between 2-(pyridin-2-yl)acetate derivatives and different alkynes has been developed, which provides regioselective and chemoselective syntheses of multiply substituted indolizines under modified reaction conditions. Plausible mechanisms have been proposed to explain the selective syntheses of indolizines. This protocol can be also applied to the stepwise synthesis of 2,2′-biindolizines.

Synthesis of 2 H-Azirines via Iodine-Mediated Oxidative Cyclization of Enamines.

A facile and practical oxidative cyclization reaction of enamines to 2 H-azirines has been developed, employing molecular iodine. The features of the present synthetic approach include no use of transition metals, mild reaction conditions, and simplicity of operation. Under the optimal reaction conditions, a variety of 2 H-azirine derivatives were synthesized from simple and readily accessible enamine precursors in an efficient and scalable fashion.

Iodine-mediated oxidative cyclization for one pot synthesis of new 8-hydroxyquinaldine derivatives containing a N-phenylpyrazole moiety as pesticidal agents

In continuation of our research aimed at discovery and development of new pesticidal agents, a series of new 8-hydroxyquinaldine derivatives containing a N–phenylpyrazole moiety were prepared and their structures were characterized by 1H NMR, IR, ESI-MS and mp. Meanwhile, an efficient way of using iodine-mediated oxidative cyclization for one pot synthesis of these 8-hydroxyquinaldine derivatives containing a N–phenylpyrazole moiety was developed. The bioassay showed that compounds 8g and 9f exhibited potent pesticidal activities against both Mythimna separata Walker and Plutella xylostella Linnaeus. The structure–activity relationships were also discussed.

Application of Sustainable Natural Bioresources in Agriculture: Iodine-Mediated Oxidative Cyclization for Metal-Free One-Pot Synthesis of N-Phenylpyrazole Sarisan Analogues as Insecticidal Agents.

In view of potential agricultural activity of sarisan (isolated from many plants or easily synthesized from sesamol, another biorenewable natural product) analogues, many research studies on the application of these biorenewable and abundant natural resources have been proceeded. A series of novel sarisan analogues containing N-phenylpyrazole were synthesized and evaluated for their insecticidal activity against a crop-threatening insect pest, Mythimna separata Walker. Meanwhile, an iodine-mediated oxidative intramolecular C–N bond formation methodology has been established for the one-pot synthesis of these N-phenylpyrazole-containing sarisan analogues. This practical one-pot methodology is metal-free and requires no separation of the less stable intermediate hydrazones. In addition, it was found that compounds 8l–r exhibited more promising insecticidal activity with the final mortality rates (FMRs) >62.1%, when compared with the positive control toosendanin. Especially, compound 8r with 2-fluoro-4-bromophenyl showed the most potent insecticidal activity, the FMR of which was 79.3%. On the basis of this, some interesting results of structure–activity relationships were also discussed.

Synthesis of 1,2,4-Triazolo[4,3-a]pyridines and Related Heterocycles by Sequential Condensation and Iodine-Mediated Oxidative Cyclization.

A facile and efficient approach to access 1,2,4-triazolo[4,3-a]pyridines and related heterocycles has been accomplished through condensation of readily available aryl hydrazines with corresponding aldehydes followed by iodine-mediated oxidative cyclization. This transition-metal-free synthetic process is broadly applicable to a variety of aromatic, aliphatic, and α,β-unsaturated aldehydes, and can be conveniently conducted on the gram scale.

Molecular Iodine Promoted Divergent Synthesis of Benzimidazoles, Benzothiazoles, and 2-Benzyl-3-phenyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazines

An unprecedented formation of a new class of 2-benzyl-3-phenyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazines has been discovered during the course of benzimidazole and benzothiazole synthesis, through the molecular iodine-mediated oxidative cyclization with a new C-N and S-N bond formation at ambient temperature.

Synthesis of the side chain of a novel carbapenem via iodine-mediated oxidative cyclization of (1R)-N-(1-aryl-3-butenyl)acetamide.

A (2R,4S)-trans-disubstituted pyrrolidine ring system was constructed by employing iodine-mediated oxidative cyclization of (1R)-N-[1-(4-bromophenyl)-3-butenyl]acetamide 3 as a key step. The resulting diastereomeric mixture of (2R)-2-aryl-4-acetoxypyrrolidine 4 was stereoselectively converted to the side-chain of a novel ultrabroad-spectrum carbapenem 1, via (2R,4R)-2-aryl-4-hydroxypyrrolidine 7.