Chuanjun Song

Convergent Formal Synthesis of (±)-Roseophilin

A facile convergent synthesis of the tricyclic core 2 of roseophilin is described, which represents the shortest route so far for the formal synthesis of roseophilin. The key step was a tandem pyrrole acylation-Nazarov cyclization reaction to form the cyclopenta[b]pyrrole moiety 4.

Template‐Induced Diverse Metal–Organic Materials as Catalysts for the Tandem Acylation–Nazarov Cyclization

In our continuing quest to develop a metal-organic framework (MOF)-catalyzed tandem pyrrole acylation-Nazarov cyclization reaction with α,β-unsaturated carboxylic acids for the synthesis of cyclopentenone[b]pyrroles, which are key intermediates in the synthesis of natural product (±)-roseophilin, a series of template-induced Zn-based (1-3) metal-organic frameworks (MOFs) have been solvothermally synthesized and characterized. Structural conversions from non-porous MOF 1 to porous MOF 2, and back to non-porous MOF 3 arising from the different concentrations of template guest have been observed. The anion-π interactions between the template guests and ligands could affect the configuration of ligands and further tailor the frameworks of 1-3. Futhermore, MOFs 1-3 have shown to be effective heterogeneous catalysts for the tandem acylation-Nazarov cyclization reaction. In particular, the unique structural features of 2, including accessible catalytic sites and suitable channel size and shape, endow 2 with all of the desired features for the MOF-catalyzed tandem acylation-Nazarov cyclization reaction, including heterogeneous catalyst, high catalytic activity, robustness, and excellent selectivity. A plausible mechanism for the catalytic reaction has been proposed and the structure-reactivity relationship has been further clarified. Making use of 2 as a heterogeneous catalyst for the reaction could greatly increase the yield of total synthesis of (±)-roseophilin.

Synthesis of 5-epi-taiwaniaquinone G.

A concise synthetic approach to the unnatural 5-epi-taiwaniaquinone G has been developed via a Lewis acid catalyzed tandem acylation-Nazarov cyclization reaction to construct the tricyclic skeleton, followed by installation of the isopropyl group through a strategy involving coumarin formation and its subsequent hydrolysis.

Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)

N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.

Synthesis of novel strobilurin–pyrimidine derivatives and their antiproliferative activity against human cancer cell lines

A series of new strobilurin-pyrimidine analogs were designed and synthesized based on the structures of our previously discovered antiproliferative compounds I and II. Biological evaluation with two human cancer cell lines (A549 and HL60) showed that most of these compounds possessed moderate to potent antiproliferative activity. Two potent candidates (8f, IC50=2.2 nM and 11d, IC50=3.4 nM) were identified with nanomolar activity against leukemia cancer cell line HL60 for further development. This activity represents a 1000- to 2500-fold improvement compared to the parent compounds I and II and is 20- to 30-fold better than the chemotherapy drug, doxorubicin. The present work provides strong incentive for further development of these strobilurin-pyrimidine analogs as potential antitumor agents for the treatment of leukemia.

Influence of the methyl position on the binding of 5-epi-taiwaniaquinone G to HSA investigated by spectrofluorimetry and molecular modeling

The interactions between human serum albumin (HSA) and 5-epi-taiwaniaquinone G (G2) or its isomeride (G1) was investigated by fluorescence, UV–visible absorption, resonance light scattering, synchronous fluorescence spectroscopy and 3D spectroscopy under mimic physiological conditions in combination with molecular modeling. The results revealed that G1 and G2 caused the fluorescence quenching of HSA by the formation of G1-HSA and G2-HSA complex, respectively. The binding constants and thermodynamic parameters at three different temperatures were obtained. Hydrophobic and electrostatic interactions played a role in the binding process of HSA and G1. Van der Waals force and hydrogen bond interaction played a role in the binding process of HSA and G2. Results showed that G2 was the stronger quencher and the position of methyl influenced the binding process between HSA and G1 (G2).

Divergent Syntheses of Carbazole Alkaloids Clausenapin, Indizoline, Claulansine M, and Clausenaline D

We described the first total syntheses of clausenapin, indizoline, claulansine M, and a novel synthetic route to clausenaline D via divergent method. Key steps involved TFAA-mediated intramolecular acylation to construct the carbazole core and subsequent Claisen rearrangement to generate key intermediates for further elaboration to target molecules.

Synthesis of 2-Cyclopentenone Derivatives via Palladium-Catalyzed Intramolecular Carbonyl α-Alkenylation

2-Cyclopentenone derivatives have been efficiently synthesized from 5-bromo-5-hexen-2-ones via palladium-catalyzed intramolecular carbonyl α-alkenylation followed by double-bond migration under mild reaction conditions.

Selective synthesis of 2,5-disubstituted furan-3-carboxylates and the isomeric 2,4-disubstituted furan-3-carboxylates

An unprecedented Ag2CO3 and DBU mediated cyclization of 3-substituted 2-(2-bromoallyl)-3-oxo-1-carboxylates leading to the formation of 2,5-disubstituted furan-3-carboxylates has been reported. In the absence of a silver salt, the isomeric 2,4-disubstituted furan-3-carboxylates are obtained.

An improved method for the synthesis of γ-DDB

A mild and efficient method for the synthesis gamma-DDB has been developed through anhydride-linker assisted intramolecular Ullmann reaction. Highly regioselective bromination of differentially protected gallate was realized by virtue of the introduction of NBS.