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1.
Org Lett ; 25(22): 4005-4009, 2023 Jun 09.
Article in English | MEDLINE | ID: mdl-37224106

ABSTRACT

A cobalt(II) mediated three-component synthesis of 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imines using sulfonyl azides, N-isocyaniminotriphenylphosphorane (NIITP), and carboxylic acids has been developed. This one-pot tandem reaction starts with a nitrene transfer to NIITP, followed by addition of the carboxylic acid to the in situ formed carbodiimide and subsequent intramolecular aza-Wittig reaction. Both the steric constraints of carboxylic acid and the stoichiometry of the employed cobalt salt determine the selectivity toward the two products, i.e. 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imine versus 5-substituted-4-tosyl-2,4-dihydro-3H-1,2,4-triazol-3-one.


Subject(s)
Cobalt , Imines , Carboxylic Acids , Molecular Structure
2.
Inorg Chem ; 61(18): 6725-6732, 2022 May 09.
Article in English | MEDLINE | ID: mdl-35477280

ABSTRACT

A new porous metal-organic framework, [Co (oba) (bpdh)]·(DMF) (TMU-63), containing accessible nitrogen-rich diazahexadiene groups was successfully prepared with the solvothermal assembly of 5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene (4-bpdh), 4,4'-oxybis(benzoic) acid (oba), and Co(II) ions. The combination of Lewis basic functional groups and porosity leads to high performance in CO2 adsorption and conversion in the cycloaddition reaction of epoxides under solvent-free conditions. To further enhance the catalytic efficiency of TMU-63, we introduced a highly acidic malonamide ligand into the structure via solvent-assisted ligand exchange (SALE) as a postsynthesis method. Incorporating different percentages of N1,N3-di(pyridine-4-yl) malonamide linker (4-dpm) into TMU-63 created a new porous structure. Powder X-ray diffraction (PXRD) and NMR spectroscopy confirmed that 4-bpdh was successfully replaced with 4-dpm in the daughter MOF, TMU-63S. The catalytic activity of both MOFs was confirmed by significant amounts of CO2 cycloaddition of epoxides under solvent-free conditions. The catalytic cycloaddition activities were found to be well-correlated with the Lewis base/Brønsted acid distributions of the materials examined in the TMU-63S series, showing that the concurrent presence of both acid and base sites was desirable for high catalytic activity. Furthermore, the heterogeneous catalysts could easily be separated out from the reaction mixtures and reused four times without loss of catalytic activity and with no structural deterioration.

3.
Faraday Discuss ; 231(0): 97-111, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34196337

ABSTRACT

In the process of designing new MOFs with the aim of having a specific morphology, the shape of the linkers and the choice of coordinating metals have major importance. In this study, the aim to create novel hnb non-interpenetrating MOFs led us to choose tritopic linkers. Novel star-shaped molecules, presenting trigonal geometry and based on aromatic rings, were synthesized. For more convenient synthesis of the library, C-C coupling reactions via a direct arylation methodology were performed. This new synthetic tool, together with the idea of a molecule as a modular combination of smaller building blocks, made possible the fast, cheap and reproducible production of this class of compounds and also its scale-up. With one of the compounds, a MOF was synthesized and characterised via its specific surface area, which varies between 1681 and 3770 m2 g-1.


Subject(s)
Metals
4.
Org Lett ; 23(8): 3100-3104, 2021 04 16.
Article in English | MEDLINE | ID: mdl-33787266

ABSTRACT

An unforeseen twist in a seemingly trivial Bischler-Napieralski reaction led to the selective formation of an unexpected carbazole product. The reaction proved to be general, providing access to a range of diversely substituted carbazoles from readily available substrates. Judicious variation of substituents revealed a complex cascade mechanism comprising no less than 10 elementary steps, that could be diverted in multiple ways toward various other carbazole derivatives.

5.
J Org Chem ; 84(18): 12058-12070, 2019 09 20.
Article in English | MEDLINE | ID: mdl-31446758

ABSTRACT

We report the intramolecular Tsuji-Trost reaction of Ugi adducts to give spiro-diketopiperazines in high yield and with high enantioselectivity. This approach allows the catalytic asymmetric construction of a broad range of these medicinally important heterocycles under mild conditions, in two steps from cheap, commercially available starting materials.

6.
Org Lett ; 21(8): 2699-2703, 2019 04 19.
Article in English | MEDLINE | ID: mdl-30964690

ABSTRACT

The reaction of 6-chloro-1-methylpyrazin-2(1 H)-one with Grignard reactants followed by quenching with different electrophiles gave access to a variety of 3,6-difunctionalized 1-methylpyrazin-2(1 H)-ones. This regioselective three-component reaction represents the first example of a tele-nucleophilic substitution of hydrogen (SNH) in which the anionic σH adduct is quenched by electrophiles (other than a proton) before elimination takes place. Quenching the reaction with iodine (I2) or bromine (Br2) provides an alternative reaction pathway, yielding a 3-functionalized 6-chloro-1-methylpyrazin-2(1 H)-one or 5-bromo-6-chloro-1-methylpyrazin-2(1 H)-one, respectively. The halogens present offer opportunities for further selective transformations.

7.
J Med Chem ; 61(24): 11221-11249, 2018 12 27.
Article in English | MEDLINE | ID: mdl-30500189

ABSTRACT

Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-ß-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.


Subject(s)
Alcohol Oxidoreductases/antagonists & inhibitors , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Hydantoins/chemistry , Actinobacteria/drug effects , Alcohol Oxidoreductases/metabolism , Bacterial Proteins/metabolism , Drug Stability , Enzyme Inhibitors/chemistry , Hep G2 Cells , High-Throughput Screening Assays/methods , Humans , Macrophages/microbiology , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Reproducibility of Results , Structure-Activity Relationship , Tuberculosis/drug therapy , Tuberculosis/microbiology
8.
Acta Crystallogr C Struct Chem ; 74(Pt 12): 1692-1702, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30516154

ABSTRACT

For five bromomethylated azobenzenes, namely (E)-[4-(bromomethyl)phenyl][4-(dibromomethyl)phenyl]diazene, C14H11Br3N2, (E)-1,2-bis[4-(dibromomethyl)phenyl]diazene, C14H10Br4N2, (E)-[3-(bromomethyl)phenyl][3-(dibromomethyl)phenyl]diazene, C14H11Br3N2, (E)-[3-(dibromomethyl)phenyl][3-(tribromomethyl)phenyl]diazene, C14H10Br4N2, and (E)-1,2-bis[3-(dibromomethyl)phenyl]diazene, C14H9Br5N2, the computationally cheap CLP PIXEL approach and CrystalExplorer were used for calculating lattice energies and performing Hirshfeld surface analysis via the enrichment ratios of atomic contacts. The procedures and caveats are discussed in detail. The findings from these tools are contrasted with the results of geometric analysis of the structures. We conclude that an energy-based discussion of the crystal packing provides substantially more insight than one based purely on geometry, as has so long been the custom in crystallography. In addition, we find a surprising shortage of halogen-halogen interactions in these highly bromomethylated compounds.

9.
Org Lett ; 20(21): 6611-6615, 2018 11 02.
Article in English | MEDLINE | ID: mdl-30350659

ABSTRACT

A stereoselective intramolecular Tsuji-Trost cascade cyclization of (homo)allylic vicinal diacetates with a pendant ß-ketoamide or related carbon nucleophile to give γ-lactam-fused vinylcyclopropanes is reported. In addition to two new rings, the products contain three new C-C stereocenters (two of which are quaternary) with a 9:1 dr. Moreover, the reaction proceeds in >94% enantiospecificity with optically enriched starting materials, using an inexpensive carbohydrate as the source of chirality.

10.
Angew Chem Int Ed Engl ; 57(46): 15232-15236, 2018 11 12.
Article in English | MEDLINE | ID: mdl-30273989

ABSTRACT

The N-iodosuccinimide-mediated spirocyclization of tryptamine-derived isocyanides to generate spiroindolenines is reported. The products contain both an imine and an imidoyl iodide as flexible handles for follow-up chemistry. Nucleophilic addition typically occurs chemoselectively on the imine moiety with complete diastereoselectivity, providing opportunities for the construction of complex molecular frameworks. The synthetic potential of the method was showcased in the formal total synthesis of (±)-aspidofractinine.

11.
Org Biomol Chem ; 16(17): 3241-3247, 2018 05 02.
Article in English | MEDLINE | ID: mdl-29664093

ABSTRACT

A zinc(ii) triflate catalyzed three component synthesis of 1,6-dihydropyridines, involving aldimines, alkynes and electron-deficient dimethyl acetylenedicarboxylate (DMAD), in good to excellent yields has been described. Besides a range of different N-substituents, a variety of both aromatic and aliphatic alkynes could be used. The application of electron-deficient propiolates instead of DMAD resulted in regiospecific incorporation of the ester functionality on the 1,6-dihydropyridine ring. The reaction proceeds via a cascade reaction involving nucleophilic addition of the metal acetylide to the imine, followed by the addition of the intermediately formed propargylic amine to the electron-deficient alkyne and subsequent 6-endo dig cyclization.

12.
ACS Comb Sci ; 20(2): 98-105, 2018 02 12.
Article in English | MEDLINE | ID: mdl-29323868

ABSTRACT

We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obtained thiazolidines proved to be suitable substrates for further transformations. Notably, both the Ugi-Joullié and the azido-Ugi reactions resulted highly diastereoselective, affording predominantly the trans-configured products, as confirmed by X-ray crystallographic analysis.


Subject(s)
Combinatorial Chemistry Techniques/methods , Indoles/chemistry , Spiro Compounds/chemistry , Thiazolidines/chemistry , Thiazolidines/chemical synthesis , Aldehydes/chemistry , Azides/chemistry , Carboxylic Acids/chemistry , Crystallography, X-Ray/methods , Cyanides/chemistry , Magnetic Resonance Spectroscopy/methods , Molecular Structure , Silanes/chemistry , Small Molecule Libraries/chemistry , Stereoisomerism , Structure-Activity Relationship
14.
European J Org Chem ; 2017(9): 1262-1271, 2017 Mar 03.
Article in English | MEDLINE | ID: mdl-28344504

ABSTRACT

We report the use of bifunctional starting materials (ketoacids) in a diastereoselective Passerini three-center-two-component reaction. Study of the reaction scope revealed the required structural features for stereoselectivity in the isocyanide addition. In this system, an interesting isomerization of the primary Passerini product - the α-carboxamido lactone - into an atypical product, an α-hydroxy imide, was found to occur under acidic conditions. Furthermore, enantioenriched Passerini products can be generated from an enantioenriched ketoacid obtained by chemoenzymatic synthesis.

15.
Molecules ; 22(4)2017 Mar 28.
Article in English | MEDLINE | ID: mdl-28350361

ABSTRACT

We report the unexpected formation of a 1-azadiene dimer from 4,6-diphenyl-3,6-dihydro-2H-1,3-thiazine-2-thiones under prolonged microwave irradiation. In this manner, thiazine-2-thiones act as "masked" 1-azadiene equivalents, which makes them useful synthetic tools to access complex heterocyclic frameworks. We compare this dimerization with earlier approaches and elaborate on the observed diastereoselectivity.


Subject(s)
Aza Compounds/chemical synthesis , Thiazines/chemistry , Thiones/chemistry , Aza Compounds/chemistry , Dimerization , Microwaves , Molecular Structure , Stereoisomerism
16.
Chem Commun (Camb) ; 52(84): 12482-12485, 2016 Oct 13.
Article in English | MEDLINE | ID: mdl-27722446

ABSTRACT

We report a highly diastereoselective interrupted Ugi reaction to construct a broad range of structurally congested and stereochemically complex spiroindolines from tryptamine-derived isocyanides. The reaction is facilitated by using fluorinated alcohols (TFE or HFIP) as solvents and tolerates a broad range of amines, aldehydes and 2-isocyanoethylindoles to give polycyclic products in moderate to excellent yields.

17.
J Med Chem ; 59(5): 1854-68, 2016 Mar 10.
Article in English | MEDLINE | ID: mdl-26785139

ABSTRACT

New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di(arylamino)pyrimidines but featuring a 2,6-di(arylamino)-3-fluoropyridine, 2,4-di(arylamino)-5-fluoropyrimidine, or 1,3-di(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains.


Subject(s)
Aniline Compounds/pharmacology , Anti-HIV Agents/pharmacology , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/drug effects , HIV-1/enzymology , Pyridines/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Aniline Compounds/chemistry , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Cell Line , Dose-Response Relationship, Drug , Fluorobenzenes/chemical synthesis , Fluorobenzenes/chemistry , Fluorobenzenes/pharmacology , HIV Reverse Transcriptase/metabolism , Humans , Microbial Sensitivity Tests , Molecular Structure , Pyridines/chemical synthesis , Pyridines/chemistry , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/chemistry , Structure-Activity Relationship
18.
Dalton Trans ; 44(38): 16824-32, 2015 Oct 14.
Article in English | MEDLINE | ID: mdl-26347226

ABSTRACT

Reaction of 5-phenyl-2,2'-bipyridine (L) with a mixture of CuI or [Cu(CH3CN)4]BF4 and PPh3 leads to mononuclear heteroleptic complexes [CuL(PPh3)I] (1) and [CuL(PPh3)2]BF4 (2). According to X-ray diffraction, L crystallizes in the monoclinic space group P21/n, exhibiting a disorder over four orientations. Complexes 1 and 2 crystallize in the monoclinic space groups P21/c and P21, respectively. 1 comprises a discrete neutral molecule, while 2 has an ionic structure containing [CuL(PPh3)2](+) and BF4(-). Both structures reveal that each tetracoordinated copper(i) atom is linked to two nitrogen atoms of L, one iodide and one PPh3 in the structure of 1, or two PPh3 in the structure of 2 with the formation of a distorted tetrahedral coordination core. The structure of 2 is additionally stabilized by a weak intramolecular ππ stacking interaction formed between two adjacent phenyl rings of two PPh3 ligands. Hirshfeld surface analysis showed that the structures of both complexes are mainly characterized by HH and CH contacts as well as by IH in the structure of 1 and FH in the structure of 2. The 2D fingerprint plots of two different molecules in the structure of L showed that both molecules exhibit contacts for ππ stacking interactions. The factors important for the stability of 1 and 2 were further quantitatively and qualitatively characterized by the charge and energy decomposition method ETS-NOCV. According to diffuse reflectance spectroscopy in the solid state, free L exhibits bands exclusively in the UV region, while the spectra of 1 and 2 also contain bands in the visible range up to about 500 and 600 nm. All three compounds were found to be emissive in the solid state. DFT calculations have shown that, while emission of L is due to the ligand-centered π→π* transition, luminescence of 1 and 2 was assigned to a (M + X)LCT and MLCT excited states, respectively.

19.
Org Lett ; 16(19): 5116-9, 2014 Oct 03.
Article in English | MEDLINE | ID: mdl-25229182

ABSTRACT

The reaction of isocyanides with N-tert-butanesulfinimines shows remarkable chemoselectivity. ß-Sulfinylamino isocyanides are formed exclusively with aromatic sulfinimines, while α-sulfeneimino acetamides result when using aliphatic derivatives. A mechanism is suggested for the latter transformation, together with an explanation for the observed selectivity. Finally, a scope study is presented for this remarkably chemoselective reaction.


Subject(s)
Acetamides/chemical synthesis , Cyanides/chemistry , Imines/chemical synthesis , Sulfonium Compounds/chemical synthesis , Acetamides/chemistry , Catalysis , Imines/chemistry , Molecular Structure , Stereoisomerism , Sulfonium Compounds/chemistry
20.
J Org Chem ; 78(19): 9803-14, 2013 Oct 04.
Article in English | MEDLINE | ID: mdl-24007399

ABSTRACT

Two strategies, "hydrogenation-hydride reduction" and "quaternization-hydride reduction", are reported that make use of mild reaction conditions (room temperature) to efficiently remove the N-pyridin-2-yl directing group from a diverse set of C-2-substituted piperidines that were synthesized through directed Ru-catalyzed sp(3) C-H functionalization. The deprotected products are obtained in moderate to good overall yields irrespective of the strategy followed, indicating that both methods are generally equally effective. Only in the case of 2,6-disubstituted piperidines, could the "quaternization-hydride reduction" strategy not be used. The "hydrogenation-hydride reduction" protocol was successfully applied to trans- and cis-2-methyl-N-(pyridin-2-yl)-6-undecylpiperidine in a short synthetic route toward (±)-solenopsin A (trans diastereoisomer) and (±)-isosolenopsin A (cis diastereoisomer). The absolute configuration of the enantiomers of these fire ant alkaloids could be determined via VCD spectroscopy.


Subject(s)
Alkaloids/chemistry , Piperidines/chemistry , Pyridines/chemistry , Ruthenium/chemistry , Catalysis , Hydrogenation , Molecular Structure , Stereoisomerism
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