Access to Conjugated Enynes via Allenyl Silver Formation/Cyclization/Decarboxylation Reaction Catalyzed by Silver Carbonate(I).

Herein, we develop a novel and straightforward access to cyclic conjugated enynes catalyzed by silver carbonate/DBU from readily available substrates with good yields. The reaction is easy to set up, broad in scope, and can also be conducted in a one-pot fashion from easily accessible substrates through a sequence Michael addition reaction/cyclization. Based on our previous works, the mechanism proposed would involve an allenyl silver intermediate and decarboxylation reaction.

Silver oxide(I) promoted Conia-ene/radical cyclization for a straightforward access to furan derivatives.

A novel access to fused furan cores using silver oxide(I) has been developed. Mechanistic investigations indicate the involvement of a Conia-ene reaction/radical cyclization for an expedient path to complex furan derivatives. The reaction is broad in scope with interesting atom economy and can also be conducted in a one-pot fashion from readily accessible α,β-unsaturated ketones.

Gold(I)-Catalyzed 7- Cyclization: A Key Step to Access the Bicyclo[4.2.1]nonane Skeleton of Vibsatin A, a Neurotrophic Diterpenoid.

Vibsatin A is a new neurotrophic vibsane-type diterpenoid comprising a bridged bicyclo[4.2.1]nonane skeleton.

Silver-catalyzed tandem cycloisomerization/hydroarylation reactions and mechanistic investigations for an efficient access to 1,2-dihydroisoquinolines.

An efficient silver-catalyzed tandem reaction for the formation of 1,2-dihydroisoquinoline derivatives is herein reported. Highly functionalized multiheterocyclic scaffolds are accessible in a straightforward manner using readily accessible starting materials under mild conditions. This methodology offers an attractive route for the synthesis and development of a biologically relevant new heterocyclic pharmacophore, merging the biological activities of isoquinolines with those of various nitrogen-containing heterocycles (indoles, pyrroles) incorporated during the tandem reaction.

Silver(I) Oxide-/DBU-Promoted Synthesis of Dihydrofuran Units through Allenyl Silver Formation.

A formal [3+2] cyclization mediated by silver(I) oxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is described herein.

Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent.

We report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1, a multi-partners transmembrane receptor overexpressed in numerous tumors, and thereby validated as promising target in oncology. The preparation of NRPa-308 proved challenging because of the orthogonality of the amide and sulphonamide bonds formation.

Visible Light-Induced Regioselective Cycloaddition of Benzoyl Azides and Alkenes To Yield Oxazolines.

Visible light catalysis allows the regioselective synthesis of oxazolines in high yields. The mild photosensitized manifold leverages the intermolecular formation of oxazolines with a wide functional group tolerance on both benzoyl azides and alkenes partners. Mechanistic investigations suggest the sensitization of the azide moiety as the key activation step.

Ti(II) and Rh(I) Complexes as Reagents toward a Thapsigargin Core.

A novel approach toward the [5-7]fused bicyclic core of thapsigargin, a subnanomolar inhibitor of the endo/sarcoplasmic calcium ATPase (SERCA), is presented. The synthetic route includes an original Ti(II)-mediated hydroxy-directed reductive coupling of an enantiomerically enriched propargylic alcohol and an intramolecular Rh(I)-catalyzed cyclocarbonylation reaction as key steps. Interestingly, through the first experiments of titanocene-mediated reductive cyclization of a 1,8-enyne, a seven-membered cycle was isolated as a unique product with a total diastereoselectivity.

Phosphine-Triggered Selectivity Switch in Silver-Catalyzed o-Alkynylbenzohydroxamic Acid Cycloisomerizations.

A silver-catalyzed cycloisomerization reaction of a series of o-alkynylbenzohydroxamic acids is reported. Several 5-exo-dig and 6-endo-dig modes of cyclization were observed with the nitrogen or oxygen atoms of the amide group acting as nucleophiles. The selectivity was strongly dependent on the silver salt used and on the presence of triphenylphosphine as an additive.

Visible light amination/Smiles cascade: access to phthalazine derivatives.

We report the synthesis of various phthalazines a new cascade reaction, initiated by visible light photocatalysis, involving a radical hydroamination reaction followed by a radical Smiles rearrangement. Phthalazine derivatives are obtained in high yields and from a broad scope readily accessible -alkynylsulfonohydrazone precursors. The mild photoredox conditions ensure an excellent functional group tolerance.

Characterization of cobalt(III) hydroxamic acid complexes based on a tris(2-pyridylmethyl)amine scaffold: reactivity toward cysteine methyl ester.

Six Co(III) complexes based on unsubstituted or substituted TPA ligands (where TPA is tris(2-pyridylmethyl)amine) and acetohydroxamic acid (A), N-methyl-acetohydroxamic acid (B), or N-hydroxy-pyridinone (C) were prepared and characterized by mass spectrometry, elemental analysis, and electrochemistry: [Co(III)(TPA)(A-2H)](Cl) (1a), [Co(III)((4-Cl(2))TPA)(A-2H)](Cl) (2a), [Co(III)((6-Piva)TPA)(A-2H)](Cl) (3a), [Co(III)((4-Piva)TPA)(A-2H)](Cl) (4a) and [Co(III)(TPA)(B-H)](Cl)(2) (1b), and [Co(III)(TPA)(C-H)](Cl)(2) (1c). Complexes 1a-c and 3a were analyzed by (1)H NMR, using 2D ((1)H, (1)H) COSY and 2D ((1)H, (13)C) HMBC and HSQC, and shown to exist as a mixture of two geometric isomers based on whether the hydroxamic oxygen was trans to a pyridine nitrogen or to the tertiary amine nitrogen. Complex 3a exists as a single isomer that was crystallized.

Synthesis, characterization, and reactivity of alkyldisulfanido zinc complexes.

The alkyldisulfanido zinc complexes Tp(iPr,iPr)Zn(SSR) and Tp(Ph,Me)Zn(SSR) where Tp(iPr,iPr) is hydridotris-((3,5-isopropyl)pyrazolyl)borate, Tp(Ph,Me) is hydridotris-((3-phenyl,5-methyl)pyrazolyl)borate, and (SSR) is tert-butyldisulfanido or triphenylmethanedisulfanido were synthesized by reaction between the corresponding hydroxo complexes TpZn(OH) and the synthetic persulfide RSSH. All the complexes were characterized by elemental analysis and (1)H NMR spectroscopy, and representative members of the class were also structurally characterized. The reactivity of the alkyldisulfanido TpZn(SSR) complexes with thiols was studied.

Synthesis and characterization of mononuclear hydroxamato and hydroximato complexes of iron(III) based on the tris-(2-pyridylmethyl)amine ligand.

The reaction of acetohydroxamic (CH3C(O)-NHOH), benzhydroxamic acid (PhC(O)-NHOH) or 1-hydroxypyridin-2(1H)-one (pyrC(O)-NOH) in the presence of tris-(2-pyridylmethyl)amine (TPA), sodium methoxide and an iron(III) salt yields the mononuclear complexes [Fe(TPA)(CH3C(O)-NHO)]2+ (), [Fe(TPA)(PhC(O)-NHO)]2+ () and [Fe(TPA)(pyrC(O)-NO)]2+ (). The hydroxamato complexes and are easily converted to their hydroximato form [Fe(TPA)(CH3C(O)=NO)]+ () and [Fe(TPA)(PhC(O)=NO)]+ () by addition of base. The complexes described were characterized by UV-vis spectroscopy, EPR and cyclic voltammetry, as well as single-crystal X-ray crystallography for and .

New aspects of catalytic intramolecular C-H amination: unexpected formation of a seven-membered ring in nitrogen-containing systems.

The first example of the formation of a seven-membered ring by way of intramolecular-catalyzed amination of saturated C-H bonds is reported (Du Bois reaction). The influence of various structural parameters was studied, and it was shown that the unexpected regioselectivity observed in nitrogen-containing systems could be rationalized by conformational factors. These results open the way to innovative strategies for the general synthesis of polyfunctionalized piperidines.

Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.

A new alpha-aminophosphinic compound able to inhibit both zinc-containing exopeptidases and endopeptidases has been crystallized with TLN as a model in order to investigate the mode of zinc recognition by the phosphinic moiety and to evaluate the potential role of the free alpha-amino group in the formation of enzyme-inhibitor complexes. In addition to the main interactions between the backbone of the inhibitor and the enzyme active site, it is observed that the phosphinic group acts as a distorted bidentate ligand for the zinc ion, while the free alpha-amino function does not directly participate in interactions within the active site. Association of the present data and the K(i) values of various analogues of the inhibitor towards TLN and neprilysin suggests differences in the hydrophobicity of the S(1)-S(2) domains of the enzymes.

The 2.2 A resolution structure of thermolysin (TLN) crystallized in the presence of potassium thiocyanate.

A new crystallization protocol for thermolysin (EC 3.4.24.

N-[2-(Indan-1-yl)-3-mercapto-propionyl] amino acids as highly potent inhibitors of the three vasopeptidases (NEP, ACE, ECE): In vitro and In vivo activities.

We have previously reported the design of a lead compound 1a for the joint inhibition of neprilysin (NEP, EC 3.4.24.