Design of iodinated radioligands for SPECT imaging of central human 5-HTR using a ligand lipophilicity efficiency approach.

A series of iodinated ligands for the SPECT imaging of 5-HT receptors was designed starting from the previously reported hit MR-26132. We focused on the modulation of the piperidine-containing lateral chain by introducing hydrophilic groups in order to decrease the liphophilicity of the new ligands. All the synthesized compounds were tested for their binding affinities on 5-HTRs and based on the Ligand Lipophilicity Efficiency approach, compound 13 was further selected for radioiodination with iodine-125 and imaging experiments.

Iodonitrene in Action: Direct Transformation of Amino Acids into Terminal Diazirines and N-Diazirines and Their Application as Hyperpolarized Markers.

A one-pot metal-free conversion of unprotected amino acids to terminal diazirines has been developed using phenyliodonium diacetate (PIDA) and ammonia. This PIDA-mediated transformation occurs three consecutive reactions and involves an iodonitrene intermediate. This method is tolerant to most functional groups found on the lateral chain of amino acids, it is operationally simple, and it can be scaled up to provide multigram quantities of diazirine.

Terminal Diazirines Enable Reverse Polarization Transfer from N Singlets.

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The N labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long-lived lifetimes. The (-CH N ) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (-CH N ) moiety to H, thus combining the advantages of long lifetimes of N polarization with superior sensitivity of H detection.

One-Pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-Sulfoximines from Sulfides.

A general efficient one-pot synthesis of S-perfluoroalkylated NH-sulfoximines from sulfides has been developed using phenyliodine diacetate (PIDA) and ammonium carbamate. Remarkable rate enhancement with trifluoroethanol was observed, presumably due to H-bonding effects. These mild and metal-free conditions are compatible with -CH F, -CFCl , -CF H, -CF Br, -C F , and -CF groups, in both the alkyl- and aryl series.

Mechanistic investigation of the NH-sulfoximination of sulfide. Evidence for λ-sulfanenitrile intermediates.

We report a new procedure for the preparation of NH-sulfoximines from sulfides using PIDA as an oxidant and ammonium carbamate as the ammonia source. Excellent yields were obtained with a wide range of sulfides. The formation of acetoxy- and methoxy-λ-sulfanenitrile as intermediates was proposed, both of which were converted to the NH-sulfoximine by the action of the solvent.

Asymmetric three-component domino reaction: an original access to chiral nonracemic 1,3-thiazin-2-ones.

A new asymmetric three-component domino process, based on a diastereoselective hetero-Diels-Alder reaction, involving an aldehyde, an alkene, and a chiral thiocarbamate was developed. The chiral auxiliary is directly removed during this process, leading to enantioenriched 2H-1,3-thiazin-2-ones with up to 96% ee.

Catalytic generation of cesium acetylide by CsF: synthesis of 1,3-benzothiazines from cyclic sulfenamides.

An efficient synthesis of enantiopure 1,3-benzothiazines has been achieved by reaction of cyclic sulfenamides and alkylpropiolate or tosylacetylene catalyzed by cesium fluoride.

Fluoride ion and phosphines as nucleophilic catalysts: synthesis of 1,4-benzothiazepines from cyclic sulfenamides.

A new methodology, using fluoride ion as a nucleophilic catalyst, was applied for the synthesis of enantiopure 1,4-benzothiazepine from cyclic sulfenamide and electron-deficient acetylene, with high efficiency and atom economy.

A novel synthesis of 1-nosyl 3,3-dichloro-beta-lactams and derivatives.

We report herein an efficient and simple route to synthesize 1-nosyl 3,3-dichloro-beta-lactams using a Staudinger reaction between N-nosyl imines and dichloroketene. The resulting dichloroazetidines were opened to afford highly functionalized building blocks.

A straightforward asymmetric synthesis of 1,2-disubstituted ferrocenylalkyl amines with the unusual (S(Fc),S) configuration.

A useful synthesis of rare 1,2-disubstituted ferrocenylalkyl amines with (S(Fc),S) configuration has been achieved in a sequential one-pot methodology from (S)-p-tolylsulfinylferrocene.

Diastereoselective addition of enantiopure lithium tert-butylsulfinylferrocene to imines.

(S)-tert-Butylsulfinylferrocene was submitted to ortho-metalation, and the corresponding lithium derivative was trapped by alkyl or aryl imines bearing various electron-withdrawing groups on the nitrogen atom (Ts, Dpp, Boc). New aminosulfoxides were obtained with complete diastereocontrol when Dpp or Boc groups were used. The absolute configuration (SS,SFc,S) has been determined by single-crystal X-ray analysis and chemical correlation.

ortho-Metalation of enantiopure aromatic sulfoxides and stereocontrolled addition to imines.

Enantiopure aromatic (phenyl, naphthyl) and heteroaromatic (pyridyl, quinolyl, diazinyl) sulfoxides have been synthesized by reaction of (S)-tert-butyl tert-butanethiosulfinate with aryl- or heteroaryllithium derivatives. The ortho-directed metalation of the sulfoxides was performed with lithium bases. Subsequent addition of the lithiated intermediates to N-tosylimines afforded tosylaminoalkyl tert-butylsulfinyl arenes.

Asymmetric induction of the iodolactonization reaction of alpha-sulfurated gamma-unsaturated amides.

The 1,3-asymmetric iodolactonization reaction of enantiopure alpha-sulfurated gamma-unsaturated amides has been investigated. With sulfinyl and sulfonyl groups, a poorly stereoselective reaction was observed, whereas with a sulfanyl moiety, the diastereoselectivity can be high as 96:4. The role of the oxygen atom on the sulfur moiety is discussed.

First enantioselective synthesis of vinyl oxiranes from aldehydes and ylides generated from allyl halides and chiral sulfides.

Asymmetric allylidenation of aldehydes with sulfur ylides is possible with proper substitution of the initial sulfide, to avoid the [2,3] sigmatropic rearrangement of the unsaturated ylides. One-pot reaction of (2R,5R)-dimethylthiolane with allyl halides, aldehydes, and sodium hydroxide in tert-butyl alcohol affords vinyl oxiranes in good yields. Enantiomeric excesses up to 90% and trans selectivities have been achieved with methallyl-type halides.

First use of axially chiral thioamides for the stereocontrol of C-C bond formation.

Several N-aryl-substituted thioamides with an axis of chirality along the N-C(aryl) bond were prepared in good to excellent yields. NMR spectra revealed preferences for the E rotamer (along the N-C(=S) bond). X-ray crystallographic analysis showed that the planes of the aryl and thioamide groups were almost perpendicular (79 degrees).