Expeditious entry into carbocyclic and heterocyclic spirooxindoles.

Spirocyclic frameworks have attracted synthetic practitioners due to their unique three-dimensional assembly, improved metabolic stability, solubility, and increased molecular complexity with regard to planar architectures. A recent surge in the number of spirocyclic oxindoles inhibiting enzymes, moderating unique protein-protein interactions, modulating receptors and transporters is testament to their prevalence. Against this background, the construction of spirocyclic frameworks containing an oxindole moiety as a torsional switch via stereoselective methods is in great demand. Herein we present a summary of the past three years in the progress of metal, organic molecule, nanostructured particle mediated, and even uncatalyzed versions of the highly diastereo- and enantioselective pathways leading to oxindole spirocycles.

Highly regio- and diastereoselective [3 + 2]-cycloadditions involving indolediones and α,ß-disubstituted nitroethylenes.

A highly diastereoselective [3 + 2]-cycloaddition strategy involving multiple oxindoles and several α,ß-disubstituted nitroethylenes is developed to access tetra-substituted α-spiropyrrolidine frameworks. A variety of α-amino acids were employed for the first time in order to generate azomethine ylides under thermal conditions, affording regioisomers 13 and 14 merely by changing the α-substituents (R = H and substituted carbons) of the α-amino acids. The reaction tolerates various sterically demanding, electron-rich and electron-deficient aryl and nitrogen substituents on glycines, oxindoles and nitroethylenes. The operational simplicity, such as the use of a metal-free and non-inert environment, the utilization of non-halogenated solvents and the ease of isolation, adhering to the principles of green chemistry, makes this process attractive for scale-up opportunities. The reaction delivers good yields (80-94%) and diastereoselectivities (up to 98 : 2) in favor of (cis,cis)-spirooxindoles, with opposite regioselectivity compared to ß-nitrostyrenes under identical conditions. Two spiropyrrolidine cycloadducts with unprotected amides exhibited significant activity against Gram-positive MRSA.

Detection of Clostridium tetani in human clinical samples using tetX specific primers targeting the neurotoxin.

Tetanus resulting from ear injury remains an important health problem, particularly in the developing world. We report the successful detection of Clostridium tetani using tetX specific primers targeting the Cl. tetani neurotoxin. The sample was obtained from an ear discharge of a case of otogenic tetanus in a 2-year-old male child. Based on the culture results of the ear discharge, Gram staining and virulence testing by genotyping, a diagnosis of tetanus was confirmed. This is the first report from India on the successful detection of Cl. tetani in a human clinical sample using tetX specific primers targeting the Cl. tetani neurotoxin.

Nickel-catalyzed Negishi cross-coupling reactions of secondary alkylzinc halides and aryl iodides.

A general Ni-catalyzed process for the cross-coupling of secondary alkylzinc halides and aryl/heteroaryl iodides has been developed. This is the first process to overcome the isomerization and ß-hydride elimination problems that are associated with the use of secondary nucleophiles, and that have limited the analogous Pd-catalyzed systems. The impact of salt additives was also investigated. It was found that the presence of LiBF(4) dramatically improves both isomeric retention and yield for challenging substrates.

Catalytic enantioselective synthesis of alpha,beta-diamino acid derivatives.

Highly enantio- and diastereoselective organocatalytic Mannich additions of alpha-isothiocyanato imides to sulfonyl imines are reported. Enantiomerically enriched syn-alpha,beta-diamino acid derivatives can be obtained in excellent yields using catalyst loadings as low as 0.25 mol %.

A stereoselective and atom-efficient approach to multifunctionalized five- and six-membered rings via a novel michael-initiated intramolecular Diels-Alder furan reaction.

[reaction: see text] A variety of key precursors to the intramolecular Diels-Alder reaction of furan diene (IMDAF) have been prepared via a very facile 1,4-addition of O-, S-, N-, and C-centered nucleophiles possessing unsaturated tether to beta-furyl nitroethylene. Subsequent IMDAF reaction of the 1,4-adducts, carried out under thermal conditions, provided five- and six-membered carbocycles and heterocycles fused to an easily cleavable oxabicycloheptene moiety. The structure and stereochemistry of the cycloadducts were determined by 2D-NMR experiments and further confirmed by X-ray crystallography. The salient features of the strategy include high degree of stereoselectivity (>80:20) in the cycloaddition, atom and step economy, and generation of multiple chiral centers and functionalities. The feasibility of the cleavage of the oxa bridge in the cycloadducts to afford novel multifunctional molecules has also been demonstrated.