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We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H.

Knowledge of protein subcellular localization is vitally important for both basic research and drug development. With the avalanche of protein sequences emerging in the post-genomic age, it is highly desired to develop computational tools for timely and effectively identifying their subcellular localization purely based on the sequence information alone. Recently, a predictor called "pLoc-mGpos" was developed for identifying the subcellular localization of Gram-positive bacterial proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems in which some proteins, called "multiplex proteins", may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mGpos was trained by an extremely skewed dataset in which some subset (subcellular location) was over 11 times the size of the other subsets. Accordingly, it cannot avoid the bias consequence caused by such an uneven training dataset. To alleviate such bias consequence, we have developed a new and bias-reducing predictor called pLoc_bal-mGpos by quasi-balancing the training dataset. Rigorous target jackknife tests on exactly the same experiment-confirmed dataset have indicated that the proposed new predictor is remarkably superior to pLoc-mGpos, the existing state-of-the-art predictor in identifying the subcellular localization of Gram-positive bacterial proteins. To maximize the convenience for most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mGpos/, by which users can easily get their desired results without the need to go through the detailed mathematics.

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Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals,n atural products and agrochemicals.A symmetric hydrogenation of a,bunsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds.Although related asymmetric hydrogenation of diand trisubstituted unsaturated acids with noble metals is well established, asymmetric hydrogenation of challenging tetrasubstituted a,b-unsaturated carboxylic acids is rarely reported. We demonstrate enantioselective hydrogenation of cyclic and acyclic tetrasubstituted a,b-unsaturated carboxylic acids via cobalt(II) catalysis.T his protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98 %y ield and 99 %e e). Combined experimental and computational mechanistic studies support aCo II catalytic cycle involving migratory insertion and s-bond metathesis processes.DFT calculations reveal that enantioselectivity may originate from the steric effect between the phenyl groups of the ligand and the substrate.