Ligand-Controlled Stereoselective Synthesis and Biological Activity of 2-Exomethylene Pseudo-glycoconjugates: Discovery of Mincle-Selective Ligands

Glycoconjugate analogues in which the sp³-hybridized C2 position of the carbohydrate structure (normally bearing a hydroxy group) is converted into a compact sp²-hybridized exomethylene group are expected to have unique biological activities. We established ligand-controlled Tsuji–Trost-type glycosylation methodology to directly prepare a variety of these 2-exomethylene pseudo-glycoconjugates, including glucosylceramide analogues, in an α- or β-selective manner. Glucocerebrosidase GBA1 cleaves these synthetic pseudo-β-glucosylceramides similarly to native glucosylceramides. The pseudo-glucosylceramides exhibit selective ligand activity towards macrophage-inducible C-type lectin (Mincle), but unlike native glucosylceramides, are inactive towards CD1d.     

Gold-catalysed intramolecular trans-allylsilylation of alkynes forming 3-allyl-1-silaindenes

3-Allyl-1-silaindenes are synthesised from alkynes having an allylsilane moiety by a gold-catalysed intramolecular trans-allylsilylation reaction.     

Synthesis of a novel D-glucose-conjugated 15-crown-5 ether with a spiro ketal structure

This paper describes a synthetic approach to a novel D-glucose-conjugated 15-crown-5 ether having a spiroketal structure starting from a 1-C-vinylated glucose derivative. The approach consists of the glycosylation of the vinylated glucose derivative to give an ethyleneoxy spacer derivative using bismuth(III) triflate, the conversion of the 1-C-vinyl group of the glucoside produced into a carboxylic acid group, and the intramolecular condensation between the carboxyl group and the terminal hydroxyl group in the ethyleneoxy spacer. A D-glucose-conjugated 15-crown-5 ether having a unique spiroketal structure was thus successfully synthesized.     

Development of highly chemoselective bulky zincate complex, tBu4ZnLi2: design, structure, and practical applications in small-/macromolecular synthesis

We present full details of the unique reactivities of the newly developed dianion-type bulky zincate, dilithium tetra-tert-butylzincate (tBu(4)ZnLi(2)). With this reagent, halogen-zinc exchange reaction of variously functionalized haloaromatics and anionic polymerization of N-isopropylacrylamide (NIPAm)/styrene with excellent chemoselectivity were realized. Halogen-zinc exchange reaction followed by electrophilic trapping with propargyl bromide provided a convenient route to functionalized phenylallenes, particularly those with electrophilic functional groups (such as cyano, amide and halogens). Spectral and computational studies of the structure in the gas and liquid phases indicated extraordinary stabilization of this dianion-type zincate by its bulky ligands.     

Synthesis of fluspidine via asymmetric NaBH4 reduction of silicon enolates of β-keto esters

Asymmetric NaBH₄ reduction catalyzed by the Co(II) complex of a chiral diamidine-type sp²N ligand, Naph-diPIM-dioxo-iPr, was successfully applied to 3-silyloxycinnamate substrates without over-reduction, giving quantitatively 3-silyloxy-3-arylpropionates with an enantiomer ratio of up to 99:1. The high utility was confirmed on a 30-g scale using 0.1?mol% catalyst. Both Z and E substrates could be converted to a single enantiomeric product by changing the ligand chirality. The relationship between the Z/E stereochemistry and the absolute configuration of the 1,4-reduction product provided important information about the mechanism underlying enantioface selection. Combination of the asymmetric catalysis with two other key steps, Suzuki coupling with an N-protected tetrahydropyridine boronic acid derivative and intramolecular bromo etherification, realized an efficient synthetic route to both enantiomers of fluspidine. The new strategy permits the introduction of substituents on the two aryl groups and piperidine ring, allowing for structural variations toward the development of higher performance σ1 receptor antagonists.     

A semidefinite programming approach to a cross-intersection problem with measures

Mathematical Programming - We present a semidefinite programming approach to bound the measures of cross-independent pairs in a bipartite graph. This can be viewed as a far-reaching extension of...     

Digitalized Mirror Array and Its Application in Large Telescope: Principle and Case Studies

In this article, we report the principle and conceptual design of a fundamentally different technology in fabricating high precision aberrationfree optical devices. The tip-tilt of facet in a mirror array is produced bydigitally controlled line-tilts of rows and columns. It has not only provided a cost-effective designing methodology in optical physics but also led to a much finer precision of 1 mili arc sec or less. As examples of the application of the proposed digitalised optics, two case studies have been given: a 10 m Schmidt telescope (off-axis) and an 8 m Cassegrain telescope (on-axis).     

Enantioselective divergent approaches to both (−)-platensimycin and (−)-platencin

Enantioselective divergent approaches to (−)-platencin and (−)-platensimycin have been developed. A rationally designed chiral synthetic intermediate, possessing a useful α,β-unsaturated sulfone functionality, which served as a masked ketone as well as a good Michael acceptor, was successfully prepared via the highly enantioselective catalytic asymmetric intramolecular cyclopropanation (CAIMCP) developed in our laboratory.