Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.     

LP narrowing: A new strategy for finding all solutions of nonlinear equations

An efficient algorithm is proposed for finding all solutions of systems of n nonlinear equations. This algorithm is based on interval analysis and a new strategy called LP narrowing. In the LP narrowing strategy, boxes (n-dimensional rectangles in the solution domain) containing no solution are excluded, and boxes containing solutions are narrowed so that no solution is lost by using linear programming techniques. Since the LP narrowing is very powerful, all solutions can be found very efficiently. By numerical examples, it is shown that the proposed algorithm could find all solutions of systems of 5000-50,000 nonlinear equations in practical computation time.     

Efficient route to 4a-methyltetrahydrofluorenes: a total synthesis of (+/-)-dichroanal B via intramolecular Heck reaction

An efficient new route based on intramolecular Heck cyclization of the diene 11 was developed to prepare the 4a-methyltetrahydrofluorene diterpenoids and utilized for the total synthesis of (+/-)-dichroanal B with significantly improved overall yield.     

Synthesis of optically active,unnatural α-substituted glutamic acid derivatives by a chiral calcium-catalyzed 1,4-addition reaction

The first catalytic asymmetric 1,4-addition reactions of azlactones with acrylic esters have been developed. A chiral coordinative calcium catalyst was found to be effective for these reactions, and the desired 1,4-adducts were obtained in good yields and enantioselectivities. The product was converted to the corresponding α-alkylated glutamic acid by acid hydrolysis.     

Inclusion Complexation of a Seleno-Organic Antioxidant, Ebselen, with Cyclodextrins in Aqueous Solution

The interaction of ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, a novel neuroprotective agent, with cyclodextrins (CyDs) in aqueous solution was studied by the solubility method and spectroscopic methods. The ability of sulfobutyl ether -CyD (SBE7--CyD, average degree of substitution= 6.2) to solubilize ebselen was greater, and its stability constant (> 2000 M^-1) was significantly higher than those (< 1000 M^-1) of other CyD complexes employed. The stability constant of the complexes rose as hydrophobicity of the substituents of CyDs increased, whereas it was negligibly affected by change in ionic strength of the medium, indicating a significant contribution of hydrophobic interaction in the complexation. SBE7--CyD gave positive and negative CD bands at around 320 and 350 nm, respectively, indicating that the guest is embedded in the asymmetric locus of the CyD cavity. ¹H-NMR spectroscopic studies suggested that the mono-substituted benzene ring of ebselen is preferably included in the cavity of SBE7--CyD. The results indicate that SBE7--CyD is useful as a solubilizing agent for ebselen.     

Studies on the terpenoids and related alicyclic compounds—XXII: Stereochemical study on the angular hydroxylation of polycyclic ketones using benzeneseleninic anhydride

Introduction of an OH group to the tertiary carbon of simple ketones (1, 2 and 6), furanoeremophilane-type ketones (12–19), and tricyclic ketones (20–22) by the use of benzeneseleninic anhydride is described. 10β-Hydroxy compounds were obtained in the case of 12–14 and 20–22. 10α-Hydroxy compounds were obtained in the case of 15 and 16. In the hydroxylation reaction of polycyclic ketones using benzeneseleninic anhydride, the results suggest that the thermodynamically more stable product was usually produced as the major product.