Lewis base catalyzed aldol additions of chiral trichlorosilyl enolates and silyl enol ethers

[structures: see text] The consequences of double diastereodifferentiation in chiral Lewis base catalyzed aldol additions using chiral enoxysilanes derived from lactate, 3-hydroxyisobutyrate, and 3-hydroxybutyrate have been investigated. Trichlorosilyl enolates derived from the chiral methyl and ethyl ketones were subjected to aldolization in the presence of phosphoramides, and the intrinsic selectivity of these enolates and the external stereoinduction from chiral catalyst were studied. In the reactions with the lactate derived enolate, the strong internal stereoinduction dominated the stereochemical outcome of the aldol addition. For the 3-hydroxyisobutyrate- and 3-hydroxybutyrate derived enolates, the catalyst-controlled diastereoselectivities were observed, and the resident stereogenic centers exerted marginal influence. The corresponding trimethylsilyl enol ethers were employed in SiCl4/bisphosphoramide catalyzed aldol additions, and the effect of double diastereodifferentiation was also investigated. The overall diastereoselection of the process was again controlled by the strong external influence of the catalyst.     

Banach spaces of locally Schlicht functions with the Hornich operations

Let \(S_ \propto ( \propto \geqq 0)\) be the set of normalized (see (1.2)) functions f holomorphic in D:|z|<1 with \(f''(z)/f'(z) = 0((1 - \left| z \right|^2 )^{ - \propto } )\) , and let be the set of normalized (see (1.6)) functions f meromorphic in D with the Schwarzian derivative \(\left\{ {f,z} \right\} = 0((1 - \left| z \right|^2 )^{ - \propto } )\) . We shall show that some topological properties of \(S_ \propto\) and , and of subsets of them, follow from those of the weighted H^∞ space \(H_ \propto ^\infty\) , consisting of functions f holomorphic in D with \(f(z) = 0((1 - \left| z \right|^2 )^{ - \propto } )\) , and those of subsets of \(H_ \propto ^\infty\) . The set S₁ is denoted by X in [3] and [4].     

A facile preparation of 4-(1-Acetyl-4(1H)-pyridylidene)-2-oxazohn-5-ones

4-(1-Acetyl-4(1H)-pyridylidene)-2-oxazolin-5-ones were prepared by the reaction of acylglycines with pyridine and acetic anhydride under oxygen. Acidic and alkaline hydrolysis of 2-oxazolin-5-ones provided oxazole derivatives, pyridine derivatives, and carboxylic acids.     

Dichloroketene-induced cyclizations of vinyl sulfilimines: application of the method in the synthesis of (+/-)-desoxyeseroline

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 degrees C to yield thioalkyl-substituted gamma-lactams. The overall process involves nucleophilic addition of the nitrogen atom of the sulfilimine onto the highly electrophilic dichloroketene to first generate a zwitterionic intermediate. A subsequent [3,3]-sigmatropic rearrangement is followed by intramolecular trapping of the Pummerer cation by the amido anion to furnish the observed gamma-lactam product. Incorporation of donor groups on the aromatic ring of the sulfonyl functionality had little effect when aryl-substituted sulfilimines were used but exhibited a major effect on the efficiency of the reaction with furanyl-substituted systems. The placement of an electron donor group (i.e., OMe) on the sulfonyl aryl group enhances the nucleophilicity of the amido anion contained within the sulfonium ion intermediate and facilitates the rate of the 3,3-sigmatropic rearrangement. Styryl-substituted sulfilimines cyclize in a stereospecific manner and produce a 3:2-mixture of gamma-lactams and the isomeric imino-lactone system. The heavily functionalized gamma-lactams are easily converted to a variety of nitrogen containing substrates. The vinyl sulfilimine cyclization method was applied to the total synthesis of the Calabar alkaloid (+/-)-desoxyeseroline.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Dispersity of stratum corneum in the mixed aqueous solutions of binary mixtures between N,N-dimethyldodecylamine oxide and sodium dodecyl sulfate or two terpenes

Solubilization of cholesterol, differential scanning calorimetric (DSC), nuclear magnetic resonance (NMR) and dynamic light scattering (DLS) measurements were performed in order to reveal the dispersion mechanisms of stratum corneum (SC) into each intact corneocytes in the following systems: (1) in the aqueous mixed solutions of sodium dodecyl sulfate (SDS) and N,N-dimethyldodecylamine oxide (C₁₂DMAO); (2) in the aqueous micellar solutions of C₁₂DMAO containing solubilized α-terpineol (α-T); and (3) in the aqueous micellar solutions of C₁₂DMAO containing solubilized limonene. The intercellular lamellar structure of SC was revealed to be disrupted and/or removed in all these solutions. However, considering the micellar sizes and the interaction among molecules in micelle, the dispersion mechanisms in these three systems were different each other. The three dispersion mechanisms of SC were estimated and discussed on the basis of the results of solubilization, DSC, NMR and DLS, respectively.     

Catalytic addition of C-H bonds to multiple bonds with the aid of ruthenium complexes

Ruthenium complexes, e.g., RuH2(CO)(PPh3)3, have been found to catalyze the direct addition of ortho carbon-hydrogen bonds of aromatic ketones to olefins and acetylenes with high efficiency and selectivity. The C-H/olefin coupling reaction is applicable to not only C-H bonds in aromatic ketones but also to those in a,b-enones and aro-matic esters. Catalytic addition of ortho carbon-hydrogen bonds of aromatic imines to olefins is found to be catalyzed by Ru3(CO)12.     

anti-Selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing beta-amino alcohols

An anti-selective direct catalytic asymmetric Mannich-type reaction is described. The Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 complex promoted a Mannich-type reaction of 2-hydroxy-2'-methoxyacetophenone (2) and N-diphenylphosphinoyl imines 3. Using as little as 0.25-1 mol % of the catalyst, we obtained Mannich adducts 4 in excellent yield (up to 99%), diastereoselectivity (anti/syn = up to >98/2), and enantiomeric excess (up to >99.5%). The anti-selectivity in the present system is complementary to that observed using previously reported methods, providing a novel efficient method to synthesize anti-beta-amino alcohols in a highly enantioselective manner. Facile deprotection of the N-diphenylphosphinoyl group and commercial availability of both Et(2)Zn solution and (S,S)-linked-BINOL 1 also make the present catalysis practical.     

Development of KiBank, a database supporting structure-based drug design

KiBank is a database of inhibition constant (K_i) values with 3D structures of target proteins and chemicals. K_i values were accumulated from peer-reviewed literature searched via PubMed. The 3D structure files of target proteins were originally from Protein Data Bank (PDB), while the 2D structure files of the chemicals were collected together with the K_i values and then converted into 3D ones. In KiBank, the chemical and protein 3D structures with hydrogen atoms were optimized by energy minimization and stored in MDL MOL and PDB format, respectively.

KiBank is designed to support structure-based drug design. It provides structure files of proteins and chemicals ready for use in virtual screening through automated docking methods, while the K_i values can be applied for tests of docking/scoring combinations, program parameter settings, and calibration of empirical scoring functions. Additionally, the chemical structures and corresponding K_i values in KiBank are useful for lead optimization based on quantitative structure–activity relationship (QSAR) techniques.

KiBank is updated on a daily basis and is freely available at http://kibank.iis.u-tokyo.ac.jp/. As of August 2004, KiBank contains 8000 K_i values, over 6000 chemicals and 166 proteins covering the subtypes of receptors and enzymes.     

A new synthesis of gamma-lactams based on the reaction of vinyl sulfilimines with dichloroketene

The reactions of several aryl-, furanyl-, and vinyl substituted sulfilimines with dichloroketene proceeded at 25 degrees C to yield thioalkyl substituted gamma-lactams which, in turn, were converted to a variety of nitrogen-containing substrates. [reaction: see text]