Chiral nitrogen-containing compounds are widely distributed in nature and include many biologically important molecules (Chart 1). In these compounds, the nitrogen-containing units are known to play important roles for their bioactivities. For the synthesis of these chiral nitrogen-containing building blocks, use of imines as electrophiles is the most promising and convenient route.1 While many approaches using chiral imines or chiral nucleophiles have been reported,1 these diastereoselective reactions have some disadvantages. First, the procedures to introduce chiral auxiliaries to substrates and to remove them after the diastereoselective reactions are often tedious. Second, more than stoichiometric amounts of chiral sources are needed to obtain chiral compounds according to these reactions. On the other hand, catalytic enantioselective reactions provide the most efficient methods for the synthesis of chiral compounds,2 because large quantities of chiral compounds are expected to be prepared using small amounts of chiral sources. While much progress has been made recently in catalytic enantioselective reactions of aldehydes and ketones such as aldol,3 allylation,4 Diels-Alder,5 cyanation reactions,6 reduction,1b,2b etc., progress in catalytic enantioselective reactions of imines is rather slow. There are some difficulties in performing catalytic enantioselective reactions of imines. For example, in the cases of chiral Lewis acid promoted asymmetric Shū Kobayashi was born in 1959 in Tokyo, Japan. He studied chemistry at the University of Tokyo and received his Ph.D. in 1988 (Professor T. Mukaiyama). After spending 11 years at Science University of Tokyo (SUT), he moved to Graduate School of Pharmaceutical Sciences, University of Tokyo, in 1998. His research interests include development of new synthetic methods, development of novel catalysts (especially chiral catalysts), organic synthesis in water, solid-phase organic synthesis, total synthesis of biologically interesting compounds, and organometallic chemistry. He received the first Springer Award in Organometallic Chemistry in 1997.

https://chemistry.mdma.ch/hiveboard/picproxie_docs/000499541-cr980414z.pdf

Catalytic enantioselective addition to imines.

2.1.8. Michael Reaction 2245 2.1.9. Others 2247 2.2. Cyclization Reactions 2248 2.2.1. Carbon Diels−Alder Reactions 2248 2.2.2. Aza-Diels−Alder Reactions 2252 2.2.3. Other Hetero-Diels−Alder Reactions 2255 2.2.4. Ionic Diels−Alder Reaction 2256 2.2.5. 1,3-Dipolar Cycloadditions 2256 2.2.6. Other Cycloaddition Reactions 2258 2.2.7. Prins-type Cyclization 2259 2.3. Friedel−Crafts Acylation and Alkylation 2259 2.4. Baylis−Hillman Reaction 2263 2.5. Radical Addition 2264 2.6. Heterocycle Synthesis 2267 2.7. Diazocarbonyl Insertion 2270 3. C−X (X ) N, O, P, Etc.) Bond Formation 2271 3.1. Aromatic Nitration and Sulfonylation 2271 3.2. Michael Reaction 2272 3.3. Glycosylation 2273 3.4. Aziridination 2275 3.5. Diazocarbonyl Insertion 2276 3.6. Ring-Opening Reactions 2277 3.7. Other C−X Bond Formations 2280 4. Oxidation and Reduction 2280 4.1. Oxidation 2280 4.2. Reduction 2281 5. Rearrangement 2283 6. Protection and Deprotection 2285 6.1. Protection 2285 6.2. Deprotection 2288 7. Polymerization 2291 8. Miscellaneous Reactions 2291 9. Lanthanide(II) Triflates in Organic Synthesis 2295 10. Conclusion 2295 11. Acknowledgment 2295 12. References 2295

Rare-earth metal triflates in organic synthesis

Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.

Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health.

Limited natural resources and an increasing demand for enantiomerically pure compounds render catalysis and especially heterogeneous asymmetric catalysis a key technology. The field has rapidly advanced from the initial use of chiral biopolymers, such as silk, as a support for metal catalysts to the modern research areas. Mesoporous supports, noncovalent immobilization, metal-organic catalysts, chiral modifiers: many areas are rapidly evolving. This Review shows that these catalysts have more to them than facile separation or recycling. Better activities and selectivities can be obtained than with the homogeneous catalyst and novel, efficient reaction mechanisms can be employed. Especially fascinating is the outlook for highly ordered metal-organic catalysts that might allow a rational design, synthesis, and the unequivocal structural characterization to give tailor-made catalysts.

Asymmetric heterogeneous catalysis.

Recent stereoselective synthetic approaches to β-amino acids

Asymmetric syntheses of .BETA.-amino acids by the addition of chiral amines to C=C double bonds.

Sterically controlled syntheses of optically active organic compounds. 28. Asymmetric syntheses of amino acids by addition of hydrogen cyanide to the Schiff bases.

Asymmetric syntheses of .BETA.-amino acids by the reduction of enamines.

The inhibitory effects of flavonoids (galangin, kaempferol, quercetin, myricetin, morin, and taxifolin) on rabbit heart carbonyl reductase (RHCR) were investigated using 4-benzoylpyridine (4BP) as the substrate. The stereochemical characteristics of the flavonoids were found to be a factor determining their inhibitory potencies toward RHCR. Furthermore, the lipophilicity, and the scavenging or antioxidative effects of the flavonoids were likely to complicate the structure-activity relationship of their inhibitory effects on RHCR. Quercetin inhibited RHCR uncompetitively with respect to NADPH and competitively with respect to 4BP, suggesting that it competes with 4BP at the substrate-binding site of RHCR. RHCR efficiently reduced benzoquinones (1,4-benzoquinone and 2-methyl-1, 4-benzoquinone) and naphthoquinones (1,4-naphthoquinone and menadione). Galangin was a potent inhibitor of RHCR when menadione was used as the substrate, and prevented the formation of the superoxide anion radical in the presence of RHCR, NADPH, and menadione. Flavonoids may be useful compounds for suppressing the cardiotoxicity of quinones by inhibiting RHCR.

Tadashi Okawara

Papers

Asymmetric syntheses of .BETA.-amino acids by the addition of chiral amines to C=C double bonds.

Sterically controlled syntheses of optically active organic compounds. 28. Asymmetric syntheses of amino acids by addition of hydrogen cyanide to the Schiff bases.

Asymmetric syntheses of .BETA.-amino acids by the reduction of enamines.

Inhibitory Effects of Flavonoids on Rabbit Heart Carbonyl Reductase

Heterocyclization of 2,4-disubstituted thiosemicarbazides with haloketones