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Chiral binaphthyl-strapped Zn(II) porphyrins with triazolium halide units were synthesized as bifunctional catalysts for kinetic resolution of epoxides with CO2. Several catalysts were screened by changing the linker length and nucleophilic counteranions, and the optimized catalyst accelerated the enantioselective reaction at ambient temperature to produce optically active cyclic carbonates and epoxides.

Hemisquaramide tweezers, a new family of H-bond donor organocatalysts, are reported. The catalysts could be synthesized within two steps. Among them, H8-binaphthyl-linked hemisquaramide 7 markedly accelerated the synthesis of cyclic carbonates from epoxides and CO2. The reactions proceeded well under mild and solvent-free conditions. Kinetic resolution was also achieved at −20 °C (s = 3.0). The adjustable bite angle and orientation of the two NH groups of the catalysts are important for the high activity.

Hexameric and tetrameric porphyrin nanorings, Z6·T6 and Z4·T4, were synthesized in 53% and 14% yields, respectively, by the Sonogashira-type self-oligomerization of porphyrin monomer 1 using hexade...

A series of pyrenes sandwiched by axially chiral 1,1′-binaphthyls were synthesized. Among them, (R,R)-3 possessing 2-hydroxy-3,3′-dimethylbinaphthyls exhibited solvent-dependent inversion of the si...

We developed a method to improve protein thermostability, “loop-walking method”. Three consecutive positions in 12 loops of Burkholderia cepacia lipase were subjected to random mutagenesis to make 12 libraries. Screening allowed us to identify L7 as a hot-spot loop having an impact on thermostability, and the P233G/L234E/V235M mutant was found from 214 variants in the L7 library. Although a more excellent mutant might be discovered by screening all the 8000 P233X/L234X/V235X mutants, it was difficult to assay all of them. We therefore employed machine learning. Using thermostability data of the 214 mutants, a computational discrimination model was constructed to predict thermostability potentials. Among 7786 combinations ranked in silico, 20 promising candidates were selected and assayed. The P233D/L234P/V235S mutant retained 66% activity after heat treatment at 60 °C for 30 min, which was higher than those of the wild-type enzyme (5%) and the P233G/L234E/V235M mutant (35%).

Among chiral macrocycles 1 synthesized, 1m with the 3,5-bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the enantioselective synthesis of cyclic carbonates from disubstituted or monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable for the enantioselective activation of epoxides. A catalytic cycle proposed was supported by DFT calculations.

Carbazole-based BODIPY dimers 2a-g were synthesized via direct arylation. They showed red-shifted solid-state fluorescence spectra as compared with the corresponding monomer. In addition, unsymmetrical dimers 2d, 2f, and 2g with two different substituents showed red fluorescence with improved quantum yields in the solid state.

Carbazole-based BODIPYs 1-6 with several different substituents at the boron atom site were synthesized. These dyes fluoresced in the solid state, and 3a with phenylethynyl groups exhibited a red-shifted and broad fluorescence spectrum, which suggested an excimer emission. Its derivatives 3b-n were synthesized, and the relationship between the solid-state emission and crystal packing was investigated. The X-ray crystal structures revealed cofacial dimers that might form excimers. From the structural optimization results, we found that the introduction of mesityl groups hindered intermolecular access and led to reduced interactions between the dimers. In addition, the red-shifted excimer fluorescence suppressed self-absorption, and dyes with ethynyl groups showed solid-state fluorescence in the vis/NIR region.

A versatile method for converting various fluorescent polycyclic aromatic hydrocarbons into circularly polarized luminescence (CPL) excimer dyes with high glum and ΦFL values is reported. This method involves the functionalization of a chiral quaternaphthyl with six fluorophores via ester linkages in the last step of the synthesis. The usefulness of this approach was demonstrated for 1-, 2-, and 4-pyrenyl, 2- and 3-perylenyl, and 2-anthryl dyes. Most of them are the first or rare examples of CPL dyes. In the ground state, the fluorophores are tightly arranged by cumulative steric and electronic effects. In the excited state, the fluorophores form a twist excimer that maintains the ground-state conformations. The local chiral excimer directly affected the CPL properties. The systematic study on the signs of the CPLs allowed us to find a rule called the excimer chirality rule: right- and left-handed excimers exhibit (+)- and (-)-CPL, respectively.

The Glaser coupling reaction of ethynyl-substituted carbazole-based isophlorins provided butadiyne-bridged dimers, which were transformed into the thiophene-bridged dimers via the annulation reaction. Oxidation of these isophlorin dimers afforded carbazole-based diporphyrins. Notable electronic interactions in the diporphyrins have been confirmed by means of UV/vis-near-infrared (NIR) absorption spectroscopy, cyclic voltammetry (CV) measurements, and density functional theory (DFT) calculations.

The intermolecular or intramolecular asymmetric benzoin reaction was catalyzed by a small amount of N-heterocyclic carbene (NHC) (0.2-1 mol %) under solvent-free conditions. The solvent-free intramolecular asymmetric Stetter reaction also proceeded efficiently with NHC (0.2-1 mol %). In some cases, even solid-to-solid or solid-to-liquid conversions took place with low catalyst loading (0.2-1 mol %).

A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3′-bipyridyl, was synthesized. The dyad 2 bearing methoxy groups exhibited ON/OFF properties in circularly polarized luminescence (CPL), yielding a |glum| of 1.6 × 10–3 or 0 without any change in fluorescence. This type of CPL switch is unprecedented. Regioisomer 4 exhibited a dextro/levo rotation switching ability in [α]D. X-ray structures as well as experimental and theoretical analyses suggested that the switching properties depended on conformational changes.

Carbazole-based BODIPYs were synthesized in three steps using an organometallic approach consisting of sequential Ir-catalyzed borylation, Suzuki-Miyaura coupling, and boron complexation. Various substituents were introduced into the carbazole moiety, and large substituent effects were confirmed by means of absorption spectroscopy, cyclic voltammetry, and DFT calculations. Dibenzocarbazoles were also converted into the corresponding BODIPYs.

Industrial enzymes lipase PS (LPS) and lipase AK (LAK), which originate from Burkholderia cepacia and Pseudomonas fluorescens, respectively, are synthetically useful biocatalysts. To strengthen their catalytic performances, we introduced two mutations into hot spots of the active sites (residues 287 and 290). The LPS_L287F/I290A double mutant showed high catalytic activity and enantioselectivity for poor substrates for which the wild-type enzyme showed very low activity. The LAK_V287F/I290A double mutant was also an excellent biocatalyst with expanded substrate scope, which was comparable to the LPS_L287F/I290A double mutant. Thermodynamic parameters were determined to address the origin of the high enantioselectivity of the double mutant. The ΔΔH‡ term, but not the ΔΔS‡ term, was predominant, which suggests that the enantioselectivity is driven by a differential energy associated with intermolecular interactions around Phe287 and Ala290. A remarkable solvent effect was observed, giving a bell-shaped profile between the E values and the log P or e values of solvents with the highest E value in i-Pr2O. This suggests that an organic solvent with appropriate hydrophobicity and polarity provides the double mutant with some flexibility that is essential for excellent catalytic performance.

We prepared bifunctional Mg(II) porphyrin catalysts 1 for the solvent-free synthesis of cyclic carbonates from epoxides and CO2. The activities of 1d, 1h, and 1i, which have Br(-), Cl(-), and I(-) counteranions, respectively, increased in the order 1i1h1d. Catalysts 1d and 1j-m, which bear four tetraalkylammonium bromide groups with different alkyl chain lengths, showed comparable but slightly different activities. Based on the excellent catalyst 1d, we synthesized Mg(II) porphyrin 1o with eight tetraalkylammonium bromide groups, which showed even higher catalytic activity (turnover number, 138,000; turnover frequency, 19,000 h(-1)). The catalytic mechanism was studied by using 1d. The yields were nearly constant at initial CO2 pressures in the 1-6 MPa range, suggesting that CO2 was not involved in the rate-determining step in this pressure range. No reaction proceeded in supercritical CO2, probably because the epoxide (into which the catalyst dissolved) dissolved in and was diluted by the supercritical CO2. Experiments with (18)O-labeled CO2 and D-labeled epoxide suggested that the catalytic cycle involved initial nucleophilic attack of Br(-) on the less hindered side of the epoxide to generate an oxyanion, which underwent CO2 insertion to afford a CO2 adduct; subsequent intramolecular ring closure formed the cyclic carbonate and regenerated the catalyst. Density functional theory calculations gave results consistent with the experimental results, revealing that the quaternary ammonium cation underwent conformational changes that stabilized various anionic species generated during the catalytic cycle. The high activity of 1d and 1o was due to the cooperative action of the Mg(II) and Br(-) and a conformational change (induced-fit) of the quaternary ammonium cation.

Metalloporphyrins undergo remarkable nonplanar distortions of the macrocycle that perturb the chemical and photochemical properties of these important protein cofactors. Further, the tertiary structure of the surrounding protein can manipulate these distortions as a means of regulating biological function. For cytochromes c, for example, an energetically unfavorable, conserved nonplanar distortion of the heme exists and likely plays a role in its electron- transfer function. The heme distortion is primarily of the ruffling (ruf, type (corresponding to the lowest frequency BI,-symmetry normal mode) in which the pyrroles are twisted about the metal-Npyrrole bond. This BI.-symmetry nonplanar distortion is commonly observed in metalloporphyrin crystal structures, as are the saddling (sad) B2,- symmetry distortion, waving (wau) E,-symmetry distortions, and doming (dom) Az,-symmetry distortion. Each of these nonplanar distortions is expected to result in unique alterations of the chemical and physical properties of the nominally planar porphyrin macrocycle. Symmetrical porphyrin substitution with tetrahedrally bonded atoms at the four meso bridging carbons generally results in the BI, ruffling distortion; therefore, we investigated a series of meso-tetrasubstituted porphyrins for which the substituents vary in size (methyl, ethyl, propyl, pentyl, isopropyl, cyclopropyl derivative lla, cyclohexyl, apopinenyl (lo), tert-butyl, adamantyl), increasing the steric crowding at the periphery. Molecular mechanics calculations show increasing degree of ruffling (CaNNCa angle for opposite pyrroles varies from 0 to 57") for this series of porphyrins, generally agreeing with the X-ray structures that are available. In addition, the frequencies of the structure-sensitive Raman lines decrease nonlinearly with increasing ruffling angle. The localization of the Bl, nonplanar distortion in only the C,-C, bond torsion (not the case for the B2" sad distortion) suggests a means by which the B1, distortion might be distinguished from other types of nonplanar distortion by using resonance Raman spectroscopy. Also, the size of the red shifts in the n - n* absorption bands depends on Ca-Cm torsion angle in a nonlinear fashion and the shift is accurately predicted by INDO/s molecular orbital calculations when the nonplanar structures obtained from molecular mechanics are used.

Highly active bifunctional metalloporphyrin catalysts were developed for the coupling reaction of epoxides with CO2 to produce cyclic carbonates. The bifunctional catalysts have both quaternary ammonium halide groups and a metal center. To elucidate the roles of these catalytic groups, DFT calculations were performed. Control reactions using tetrabutylammonium halide as a catalyst were also investigated for comparison. In the present article, the results of our computational studies are overviewed. The computational results are consistent with the experimental data and are useful for elucidating the structure-activity relationship. The key features responsible for the high catalytic activity of the bifunctional catalysts are as follows: 1) the cooperative action of the halide anion (nucleophile) and the metal center (Lewis acid); 2) the near-attack conformation, leading to the efficient opening of the epoxide ring in the rate-determining step; and 3) the conformational change of the quaternary ammonium cation to stabilize various anionic species generated during catalysis, in addition to the robustness (thermostability) of the catalysts.

Iron oxide produced by iron-oxidizing bacteria, Leptothrix ochracea , (biogenous iron oxide: BIO) was used as a support for immobilized palladium catalysts with organic cross-linkers. Palladium immobilized on BIO bearing imidazolium chloride delivered the desired biaryl products in sufficient yields in the Suzuki–Miyaura coupling reactions under solvent-free conditions and could be reused several times without significant loss of catalytic activity. It is shown that BIO can be exploited as a useful support for immobilization of palladium and the BIO-immobilized palladium catalyst effectively promotes the solvent-free Suzuki–Miyaura coupling reactions.

The bioreduction of α,α-difluorinated ketones, ethyl 2,2-difluoro-3-oxobutanoate ( 2a ) and 2,2-difluoro-1-phenyl-1,3-butanedione ( 2b ), with cells of recombinant Escherichia coli overproducing SCR ( Saccharomyces cerevisiae carbonyl reductase from bakers’ yeast) and GDH (glucose dehydrogenase from Bacillus megaterium ) gave enantiomerically pure alcohols, ethyl ( S )-2,2-difluoro-3-hydroxybutanoate (( S )- 1a ) and ( S )-2,2-difluoro-3-hydroxy-1-phenyl-1-butanone (( S )- 1b ), respectively, in the presence of NADP + and glucose in buffer. The reductions of 2a and 2b proceeded completely at the substrate concentrations of 0.4 M (67 g/L) and 1.0 M (200 g/L), respectively. The opposite enantiomers ( R )- 1a and ( R )- 1b were also produced by enzyme E039 (a mixture of carbonyl reductase and formate dehydrogenase) contained in Chiralscreen OH (Daicel Chemical Industries) in the presence of NADH and sodium formate in buffer. Enantiomerically pure ( S )- 1a was converted by organic synthetic methods into an α,α-difluorinated derivative of ( R )-β-aminobutyric acid (BABA) in three steps.

We derived a novel equation capable of predicting the degree of enantioselectivity in a catalytic reaction without any knowledge of the reaction mechanism and/or the transition-state structure, and tested the validity of this equation by changing substrates systematically in the lipase or oxazaborolidine-catalyzed reactions. A good correlation was observed between the predicted and observed E values, and the stereochemistry of the products could be predicted correctly in most cases (28 out of 30).

Bicyclic tertiary alcohols 1 bearing quaternary stereocenters at the two adjacent bridgehead positions were synthesized with high stereoselectivity via the intramolecular crossed benzoin reactions catalyzed by NHC organocatalysts.

Synthetically useful cyanohydrin acetates, ArCH(OAc)CN (Ar=C6H5, 3,4-methylenedioxyphenyl, 4-Me–C6H4, 4-Cl–C6H4, 4-F–C6H4, 4-CF3–C6H4), were successfully synthesized in high enantiomeric purities (79–93% ee) via the lipase-catalyzed dynamic kinetic resolution (DKR) of cyanohydrins synthesized in situ from the corresponding aldehydes and acetone cyanohydrin. The combined use of silica-supported BTAH (benzyltrimethylammonium hydroxide) and porous ceramic-immobilized lipase under the optimized reaction conditions enabled the remarkable acceleration of the enantioselective DKR reactions.

The gene encoding a versatile biocatalyst that shows high enantioselectivity for a variety of ketones, SCR (Saccharomyces cerevisiae carbonyl reductase), has been identified, cloned, and expressed in Escherichia coli. Two types of expression systems with high NADPH-regenerating capacities have been constructed. One is the tandem system, where the genes encoding SCR and GDH (glucose dehydrogenase) are located in the same plasmid, and the other is the two-plasmid system, where each of the SCR and GDH genes is located in separate plasmids that can coexist in one E. coli cell. Asymmetric reduction of ketones with the recombinant E. coli cells gave synthetically useful 20 alcohols, 11 of which were enantiomerically pure. The productivity of one of these products was as high as 41 g/L.

A molecular tweezer bearing two pentafluorophenyl groups 2b and its o-methylated aryl homologue 2c were newly synthesized by the slight modification of the known procedure. The low yield in the introduction of pentafluorophenyl group to the precursor dibromide 6 was improved by application of the modified Suzuki–Miyaura coupling reaction using C6F5B(OH)2 with Pd2(dba)3/P(t-Bu)3/CsF/Ag2O catalytic system, which was recently developed by us.

A new type of chiral receptor (R,R)- or (S,S)-1b with C(2) symmetry was synthesized. An induced-fit type of binding behavior of 1b for diamines was revealed by CD spectroscopy. NMR studies demonstrated that 1b can function as a highly sensitive chiral shift reagent for the determination of the enantiomeric purity of chiral diamines, aziridine, and isoxazoline at the microgram level. [structure: see text]

Presence of an unique atom-to-face alcoholic oxygen atom⋯π interaction between a pentafluorophenyl group and alcoholic oxygen (O⋯π) has been demonstrated by X-ray analysis of the novel chiral amino alcohol instead of the well-known interaction between usual aromatic ring and alcoholic hydrogen atom (OH⋯π).

Lipases and subtilisins are versatile enzymes capable of showing high enantioselectivity and broad substrate specificity simultaneously. The transition-state models previously proposed to rationalize this important feature were intensively examined from kinetic and thermodynamic viewpoints. Kinetic measurements reaffirmed that chiral discrimination originates from the transition state and that the enantioselectivity results from the reduced activity of the enzymes for the slower-reacting enantiomer, but not from the enhanced activity for the faster-reacting enantiomer relative to a reference alcohol, cyclopentanol. The larger substituent of the slower-reacting enantiomers interacts repulsively with the protein in the transition state, and even the larger substituent of the faster-reacting enantiomers interacts unfavorably to some degree with the protein. A number of thermodynamic parameters, ΔΔ H ‡ and ΔΔ S ‡ , for the subtilisin-catalyzed acylations of secondary alcohols were determined. A linear compensation effect was found between the ΔΔ H ‡ and ΔΔ S ‡ values. As the ΔΔ H ‡ value becomes negatively large, the ΔΔ S ‡ value also becomes negatively large. This observation is explained in terms of the transition-state model. Because the widely accepted concepts such as the lock-and-key mechanism and the induced-fit mechanism cannot account for the peculiar behavior of these enzymes toward unnatural substrates, a new category, the non-lock-and-key mechanism, has been proposed.

Chiral macrocycles featuring sulfonamide and/or amide groups as anion-binding sites were synthesized. X-ray crystal structures and DFT calculations have shown that they adopt different conformations that may lead to unique binding behavior. Indeed, various anions could be sensed by their colorimetric and/or fluorescence signal output. The chiral macrocycles showed chiral recognition for chiral anions. Furthermore, a multisensor array with two or four chiral receptors discriminated seven phosphate anions (AMP, ADP, ATP, CMP, GMP, Pi, and PPi) with 100% classification accuracy.

The biogenous iron oxide (BIO) from Leptothrix ochracea was transformed to an organic-inorganic hybrid support to prepare an excellent immobilized enzyme showing high catalytic performance.

Large secondary alcohols, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin ( 1a ) and the zinc complex 1b , designed on the basis of the transition-state model recently proposed by us, were subjected to the lipase-catalyzed transesterifications. The alcohols were resolved using lipases from Pseudomonas cepacia (lipase PS), Candida antarctica (CHIRAZYME L-2), Rhizomucor miehei (CHIRAZYME L-9), and Pseudomonas aeruginosa (lipase LIP) with high enantioselectivities ( E > 100).

The lipase-catalyzed kinetic resolution of (±)-2-acyloxy-2-(pentafluorophenyl)acetonitrile (±)- 1 gave optically active cyanohydrin (S)- 2 and its antipodal ester (R)- 1 ( E = 211), the former of which was transformed (TBSOTf, DMAP) into its TBS-ether (S)- 3 , a new fluorinated chiral building block, and into naproxen ester 4 for X-ray analysis to determine the absolute configuration.

[structure: see text] Bifunctional macrocycle 1 with C2 symmetry was newly synthesized. NMR studies demonstrated that receptor 1 functions as a chiral shift reagent (solvating agent) that is highly effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, lactone, alcohol, sulfoxide, sulfoximine, isocyanate, or epoxide functionality. Binding constants were determined to investigate the binding behavior of 1.

Efficient kinetic resolution of racemic 3-hydroxy-3-(pentafluorophenyl)- propionitrile (±)-1 by a lipase-catalyzed transesterification gave optically pure (S)-3-hydroxy-3-(pentafluorophenyl)-propionitrile (S)- 1 and (R)-(+)-3- acetoxy-3-(penta-fluorophenyl)propionitrile (R)- 1 [>99% ee, respectively, E = 1057], the former of which was further transformed into (S)-(−)-3-amino-1-(pentafluorophenyl)-1-propanol (S)- 7 in four steps.

[reaction: see text] We have found new conditions for the Suzuki-Miyaura coupling reaction applicable to pentafluorophenylboronic acid (C(6)F(5)B(OH)(2)) (1), which is an inactive substrate under normal conditions. The reactions of 1 with phenyl iodide or bromide under Pd(PPh(3))(4)/CsF/Ag(2)O or Pd(2)(dba)(3)/P(t-Bu)(3)/CsF/Ag(2)O catalytic system conditions gave 2,3,4,5,6-pentafluoro-1,1'-biphenyl (3a) in more than 90% yields. Combination of CsF and Ag(2)O was essential for promoting these reactions.

As a model of molecular recognition of a flexible guest through multi-point recognition, the two-point fixation of the NH 2 group and the C=O group of amino acid esters to porphyrin host was investigated from thermodynamic point of view. The negative entropy change owing to restriction of internal rotation around the C α -C(carbonyl) bond of guest as driven by the two-point fixation was calculated from the following steps: (1) ab initio molecular orbital calculations at the 3-21G level to generate a potential energy surface for internal rotation along the C α -C(carbonyl) bond and the C α -C β bond, and (2) a calculation of partition function of the system based on classical statistical mechanics. The entropy loss due to the restriction of a rotation around the C α -C(carbonyl) bond was 5.0 cal·K −1 ·mol −1 for alanine methyl ester and 1.9 cal·K −1 ·mol −1 for valine methyl ester, indicating that valine methyl ester is more rigid with respect to the C α -C(carbonyl) rotation. This entropy loss was found to originate from the correlated rotation of the C α -C(carbonyl) bond and the C α -C β bond.

Secondary alcohols having bulky substituents on both sides of the hydroxy group are inherently poor substrates for most lipases. In view of this weakness, we redesigned a Burkholderia cepacia lipase to create a variant with improved enzymatic characteristics. The I287F/I290A double mutant showed a high conversion and a high E value (200) for a poor substrate for which the wild-type enzyme showed a low conversion and a low E value (5). This enhancement of catalytic activity and enantioselectivity of the variant resulted from the cooperative action of two mutations: Phe287 contributed to both enhancement of the (R)-enantiomer reactivity and suppression of the (S)-enantiomer reactivity, while Ala290 created a space to facilitate the acylation of the (R)-enantiomer. The kinetic constants indicated that the mutations effectively altered the transition state. Substrate mapping analysis strongly suggested that the CH/π interaction partly enhanced the (R)-enantiomer reactivity, the estimated energy of the CH/π interaction being -0.4 kcal mol(-1). The substrate scope of the I287F/I290A double mutant was broad. This biocatalyst was useful for the dynamic kinetic resolution of a variety of bulky secondary alcohols for which the wild-type enzyme shows little or no activity.

A selective synthetic route to unsymmetrical meso -arylporphyrins is described. New hybrid type of unsymmetrical porphyrin with C 2v symmetry was prepared according to the new method.

Chiral macrocycles with the hydrogen bond donor/acceptor sites in the cavity were synthesized and covalently bonded to silica gel to give chiral stationary phases (CSPs), which showed excellent abilities to resolve various chiral compounds, such as benzoin and Co(acac)3, in HPLC. Various organic solvents could be used as the mobile phase to optimize the resolution efficiency of CSPs, and in some cases, even MeCN, MeOH, and CO(2) could be used for the complete resolution of enantiomers.

Bifunctional macrocycles 1-4 and diamide 5 were designed and synthesized. NMR studies demonstrated that, among them, receptor 1 functions as the best chiral solvating agent (shift reagent), which is effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, carbonate, lactone, alcohol, sulfoxide, sulfoximine, sulfinamide, isocyanate, or epoxide functionality. The addition of only 5 mol % (69 microg, 0.15 mM) of 1 splits the enantiomeric signals of sulfoxide 13. The excellent performance of 1 as a chiral solvating agent, such as versatility, signal sharpness, high splitting ability, high sensitivity, wide detection window, and synthetic accessibility, is reported. NMR studies revealed that the principal binding site of 1 is the two amide NH groups of the lower segment and that the additional binding site is the pyridyl nitrogen. The V-shaped arrangement of the two 2,6-diacylaminopyridine moieties as constructed in 1 was found to be much more effective for binding a variety of compounds than the parallel alignment of the two binding motifs as constructed in 4. The NO2 group in 1 enhanced not only the binding ability but also the degree of enantioselectivity. Unexpectedly, the comparisons between 1 and 3 enabled us to find the importance of the relative orientation of the binaphthyl moiety; the orthogonal disposition of the binaphthyl moiety in 1 most effectively brings about the differential ring-current effect on the chiral guest molecule bound, which leads to the high degree of chiral discrimination in NMR.

Methyl (R)-o-chloromandelate ((R)-1), which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) (up to 1.0 M) with recombinant E. coli overproducing a versatile carbonyl reductase.

An asymmetric reduction of ethyl pyruvate was carried out using bakers’ yeast cell free extract with addition of NADPH in catalytic amounts and glucose as a hydride source. The total turnover number of NADPH reached 7680. The efficiency of the cell free extract is discussed.

1,2,3,4-Tetra-t-butylnaphthalene (2), a highly crowded naphthalene derivative, has been synthesized. Upon irradiation, 2 underwent photovalence isomerization to afford 1,2,5,6-tetra-t-butyl-3,4-benzo-3-tricyclo[3.1.0.02,6]-hexene (3). The synthesis of 1,4,5,6-tetra-t-butyl-2,3-benzo-2,5-bicyclo[2.2.0]hexadiene (1), which was used for the synthesis of 2, is also described.

Low-temperature method (−40 °C at best) for enhancement of the enantioselectivity in a lipase-catalyzed transesterification was proved to be widely applicable to primary and secondary alcohols and enabled theoretical prediction of the course of enhancement of the enantioselectivity physicochemically.

Optically active dimeric porphyrin covalently linked by a chiral cyclophane was synthesized; the two porphyrin chromophores were disposed in a slipped cofacial fashion, which was found to be tunable by cooperative coordination of diamines with various chain lengths.

In the subtilisin-catalyzed transesterifications of a variety of secondary alcohols, the ( S )-enantiomers were acylated faster. Kinetic measurements indicated that the enantioselectivity originates from chiral discrimination in the transition state. A transition-state model capable of explaining the S -preference of subtilisin toward secondary alcohols has been proposed.