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Organocopper-mediated alkylation of β-( N-Boc-2-oxo-1,3-oxazolidin-5-yl)-α,β-enoates has been intensively investigated. Alkylation proceeded regio- and stereoselectively by anti- SN2′ ring-opening to provide a new route to the synthesis of ψ[( E)-CHCH]-, ψ[( E)-CMeCH]- and ψ[( E)-CMeCMe]- type alkene dipeptide isosteres from chiral amino acid derivatives. These resulting agents are potential mimetics of type II and type II′ β-turn substructure.

The structure of intracellular third loop peptide (betaIII-2: RRSSKFCLKEKKALK) was studied by CD and NMR spectroscopy. According to the CD study, this peptide forms a helix in the TFE solution. The three-dimensional molecular structure in TFE was determined by the 2D (1)H NMR spectroscopy. The structure consists of a positive charge cluster on the C-terminal side of the peptide chain. This part will be an active site of the peptide interacting with the G-protein.

In order to identify the important factors involved in cationic liposome-mediated gene transfer, in vitro transfection efficiencies by plasmid DNA complexed with DOTMA/DOPE liposomes at different DNA/liposome mixing ratios were evaluated using four types of cultured cells with respect to their physicochemical properties. Significant changes were observed in the particle size and zeta potential of the complexes as well as in their structures, assessed by atomic force microscopy, which depended on the mixing ratio. In transfection experiments, except for RAW 264.7 cells (mouse macrophages), efficient gene expression was obtained in MBT-2 cells (mouse bladder tumor), NLH3T3 cells (mouse fibroblasts) and HUVEC (human umbilical vein endothelial cells) at an optimal ratio of 1:5, 1:7.5 or 1:5, respectively. On the other hand, cellular uptake of the [32P]DNA/liposome complexes increased in all cell types with an increase in the mixing ratio, which was not reflected by the transfection efficiency. The cellular damage determined by MTT assay was minimal even at the highest DNA/liposome ratio (1:10), indicating that the lower gene expression level at the higher ratio was not due to cytotoxicity induced by the complex. An ethidium bromide intercalation assay showed that the release of plasmid DNA from the complex, following the addition of negatively charged liposomes, was restricted as the mixing ratio increased. Furthermore, confocal microscopic studies using HUVEC showed that the 1:5 complexes exhibited a dispersed distribution in the cytoplasm whereas a punctuate intracellular distribution was observed for the 1:10 complexes. This suggests that there was a significant difference in intracellular trafficking, probably release from the endosomes or lysosomes, of the plasmid DNA/cationic liposome complexes between these mixing ratios. Taken together, these findings suggest that the DNA/liposome mixing ratio significantly affects the intracellular trafficking of plasmid DNA complexed with the cationic liposomes, which is an important determinant of the optimal mixing ratio in cationic liposome-mediated transfection.

Treatment of acyclic conjugated (η4-4–7)-triene Fe(CO)3 complexes bearing an electron-withdrawing group at a terminal position with a base such as KN(SiMe3)2 and NaH promoted 1,3-migration of an Fe(CO)3 group on the triene, giving (η4-2–5)-triene Fe(CO)3 complexes. The 1,3-migration of an Fe(CO)3 group is revealed to proceed in a stereospecific manner.

Whereas treatment of the allylic mesylates of N -protected 2-alkyl-4-amino-( E )-2-alken-1-ols with sodium hydride in DMF yields exclusively the corresponding 2,3- trans -2-alkenyl-3-alkylaziridines, exposure of the methyl carbonates of N -protected 2-alkyl-4-amino-( E )-2-alken-1-ols to Pd(PPh 3 ) 4 (5–20 mol%) in THF or 1,4-dioxane affords predominantly the corresponding 2,3- cis -2-alkenyl-3-alkylaziridines. These reactions can be used to synthesize either of two diastereomers from single common intermediates.

Amino allenes have been synthesized from 2-ethynylaziridines via organocopper-mediated reactions. Whereas treatment of enantiomerically pure (2 R,3 S)-2,3-trans-3-alkyl-2-ethynylaziridines with RCu(CN)M (M = Li or MgX) yield exclusively (S,S)-allenylamines in high yields, isomeric (2 S,3S)-2,3-cis-3-alkyl-2-ethynylaziridines afford (S,R)-allenylamines in comparable high yields.

The enantiomers, (R)-(-)-1 and (S)-(+)-1, of (+/-)-4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3- dihydro-2-methylbenzo[b]furan-7-carboxamide [(+/-)-1] were prepared from optically active benzyl 4-acetylamino-2,3-dihydro-2-methylbenzo[b]furan-7-carboxylate [(R)-(+)-6, (S)-(-)-6], respectively. The requisite (R)-(+)-6 and (S)-(-)-6 were prepared by large-scale preparative HPLC on chiral stationary phases (CSPs). The absolute configuration of (S)-(+)-1 was determined by single crystal X-ray analysis. The serotonin 5-HT4 receptor agonistic activity of (S)-(-)-1 hemifumarate (SK-951) which was hemifumarate of (S)-(+)-1 was about twice that of the other enantiomer (R)-(+)-1 hemifumarate which was hemifumarate of (R)-(-)-1.

The title model compound represents a redox property of the active site of flavoenzymes and an environmental effect of the apoproteins. Its stereostructure was elucidated by 1 H-NMR spectra and energy minimum calculations. The stereoselectivity of this model was observed during the reaction with Me 2 PNPH, as NAD(P)H model.

Palladium(0)-catalyzed reactions of N-methanesulfonyl- or N-(arenesulfonyl)-3-alkyl-2-vinylaziridines reveal that 2,3-cis-isomers are more stable than the corresponding 2,3-trans-isomers in accord ...

Azamacrocycles 1–4 were synthesized from 9 in 20–30% overall yields. Compounds 1 and 2 extracted some metal ions into organic solvents, but 3 and 4 did not. The crystal structure of the Ag(I) complex of 1 has been determined.

Methyl 3-(4-chlorophenyl)-1-[N-(4-chlorophenyl)carbamoyl]-4-methyl-2-pyrazoline-4-carboxylate was converted to corresponding (1R)- and (1S)-phenethyl esters via its carboxylic acid and acid chloride at the C-4 atom to separate the diastereomers. Their configurations were confirmed by X-ray analysis. Both isomers of the (1R)methylbenzyl ester were subjected to transesterification with sodium methoxide to obtain enantiomers of the starting methyl ester. Their insecticidal activity was measured against American cockroaches (Periplaneta americana (L.)) by injection and against house flies (Musca domestica L.) by topical application under various synergistic conditions with metabolic inhibitors. The activity values of the four α-methylbenzyl esters and the R-isomer of the starting methyl ester were similar. The S-enantiomer of the methyl ester was about 10 and 100 times more active than the R-isomer against the cockroach and the fly, respectively. Some N-arylacetyl and N-aryloxyacetyl derivatives of the starting N-(4-chlorophenyl)carbamoyl compound gave very low activity. Conformation-energy profiles for some compounds suggested that the conformation of substituents on the N-1 atom in the pyrazoline ring has a specific role for the potential insecticidal effects.

The structures of nine new diterpenoids from the leaves and stems of Taxus chinensis were elucidated by means of NMR spectroscopy. Some of the new diterpenes were subjected to X-ray crystallographic analysis. Taxchinins D, G, E, H, I, J, K have an 11(15 → 1)-abeotaxane skeleton. Taxchins A and B possess an ordinary taxane skeleton, and belong to the first example of taxoids without an oxygen functionality or the sp 2 -hybridized carbon at C-4. Taxchinins D, E, I, and J exist as a mixture of conformational isomers in solution, whose behavior was investigated by variable-temperature NMR spectra and compared with the conformation obtained from X-ray analysis.

A conformational analysis of tetragastrin in an aqueous solution was carried out by a Monte-Carlo simulation, assuming a molecular model in a continuous media. The hydration energy of the peptide was evaluated from a calculations of the peptide–water accessible surface area. The tetrapeptide conformers in the low-energy state take an extended form, in which the two aromatic rings on both termini of the peptide are apart. The extended conformation in which the hydrophilic portions are exposed to solvent water is quite different from that in DMSO.

The statistical properties of the bilayer membranes of diparmitoylphosphatidylcholine (DPPC) in the gel and liquid-crystal phases were studied by Monte Carlo (MC) simulation using potential functions of the Lennard-Jones, the simple Coulomb, and the bond torsion. The simulation was undertaken on a two-dimensional periodic condition imposed on the bilayer model consisting of faithfully described molecules. The structure and ordering of the model bilayers accorded well with experiments, and the segment order parameters were in agreement with those of the nuclear magnetic resonance (NMR) experiments. The two kinds of lipid chains of DPPC do not equivalently behave in the bilayers, and chain 2 has lower ordering than chain 1. The order parameters of the first eight segments of chain 2 in the liquid-crystal model are particularly small and are roughly constant. From electron density analysis, it has been observed that the liquid-crystal bilayer has about one excess water molecule per one lipid molecule in comparison with the gel bilayer. The energy difference between the two bilayer models, taking account of the water contribution, is consistent with the latent heat of the phase transition. © 1995 by John Wiley & Sons, Inc.

Methyl methacrylate (MMA) was graft-copolymerized onto cellulose in an aq. FeCl3 solution by the irradiation of UV light. The copolymerization was found to proceed even after the interruption of the irradiation. The addition of the monomer into the polymerization system, which had been beforehand preirradiated in the absence of the monomer, was not followed by the copolymerization. The after effect also increased the molecular weight of the graft PMMA, being isolated from graft product by means of complete hydrolysis of trunk cellulose molecules. However, the increase was not always proportional to the weight increase observed after the interruption. On the other hand, the increase of kinetic chain length caused by the after effect in the AIBN-sensitized grafting systems was found to be nearly proportional to the weight increase of the graft PMMA, The chain lengths were calculated from the number-average molecular weight of the graft PMMA and the weight fraction of truly grafted PMMA chain in the graft PMMA which was determined by subjecting the graft PMMA to thin-layer chromatography. These results may imply that the propagating polymeric free radicals are long-lived ones. In the case of the graft copolymerization by chemical method initiated with AIBN, a linear relationship between the reciprocal of number-average molecular weights of graft PMMA and the first power of the AIBN concentrations shows that the termination mechanism of graft copolymerization is not bimolecular one.

Regio- and stereo-selective synthesis of (E)-alkene dipeptide isosteres has been successfully achieved by exposing both (E)- and (Z)-N-(4-methylphenyl)sulfonyl-γ,δ-epimino-α,β-enoates to organocopper reagents at –78 °C for 30 min.

The crystal structures of the isovaline-containing dipeptides, Boc-D-Iva-L-Pro-NHBzl 4 and Boc-L-Iva-L-Pro-NHBzl 5 were determined by X-ray diffraction. The diastereoisomeric peptides adopt intramolecular hydrogen-bonded β-turn conformations closely similar to each other (4:φIva–51°, ψIva–38°, φPro–70° and ψPro–17° and 5: φIva–53°, ψIva–35°, φPro–72° and ψPro–14°). The Pro ring of each peptide is in Cγ-exo conformation. These conformations are essentially the same as those in the reported crystal structures of the Aib-L-Pro sequence possessing an NH group directly attached to the carbonyl of the L-Pro, indicating that replacement of either one of the two methyl groups of the Aib moiety with an ethyl group does not cause any significant change in the β-turn conformation of the Aib-L-Pro sequence in the crystalline state.CD spectral analysis of the terminal chromophoric group-carrying peptides Dnp-Gly-X-L-Pro-Gly-pNA (X = Aib 6 and D/L-Iva 7/8) has shown that these three tetrapeptides in CHCl3 and THF solutions also adopt a β-turn-type conformation. CD spectra of glycolic acid residue-containing analogues in place of the fourth Gly residue revealed a lack of β-turn tendency in these analogues, indicating the importance of intramolecular hydrogen bonding for the β-turn conformation of the central dipeptide moieties. The results are consistent with the reported unturned crystal structures of Aib-L-Pro arid D/L-Iva-L-Pro sequence-containing peptides lacking the NH group which directly follows the Pro residue available for intramolecular hydrogen bonding.

Methyl methacrylate (MMA) was efficiently graft-copolymerized in aq. FeCl3 solution onto cellulose by the UV irradiation from a high-pressure mercury lamp. While the oxygen removal from the system by means of vigorous evacuation caused the drastic decrease of percent grafting. In this connection PMMA chains prepared in FeCl3-saccharide systems by the UV irradiation were found to scarcely contain saccharide residues at the chain ends, irrespective of the species of the saccharides used. The formation of both Fe2+ and hydrogen peroxide as a result of the irradiation on the reaction systems was confirmed by conducting model reactions. It was suggested from these results that the homopolymerization is initiated with free radicals resulted from the redox reaction between Fe2+ and H2O2, and followed by the grafting via the transfer reaction of the growing homopolymer radicals to cellulose molecules.

Polarized infrared spectra of well-oriented crystalline thin films of dodecylbutyldimethylammonum bromide monohydrate (DBDM·H 2 O) were recorded in the region 5400-250 cm −1 . From the results of the polychroism measurements and the X-ray analysis, water bands were divided into three symmetry species ( A 1 , B 1 , and B 2 ). With the aid of frequencies and isotopic frequency ratios, the water bands were assigned to the three fundamental vibrations, two librations, and their overtones and combinations. In the crystalline environment, we have observed the doublets for each of the vibrationally isolated OH and OD stretching bands of HOD in isotopically diluted monohydrates DBDM·HOD. This spectral feature suggests the presence of two distinct configurations of the water molecule, one forming a strong and linear O 1 H ⋯ Br 1 hydrogen bond and the other forming a weak and slightly bent O 1 H ⋯ Br 2 hydrogen bond. The results in this work are discussed in connection with previous work. The OH stretcing bands in DBDM·H 2 O appear at higher frequency than in dodecylpropyldimethylammonium bromide (DPDM)·H 2 O or in DPDM· 1 2 H 2 O, while the HOH scissoring, rocking, and wagging modes occur at lower frequency. These are consistent with the weaker hydrogen bond of the water molecule and the longer O ⋯ Br hydrogen bond distance in DBDM·H 2 O than in the DPDM hydrates. Correlation between ν(OD) and the O ⋯ Br distance is also argued.

Several chiral 2-nitro-1-sulfinylalkenes were prepared and examined for their utility as dienophiles for asymmetric [4+2] cycloaddition. Trisu- bstituted dienophiles (3-6) undergo distereoselective cycloaddition with cyclopentadiene in the presence of Lewis acids. Even the tetrasubsti- tuted chiral sulfinyl dienophiles (1) and (2) could be coerced into un- dergoing [4+2] cycloaddition to afford the cycloadducts in high yield without concomitant elimination if the reaction was conducted under high pressure. Generally, the Z-sulfinyl dienophiles (1-4) showed higher diastereo- and exdo/exo-selectivity than the E-dienophiles (5) and (6)

Solvent effects were introduced into a Monte-Carlo simulation of peptide conformations by the use of a new potential function for evaluating the nonbonding interactions between solute and solvent molecules. The Monte-Carlo program, which included the electrostatic and nonbonding interactions of the solvent, was tested for a conformation analysis of the zwitterionic tetragastrin in DMSO. The theoretical coupling constants were in good agreement with the NMR data. The conformation of the zwitterion was a folded compact form at the lowest energy, which was different from those obtained from a simulation in vacuo and that without nonbonding solvent effects.

In the graft copolymerization of styrene onto cellulose using benzoyl peroxide (BPO) as initiator graft copolymer was not formed and at the same time the phenomenon suggesting the consumption of BPO with cellulose was observed. Model reactions revealed that the degradation of BPO was accelerated with cellulose and that cellulose was readily oxidized with BPO. These results may imply that BPO/cellulose redox system lacks the ability to intiate graft copolymerization. On the other hand, α, α'-azobisisobutyronitrile was confirmed to bring about the graft copolymerization induced by the transfer reaction of propagating radicals. In this case, the initiator was not consumed with cellulose.

X-Ray crystallographic analysis of two steroid derivatives, 5α,6α-epoxyphysalin B and 2,3-dihydrophysalin B, have been undertaken, revealing their closely similar crystal structures to each other. Their 1H NMR spectra, as well as that of the parent compound physalin B, a 13,14-seco-16,24-cyclosteroid from Physalis alkekengi, have been analyzed based on the crystal structures of these derivatives.

Five new diterpenoids, taxchinins A {3}, B{4}, and C{5}, 19-hydroxy-7-epibaccatin III {6}, and 10-deacetyl-10-oxobaccatin V {7}, have been isolated from the needles and stems of Taxus chinensis together with twelve known compounds including taxol {1}. These structures were elucidated and identified by spectroscopic techniques. A single X-ray crystallographic analysis of taxchinin A {3} determined its unique 51716-membered ring system. Taxchinins B {4} and C {5} were shown to have the same ring system

The crystal structures of the isovaline (Iva) containing dipeptides, Boc-D-Iva-L-Pro-OBzl and Boc-L-Iva-L-Pro-OBzl, were determined by x-ray diffraction. The diastereomeric peptides were shown to adopt unturned conformations closely similar to each other (phi Iva 52 degrees, psi Iva 46 degrees, phi Pro -65 degrees, and psi Pro 143 degrees for D-Iva-L-Pro sequence and phi Iva 52 degrees, psi Iva 44 degrees, phi Pro -63 degrees, and psi Pro 148 degrees for L-Iva-L-Pro sequence). The Pro ring of each peptide was in C gamma-endo conformation. The unusually large angle CIva-NPro-C delta Pro values (131 degrees in both peptides) were observed, that was due to steric repulsion between the delta-methylene of Pro and the alkyl side chain of Iva residue. These conformations were essentially the same as that of the corresponding alpha-aminoisobutyric acid (Aib)-containing peptide Boc-Aib-L-Pro-OBzl. The result has demonstrated that replacement of either one of the two methyl groups of the Aib residue in Boc-Aib-L-Pro-OBzl with an ethyl group does not cause any significant change in the unturned conformation of the dipeptide.

A chiral phosphonoacetate 2 differentiates the enantiotopic carbonyl groups in an α-diketone 5 to afford the Z-olefin 6 in high yield and ee. The absolute stereochemistry of 6 was determined by X-ray analysis of 8 derived from 6.

The crystal and molecular structure of β- d -fructofuranosyl α- d -xylopyranoside (xylosucrose) hemihydrate, C 11 H 20 O 10 ·0.5H 2 O, is orthorhombic, P 2 1 2 1 2, with a = 20.919(5), b = 18.727(2), c = 7.071(1) A, V = 2770.1(2) A 3 , Z = 8, and D x = 1.541 g·cm −3 . The structure was solved by direct methods and refined to R = 0.040 for 2564 observed reflections. Two independent xylosucrose molecules exist in the unit cell, and their conformations about the 1 → 2′ glycosidic bond are similar to sucrose. The orientations of the primary hydroxyl groups in the two molecules differ. An O-1′ ··· O-2 intramolecular hydrogen bond was observed in the one molecule, while an O-6′ ··· O-5 intramolecular hydrogen bond was observed in the other involving disorder of O-6′.

The reactions of protected serine- and threonine-derived γ-(mesyloxy) α,β-unsaturated esters with various magnesio organocyanocopper Lewis acid complexes have been investigated. The formation of syn-S N 2' products in addition to the normally expected anti-S N 2'products is taken as an indication that the reaction proceeds by a mechanism involving coordination of the magnesiocuprate with the C(δ)-N:C(γ)-O syn-γ-(mesyloxy) α,β-enoates

Acrylonitrile (AN) and vinyl acetate (VAc), respectively, were grafted onto viscose rayon (MW=5.0×104) in vapor phase by using potassium persulphate as an initiator. Each graft product was refluxed in 10% aq NaOH for 2hr to yield the viscous solutions. The alkaline solution from the AN graft product was dialyzed for 100hr against running water by the use of cellophane tube as semipermeable membrane to yield the transparent dialyzate solution. The solution from the VAc graft product was neutralized and then dialyzed under the same conditions to produce the transparent dialyzate solution. IR spectra of the solutes of the dialyzate showed characteristic absorptions of both cellulose molecule and the hydrolyzed graft chains. Huggins constant determined for the water-soluble dialyzate from the VAc graft product was about six times that of the PVA sample obtained by hydrolyzing the trunk cellulose molecules. From these results, it may be concluded that water-soluble cellulose graft copolymers could be obtained by grafting hydrophylic vinyl monomers onto cellulose.

The Diels-Alder reaction of chiral 2-alkylsulfinyl-1-nitroalkene 1 and Danishefsky's diene (2) afforded adducts 3 and 4 in good chemical yield with a high enantiomeric excess, while diastereomeric nitroalkene 7 gave 8 and 9 , enantiomeric to 3 and 4 , respectively

The previously proposed structure of an acid-induced dehydration product of physalin A, a 13,14-seco-16,24-cyclosteroid, is revised as having a new carbon skeletal structure named neophysalin. The reaction from physalins to neophysalins proceed via a kind of the benzilic acid rearrangement.

Using the high pressure technique, asymmetric Diels-Alder reaction utilizing chiral 2-nitro-1-sulfinylolefins and dienes proceeded smoothly to give highly functionalized cyclohexene derivatives with satisfactory chemical yield and high diastereomeric excess.

The asymmetric total synthesis of thienamycin-like γ-lactam 1 and its analogue 2 has been accomplished by utilising highly diastereoselective alkylation of tin(II) enolate 5 on acyl imine obtained in situ from chiral 3-substituted 5-acetoxypyrrolidin-2-one 3.

New 5-deazaflavinocyclophane with planar chirality, a novel flavoenzyme model, has been synthesized. This compound provides the first example for selective diastereoface-differentiation during its own reduction and oxidation.

The reactions of protected serine- and threonine-derived γ-(mesyloxy) α,β-unsaturated esters with various magnesio organocyanocopper Lewis acid complexes have been investigated. The formation of syn-S N 2' products in addition to the normally expected anti-S N 2'products is taken as an indication that the reaction proceeds by a mechanism involving coordination of the magnesiocuprate with the C(δ)-N:C(γ)-O syn-γ-(mesyloxy) α,β-enoates

A chiral phosphonoacetate 2 differentiates the enantiotopic carbonyl groups in an α-diketone 5 to afford the Z-olefin 6 in high yield and ee. The absolute stereochemistry of 6 was determined by X-ray analysis of 8 derived from 6.

The stereoselective synthesis of biologically important vinylglycine derivatives by reaction of homochiral 4-methoxycarbonyl-5-vinyloxazolidin-2-ones with organocopper reagents is described; 4,5-trans-oxazolidin-2-one 6 yields (E)-vinylglycines as the major products by treatment with the ‘higher order’ cyanocuprate–BF3 reagents or trialkylzincates in the presence of cuprous cyanide, 4,5-cis-oxazolidin-2-one 10 affords only the desired (E)-vinylglycines.

Several chiral 2-nitro-1-sulfinylalkenes were prepared and examined for their utility as dienophiles for asymmetric [4+2] cycloaddition. Trisu- bstituted dienophiles (3-6) undergo distereoselective cycloaddition with cyclopentadiene in the presence of Lewis acids. Even the tetrasubsti- tuted chiral sulfinyl dienophiles (1) and (2) could be coerced into un- dergoing [4+2] cycloaddition to afford the cycloadducts in high yield without concomitant elimination if the reaction was conducted under high pressure. Generally, the Z-sulfinyl dienophiles (1-4) showed higher diastereo- and exdo/exo-selectivity than the E-dienophiles (5) and (6)

Regio- and stereo-selective synthesis of (E)-alkene dipeptide isosteres has been successfully achieved by exposing both (E)- and (Z)-N-(4-methylphenyl)sulfonyl-γ,δ-epimino-α,β-enoates to organocopper reagents at –78 °C for 30 min.

The stereospecific synthesis is described of the first member of a new class of C-nucleoside analogues in which the sugar ring is replaced with a 1, 3-thiazolidine ring. The 1, 3-thiazolidin-2-yl analogues (1) and (2) of pseudouridine were prepared stereospecifically via condensation of L or D-cysteine with a formylated nucleobase.

Enantiomerically pure (1 R ,2 R ,4 R ,5 R )- and (1 S ,2 R ,4 S ,5 R )-2,5-diphenyl-1,4-diazabicyclo[2.2.2]octane (2,5-diphenyl-DABCO) have been prepared and their crystal structures studied.

Azamacrocycles 1–4 were synthesized from 9 in 20–30% overall yields. Compounds 1 and 2 extracted some metal ions into organic solvents, but 3 and 4 did not. The crystal structure of the Ag(I) complex of 1 has been determined.

The enantiomers, (R)-(-)-1 and (S)-(+)-1, of (+/-)-4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3- dihydro-2-methylbenzo[b]furan-7-carboxamide [(+/-)-1] were prepared from optically active benzyl 4-acetylamino-2,3-dihydro-2-methylbenzo[b]furan-7-carboxylate [(R)-(+)-6, (S)-(-)-6], respectively. The requisite (R)-(+)-6 and (S)-(-)-6 were prepared by large-scale preparative HPLC on chiral stationary phases (CSPs). The absolute configuration of (S)-(+)-1 was determined by single crystal X-ray analysis. The serotonin 5-HT4 receptor agonistic activity of (S)-(-)-1 hemifumarate (SK-951) which was hemifumarate of (S)-(+)-1 was about twice that of the other enantiomer (R)-(+)-1 hemifumarate which was hemifumarate of (R)-(-)-1.