Yasutaka Shimotori

Enantioselective Synthesis of δ-Lactones with Lipase-Catalyzed Resolution and Mitsunobu Reaction

Abstract Both enantiomers of a series of δ-lactones (e.g., δ-decalactone, δ-dodelactone, and δ-hexadecalactone) were synthesized stereoselectively by Novozym 435–catalyzed resolution. Furthermore, only (S)-enantiomers of δ-lactones were synthesized with a combination of Novozym 435–catalyzed resolution and Mitsunobu reaction. GRAPHICAL ABSTRACT

Synthesis of hydroxycinnamoyl β-d-xylopyranosides and evaluation of their antioxidant properties

Various hydroxycinnamoyl β-d-xylopyranosides were efficiently prepared from 2,3,4-tri-O-acetyl-α-d-xylopyranosyl bromide (TAXB) with amine by amine-promoted glycosylation. The resulted acetylated hydroxycinnamoyl β-d-xylopyranosides with acetoxy groups at C-2, C-3, and C-4 were regioselectively deacetylated at C-4 position with Novozym 435. Antioxidant activities of free hydroxycinnamic acids and the respective β-d-xylopyranosides were evaluated by DPPH radical scavenging activity as well as their inhibitory effect on autoxidation of bulk methyl linoleate. The radical scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) decreased in the order ferulic acid>caffeic acid≈caffeoyl β-d-xylopyranosides≈sinapinic acid>sinapoyl β-d-xylopyranosides≈feruloyl β-d-xylopyranosides>p-coumaric acid>p-coumaroyl β-d-xylopyranosides. In bulk methyl linoleate, the antioxidant activity order against autoxidation was almost consistent with the scavenging activity order. The results showed that caffeoyl β-d-xylopyranosides and sinapoyl β-d-xylopyranosides were as effective as free caffeic acid, sinapinic acid, and ferulic acid.

Solventless Delignification of Wood Flour with TiO2/poly(ethylene oxide) Photocatalyst System

A novel solventless delignification of a defatted Picea glehnii wood flour sample was performed using a TiO2/polyethylene oxide (PEO) photocatalyst system. A cell wall structure of the wood flour was directly observed, showing that its lignin fraction was removed by the photodegradation. The total lignin amount was slightly decreased as compared with that of the pristine sample, and the vanillin formation was confirmed by the 1H-NMR measurement. The TiO2 worked as a radical initiator, and simultaneously acid and aldehyde compounds produced by the PEO photolysis did as an accelerator for the solventless delignification. Although the photocatalyst system showed high delignification activity even for a low molecular lignin model, the delignification of the wood flour sample was confined to the surface. It was found that the suppressed delignification behavior was due to crosslinked structure of lignin.

Synthesis of glycosyl ferulate derivatives by amine-promoted glycosylation with regioselective hydrolysis using Novozym 435 and evaluation of their antioxidant properties

Various glycosyl ferulates were efficiently synthesized from 2,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (TAGB) with amine by amine-promoted glycosylation without using heavy metal. The resulted acetylated glycosyl ferulates with acetoxyl groups at C-2, C-3 and C-4 were regioselectively deacetylated at C-4 and C-6 positions with Novozym 435. Antioxidant abilities of free ferulic acids and its synthetic glycosyl ferulates were evaluated by inhibitory effect on autoxidation of bulk methyl linoleate as well as their radical scavenging activity. The radical scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH·) decreased in the order ferulic acid>sinapinic acid ≈ glycosyl sinapinates ≈ glycosyl ferulates>p-coumaric acid>glycosyl p-coumarates. In bulk methyl linoleate, the antioxidant activity order against autoxidation was very consistent with the scavenging activity order. The results showed that glycosyl ferulates and sinapinates were effective as well as free carboxylic acid forms.

Preparation of Optically Pure δ-Lactones Using Diastereomeric Resolution with Amino Acid as Resolving Agent

Synthesis of optically pure δ-lactones by diastereomeric resolution was investigated. Amino acid derivatives, which can be obtained at a relatively low cost, were used as resolving agents. Six optically pure δ-lactones were efficiently synthesized using Cbz-L-alanine without other expensive resolving agents. Both enantiomers of δ-lactone obtained had over 98% enantiomeric excesses. This diastereomeric resolution is very efficient for the preparation of optically pure δ-lactones.

Combination of Novozym 435-catalyzed Enantioselective Hydrolysis and Amidation for the Preparation of Optically Active δ-Hexadecalactone

A new enzymatic method for synthesis of enantiomerically enriched δ-hexadecalactone (3) based on the enzymatic kinetic resolution of N-methyl-5-acetoxyhexadecanamide (1) is described. A combination of lipase-catalyzed hydrolysis and amidation improved enantioselectivity. Lipase-catalyzed amidation was also investigated. Detailed screening of solvents and additive amines was performed. The addition of cyclohexylamine to lipase-catalyzed hydrolysis afforded the best results to give both enantiomers of 3 with more than 90% enantiomeric excess.

Preparation of Optically Active δ-Tri- and δ-Tetradecalactones by a Combination of Novozym 435-catalyzed Enantioselective Methanolysis and Amidation

A combination of Novozym 435-catalyzed methanolysis and amidation using racemic N-methyl-5-acetoxytridecan- and tetradecanamides as a substrate proceeded in good enantioselectivity to afford the corresponding (R)-N-methyl-5-acetoxyalkanamides, (S)-N-methyl-5-hydroxyalkanamides, and (S)-N-cyclohexyl-5-hydroxyalkanamides. Both enantiomers of δ-tri- and δ-tetradecalactones were synthesized in over 90% enantiomeric excesses from the corresponding (R)- or (S)-alkanamides. Addition of cyclohexylamine to Novozym 435-catalyzed methanolysis shortened 24-hour reaction time to reach about 50% conversion. Enantiomers of optically active δ-tri- and δ-tetradecalactones had different odors and thresholds.

Microbial xylitol production from culm of Sasa kurilensis using the yeast Candida magnoliae

Abstract A sugar solution containing 31 g l-1 xylose was prepared from the culm of Sasa kurilensis by hydrolysis with 2% sulfuric acid with a liquor-to-solid ratio of 6 (g g-1) at 121°C for 1 h. During acid hydrolysis, also some byproducts were generated, such as acetic acid, furfural, 5-hydroxymethylfurfral, and low molecular weight phenolics, which inhibit bioconversion of xylose to xylitol. Except for acetic acid, these inhibitors were successfully removed from the hydrolysate by contacting with a steam-activated charcoal (15 g l-1 dose) for 24 h. Bioconversion of the detoxified hydrolysate to xylitol by the yeast, Candida magnoliae, was investigated under various microaerobic conditions. The oxygen transfer rate (OTR) varied from 8.4 to 27.6 mmol-O2 l-1 h-1. The maximum xylitol yield (0.62 g-xylitol g-xylose-1) was attained at the OTR of 1.2 mmol-O2 l-1 h-1. An additional increase in the OTR brought about cell growth, which consumed xylose. A proper control of the oxygen supply is necessary to produce efficiently xylitol from the culm hydrolysate.

One-pot synthesis of 1-arylmethyl-4-[(E)-alk-1-enyl]-1H-1,2,3-triazoles via a cross-coupling/click reaction sequence

1-Arylmethyl-4-[(E)-alk-1-enyl]-1H-1,2,3-triazoles have been synthesized from terminal conjugated (E)-enynes, prepared by copper-mediated cross-coupling reaction of (E)-alk-1-enyldisiamylboranes with (trimethylsilyl)ethynyl bromide, benzyl bromides and sodium azide in a one-pot fashion. In this cross-coupling/click reaction sequence, the copper precursor Cu(acac)2 can serve as a tandem catalyst.

Synthesis of dibenzothiazepine analogues by one-pot S-arylation and intramolecular cyclization of diaryl sulfides and evaluation of antibacterial properties

Abstract Dibenzothiazepine analogues containing lactam, amidine and imine moieties were prepared from 2-aminophenyl disulfides via one-pot S-arylation. The S-arylation involved cleavage of an S-S bond of disulfides and SNAr reaction in aqueous ammonia solution of L-cysteine to afford diaryl sulfides. Dibenzothiazepine analogues having lactam and amidine moieties were obtained by cyclization of the corresponding diaryl sulfides under acidic conditions. One-pot S-arylation of 2-bromo-5-nitrobenzaldehyde gave dibenzothiazepine analogues with an imine moiety in one step through intramolecular cyclization. Compounds with antibacterial activities against Staphylococcus aureus and Escherichia coli were obtained.