Tadashi Kometani

The effect of vinyl esters on the enantioselectivity of the lipase-catalysed transesterification of alcohols

Abstract The enantioselectivity of the lipase from Pseudomonas cepacia (PCL) in the transesterification of 2-phenyl-1-propanol 1 was studied using a series of vinyl 3-arylpropanoates as acyl donors. The most enantioselective transesterification reaction of the alcohol was attained by using vinyl 3-( p -iodophenyl)- or 3-( p -trifluoromethylphenyl)propanoates, with enantiomer ratios, E , of 116 and 138, respectively. Vinyl 3-phenylpropanoate was also effective for the resolution of 1 mediated by lipases from P . fluorescens and porcine pancreas and for the PCL-catalysed transesterification of several 2-phenyl-1-alkanols. The enantiomeric resolution of 1 was practically carried out by the first enantioselective transesterification using PCL and vinyl 3-( p -iodophenyl)propanoate to afford ( R )- 1 and then the enantioselective hydrolysis of the resultant ester to afford ( S )- 1 .

Large-scale preparation of (S)-ethyl 3-hydroxybutanoate with a high enantiomeric excess through baker's yeast-mediated bioreduction

Abstract Large-scale preparation of ( S )-ethyl 3-hydroxybutanoate (E 3-HB), an important chiral starting material, by bakers yeast-mediated bloreduction of ethyl acetoacetate was investigated. In preliminary studies, we found that the procedure using ethanol as an energy source for the bioreduction, which we developed recently, was better than that using carbohydrate for large-scale preparation, as the cells were inactivated faster with carbohydrate than ethanol. Both the yield and the optical purity of the product were considerably improved by applying the fed-batch operation to the yeast-mediated bioreduction using ethanol as an energy source. In this method, the concentrations of ethyl acetoacetate and ethanol were maintained during the reaction at less than 1 mM and about 200 mM, respectively. Finally, large-scale preparation of ( S )-E 3-HB was effectively performed using a bubble-column reactor with 10 l of medium, and the final reaction medium contained 6% (w/w) ( S )-E 3-HB with > 99% enantiomeric excess. Thus, a new scaled-up method based on the use of ethanol as the energy source was devised for bakers yeast-mediated bioreduction.

Oxidation of Linoleic Acid Encapsulated with Soluble Soybean Polysaccharide by Spray-drying

Linoleic acid was encapsulated with a soluble soybean polysaccharide, gum arabic, or a mixture of both together with maltodextrin, and the oxidation process of the encapsulated acid was measured at 37°C and at a relative humidity of 12%. The soybean polysaccharide was more effective for encapsulating the acid and suppressing the oxidation of the encapsulated acid than gum arabic. A mixture of the soybean polysaccharide and maltodextrin was also effective for this purpose when the weight fraction of the polysaccharide was equal to or greater than 0.75.

Lipase-catalyzed transesterification of 2-phenyl-1-propanol with vinyl esters having aromatic ring in acyl moiety

Abstract The highly enantioselective transesterification of 2-phenyl-1-propanol, which has not been efficiently resolved by lipase-catalyzed reactions, was attained by using either vinyl 3-( p -tolyl)propanoate or vinyl 3-(2-naphthyl)propanoate as the acyl donor.

Baker's yeast mediated bioreduction: Practical procedure using EtOH as energy source

Abstract Bakers yeast mediated bloreduction of prochiral ketones was investigated with respect to its energy source. The rate of glucose consumption was five times that of the reduction of ethyl acetoacetate (EA), and the reduction of EA proceeded under aerobic condition after glucose had been consumed. From these results, reduction by bakers yeast based on the regeneration system for NAD (P) H through the oxidative pathway of ethyl alenhol (EtOH) was developed. Under anaerobic conditions, reduction by the new procedure did not occur. The optimum conditions of EtOH concentration and temperature were about 200 mM and 30°C, respectively. At higher than 400 mM EtOH concentration, the reduction soon leveled off. The rate of EtOH consumption was less than twice that of EA reduction, and no by-products except for carbon dioxide were detected, so the new procedure is a practical one.

Asymmetric synthesis of 2-substituted chroman-4-ones using lipase-catalyzed kinetic resolutions

2-Methylchroman-4-one and 2-phenylchroman-4-one were synthesized in optically active form. Their chiral intermediates were obtained via lipase-catalyzed enantioselective reactions.

NAD(P)H regeneration using ethanol as an energy source in baker's yeast-mediated bioreduction

Abstract A scheme for NAD(P)H regeneration from the corresponding oxidized form through the oxidative pathway of ethanol in bakers yeast cells was studied. Bakers yeast-mediated bioreduction of carbonyl compounds coupled with the oxidative pathway of ethanol is efficient and clean compared with the earlier procedure using carbohydrates as the energy source. To study NADH regeneration, the bioreduction of acetol catalyzed by NADH-dependent carbonyl-reducing enzymes was examined by using ethanol or acetate as the energy source under several aeration conditions, including an anaerobic environment. The results suggested that NAD+ formed on the reduction of the carbonyl group was mainly regenerated as NADH through alcoholic oxidation into acetate. NADPH regeneration was then studied in the same manner by examining the bioreduction of ethyl acetoacetate catalyzed by NADPH-dependent carbonyl-reducing enzymes. The results suggested that NADPH was regenerated through acetate oxidation into carbon dioxide. Thus, a total scheme for NAD(P)H regeneration using ethanol as the energy source, coupled with bioreduction, was proposed.

Large-scale preparation of (R)-1,2-propanediol through baker's yeast-mediated bioreduction

Abstract A procedure for the preparation of ( R )-1,2-propanediol on a large scale by bakers yeast-mediated bioreduction of acetol using ethanol as an energy source is reported. The bioreduction, catalyzed by NADH-dependent oxidoreductase, was effectively performed using a bubble-column reactor with fed-batch operation. When the reactor with 10 l of medium was bubbled at an aeration rate of 3 l /min, the final reaction medium contained 4 %(w/w) ( R )-1,2-propanediol with >98% enantiomeric excess.

A synthesis of succinimides and glutarimides from cyclic anhydrides

Abstract The transformation of cyclic anhydrides to their corresponding imides involves a mild three-step sequence: (1) reaction with a primary amine, (2) conversion of the intermediate monoamide to an N-hydroxysuccinimidyl ester using N,N′-disuccinimidyl oxalate (DSO), and (3) cyclization by heating the NHS ester in trichloroethylene in the presence of 4-(dimethylamino)pyridine.

Pyranonaphthoquinone antibiotics. Part 2. Syntheses of (±)-nanaomycin A and (±)-eleutherins

Two routes for the synthesis of (±)-nanaomycin A (1) starting with 2-bromo-8-methoxy-1,4-naphthoquinone (2) are described. The benzindanone (3) prepared from (2) in three steps was treated with methylmagnesium iodide and then with hydrochloric acid to afford the benzindene (8). Lemieux–Johnson oxidation of (8) gave the ketoaldehyde (9), which was converted into the conjugated ester (10) by reaction with methoxycarbonylmethylenetriphenylphosphorane. Reductive cyclisation of (10) with sodium borohydride afforded a ca. 1 : 1.9 mixture of the cis-naphthopyran (11) and its trans-isomer (12). Oxidative demethylation of (11) and (12) with cerium (IV) followed by treatment with aluminium chloride yielded the corresponding quinones (15) and (16). Ester hydrolysis of (16) formed (±)-nanaomycin A (1). Reductive methylation of the 2-allyl derivative of (2) afforded the bromonaphthalene (18), which was treated with butyl-lithium followed by acetaldehyde to give the naphthylcarbinol (19). The lactol (20) obtained by Lemieux–Johnson oxidation of (19) was treated with trimethyl phosphonoacetate–sodium hydride to yield a ca. 2.1 : 1 mixture of the naphthopyrans (11) and (12). Cyclisation of (19) with mercury-(II) acetate–sodium borohydride yielded a ca. 1 : 0.9 mixture of the cis-naphthopyran (21) and its trans-isomer (22), which were oxidatively demethylated to give (±)-eleutherin (4) and (±)-isoeleutherin (5) respectively.